Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic architecture and treatment outcome in pediatric acute myeloid leukemia: a Children's Oncology Group report.

Childhood acute myeloid leukemia (AML) is frequently characterized by chromosomal instability. Approximately 50% of patients have disease relapse, and novel prognostic markers are needed to improve risk stratification. We performed genome-wide genotyping in 446 pediatric patients with de novo AML enrolled in Children's Oncology Group (COG) studies AAML0531, AAML03P1, and CCG2961. Affymetrix and Illumina Omni 2.5 platforms were used to evaluate copy-number alterations (CNAs) and determine their associations with treatment outcome. Data from Affymetrix and Illumina studies were jointly analyzed with ASCAT and GISTIC software. An average of 1.14 somatically acquired CNAs per patient were observed. Novel reoccurring altered genomic regions were identified, and the presence of CNAs was found to be associated with decreased 3-year overall survival (OS), event-free survival (EFS), and relapse risk from the end of induction 1 (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.2-2.4; HR, 1.4; 95% CI, 1.0-1.8; and HR, 1.4; 95% CI, 1.0-2.0, respectively). Analyses by risk group demonstrated decreased OS and EFS in the standard-risk group only (HR, 1.9; 95% CI, 1.1-3.3 and HR, 1.7; 95% CI, 1.1-2.6, respectively). Additional studies are required to test the prognostic significance of CNA presence in disease relapse in patients with AML. COG studies AAML0531, AAML03P1, and CCG2961 were registered at www.clinicaltrials. gov as #NCT01407757, #NCT00070174, and #NCT00003790, respectively.
Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 5th ed.

Since publication of the First Edition in 1982, Hemostasis and Thrombosis has established itself as the pre-eminent book in the field of coagulation disorders. No other book is as inclusive in scope, with coverage of the field from the standpoint of both basic scientists and clinicians. This comprehensive resource details the essentials of bleeding and thrombotic disorders and the management of patients with these and related problems, and delivers the most up-to-date information on normal biochemistry and function of platelets or endothelial cells, as well as in-depth discussions of the pharmacology of anticoagulant, fibrinolytic, and hemostatic drugs.
Micrometastases: marker of metastatic potential or evidence of residual disease?

BACKGROUND: Micrometastases within bone marrow have been shown to indicate a poor prognosis in patients with epithelial tumours. However, the degree to which micrometastases represent true residual disease or cell shedding and metastatic potential, is unclear. AIM: To explore whether micrometastases represent residual disease, bone marrow taken from carefully staged patients before and after (> 6 months) "curative" resection of a primary gastrointestinal cancer was studied prospectively. PATIENTS/METHODS: Seventy two consecutive patients were studied; the only exclusions were patients with known overt metastatic disease at the time of surgery. Micrometastatic cells were quantified per 10(5) marrow cells by flow cytometry after staining for contaminant cytokeratin-18 positive cells. RESULTS: Micrometastases were detected preoperatively in 22% (16/72) of all patients, comprising 11 (23%) of 48 with colorectal cancer, five (33%) of 15 with gastric adenocarcinoma and none (0%) of nine with oesophageal squamous cancer. Although fewer metastatic cells were detected in postoperative bone marrow, and clearance of marrow deposits was evident in most patients, the persistence of micrometastases in five of 16 patients after resection, without evidence of tumour recurrence, indicates a subset with true residual disease. Detection of micrometastases postoperatively (persistent or newly developed) was significantly associated with development of overt metastases during the subsequent 12-18 months of follow up (nine of 19 patients) when compared with patients testing negative for micrometastases (eight of 53; p < 0.01). CONCLUSIONS: Preoperative detection of micrometastases may reflect either transient shedding of cells, metastatic potential or residual disease, but postoperative micrometastases indicate minimal residual disease. Identification of these patients is important because they may benefit from adjuvant therapy.
The epidemiology of hepatitis C in a UK health regional population of 5.12 million

BACKGROUND The epidemiology and natural history of hepatitis C virus (HCV) infection in the UK are uncertain. Previous reports are from small or selected populations such as blood donors or tertiary referral centres. AIMS To study the epidemiology and natural history of HCV infection. METHODS Prospective study incorporating five centres within the Trent region. Patients were managed and followed up according to a commonly agreed protocol. SUBJECTS A total of 1128 HCV positive patients. Patients with haemophilia, human immunodeficiency virus, and chronic renal failure were excluded. RESULTS Between September 1991 and December 1998, 2546 anti-HCV positive patients were identified of whom 1128 (44%) were enrolled in the cohort. A risk factor(s) for infection was identified in 93.4% of patients who completed the questionnaire; 81% of patients were HCV RNA positive. A total of 397 initial liver biopsies were scored by a single pathologist. These showed a correlation between high alcohol intake and fibrosis score. Multivariate analysis showed fibrosis to be associated with age over 40, past evidence of hepatitis B virus infection, and higher necroinflammatory grade but not with sex, viral genotype, maximum known alcohol intake, estimated duration of infection, or mode of transmission. Twelve (7.8%) of 153 patients who received interferon therapy had sustained serum virus clearance. Sixty six patients have died during the follow up period, 31 with a liver related cause of death. This represents a considerable excess over the expected death rate for a cohort of this age and sex distribution. CONCLUSIONS HCV infection is an emerging health problem in the Trent region. Identifying risk factors for infection and disease severity will enhance understanding and facilitate improved intervention. An excess mortality in infected individuals is already evident in this unselected cohort.
High versus Low Density Special Care Units: Impact on the Behaviour of Elderly Residents with Dementia

RÉSUMÉ L'ouverture d'une nouvelle unité de soins spéciaux a permis d'étudier l'effet de la densité sociale réduite (moins de résidents) et de la densité spatiale (plus d'espace par personne) sur le comportement de résidents avec démence. Deux groupes (N = 64) ont été observés pendant trois périodes espacées de six mois chacune. Tel que théorisé, il y a eu plus d'amélioration dans le comportement perturbateur et non perturbateur du groupe expérimental (passant de haute à basse densité) par rapport au groupe de comparaison (haute densité constante). Les résultats indiquent que la densité de l'unité résidentielle est un déterminant important pour le comportement des résidents âgés avec démence. ABSTRACT The opening of a new Special Care Unit provided the opportunity to study the effect of reduced social density (fewer residents) and spatial density (more area per person) on the behaviour of residents with dementia. Two groups (N = 64) were observed at three periods spaced six months apart. As hypothesized, there was a greater improvement in Disruptive and Nondisruptive behaviour in the experimental group (move from high to low density) compared to the comparison group (constant high density). Findings suggest that unit density is an important determinant of behaviour in elderly residents with dementia.
Overexpression of the CD155 gene in human colorectal carcinoma

BACKGROUND AND AIMS The Tage4 gene (tumour associated glycoprotein E4) is overexpressed in rat colon tumours and Min mouse intestinal adenomas. The rat Tage4 protein has approximately 40% identity with human CD155, a member of the immunoglobulin superfamily coding for a transmembrane protein capable of serving as an entry receptor for poliovirus, porcine pseudorabies virus, and bovine herpesvirus 1. Analysis of the ratTage4 gene has revealed structural and functional similarities with the human CD155gene. We therefore investigated expression of theCD155 gene in human colorectal carcinomas. METHODS Overall CD155 expression was assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analysis using tissue specimens from patients with colorectal adenomas and adenocarcinomas. We also used a qualitative RT-PCR assay to determine relative expression of different splicing variants in each sample. RESULTS mRNA levels of CD155 were increased in six of six colorectal cancer tissues compared with the tumour free colon mucosa. Immunohistochemical analysis revealed an increased level of CD155 protein in 12 of 12 samples. The qualitative RT-PCR assay revealed that relative expression of the different CD155 variant transcripts was similar in the different normal and cancer samples tested, indicating that this overexpression is not associated with a particular mRNA variant generated by alternative splicing of the CD155 gene. CONCLUSION We have shown for the first time that the CD155 gene is overexpressed in colorectal carcinoma and that this overexpression begins at an early stage in tumorigenesis and continues to late stages.
Blocking transferrin receptor inhibits the growth of lung adenocarcinoma cells in vitro

Transferrin receptor (TfR) is expressed in most lung cancers and is an indicator of poor prognosis in certain groups of patients. In this study, we blocked cell surface TfR to inhibit lung adenocarcinoma (LAC) cell growth in vitro and investigated the associated molecular mechanisms to determine a potential therapeutic target in human LAC.
Extracellular MUC3 mucin secretion follows adherence of Lactobacillus strains to intestinal epithelial cells in vitro

Background: Mucins are large complex glycoproteins that protect intestinal mucosal surfaces by limiting access of environmental matter to their epithelial cells. Several mucin genes have been described, including MUC3 that is a membrane associated mucin of the small intestine. Increased MUC3 mRNA transcription is induced by incubation of intestinal epithelial cells with a Lactobacillus strain known to be adherent to them. Aims: To determine whether increased epithelial cell MUC3 mucin expression in response to Lactobacillus strains results in increased extracellular secretion of MUC3 mucins and the importance of epithelial cell adherence in modulation of MUC3 mucin expression. Methods: HT29 cells grown to enhance expression of MUC3 mucins were incubated with selected Lactobacillus strains. Spent cell culture medium was collected for detection of secreted MUC3 mucins using dot blot immunoassay with a generated MUC3 antibody. Post-incubation HT29 cell RNA was collected for analysis of MUC3 expression by northern blot analysis using a MUC3 cDNA probe. In vitro binding studies using Lactobacillus strains incubated alone or coincubated with enteropathogenic Escherichia coli strain E2348/69 were used for adherence and inhibition of adherence studies, respectively. Results:Lactobacillus strains with minimal ability to adhere to HT29 cells failed to induce upregulation of mucin gene expression. There was a direct correlation between upregulation of MUC3 mucin mRNA expression and extracellular secretion of MUC3 mucin. The same Lactobacillus strains that increased extracellular secretion of MUC3 mucin led to reduced adherence of enteropathogen E coli E2348/69 during coincubation experiments. Conclusion: Probiotic microbes induce MUC3 mucin transcription and translation with extracellular secretion of the MUC3 mucins. Epithelial cell adherence enhances the effects of probiotics on eukaryotic mucin expression.
Hitting the target in IDH2 mutant AML.

In this issue of Blood, Stein et al1 demonstrate the feasibility and clinical efficacy of targeted inhibition of mutant isocitrate dehydrogenase 2 (IDH2) in patients with acute myeloid leukemia (AML). In a related paper, Amatangelo et al2 investigate mechanisms of response in samples derived from the same patients.
Genetic risk stratification to reduce inhibitor development in the early treatment of hemophilia A: a SIPPET analysis.

A recent randomized trial, the Survey of Inhibitors in Plasma-Product Exposed Toddlers (SIPPET), showed a higher risk of inhibitor development with recombinant factor VIII (rFVIII) than plasma-derived concentrates (pdFVIII). We investigated whether risk stratification by F8 mutation identifies patients who do not suffer this deleterious effect of rFVIII. Among 235 randomized patients with severe hemophilia A previously untreated with FVIII concentrate, 197 with null mutations were classified as high risk and 38 with non-null mutations were classified as low risk. With pdFVIII, no inhibitors occurred in those with low genetic risk, whereas high-risk patients had a cumulative incidence of 31%. The risk among low- and high-risk patients did not differ much when they were treated with rFVIII (43% and 47%, respectively). This implies that patients with low genetic risk suffer disproportionate harm when treated with rFVIII (risk increment 43%), as also shown by the number needed to harm with rFVIII, which was 6.3 for genetically high-risk patients and only 2.3 for low-risk patients. Risk stratification by F8 mutation does not identify patients who can be safely treated with rFVIII, as relates to immunogenicity. This trial was registered at the European Clinical Trials Database (EudraCT) as #2009-011186-88 and at www.clinicaltrials. gov as #NCT01064284.
Development and Psychometric Evaluation of a Questionnaire Based on the Nursing Outcomes Classification to Determine the Knowledge of Parents on Breast-Feeding: Research Protocol.

PURPOSE To develop and psychometrically evaluate a questionnaire based on the outcome "Knowledge: Breast-feeding" of the Nursing Outcomes Classification (NOC) to determine the knowledge of parents on breast-feeding. BACKGROUND The NOC outcome "Knowledge: Breast-feeding" allows for nurses/midwives to assess the efficacy of interventions aimed to improve the knowledge on breast-feeding in parents thought the clinical interview/observation. However, the use of self-administered questionnaires by patients could facilitate its evaluation. METHODS Two-phased study: (1) Development of the questionnaire based on experts' opinions; (2) Methodological design to assess its psychometric properties. IMPLICATIONS FOR NURSING PRACTICE The availability of tools that enable the determination of the knowledge of patients would facilitate nurses/midwives to set objectives, individualize interventions, and measure their effectiveness.
Allogeneic mesenchymal stem cell transplantation in seven patients with refractory inflammatory bowel disease

We refer to two articles by Duijvestein et al and Ciccocioppo et al 1 2 in which the authors suggest that administration of autologous bone marrow-derived mesenchymal stem cells (MSCs) is safe and feasible in the treatment of refractory Crohn's disease (CD). However, to date there are few data about allogeneic MSC transplantation (MSCT) for patients with inflammatory bowel disease (IBD). We wish to report our experience of allogeneic MSCT in seven patients with IBD. Infused allogeneic MSCs were obtained from the bone marrow or umbilical cord. Bone marrow was aspirated from healthy relatives of three patients. Umbilical cords were obtained from local maternity hospitals after normal deliveries. The isolated MSCs were given by intravenous infusions …
A block matching algorithm with 16:1 subsampling and its hardware design

Conventional full search block matching algorithm (BMA) for motion estimation is computationally intensive and the resulting hardware cost is very high. In this paper, we present an efficient BMA using a 16:1 subsampling technique, and describe its hardware design. The algorithm reduces the number of pixels in calculating the mean absolute difference at each search location, instead of reducing the search locations. The algorithm is an extension of the BMA with 4:1 subsampling proposed by Lin and Zaccarin (1993) such that the amount of computation is reduced by a factor of 4 (16 compared to the full search BMA) while producing similar performance. The algorithm can efficiently be designed into a hardware for real-time applications.
Hepatic cell-to-cell transmission of small silencing RNA can extend the therapeutic reach of RNA interference (RNAi)

Background/aims RNA interference (RNAi), a sequence-specific gene silencing technology triggered by small interfering RNA (siRNA), represents promising new avenues for treatment of various liver diseases including hepatitis C virus (HCV) infection. In plants and invertebrates, RNAi provides an important mechanism of cellular defence against viral pathogens and is dependent on the spread of siRNA to neighbouring cells. A study was undertaken to investigate whether vector-delivered RNAi can transfer between hepatic cells in vitro and in mice, and whether this exchange could extend the therapeutic effect of RNAi against HCV infection. Methods Transmission of RNAi was investigated in culture by assessing silencing of HCV replication and expression of viral entry receptor CD81 using a human hepatic cell line and primary B lymphocytes transduced with siRNA-expressing vectors. In vivo transmission between hepatic cells was investigated in NOD/SCID mice. Involvement of exosomes was demonstrated by purification, uptake and mass spectrometric analysis. Results Human and mouse liver cells, as well as primary human B cells, were found to have the ability to exchange small RNAs, including cellular endogenous microRNA and delivered siRNA targeting HCV or CD81. The transmission of RNAi was largely independent of cell contact and partially mediated by exosomes. Evidence of RNAi transmission in vivo was observed in NOD/SCID mice engrafted with human hepatoma cells producing CD81 siRNA, causing suppression of CD81 expression in mouse hepatocytes. Conclusion Both human and mouse hepatic cells exchange small silencing RNAs, partially mediated by shuttling of exosomes. Transmission of siRNA potentially extends the therapeutic reach of RNAi-based therapies against HCV as well as other liver diseases.
Effects of the Frontiers Prevention Project in Ecuador on sexual behaviours and sexually transmitted infections amongst men who have sex with men and female sex workers: challenges on evaluating complex interventions

In this study, the authors evaluate the impact of the Frontiers Prevention Project (FPP), a community-based strategy for HIV prevention amongst female sex workers (FSW) and men who have sex with men (MSM) in Ecuador. The FPP impact evaluation methodology consisted of a community trial with randomised intervention/comparison assignment and pre-post surveys in six cities in Ecuador (2003–2007). The results suggest prevention strategies involving key populations in their design and implementation can contribute to abating risk behaviours in Ecuador. However, the FPP experience also shows that implementing and evaluating large-scale HIV prevention programmes still present important challenges.
Non-rigid connectors in fixed prosthodontics: Current concepts with a case report

The occlusal forces applied to a fixed partial denture (FPD) are transmitted to the supporting structures through the pontic, connectors, and retainers. Variables that may influence the longevity of an FPD and its abutment include occlusion, span length, bone loss, and quality of periodontium. The excessive flexing of the long-span FPD, which varies with the cube of the length of span, can lead to material failure of prosthesis or to an unfavorable response. Biomechanical factors such as overload, leverage, torque and flexing, induce abnormal stress concentration in an FPD. Stress concentration is found in the connectors of the prosthesis and in the cervical dentin area near the edentulous ridge. This factor plays an important role in the potential for failure in long-span FPD. The conventional use of a nonrigid connector (NRC) aids in compensating for the difference in the resistance and retention form between the abutments. The design and passive fit of NRC is critical to the success of a long-span FPD. This paper presents the current concepts in the design of an NRC and a case report of Pier abutment treated with FPD having Tenon-Mortise Connector.
Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment

Background and aims The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation. Methods Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells. Results Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect. Conclusions Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.