Miracle-dz/UniFAR-FTUs huggingface dataset:
Farnesyl Pyrophosphate Inhibits Epithelialization and Wound Healing through the Glucocorticoid Receptor*

Farnesyl pyrophosphate (FPP), a key intermediate in the mevalonate pathway and protein farnesylation, can act as an agonist for several nuclear hormone receptors. Here we show a novel mechanism by which FPP inhibits wound healing acting as an agonist for glucocorticoid receptor (GR). Elevation of endogenous FPP by the squalene synthetase inhibitor zaragozic acid A (ZGA) or addition of FPP to the cell culture medium results in activation and nuclear translocation of the GR, a known wound healing inhibitor. We used functional studies to evaluate the effects of FPP on wound healing. Both FPP and ZGA inhibited keratinocyte migration and epithelialization in vitro and ex vivo. These effects were independent of farnesylation and indicate that modulation of FPP levels in skin may be beneficial for wound healing. FPP inhibition of keratinocyte migration and wound healing proceeds, in part, by repression of the keratin 6 gene. Furthermore, we show that the 3-hydroxy-3-methylglutaryl-CoA-reductase inhibitor mevastatin, which blocks FPP formation, not only promotes epithelialization in acute wounds but also reverses the effect of ZGA on activation of the GR and inhibition of epithelialization. We conclude that FPP inhibits wound healing by acting as a GR agonist. Of special interest is that FPP is naturally present in cells prior to glucocorticoid synthesis and that FPP levels can be further altered by the statins. Therefore, our findings may provide a better understanding of the pleiotropic effects of statins as well as molecular mechanisms by which they may accelerate wound healing.
A Modeling Study of Interannual Variability of Bay of Bengal Mixing and Barrier Layer Formation

The year to year variability of surface mixing in the Bay of Bengal (BoB) is examined with the help of an Ocean Dynamic-Thermodynamic Model (ODTM) and observational data. The model embeds a conventional nonlinear primitive equation based reduced gravity model (RGM) with ‘‘N’’ active layers overlying a 1/2 quiescent layer. The model is coupled to a high-resolution mixed layer model (MLM) to capture the physics of the mixed layer. The MLM incorporates a level-2 turbulence closure mixing scheme based on Mellor and Yamada (1982). As a result of the coupling, our model calculates the net hydrostatic pressure as a sum of those due to the thickness of RGM layers with constant densities and due to the dynamic topography of MLM levels with variable densities. At each time step the coupling between RGM and MLM is achieved as follows: (i) a layer-averaged tendency of momentum and tracers (i.e., temperature and salinity) of the MLM is updated to the RGM, (ii) momentum and tracers of the MLM get advected by large-scale horizontal dynamics of the RGM, and (iii) horizontal layer divergence of the RGM aides for the vertical advection of the MLM. By virtue of this coupling, the model faithfully reproduces the seasonal cycle of temperature, salinity, sea surface height, thermocline, mixed and barrier layer thickness of the tropical Indian Ocean. A simulation with Coordinated Ocean-Ice Reference Experiment (CORE) forcing for 15 years (from 1995 to 2009) is used as a test case to study the interannual variability (IAV) of the mixed layer depth and barrier layer thickness (BL) in BoB. The dominant modes of IAV in the BoB
Integration of quantitative and qualitative techniques for deformable model fitting from orthographic, perspective, and stereo projections

The authors synthesize a new approach to 3-D object shape recovery by integrating qualitative shape recovery techniques and quantitative physics-based shape estimation techniques. They first use qualitative shape recovery and recognition techniques to provide strong fitting constraints on physics-based deformable model recovery techniques. Previously developed techniques of fitting deformable models to occluding image contours are then extended to the case of image data captured under general orthographic, perspective, and stereo projections. Experimental results are presented to illustrate the shape recovery approach. <<ETX>>
Causes and Mechanisms of Nondipping Hypertension

Growing evidence indicates that nondippers have worsened cardiovascular outcomes than dippers. Ambulatory blood pressure monitoring with a lack of nocturnal BP fall (nondipping) have also been shown to be more closely associated with target organ damage and worsened cardiovascular outcome than in patients with essential hypertension with dipping pattern. The underlying pathogenetic mechanisms potentially linking nondipping with cardiovascular disease are not fully understood. There are multiple possible underlying pathophysiologic mechanisms in the impaired BP decline during the night. Extrinsic and intrinsic factors including abnormal neurohormonal regulation, lack of physical activity, nutritional factors such as increased dietary sodium intake, and smoking of tobacco have been implicated for blunted circadian rhythm of BP. Certain diseases such as diabetes and chronic renal diseases also affect the circadian BP rhythm. Currently, the clinical importance of nondipping is known well; however, the relationship between certain disease states and nondipping has not been fully explained yet. This paper will attempt to address to clarify the underlying basis for nondipping and the specific associations with various disease states.
Patient Satisfaction With Videoconferencing-based Treatment for Alcohol Use Disorders

Objectives:The objectives of this study are (1) to compare the satisfaction between patients who have received treatment as usual face-to-face (TAU group) and patients who have received optional videoconferencing-based treatment for alcohol use disorders (TAU+I group); and (2) to elaborate on the TAU+I group’s satisfaction with the treatment in general and the technical equipment. Methods:The design consisted of mixed methods: a survey and a qualitative study. Data consisted of self-reported data from questionnaires filled out by both groups and semistructured interviews with the TAU+I group. Data from the questionnaires were analyzed statistically using Stata. The semistructured interviews were analyzed using a general inductive approach. Results:The survey indicated that the TAU+I group and TAU group were equally satisfied with the elements in the treatment. The interview indicated that the TAU+I group seemed to have a high satisfaction with most elements in the treatment. Patients who used videoconferencing were satisfied with establishing the videoconferencing connection and with the picture quality but less satisfied with the sound quality. Conclusions:Overall, the patients were satisfied with the treatment. We saw a nonsignificant tendency that the TAU+I group were more satisfied with the treatment in general, compared with the TAU group. It is a possibility that patients in this group felt more satisfied with the treatment as they had the opportunity to choose videoconferencing. Offering videoconferencing-based treatment may be a positive feature in the treatment and lead to improved outcomes of the treatment courses. The technical equipment and routine using it should be improved in future studies or during implementation.
Human Immunodeficiency Virus Infection of the Brain: Pitfalls in Evaluating Infected/Affected Cell Populations

Monocyte/macrophages and CD4 T‐cells are the primary hematopoietic targets of productive HIV infection. In the brain, potential cellular targets for HIV infection include perivascular and parenchymal macrophages/microglia, oligodendrocytes, endothelia, neurons, and astrocytes. We examine evidence of productive and non‐productive infection for each cell type in the brains of HIV‐infected patients with and without HIV encephalitis. Despite the voluminous literature and substantial experimental effort over the past two decades, evidence for productive infection of any brain cell other than macrophages is left wanting.
EEG epoch selection: Lack of alpha rhythm improves discrimination of Alzheimer's disease

In this work we propose a detailed EEG epoch selection method and compare epochs with rare and abundant alpha rhythm (AR) of patients with Alzheimer's disease (AD) and normal controls. Epochs were classified as Dominant Alpha Scenario (DAS) and Rare Alpha Scenario (RAS) according to the AR percentage (energy within the 8-13 Hz bandwidth) in O1, O2 and Oz electrodes. Participants were divided into four groups: 17 DAS controls (N1), 15 DAS mild-AD patients (AD1), 12 RAS controls (N2) and 15 RAS mild-AD patients (AD2). We found out that scenario factor (DAS vs. RAS, two-way ANOVA) is significant over a great amount of electrode-bandwidth situations. Furthermore, one-way ANOVA showed significant differences between RAS AD and RAS controls in much more situations as compared to DAS. This is the first study using AD awake EEG reporting the decisive influence of alpha rhythm on epoch selection, where our results revealed that, contrary to what was initially expected, EEG epochs with poor alpha (RAS) discriminate mild AD much better than those presenting richer alpha content (DAS).
Comparative effectiveness of different beta-adrenergic antagonists on mortality among adults with heart failure in clinical practice.

BACKGROUND Randomized trials have demonstrated the efficacy of selected beta-blockers in systolic heart failure, but the comparative effectiveness of different beta-blockers in practice is poorly understood. METHODS We compared mortality associated with different beta-blockers following hospitalization for heart failure between 2001 and 2003. Longitudinal exposure to beta-blockers was ascertained from pharmacy databases. Patient characteristics and other medication use were identified from administrative, hospitalization, outpatient, and pharmacy databases. Death was identified from administrative, state mortality, and Social Security Administration databases. Multivariate Cox regression was used to examine the association between different beta-blockers and death. RESULTS Among 11 326 adults surviving a hospitalization for heart failure, 7976 received beta-blockers (atenolol, 38.5%; metoprolol tartrate, 43.2%; carvedilol, 11.6%; and other, 6.7%) during follow-up. The rate (per 100 person-years) of death during the 12 months after discharge varied by exposure and type of beta-blocker (atenolol, 20.1; metoprolol tartrate, 22.8; carvedilol, 17.7; and no beta-blockers, 37.0). After adjustment for confounders and the propensity to receive carvedilol, the risk of death compared with atenolol was higher for metoprolol tartrate (adjusted hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.01-1.34) and no beta-blockers (HR, 1.63; 95% CI, 1.44-1.84) but was not significantly different for carvedilol (HR, 1.16; 95% CI, 0.92-1.44). CONCLUSIONS Compared with atenolol, the adjusted risks of death were slightly higher with shorter-acting metoprolol tartrate but did not significantly differ for carvedilol in adults with heart failure. Our results should be interpreted cautiously and they suggest the need for randomized trials within real-world settings comparing a broader spectrum of beta-blockers for heart failure.
TRAIL decoy receptors mediate resistance of acute myeloid leukemia cells to TRAIL.

BACKGROUND AND OBJECTIVES The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is regarded as a potential anticancer agent. However, many cancer cells are resistant to apoptosis induction by TRAIL. The present study was designed to evaluate the sensitivity to TRAIL-induced apoptosis in acute myeloblastic leukemias (AML). DESIGN AND METHODS TRAIL/TRAIL receptor (TRAIL-R) expression and sensitivity to TRAIL-mediated apoptosis were explored in 79 AML patients, including 17 patients with acute promyelocytic leukemia (APL). RESULTS In non-APL AML we observed frequent expression of TRAIL decoy receptors (TRAIL-R3 and TRAIL-R4), while TRAIL-R1 and TRAIL-R2 expression was restricted to AML exhibiting monocytic features. Total leukemic blasts, as well as AML colony-forming units (AML-CFU), were invariably resistant to TRAIL-mediated apoptosis. APL express membrane-bound TRAIL on their surface and exhibit a pattern of TRAIL-R expression similar to that observed in the other types of AML. Before, during and after retinoic acid treatment APL cells are TRAIL-resistant. The induction of granulocytic maturation of APL cells by retinoic acid was associated with a marked decline of TRAIL expression. INTERPRETATION AND CONCLUSIONS The analysis of experimental APL models (i.e., U937 cells engineered to express PML/RAR-Eo and NB4 cells) provided evidence that PML/RAR-Eo expression was associated with downmodulation of TRAIL-R1 and with resistance to TRAIL-mediated apoptosis. We suggest that AML blasts, including APL blasts, are resistant to TRAIL-mediated apoptosis, a phenomenon seemingly related to the expression of TRAIL decoy receptors on these cells. Finally, APL blasts express membrane-bound TRAIL that could confer an immunologic privilege to these cells.
Microbiology of periapical abscesses and associated maxillary sinusitis.

Aspirate of pus from 5 periapical abscesses of the upper jaw and their corresponding maxillary sinusitis were studied for aerobic and anaerobic bacteria. Polymicrobial flora were found in all instances, where the number of isolates varied from 2 to 5. Anaerobes were recovered from all specimens. The predominant isolates were Prevotella sp. , Porphyromonas sp. , Fusobacterium nucleatum, and Peptostreptococcus sp. Concordance in the microbiological findings between periapical abscess and the maxillary sinus flora was found in all instances. However, certain organisms were only present at one site and not the other. Five beta-lactamase-producing organisms were present in the five specimens. These data confirm the importance of anaerobic bacteria in periapical abscesses and demonstrate their predominance in maxillary sinusitis that is associated with them.
Identification of a cancer stem cell enriched side population using Hoechst 33342 based isolation

The surge in interest in identifying and characterizing the tumor initiating cell or cancer stem cell (CSC) has a defining ethos which includes the discovery of novel diagnostic and prognostic markers and facilitation of the understanding of basic biology and cellular signaling pathways. The ultimate aim of this is to generate new therapeutic approaches to the treatment of cancer. However, a major hurdle to this process has been the lack of a truly specific cancer stem cell biomarker. Attention has therefore focused on the identification of CSCs using functional assays based on fundamental stem cell characteristics. One such property is the ability of the stem cells to efflux DNA based dyes such as Hoechst 33342 from the cell via the ABC transporter mechanisms,ABCG1 (MDRP) and ABCG2 (BCRP). This property gives rise to a characteristic side population (SP) which is dentifiable from the cellular milieu using flow cytometry, enabling separation and enrichment of this ub-population of cells from the other terminally differentiated cells. Here we review the development of theHoechst 33342 based method for isolation and characterization of the SP from tumor and non-tumor areas derived from solid tissues, showing that the cells within the SP share many of the characteristics of tumor initiating cells and that this SP characteristic / mechanism is conserved in different tumor tissue. In theabsence of other definitive biomarkers for cancer initiating or ? stem? cells the Hoechst 33342 dye efflux assay is a powerful technique for their isolation and characterization
Retrieving landmark and non-landmark images from community photo collections

State of the art data mining and image retrieval in community photo collections typically focus on popular subsets, e.g. images containing landmarks or associated to Wikipedia articles. We propose an image clustering scheme that, seen as vector quantization compresses a large corpus of images by grouping visually consistent ones while providing a guaranteed distortion bound. This allows us, for instance, to represent the visual content of all thousands of images depicting the Parthenon in just a few dozens of scene maps and still be able to retrieve any single, isolated, non-landmark image like a house or graffiti on a wall. Starting from a geo-tagged dataset, we first group images geographically and then visually, where each visual cluster is assumed to depict different views of the the same scene. We align all views to one reference image and construct a 2D scene map by preserving details from all images while discarding repeating visual features. Our indexing, retrieval and spatial matching scheme then operates directly on scene maps. We evaluate the precision of the proposed method on a challenging one-million urban image dataset.
Autistic trait interactions underlie sex-dependent facial recognition abilities in the normal population

Autistic face processing difficulties are either uniquely social or due to a piecemeal cognitive “style. ” Co-morbidity of social deficits and piecemeal cognition in autism makes teasing apart these accounts difficult. These traits vary normally, and are more separable in the general population, suggesting another way to compare accounts. Participants completed the Autism Quotient survey of autistic traits, and one of three face recognition tests: full-face, eyes-only, or mouth-only. Social traits predicted performance in the full-face condition in both sexes. Eyes-only males' performance was predicted by a social × cognitive trait interaction: attention to detail boosted face recognition in males with few social traits, but hindered performance in those reporting many social traits. This suggests social/non-social Autism Spectrum Conditions (ASC) trait interactions at the behavioral level. In the presence of few ASC-like difficulties in social reciprocity, an ASC-like attention to detail may confer advantages on typical males' face recognition skills. On the other hand, when attention to detail co-occurs with difficulties in social reciprocity, a detailed focus may exacerbate such already present social difficulties, as is thought to occur in autism.
Analysis of Functional and Anatomic Success following Endonasal Dacryocystorhinostomy

Objectives: The aim of this study was to assess the concomitant perioperative procedures, the causes of nasolacrimal duct obstruction, the success rate, and the complications associated with endonasal dacryocystorhinostomy (ENDCR). Methods: In this single-center retrospective study, 98 patients underwent 104 ENDCRs between January 1994 and February 2006. There were 78 patients with 84 nasolacrimal duct obstructions who were included in this study. Results: The overall functional success rate with improvement in symptoms was 94.9% for primary surgery (59 of 84 obstructions) and 63.6% for salvage surgery after failure of primary surgery performed in another hospital (25 of 84 obstructions). The mean follow-up time was 36.8 ± 17.11 months. Primary surgery showed better results, with a complete success rate of 93.2%, than did salvage surgery, with a success rate of only 68%. Persistent symptoms, despite an open rhinostomy, were found in 1.7% of patients with primary surgery and in 12% of those with salvage surgery. Failure of ENDCR was observed in 3.4% of patients after primary surgery and in 20% after salvage surgery. We encountered only minimal perioperative complications, and these were essentially related to lacrimal intubation. Conclusions: Because of the possibility of treating concomitant sinonasal disorders, the cosmetic advantages, and the excellent results, ENDCR represents the procedure of choice for treating nasolacrimal duct obstructions. The main challenge lies in the exact preoperative assessment, as well as postoperative evaluation in case of failure.
Factors that influence women's decisions about whether to participate in research: an exploratory study.

BACKGROUND Women are increasingly being asked to consider participating in medical research. We sought to investigate views of women who participated in and declined to participate in a study that was part of a program of maternity care research. METHODS An exploratory study using focus group interviews and semistructured interviews was conducted. A purposive sample of 17 postnatal women who had participated in research, from a hospital in the North West of England, were interviewed. An open coding mechanism to identify emergent themes was used for the analysis of data. RESULTS Of women who had not declined to participate in any research, the following themes were identified: altruism versus self-protection, enhanced versus inferior care, professional guidance versus self-direction, and welcome versus unacceptable methodology. Of women who had participated in some research but declined to participate in other research, the following themes were identified: feeling disempowered by the process, inability to believe equipoise existed, and practical inconvenience. CONCLUSIONS These findings suggest that although health care researchers adopt an individualistic approach to care, they may fail to adopt a similar approach within research. What is important and acceptable to women needs to be ascertained to develop appropriate research strategies. This plan will ensure that research is carried out to the highest ethical standard, which may increase recruitment rates.
Solid Titration of Octacalcium Phosphate

Octacalcium phosphate (OCP) is of considerable importance as a precursor in the formation of dental enamel and an intermediate phase in the precipitation of hydroxyapatite (HAp) in bone. However, agreement is poor on the solubility product (pKsp), possibly due to the formation of the more stable phase HAp. The system was investigated using solid titration, which has shown reliability in work on HAp and related fluoride minerals, with OCP in 100 mM KCl at 37.0 ± 0.1°C. The constitution of the end point precipitate was determined by X-ray diffraction and selected-electron area diffraction; the particle morphology and elements present were examined by high-resolution field emission scanning, transmission electron microscopy and energy-dispersive X-ray analysis. The titration curve for OCP was found for pH ∼3.4–7.4. The precipitate was HAp at pH 3.6 and 4.5; no residual OCP or other phase was detected. Dicalcium phosphate dihydrate (DCPD) was then found to form at pH 3.6 on further addition of OCP titrant after equilibrium had been achieved, possibly due to easier nucleation at lower pH. However, markedly crystalline HAp was formed in equilibrium for OCP titration with HAp seeding, verifying HAp as the more stable phase. A solubility isotherm for OCP was not obtained as HAp appears to be less soluble in the pH range studied. This adds weight to the view that HAp may be the most stable phase of all calcium phosphates, with further doubt being cast on DCPD being the most stable phase below pH 4.2. However, metastable DCPD may form in an Ostwald succession, depending on supersaturation and nucleation conditions.
Sodium ascorbate kills Candida albicans in vitro via iron-catalyzed Fenton reaction: importance of oxygenation and metabolism.

AIM Ascorbate can inhibit growth and even decrease viability of various microbial species including Candida albicans. However the optimum conditions and the mechanism of action are unclear. Materials/methodology: Candida albicans shaken for 90 min in a buffered solution of ascorbate (90 mM) gave a 5-log reduction of cell viability, while there was no killing without shaking, in growth media with different carbon sources or at 4°C. Killing was inhibited by the iron chelator 2,2'-bipyridyl. Hydroxyphenyl fluorescein probe showed the intracellular generation of hydroxyl radicals. RESULTS/CONCLUSION Ascorbate-mediated killing of C. albicans depends on oxygenation and metabolism, involves iron-catalyzed generation of hydroxyl radicals via Fenton reaction and depletion of intracellular NADH. Ascorbate could serve as a component of a topical antifungal therapy.