Miracle-dz/UniFAR-FTUs huggingface dataset:
Neovascular targeting therapy: paclitaxel encapsulated in cationic liposomes improves antitumoral efficacy.

PURPOSE Cationic liposomes have been shown to selectively target tumor endothelial cells. Therefore, the encapsulation of antineoplastic drugs into cationic liposomes is a promising tool to improve selective drug delivery by targeting tumor vasculature. It was the aim of our study to evaluate tumor selectivity and antitumoral efficacy of paclitaxel encapsulated in cationic liposomes in comparison with the free drug paclitaxel (Taxol(R)) in vivo. EXPERIMENTAL DESIGN Experiments evaluating tumor selectivity were carried out in male Syrian golden hamsters bearing the amelanotic hamster melanoma A-Mel-3 in dorsal skinfold preparations. Growth of tumor cells was observed after s.c. inoculation (day 0). On days 5, 7, 9, 12, 14, and 16, animals were treated by continuous i.v. infusion over 90 min with 5% glucose, Taxol(R), unloaded cationic liposomes, or paclitaxel encapsulated into cationic liposomes (LipoPac), respectively (lipid dose, 150 mg/kg body weight; paclitaxel dose, 5 mg/kg body weight). Tumor volumes and presence of regional lymph node metastases were quantified. RESULTS Vascular targeting of rhodamine-labeled cationic liposomes was maintained after encapsulation of paclitaxel as revealed by in vivo fluorescence microscopy (ratio of dye concentration, tumor:normal tissue = 3:1). The s.c. tumor growth revealed a remarkable retardation of tumor growth after treatment with LipoPac (1.7 +/- 0.3 cm(3)). In contrast, control tumors showed exponential tumor growth [tumor volume at the end of the observation period (mean +/- SE): 5% glucose, 17.7 +/- 1.9 cm(3); unloaded cationic liposomes, 10.0 +/- 1.6 cm(3); Taxol(R), 10.7 +/- 1.7 cm(3)]. In addition, the appearance of regional lymph node metastases was significantly delayed by treatment with paclitaxel encapsulated into cationic liposomes in comparison with all other groups. CONCLUSIONS The data suggest that cationic liposomes are a powerful tool for selective and efficient drug delivery to tumor microvessels. This may serve as proof of the concept of neovascular tumor targeting therapy by cationic liposomes.
Evolution in pancreas transplantation techniques: simultaneous kidney-pancreas transplantation using portal-enteric drainage without antilymphocyte induction.

OBJECTIVE To report initial experience with the combination of a novel technique of portal-enteric pancreas transplantation with newer immunosuppressive strategies that eliminate antilymphocyte induction therapy. BACKGROUND A new surgical technique of pancreas transplantation has been developed with portal venous delivery of insulin and enteric drainage of the exocrine secretions (portal-enteric). The introduction of potent immunosuppressive agents may allow simultaneous kidney and pancreas transplants (SKPT) to be performed without antilymphocyte induction. METHODS From September 1996 to November 1998, the authors performed 28 primary SKPTs with portal-enteric drainage and no antilymphocyte induction. All patients received triple immunosuppression with tacrolimus, mycophenolate mofetil, and steroids. The study group had a mean age of 38 years and a mean preoperative duration of diabetes of 25 years. Four patients (14%) had prior kidney transplants. RESULTS All patients had immediate renal allograft function. Actual patient, kidney, and pancreas graft survival rates were 86%, 82%, and 82%, respectively, after a mean follow-up of 12 months. Four patients died, three as a result of cardiac events unrelated to SKPT. Five kidney and five pancreas grafts were lost, including five deaths with function and three cases of chronic rejection. The mean length of stay and total charges for the initial hospital stay were 12.5 days and $99,517. The mean number of readmissions was 2.9, and 10 patients (36%) had no readmissions. Six patients (21 %) developed acute rejection, with five (18%) receiving antilymphocyte therapy. Seven patients (25%) underwent relaparotomy, including two (7%) for intraabdominal infection. Nine patients (32%) had major infections, including three (11%) with cytomegaloviral infection. Of the 24 surviving patients, 22 (92%) are both dialysis- and insulin-free. CONCLUSION These preliminary results suggest that SKPT with portal-enteric drainage without antilymphocyte induction can be performed with excellent outcomes.
Estresse e correlatos com características de saúde e sociodemográficas de estudantes de medicina

Introducao : O estresse e uma resposta inespecifica do organismo mediante uma pressao exercida sobre ele, suas reacoes fisiologicas sao chamadas de “sindrome de adaptacao geral”, dividida em tres fases: alerta, resistencia e exaustao. Objetivo: Analisar as fases do estresse e seus correlatos com caracteristicas de saude e demograficas de estudantes de medicina de uma faculdade do interior da Paraiba. Metodo : Pesquisa de carater descritivo, transversal, com abordagem quantitativa, teve como cenario de estudo uma Instituicao de Ensino Superior (IES) localizada no sertao paraibano. A amostra foi composta por 138 alunos do curso de Medicina da IES. Resultados : 21,02% dos academicos nao apresentam estresse e 78,98% apresentam: 0,72% encontram-se na fase de alerta; 61,59% na de resistencia; 16,67% na de exaustao. Correlacionando os fatores de saude e sociodemograficos, constatou-se que os alunos do sexo feminino, sem bolsa de estudo, que pensam em desistir do curso, tomam medicamento e que nao procuram tratamento psicologico possuem maiores pontuacoes de estresse nas fases de resistencia e exaustao. Conclusao : E necessario incorporar estrategias, como servicos de apoio psicologico, que possibilitem aos academicos a lidar com essa realidade de forma adaptativa, valorizando e reconhecendo seus limites. DOI: 10.21615/cesmedicina.32. 3.3
Relationship between Mycobacterium avium, Mycobacterium paratuberculosis and “wood pigeon mycobacteria”

The DNA‐DNA homology percentages obtained in this study indicate that M. avium and M. paratuberculosis belong to one species. Consequently, M. paratuberculosis ought to be considered a variant of M. avium, and the following designations are proposed: Mycobacterium avium, subsp. avium. Mycobacterium avium, subsp. paratuberculosis. Identification and classification of “wood pigeon mycobacteria” occurring in wild animals have been problematic due to their dysgonic and mycobactin‐dependent growth. DNA‐DNA homology percentages indicate that these bacteria are closely related to reference strains both of M. avium and of M. paratuberculosis. “Wood pigeon mycobacteria” should therefore be classified as atypical strains of M. avium, and the following designation is proposed: Mycobacterium avium subsp. columbae.
Development of measures of individual leadership for health promotion.

PURPOSE This purpose of this research was to develop and establish psychometric properties of scales measuring individual leadership for health promotion. DESIGN/METHODOLOGY/APPROACH Scales to measure leadership in health promotion were drafted based on capacity assessment instruments developed by other provinces involved in the Canadian Heart Health Initiative (CHHI), and on the literature. Content validity was established through a series of focus groups and expert opinion appraisals and pilot testing. Psychometric analyses provided empirical evidence of the construct validity and reliability of the leadership scales in the baseline survey (n = 144) of the Alberta Heart Health Project. FINDINGS Principal component analysis verified the construct of the leadership scales of personal work-related practices and satisfaction with work-related practices. Each of the theoretically a prior determined scales factored into two scales each for a total of four final scales. Scale alpha coefficients (Cronbach's alpha) ranged between 0.71 and 0.78, thus establishing good scale internal consistencies. RESEARCH LIMITATIONS/IMPLICATIONS Limitations include the relatively small sample size used in determining psychometric properties. In addition, further qualitative work would enhance understanding of the complexity of leadership in health organizations. These measures can be used by both researchers and practitioners for the assessment leadership for health promotion and to tailor interventions to increase leadership for health promotion in health organizations. ORIGINALITY/VALUE Establishing the psychometric properties and quality of leadership measures is an innovative step toward achieving capacity assessment instruments which facilitate evaluation of key relationships in developing health sector capacity for health promotion.
Integrating the Illness Beliefs Model in Clinical Practice

To promote the integration of Family Systems Nursing (FSN) in clinical practice, we need to better understand how nurses overcome the challenges of FSN knowledge utilization. A qualitative exploratory study was conducted with 32 practicing female nurses from hospital and community settings who had received FSN intervention training and skill development based on the Illness Beliefs Model and the Calgary Family Assessment and Intervention Models. The participants were interviewed about how they utilized FSN knowledge in their nursing practice. From the data analysis, a FSN Knowledge Utilization Model emerged that involves three major components: (a) nurses’ beliefs in FSN and in their FSN skills, (b) nurses’ knowledge utilization strategies to address the challenges of FSN practice, and (c) FSN positive outcomes. The FSN Knowledge Utilization Model describes a circular, incremental, and iterative process used by nurses to integrate FSN in daily nursing practice. Findings point to a need for re-evaluation of educational and management strategies in clinical settings for advancing the practice of FSN.
The Austin, Texas, diphtheria outbreak. Clinical and epidemiological aspects.

During a 19-month period, October 1967 through April 1969, an outbreak of 88 cases of diphtheria occurred in Austin, Tex. Most of the cases were considered mild, and the severe illness, including three deaths, affected only poorly immunized persons. In spite of a mass immunization campaign at the height of the epidemic, cases continued to occur. The outbreak probably began from endemic foci; incomplete immunizations, lack of immunizations, crowding, and poor environmental and personal hygiene probably contributed to the spread of the disease. The evidence suggests that a level of immunization above 90% for all age groups could prevent community-wide diphtheria.
Radiosensitization with Hyperthermia and Chemotherapeutic Agents: Effects on Linear-Quadratic Parameters of Radiation Cell Survival Curves

Radiosensitization effects of hyperthermia and chemotherapeutic agents as currently exploited in the clinic are discussed with respect to the linear quadratic parameters of dosesurvival curve presentations. Studies of different human tumour cell lines show that a synergistic interaction can be obtained between hyperthermia, chemotherapy and radiation and that this interaction is more likely to occur in cell lines which are relatively sensitive to chemotherapy. The influence of modifying agents on radiation dose survival curves can adequately be analysed with the use of the linear-quadratic model: S(D)/S(O)= exp(┙D+┚D2). The linear parameter, ┙, represents lethal damage from single particle events and describes the low dose area while the quadratic parameter, ┚, indicating sub lethal damage (SLD) dominates the effectiveness in the high dose region (Barendsen, 1990, 1994, 1997). The linear-quadratic model is based on well accepted biophysical concepts, involving the assumption that lethal damage can be induced by single-particle tracks and by interaction of damage from multiple particles. It has been found to describe the low-dose region of the survival curves up to 6 Gy rather accurately. Furthermore the LQ-model has been shown to describe adequately dose fractionation effects for normal tissue tolerance and for experimental tumours. The LQ-model has also the advantage that it requires only two parameters to describe radiation dose-survival curves. It allows the separate analysis of changes in effectiveness in the low dose range, mainly determined by the linear term and in the high dose range determined mainly by the quadratic term (Barendsen, 1982; Joiner &
Altered polarity and expression of H+-ATPase without ultrastructural changes in kidneys of Dent's disease patients.

BACKGROUND Dent's disease is a proximal tubule (PT) disorder characterized by low-molecular-weight proteinuria (LWMP) that may be associated with hypercalciuria, nephrocalcinosis, and renal failure. It is caused by inactivating mutations of the renal chloride channel ClC-5, which colocalizes with the vacuolar H+-ATPase in PT cells and alpha-type intercalated cells. Examinations of knockout mice have established the role of ClC-5 in PT endocytosis, but the consequences of ClC-5 mutations on the polarity of H+-ATPase and other plasma membrane proteins remain unknown. METHODS We have studied renal biopsies from eight patients with Dent's disease, due to inactivating ClC-5 mutations, by light and electron microscopy, and by immunohistochemical staining. All patients exhibited LMWP, and renal function ranged from normal to end-stage renal failure. RESULTS Light microscopy revealed either normal renal architecture or glomerulosclerosis, tubular dedifferentiation and atrophy, and mild interstitial fibrosis. Focal, hyaline casts, sometimes calcified, were identified at all stages. Electron microscopy did not reveal any ultrastructural abnormalities in PT cells, and the endocytic apparatus was apparently normal. However, immunohistochemical studies demonstrated a consistent inversion of H+-ATPase polarity in PT cells to a basolateral distribution contrasting with its apical location in the normal kidney. This inversion of polarity was specific for H+-ATPase and did not affect distribution of aminopeptidase, megalin, and Na+/K+-ATPase. Furthermore, apical H+-ATPase expression was absent in alpha-type intercalated cells. CONCLUSION ClC-5 mutations are associated with modifications in the polarity and expression of H+-ATPase, but not ultrastructural alterations in PT cells. These findings help further understanding of the role of ClC-5 and the pathophysiology of Dent's disease.
Suppression of Mature Dendritic Cell Function by Regulatory T Cells In Vivo Is Abrogated by CD40 Licensing1

The priming of CD4+ effector T cells (Teff) in vivo is induced by mature dendritic cells (DC) and controlled by CD4+CD25+Foxp3+ regulatory T cells (Treg). It remains unclear,however, how Teff priming vs Treg suppression are regulated during Ag presentation by DC in secondary lymphoid organs at the simultaneous presence of Teff and Treg. In this study, we used an peptide-specific DO11.10 TCR-transgenic adoptive transfer model to follow the Teff priming kinetics and the mechanisms of suppression by Treg. Treg activation was slower as compared with Teff and could not influence the early Teff expansion but limited the Teff response leading to lower Teff numbers in the memory phase. DC-Treg cell contacts remained unaltered during suppression by Treg and led to a down-regulation of the costimulatory molecules CD80, CD86, PD-L1, and PD-L2 but not MHC II, CD40, ICOS-L, or CD70 from the mature DC surface. This effect was observed only after DC maturation with TNF or LPS but not after additional CD40 licensing. Together, our data indicate that Treg suppression against nonself Ags in vivo occurs delayed due to the slower Treg response, is mediated to a large extent through DC modulation, but is controlled by the type of DC maturation.
Quantitative Analysis of Polarimetric Model-Based Decomposition Methods

In this paper, we analyze the robustness of the parameter inversion provided by general polarimetric model-based decomposition methods from the perspective of a quantitative application. The general model and algorithm we have studied is the method proposed recently by Chen et al., which makes use of the complete polarimetric information and outperforms traditional decomposition methods in terms of feature extraction from land covers. Nevertheless, a quantitative analysis on the retrieved parameters from that approach suggests that further investigations are required in order to fully confirm the links between a physically-based model (i.e., approaches derived from the Freeman–Durden concept) and its outputs as intermediate products before any biophysical parameter retrieval is addressed. To this aim, we propose some modifications on the optimization algorithm employed for model inversion, including redefined boundary conditions, transformation of variables, and a different strategy for values initialization. A number of Monte Carlo simulation tests for typical scenarios are carried out and show that the parameter estimation accuracy of the proposed method is significantly increased with respect to the original implementation. Fully polarimetric airborne datasets at L-band acquired by German Aerospace Center’s (DLR’s) experimental synthetic aperture radar (E-SAR) system were also used for testing purposes. The results show different qualitative descriptions of the same cover from six different model-based methods. According to the Bragg coefficient ratio (i.e., β ), they are prone to provide wrong numerical inversion results, which could prevent any subsequent quantitative characterization of specific areas in the scene. Besides the particular improvements proposed over an existing polarimetric inversion method, this paper is aimed at pointing out the necessity of checking quantitatively the accuracy of model-based PolSAR techniques for a reliable physical description of land covers beyond their proven utility for qualitative features extraction.
Bicyclomycin sensitivity and resistance affect Rho factor-mediated transcription termination in the tna operon of Escherichia coli

The growth-inhibiting drug bicyclomycin, known to be an inhibitor of Rho factor activity in Escherichia coli, was shown to increase basal level expression of the tryptophanase (tna) operon and to allow growth of a tryptophan auxotroph on indole. The drug also relieved polarity in the trp operon and permitted growth of a trp double nonsense mutant on indole. Nine bicyclomycin-resistant mutants were isolated and partially characterized. Recombination data and genetic and biochemical complementation analyses suggest that five have mutations that affect rho, three have mutations that affect rpoB, and one has a mutation that affects a third locus, near rpoB. Individual mutants showed decreased, normal, or increased basal-level expression of the tna operon. All but one of the resistant mutants displayed greatly increased tna operon expression when grown in the presence of bicyclomycin. The tna operon of the wild-type drug-sensitive parent was also shown to be highly expressed during growth with noninhibitory concentrations of bicyclomycin. These findings demonstrate that resistance to this drug may be required by mutations at any one of three loci, two of which appear to be rho and rpoB.
The Measurement of the Nematic Order Parameter by X-ray Scattering Reconsidered

This paper reviews and extends the procedure used to measure the nematic order parameter by X-ray scattering. We show that the well-known integral equation derived by Leadbetter and coworkers, relating the scattered intensity 1(0) to the orientational distribution function f(fl), can be analytically simplified both in the general case and in the case of the Maier-Saupe distribution function. The Maier-Saupe distribution leads to a particularly simple analytical result previously obtained by Paranjpe and Kelkar. This result is extensively discussed here and tested on a large variety of thermotropic liquid crystals. In most cases, this very simple and practical approach provides a good description of the data This supports at the same time the analysis of the scattering leading to Leadbetter's integral equation and the Maier-Saupe distribution. We also discuss the validity and accuracy of this simple method compared to other ones.
An open-database of Grape Harvest dates for climate research : data description and quality assessment

V. Daux, I. Garcia de Cortazar-Atauri, P. Yiou, I. Chuine, E. Garnier, E. Le Roy Ladurie, O. Mestre, and J. Tardaguila LSCE/IPSL, laboratoire CEA/CNRS/UVSQ, UMR8212, Gif/Yvette, France Université Versailles-Saint Quentin en Yvelines, Versailles, France INRA-Agroclim, Avignon, France CEFE, UMR5175, Montpellier, France CRHQ UMR CNRS Université de Caen, Caen, France Institut Universitaire de France, Paris, France Collège de France, Paris, France Météo-France, Toulouse, France Universidad de la Rioja, Logroño, Spain
A Genetic Expression Profile Associated with Oral Cancer Identifies a Group of Patients at High Risk of Poor Survival

Purpose: To determine if gene expression signature of invasive oral squamous cell carcinoma (OSCC) can subclassify OSCC based on survival. Experimental Design: We analyzed the expression of 131 genes in 119 OSCC, 35 normal, and 17 dysplastic mucosa to identify cluster-defined subgroups. Multivariate Cox regression was used to estimate the association between gene expression and survival. By stepwise Cox regression, the top predictive models of OSCC-specific survival were determined and compared by receiver operating characteristic analysis. Results: The 3-year overall mean ± SE survival for a cluster of 45 OSCC patients was 38.7 ± 0.09% compared with 69.1 ± 0.08% for the remaining patients. Multivariate analysis adjusted for age, sex, and stage showed that the 45 OSCC patient cluster had worse overall and OSCC-specific survival (hazard ratio, 3.31; 95% confidence interval, 1.66-6.58 and hazard ratio, 5.43; 95% confidence interval, 2.32-12.73, respectively). Stepwise Cox regression on the 131 probe sets revealed that a model with a term for LAMC2 (laminin γ2) gene expression best identified patients with worst OSCC-specific survival. We fit a Cox model with a term for a principal component analysis-derived risk score marker and two other models that combined stage with either LAMC2 or PCA. The area under the curve for models combining stage with either LAMC2 or PCA was 0.80 or 0.82, respectively, compared with 0.70 for stage alone (P = 0.013 and 0.008, respectively). Conclusions: Gene expression and stage combined predict survival of OSCC patients better than stage alone.
Early adolescent alcohol use in context: How neighborhoods, parents, and peers impact youth

Abstract Developmental–ecological models are useful for integrating risk factors across multiple contexts and conceptualizing mediational pathways for adolescent alcohol use, yet these comprehensive models are rarely tested. This study used a developmental–ecological framework to investigate the influence of neighborhood, family, and peer contexts on alcohol use in early adolescence (N = 387). Results from a multi-informant longitudinal cross-lagged mediation path model suggested that high levels of neighborhood disadvantage were associated with high levels of alcohol use 2 years later via an indirect pathway that included exposure to delinquent peers and adolescent delinquency. Results also indicated that adolescent involvement with delinquent peers and alcohol use led to decrements in parenting, rather than being consequences of poor parenting. Overall, the study supported hypothesized relationships among key microsystems thought to influence adolescent alcohol use, and thus findings underscore the utility of developmental–ecological models of alcohol use.