Miracle-dz/UniFAR-FTUs huggingface dataset:
Morphological effects of lipopeptides against Aspergillus fumigatus correlate with activities against (1,3)-beta-D-glucan synthase

The lipopeptide antifungal agents, echinocandins, papulacandins, and pneumocandins, kill Candida albicans by inhibiting glucan synthesis. For this fungus, there is a good correlation of in vitro enzyme inhibition with in vitro assays of MICs. Semisynthetic lipopeptides such as cilofungin, LY303366, L-693,989, and L-733,560 have activity in vivo against Aspergillus infections but appear to be inactive in broth dilution in vitro tests (MICs, > 128 micrograms/ml). To understand how compounds which lack activity in vitro can have good in vivo activity, we monitored the effect of pneumocandins on the morphology of Aspergillus fumigatus and A, flavus strains by light microscopy and electron microscopy and related the changes in growth to inhibition of glucan synthesis. Pneumocandin B0 caused profound changes in hyphal growth; light micrographs showed abnormally swollen germ tubes, highly branched hyphal tips, and many cells with distended balloon shapes. Aspergillus electron micrographs confirmed that lipopeptides produce changes in cell walls; drug-treated germlings showed very stubby growth with thick walls and a conspicuous dark outer layer which was much thicker in the subapical regions. The rest of the hyphal tip ultrastructure was unaffected by the drug, indicating considerable specificity for the primary target. The drug-induced growth alteration produced very compact clumps in broth dilution wells, making it possible to score the morphological effect macroscopically. The morphological changes could be assayed quantitatively by using conventional broth microdilution susceptibility assay conditions. We defined the endpoint as the lowest concentration required to produce the morphological effect and called it the minimum effective concentration to distinguish it from the no-growth endpoints used in MIC determinations. The minimum effective concentration assay was related to inhibition of glucan synthase activity in vitro and may provide a starting point for development of susceptibility testing methods for lipopeptides.
Who may benefit from donor leucocyte infusions after allogeneic stem cell transplantation?

Allogeneic stem cell transplantation (SCT) is the treatment of choice for some patients with haematological malignancies who have a suitable bone marrow donor. The ability of allogeneic SCT to eradicate leukaemia is determined by both the intensity of the conditioning regimen and the graftversus-leukaemia (GVL) reaction. GVL might be defined as the antileukaemic effect of the graft mediated by immune cells of donor origin. The presence of GVL is supported by the following observations: anecdotal reports that patients with relapsed leukaemia after bone marrow transplantation (BMT) may re-enter remission after withdrawal of immunosuppressive drugs such as cyclosporin A; the lower risk of relapse associated with the development of graft-versus-host disease (GVHD) (Weiden et al, 1979); and an increased risk of relapse in patients receiving syngeneic transplants or T-cell-depleted allogeneic marrow grafts even when controlled for similar degrees of GVHD (Horowitz et al, 1990). This last finding suggests that in some patients the donor lymphocytes present in the marrow graft mediate a GVL effect in the absence of clinical GVHD. This evidence for a GVL effect is particularly compelling in patients with a diagnosis of chronic myeloid leukaemia (CML) (Horowitz et al, 1990).
Desirable Immunologic Characteristics for the Development of an Ideal Vaccine

Abstract The efficacy of vaccines for prophylactic use is a function of the immune response elicited by activated lymphocytes. Based on the current understanding of these responses, their induction, and the most effective ways to obtain long-lived immunity, a novel protocol for the vaccination of children against seven childhood diseases, involving only two visits for vaccine administration, is proposed.
Testing Complex Correlational Hypotheses With Structural Equation Models

It is often of interest to estimate partial or semipartial correlation coefficients as indexes of the linear association between 2 variables after partialing one or both for the influence of covariates. Squaring these coefficients expresses the proportion of variance in 1 variable explained by the other variable after controlling for covariates. Methods exist for testing hypotheses about the equality of these coefficients across 2 or more groups, but they are difficult to conduct by hand, prone to error, and limited to simple cases. A unified framework is provided for estimating bivariate, partial, and semipartial correlation coefficients using structural equation modeling (SEM). Within the SEM framework, it is straightforward to test hypotheses of the equality of various correlation coefficients with any number of covariates across multiple groups. LISREL syntax is provided, along with 4 examples.
Adverse metabolic phenotype of adolescent girls with non‐alcoholic fatty liver disease plus polycystic ovary syndrome compared with other girls and boys

Non‐alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) share risk associations of adiposity and insulin resistance. We examined the impact of a PCOS diagnosis on the metabolic phenotype of adolescent girls with NAFLD and compared this to girls without PCOS or NAFLD and to age‐matched boys.
‘A Succession of Feelings, in and of Itself, is Not a Feeling of Succession’

Variants of the slogan that a succession of experiences (in and of itself) does not amount to an experience of succession are commonplace in the philosophical literature on temporal experience. I distinguish three quite different arguments that might be captured using this slogan: the individuation argument, the unity argument, and the causal argument. Versions of the unity and the causal argument are often invoked in support of a particular view of the nature of temporal experience sometimes called intentionalism, and against a rival view sometimes called extensionalism. I examine these arguments in light of the individuation argument. In particular, I show that the individuation argument is, at least prima facie, neutral between those two views of temporal experience; and once the individuation argument is in place, the unity and causal argument also lose their force against extensionalism.
ANGIOGENESIS and ANGIOGENIC MEDIATORS IN HAEMATOLOGICAL MALIGNANCIES

Neovascularization of solid tumours is suggested to be important for tumour growth and metastasis (Folkman et al, 1989). Various investigators have reported that tumours promote angiogenesis by secreting growth factors that stimulate endothelial cell migration and capillary proliferation (Folkman, 1995a,b; Mantovani et al, 1997; Nicosia, 1998) Indeed, angiogenic activity in a given tumour governs the potential for metastases and inhibition of angiogenesis may prove significant in suppressing neoplastic growth and invasiveness (Folkman, 1995b; Boehm et al, 1997; Cheresh, 1998; Benjamin et al, 1999). The role of angiogenesis in haematological malignancies is beginning to be identified (Vacca et al, 1995, 1997; Ribatti et al, 1996; Perez-Atayde et al, 1997). It is reported that the circulation within the bone marrow is similar to lymphoid tissues, i.e. lymph nodes, liver and spleen, and the lymphohaemopoietic tissue growth and function is dependent on its intravascular bed (Branemark, 1968; Bruyn et al, 1970). The prognostic role of neovascularization in lymphohaemopoietic malignancies remains contentious. This review focuses on the development of the microvascular bed, assessment of angiogenesis, its prognostic value and the possible therapeutic role of antiangiogeneic factors in haematological malignancies.
Long-term effects of an intensive voice treatment for vocal fold nodules

Abstract Purpose: The purpose of the current study was to examine the long-term effects of intensive voice treatment for vocal fold nodules, compared to outcomes for patients treated with traditional voice therapy. It was hypothesised that intensive treatment would provide comparable maintenance of vocal function, voice quality, and patients’ perception of quality-of-life when compared with traditional treatment at 6 month follow-up. Method: Thirty-six women diagnosed with bilateral vocal fold nodules who were treated with either traditional (n = 20; once a week for 8 weeks) or intensive (n = 16; eight sessions within 3 weeks) therapy. Each participant completed voice, stroboscopic, and acoustic assessments and the Voice Handicap Index before, immediately post and 6 months post-treatment. Result: Results revealed most improved perceptual, stroboscopic and acoustic parameters were maintained in both groups at 6 months post-treatment, with no significant differences between the two groups. In addition, both groups maintained satisfaction on their perception of vocal function, with no significant difference between the two groups. Conclusion: The investigation provided further evidence that individuals with vocal fold nodules are able to maintain improved voice quality and vocal health following intensive voice treatment to a similar degree to traditional voice treatment.
Combining HLA-DR risk alleles and anti-Epstein-Barr virus antibody profiles to stratify multiple sclerosis risk

Background: Risk factors for multiple sclerosis (MS) include human leukocyte antigen (HLA)-DR and Epstein-Barr virus (EBV)-specific antibody responses, including an epitope within EBV nuclear antigen 1 (EBNA-1) that is of recent interest. Objective: The objective of this paper is to assess case-control associations between MS risk and anti-EBV antibody levels as well as HLA-DR profiles, gender and age in a population-based cohort. Methods: Serological responses to EBV were measured in 426 MS patients and 186 healthy controls. HLA-DR typing was performed using sequence-based methods. Results: MS patients had significantly higher levels of antibodies against epitope-specific and polyspecific EBNA-1 and viral capsid antigen (VCA), compared with controls (all p < 10−15). In regression analyses, anti-EBNA-1 and anti-VCA antibody levels, protective HLA-DR*04/07/09 alleles and gender (all p < 0.003) contributed independently to a model that classified cases and controls with an odds ratio > 20 (sensitivity 92%, specificity 64%). Notably, the strong influence of high-risk HLA-DR alleles was abrogated after inclusion of EBV serology results. Conclusions: The ability to discriminate MS cases and controls can be substantially enhanced by including anti-EBV serology as well as HLA-DR risk profiles. These findings support the relevance of EBV-specific immunity in MS pathogenesis, and implicate both HLA-dependent and HLA-independent immune responses against EBNA-1 as prominent disease risk factors.
Specificity of peptide transport systems in Lactococcus lactis: evidence for a third system which transports hydrophobic di- and tripeptides

A proton motive force-driven di-tripeptide carrier protein (DtpT) and an ATP-dependent oligopeptide transport system (Opp) have been described for Lactococcus lactis MG1363. Using genetically well-defined mutants in which dtpT and/or opp were inactivated, we have now established the presence of a third peptide transport system (DtpP) in L. lactis. The specificity of DtpP partially overlaps that of DtpT. DtpP transports preferentially di- and tripeptides that are composed of hydrophobic (branched-chain amino acid) residues, whereas DtpT has a higher specificity for more-hydrophilic and charged peptides. The toxic dipeptide L-phenylalanyl-beta-chloro-L-alanine has been used to select for a di-tripeptide transport-negative mutant with the delta dtpT strain as a genetic background. This mutant is unable to transport di- and tripeptides but still shows uptake of amino acids and oligopeptides. The DtpP system is induced in the presence of di- and tripeptides containing branched-chain amino acids. The use of ionophores and metabolic inhibitors suggests that, similar to Opp, DtpP-mediated peptide transport is driven by ATP or a related energy-rich phosphorylated intermediate.
Mitochondrial Gene Introgression between Spined Loaches via Hybridogenesis†

Abstract This report deals with an unusual mode of mitochondrial gene introgression between Cobitis hankugensis (C. sinensis) and C. longicorpus which is mediated by a unisexual hybridogenetic system of diploid-triploid C. hankugensis-longicorpus complex. Mitochondrial DNA sequences of 3329-3330bp encompassing from upstream ND6 to 12S rDNA indicated that mitochondrial genomes from the diploid hybrids, triploid hybrids, and their parental species are almost identical. Because triploid hybrids produce haploid ova with C. hankugensis chromosome set, normal diploid C. hankugensis regenerates upon insemination with C. hankugensis sperm. If the hybrid carries C. longicorpus mitochondrial genome, the regenerated C. hankugensis is a nucleo-cytoplasmic hybrid, thus accomplishing the unusual mode of mitochondrial gene introgression.
Sensitivity to topical medicaments among suspected cases of footwear dermatitis

7. Jerez J, Martin-Gil D, Jimenez I, Rodriguez F, Anton E, Garces M, Duque S. Fiabilidad de las pruebas diagn6sticas en el exantema fijo, eritema multiforme y necrolisis epidermica (sindrome de Lyell) por medicamentos. Rev Esp A/ergo! Immunol Clin 1990: 5: (suppl. 2): 62-69. 8. McKerrow K J, Greig D E. Piroxicam-induced photosensitive dermatitis. JAm Acad Dermato/1986: 15: 1237-1241. SHORT COMMUNICATIONS
Risk Perception by Offshore Oil Personnel During Bad Weather Conditions

This article presents the results of analyses of employee subjective risk assessments caused by platform movements on an offshore oil installation in the Norwegian sector of the North Sea. The results are based on a self‐completion questionnaire survey conducted among 179 respondents covering three shifts on the platform. The data collection was carried out during the spring of 1994. A minority expressed worry due to platform movements. A greater proportion of the personnel stated worry about the construction of the platform. The personnel were more unsafe when they assessed their own safety attitudes with regard to specific potentially hazardous consequences of platform movements. Two approaches aimed at modeling worry and concern caused by platform movements were tested. The models were the mental imagery approach and the rationalistic approach. The rationalistic and mental imagery models fitted equally well. Implications of the results for risk communication are discussed.
Impact of early valve surgery on outcome of Staphylococcus aureus prosthetic valve infective endocarditis: analysis in the International Collaboration of Endocarditis-Prospective Cohort Study.

BACKGROUND The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. METHODS Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. RESULTS EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). CONCLUSIONS In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.
Hemostatic defects in dengue hemorrhagic fever.

Dengue hemorrhagic fever is characterized by a sudden onset of fever that lasts for 2-7 days and then subsides, at which time hemorrhagic manifestations become evident. Sometimes there is an associated form of hypovolemic shock known as dengue shock syndrome. There are usually significant changes in the liver, the reticuloendothelial system, and the vascular system (e.g., necrosis of liver cells and focal hemorrhage, increase in turnover of lymphocytes, and diapedesis of erythrocytes through vessel walls). Because of the lack of pathologic findings in major organs and the rapid recovery (without sequelae) of survivors, physiologic dysfunction is thought to be secondary to the action of biologic mediators that are capable of producing severe illness with minimal structural injury.
Barriers and opportunities for implementation of adaptive designs in pharmaceutical product development

Background This review discusses barriers to implementing adaptive designs in a pharmaceutical R&D environment and provides recommendations on how to overcome challenges. A summary of findings from a survey conducted through PhRMA’s working group on adaptive designs is followed by a report based on our experience as statistical and clinical consultants to project teams charged with establishing the clinical development strategy for investigational compounds and interested in applying innovative approaches. Findings and recommendations Adaptive designs require additional work in that clinical trial simulations are needed to develop the design. Some project teams, due to time and resource constraints, are unable to invest the additional effort required to conduct necessary scenario analyses of options through simulation. We recommend formally integrating the planning time for scenario analyses and to incentivize optimal designs (e.g., designs offering the highest information value per resource unit invested). Regardless of the trial design ultimately chosen, quantitatively comparing alternative trial design options through simulation will enable earlier and better decision making in the context of the overall clinical development plan. Adhering to ‘Good Adaptive Practices’ will be key to achieving this goal. Outlook Implementing adaptive designs efficiently requires top—down and bottom— up support and the willingness to invest into integrated process and information technology infrastructures. Success is conditional on the willingness of the R&D environment to embrace the implementation of adaptive designs as a Change Management Initiative in the spirit of the Critical Path of the Food and Drug Administration. Clinical Trials 2010; 7: 167—173. http://ctj.sagepub. com
Case of spinocerebellar ataxia type 17 (SCA17) associated with only 41 repeats of the TATA‐binding protein (TBP) gene

1. Weetman AP. Autoimmune thyroid disease. Autoimmunity 2004; 37:337–340. 2. Fatourechi V. Hashimoto’s encephalopathy: myth or reality? an endocrinologist’s perspective. Best Pract Clin Endocrinol Metab 2005;19:53–66. 3. Morrison T, Young B. Progressive encephalomyelitis with rigidity (PREM) in a young woman with GAD-65 antibodies and other autoimmune dysfunction. Can J Neurol Sci 2003;30(Suppl. 2):S54. 4. Loh LM, Hum AYM, Teoh HL, Lim ECH. Graves’ disease associated with spasmodic truncal flexion. Parkinsonism Relat Disord 2005;11:117–119.
Psychometric Properties of an HIV Knowledge Scale Administered With Populations at High Risk for HIV Infection

HIV prevention programs targeting men who have sex with men, Blacks, and young adults commonly use measures of HIV knowledge as an important component of demonstrating overall program effectiveness. These scales, however, are rarely subjected to repeated analysis to confirm reliability and validity and the results of psychometric analysis rarely include subpopulation variations. In this study, we administered an adapted version of a previously validated HIV knowledge scale to participants of a large, city-wide HIV prevention program (n = 5,027) and performed psychometric analysis to determine if differences existed across populations. Analysis showed that the HIV knowledge scale performed poorly for men who have sex with men, but very well for transgenders. Results were similar for Blacks, Hispanics, and Whites, very poor for 30- to 39-year-olds, but very well for 60+ year olds. Findings underscore the need for further research on the measurement of HIV knowledge among high-risk populations and the importance of culturally appropriate survey items tailored to each population.
Caries Management Strategies for Primary Molars

Minimal invasive approaches to managing caries, such as partial caries removal techniques, are showing increasing evidence of improved outcomes over the conventional complete caries removal. There is also increasing interest in techniques where no caries is removed. We present the 1-yr results of clinical efficacy for 3 caries management options for occlusoproximal cavitated lesions in primary molars: conventional restorations (CR; complete caries removal and compomer restoration), Hall technique (HT; no caries removal, sealing in with stainless steel crowns), and nonrestorative caries treatment (NRCT; no caries removal, opening up the cavity, teaching brushing and fluoride application). In sum, 169 children (3-8 yr old; mean, 5.56 ± 1.45 yr) were enrolled in this secondary care–based, 3-arm, parallel-group, randomized clinical trial. Treatments were carried out by specialist pediatric dentists or postgraduate trainees. One lesion per child received CR, HT, or NRCT. Outcome measures were clinical failure rates, grouped as minor failure (restoration loss/need for replacement, reversible pulpitis, caries progression, etc.) and major failure (irreversible pulpitis, abscess, etc.). There were 148 children (87.6%) with a minimum follow-up of 11 mo (mean, 12.23 ± 0.98 mo). Twenty teeth were recorded as having at least 1 minor failure: NRCT, n = 8 (5%); CR, n = 11 (7%); HT, n = 1 (1%) (p = .002, 95% CI = 0.001 to 0.003). Only the comparison between NRCT and CR showed no significant difference (p = .79, 95% CI = 0.78 to 0.80). Nine (6%) experienced at least 1 major failure: NRCT, n = 4 (2%); CR, n = 5 (3%); HT, n = 0 (0%) (p = .002, 95% CI = 0.001 to 0.003). Individual comparison of NRCT and CR showed no statistically significant difference in major failures (p = .75, 95% CI = 0.73 to 0.76). Success and failure rates were not significantly affected by pediatric dentists’ level of experience (p = .13, 95% CI = 0.12 to 0.14). The HT was significantly more successful clinically than NRCT and CR after 1 yr, while pairwise analyses showed comparable results for treatment success between NRCT and CR (ClinicalTrials.gov NCT01797458).
High resolution DSM generation from ALOS PRISM - Archiving and mosaicking

Panchromatic Remote-sensing Instrument for Stereo Mapping (PRISM) carried by Advanced Land Observing Satellite (ALOS) was designed to generate worldwide topographic data with its high resolution and stereoscopic observation. According to this aim, we developed the software of generating Digital Surface Model (DSM) data. Following the accumulations of PRISM stereoscopic observation data during over five year operations, the capabilities of the matching-algorithm for stereo images, as well as the characteristics of processed DSMs, were widely validated. This paper reports on the latest validation results, archiving status, and the mosaicking results of the DSM.