Miracle-dz/UniFAR-FTUs huggingface dataset:
Associations of Vitamin D–Binding Globulin and Bioavailable Vitamin D Concentrations With Coronary Heart Disease Events: The Multi-Ethnic Study of Atherosclerosis (MESA)

Context Low 25-hydroxyvitamin D [25(OH)D] is associated with coronary heart disease (CHD) in people who are white and Chinese but not black or Hispanic. Vitamin D binding globulin (VDBG) avidly binds 25(OH)D, reducing its bioavailability, and differs in isoform and concentration by race. Objective Evaluate associations of VDBG with CHD and whether accounting for VDBG or estimating bioavailable 25(OH)D explains the heterogeneity of the association of 25(OH)D with CHD. Design and Setting We conducted a case-cohort study within the Multi-Ethnic Study of Atherosclerosis. Participants with an incident CHD event over 12 years of follow-up (n = 538) and a randomly assigned subcohort (n = 999) were included. We measured baseline 25(OH)D, VDBG, and isoforms using mass spectrometry and estimated bioavailable 25(OH)D from published equations. Results VDBG was associated with an increased risk of CHD [hazard ratio, 1.77 (95% confidence interval, 1.46 to 2.14) per standard deviation increment, P < 0.0001], without evidence of heterogeneity by race or isoform (each P for interaction > 0.1). Low total 25(OH)D was differentially associated with CHD events, by race, with or without adjustment for VDBG (P for interaction = 0.04 or 0.05, respectively). Associations of 25(OH)D with CHD were strengthened with adjustment for VDBG among participants who were white or Chinese, and bioavailable 25(OH)D was associated with CHD events only among white participants. Conclusions High VDBG concentration was associated with CHD events in all racial and ethnic groups. Incorporation of VDBG strengthened existing associations of 25(OH)D with CHD but did not explain racial heterogeneity in associations of 25(OH)D with CHD.
Phenotypic Characterization of Mesenchymal Stem Cells from Various Tissues

Research on expanded human stem cells has become an increasing field of interest during the last decade. The increasing interest in adult stem cells, especially mesenchymal stem and mesenchymal stromal cells, in hematology and regenerative medicine is also based on the simplicity of isolation and ex vivo expansion of these cells. These processes require an adequate quality control of source and product. In this review, we summarize various different attempts to characterize mesenchymal stem cells based on surface protein expression by flow cytometry and to define multipotent subpopulations of mesenchymal stem cells for prospective isolation. The importance of defining functional assays and a unique marker panel to characterize mesenchymal stem cells for clinical trials as well as the factors that can modulate the marker expression is discussed.
Ab-initio melting curve and principal Hugoniot of tantalum

We report first principles calculations of the melting curve and principal Hugoniot (P - V curve) of body centered cubic (bcc) tantalum in the pressure range 0-300 GPa. A description of lattice dynamics and thermal properties of bcc Ta using finite temperature density functional theory (DFT) is presented. The approach works within the projector augmented wave (PAW) implementation of DFT and explicitly treats in valence the 5p, 6s and 5d electrons. The principal Hugoniot (P - V curve), obtained using the Rankine-Hugoniot equation, is investigated using the generalized gradient approximations (GGA). Very good agreement with the shock experiments is obtained with GGA in all the range of pressure. We also report the temperature-pressure relation on the shock Hugoniot and the full ab-initio melting curve of Ta.
Pharmacogenetic investigation of lapatinib-associated diarrhea in metastatic breast cancer clinical trials.

552 Background: Diarrhea is common during lapatinib treatment. Most events are mild to moderate, self-limiting and managed proactively to prevent serious complications, however diarrhea may lead to non-compliance and possibly poor treatment outcomes. Pharmacogenetic associations with diarrhea caused by tyrosine kinase inhibitors have been reported for the functional variants CYP2C19*2 (lapatinib), ABCG2 Q141K (gefitinib) and EGFR -216G>T (erlotinib) in studies with few diarrhea cases (n<40). The present study evaluated these variants and explored additional genetic influences in a larger dataset in metastatic breast cancer (MBC) patients from lapatinib treatment (monotherapy or combination) clinical trials. METHODS In the primary dataset (8 trials), cases (n=285) were defined as patients who experienced NCI CTC AE grades ≥2 for diarrhea during lapatinib treatment. Controls (n=319) were patients who did not experience diarrhea and received lapatinib for at least 9days (median onset for diarrhea). Germline DNA was extracted from peripheral blood and genotypes were determined by standard methods. In addition to the four specified variants, genome wide association screen data (GWAS, 1M SNPs) including ∼500 tagging SNPs selected in 36 candidate genes for lapatinib metabolism or mechanism pathways were also investigated for diarrhea association using penalised logistic regression. Nominally significant associations were evaluated for confirmation in an independent dataset comprising 120 cases and 124 controls from a single MBC trial. RESULTS The reported variants in CYP2C19, ABCG2 and EGFR did not show significant association (p>0.05) with lapatinib associated diarrhea, despite >80% power to demonstrate similar effects. No GWAS SNPs achieved a genome-wide significance threshold (p=5×10-8), however 57 polymorphisms achieved p<10-4. None of these associations were confirmed in the second independent lapatinib dataset. CONCLUSIONS Previously reported EGFR, ABCG2 and CYP2C19 variants were not found to be associated with lapatinib induced diarrhea. No robust associations were identified following candidate gene and genome-wide evaluation of common variants.
Screening urine samples by leukocyte esterase test and ligase chain reaction for chlamydial infections among asymptomatic men

Urine samples from 358 asymptomatic males were screened for urethral inflammation by the leukocyte esterase (LE) test and for Chlamydia trachomatis by the ligase chain reaction (LCR). LE and LCR positivity rates were 7.5% (27 of 358 samples) and 2.8% (10 of 358 samples), respectively. Eight of the 10 LCR-positive samples were detected by the LE screening test. The urine LE prescreening test in combination with the LCR assay may be a reasonable approach for genitourinary chlamydial disease control.
Recording knowledge-related activities in practice: Methodological bases and a method of knowledge auditing

Purpose ‐ The paper seeks to offer a generalized methodology for knowledge auditing. The context of information and knowledge perspectives is established and knowledge auditing is located in an evolving context of information research and practice. Design/methodology/approach ‐ A 15-element inventory is developed which takes its design from business strategy and process and links it to the generalized cycle of information and communication activity. Findings ‐ The elements are systematically reviewed in terms of a general aspect, a typical interpretation and a threshold to indicate the type of practical application and data representation associated with each element. Practical implications ‐ The model is widely adaptable to different settings as a tool for business enterprises, organizations in different sectors and for use in communities of practice and learning/knowledge settings. Originality/value ‐ This is an area of application where a more standard framework approach to information and knowledge auditing would be beneficial. The structure provides a working basis for further development.
Psychiatric interview and psychometric predictors of cardiac transplant survival.

OBJECTIVE This study prospectively investigated the relation between pretransplant assessment of psychiatric diagnosis, coping skills, and social support and outcome measures of survival and health care utilization. METHOD Ninety-four heart transplant patients underwent structured interviews and completed a battery of self-report psychometric tests assessing coping style, health status, and psychosocial supports. Follow-up that ranged from 9 to 56 months after transplant produced a group of 63 survivors and 31 nonsurvivors, who were found to be comparable in terms of pretransplant cardiac status and severity of illness. RESULTS Survival analysis showed that dimensional psychometric measures of coping and social support based on patient self-assessment were the best significant predictors of survival. Considered separately, interview-determined ratings of social support and pretransplant compliance with treatment regimens were also potential predictors. Formal DSM-III-R diagnoses were related specifically to posttransplant hospital utilization (axis I diagnoses) and posttransplant health behavior (axis II diagnoses). CONCLUSIONS The data demonstrate the value of multifaceted assessment, since psychiatric diagnosis, coping style, and psychosocial support may contribute differently to prediction of such aspects of outcome as mortality and health care utilization.
Small-bowel obstruction: coronal reformations from isotropic voxels at 16-section multi-detector row CT.

PURPOSE To retrospectively assess the added value of coronal reformations of the abdomen and pelvis from isotropic voxels by using 16-section multi-detector row computed tomography (CT) for the diagnosis of small-bowel obstruction (SBO). MATERIALS AND METHODS This HIPAA-compliant study was approved by the institutional review board of this medical center with a waiver of informed consent. One hundred consecutive patients (40 men and 60 women; mean age, 55 years) suspected of having SBO and abdominal pain underwent 16-section multi-detector row CT with coronal reformations. Twenty-nine patients had a final diagnosis of SBO, and 71 patients did not. Three independent readers blinded to the diagnosis interpreted the CT scout scan, then transverse scans alone, and then transverse plus coronal scans for the presence of SBO and abnormal wall enhancement. Confidence was scored with a 1-5 scale (1 = absent, 5 = present). RESULTS Mean sensitivity and specificity of CT scout alone, transverse CT alone, and transverse plus coronal CT for the diagnosis of SBO were 88% and 86%, 87% and 87%, and 87% and 90%, respectively (not significant). In patients without SBO, transverse plus coronal CT enhanced confidence in the exclusion of SBO (P = .01). In patients with SBO, transverse plus coronal CT enhanced confidence in the diagnosis of SBO and identification of abnormal wall enhancement (P = .01). CONCLUSION Transverse 16-section multi-detector row CT data sets are an excellent test for the diagnosis of SBO, while the addition of coronal reformations obtained from these isotropic data sets adds confidence to the diagnosis and exclusion of SBO.
Preconditioning of Indefinite and Almost Singular Finite Element Elliptic Equations

This paper deals with two ways of solving discretized finite element elliptic equations with indefinite and almost singular matrices. Such problems typically arise when applying the shifted inverse power iteration (SIPI) method to the generalized eigenvalue problem $A{\bf u}=\lambda\,B{\bf u}$ where A is defined from some discretized equation by a finite element self-adjoint coercive second-order elliptic operator and B is a mass-matrix operator. Both methods explore two-by-two block partitioning of the given matrices. One of the main matrix blocks corresponds to a coarse space (or, equivalently, to coarse-grid degrees of freedom) and contains the main singularity of the original problem. The other major block, possibly indefinite, is not as close to singular as the original matrix and is inverted by a preconditioned minimal residual (MINRES) method in the first method. The second method, which we use for comparison, exploits preconditioned MINRES iterations for the reduced problem obtained by eliminating the block unknowns that correspond to the coarse discretization space. Here each iteration involves solving a coarse-grid problem. Numerical examples are presented that demonstrate the various aspects of both approaches for solving generalized eigenvalue problems applied to second-order finite element elliptic equations.
Mating between Echinacea angustifolia (Asteraceae) individuals increases with their flowering synchrony and spatial proximity.

PREMISE OF THE STUDY Although spatial distance is considered the primary factor in determining plant mating patterns, flowering time and synchrony are also likely to be important. METHODS We quantified the relationships of both distance and flowering phenology to the probability of mating between individual plants. In an experimental plot, we followed daily flowering phenology in Echinacea angustifolia, a self-incompatible perennial pollinated by solitary bees. We assigned paternity to 832 of 927 seedlings from 37 maternal plants using 11 microsatellite loci. Potential pollen donors included the experiment plot's 202 flowering plants and a nearby plot's 19 flowering plants. For each maternal plant sampled, we examined the pollen pool by quantifying correlated paternity and the effective number of pollen donors. KEY RESULTS Significantly more pollinations occurred between neighboring and synchronous plants than expected under random mating, with distance being more important than flowering synchrony. The distance pollen moved varied over the course of the season, with late flowering plants mating with more distant plants compared to early or peak flowering plants. All maternal plants had a diverse set of mates (mean number of effective pollen donors = 23.7), and the composition of the pollen pools overlapped little between maternal plants. CONCLUSION Both distance and flowering synchrony influenced pollination patterns in E. angustifolia. Our results suggest that pollen movement between incompatible mates and flowering asynchrony could be contributing to the reduced seed set observed in small E. angustifolia remnants. However, we also found that individual plants receive pollen from a diverse group of pollen donors.
Galectin-9 Signaling through TIM-3 Is Involved in Neutrophil-Mediated Gram-Negative Bacterial Killing: An Effect Abrogated within the Cystic Fibrosis Lung

The T cell Ig and mucin domain–containing molecule (TIM) family of receptors have emerged as potential therapeutic targets to correct abnormal immune function in chronic inflammatory conditions. TIM-3 serves as a functional receptor in structural cells of the airways and via the ligand galectin-9 (Gal-9) can modulate the inflammatory response. The aim of this study was to investigate TIM-3 expression and function in neutrophils, focusing on its potential role in cystic fibrosis (CF) lung disease. Results revealed that TIM-3 mRNA and protein expression values of circulating neutrophils were equal between healthy controls (n = 20) and people with CF (n = 26). TIM-3 was detected on resting neutrophil membranes by FACS analysis, and expression levels significantly increased post IL-8 or TNF-α exposure (p < 0.05). Our data suggest a novel role for TIM-3/Gal-9 signaling involving modulation of cytosolic calcium levels. Via TIM-3 interaction, Gal-9 induced neutrophil degranulation and primed the cell for enhanced NADPH oxidase activity. Killing of Pseudomonas aeruginosa was significantly increased upon bacterial opsonization with Gal-9 (p < 0.05), an effect abrogated by blockade of TIM-3 receptors. This mechanism appeared to be Gram-negative bacteria specific and mediated via Gal-9/ LPS binding. Additionally, we have demonstrated that neutrophil TIM-3/Gal-9 signaling is perturbed in the CF airways due to proteolytic degradation of the receptor. In conclusion, results suggest a novel neutrophil defect potentially contributing to the defective bacterial clearance observed in the CF airways and suggest that manipulation of the TIM-3 signaling pathway may be of therapeutic value in CF, preferably in conjunction with antiprotease treatment.
Naturally Occurring V1-env Region Variants Mediate Simian Immunodeficiency Virus SIVmac Escape from High-Titer Neutralizing Antibodies Induced by a Protective Subunit Vaccine

ABSTRACT Macaques which developed high-titer neutralizing antibodies (htNAb) after immunization with a virion-derived oligomeric envelope glycoprotein subunit vaccine were protected against a homologous simian immunodeficiency virus SIVmac challenge. Here we demonstrate that the htNAb could be overcome by V1-env region variants isolated ex vivo from an SIVmac-infected macaque. The results further suggest that the development of V1-env region neutralization escape mutants is also necessary for survival of the virus in infected macaques. The immunological capacity of a single variable region to induce neutralizing antibodies in vaccinated and infected macaques initiate new ideas for a successful vaccine strategy.
Treatment of osteoporosis secondary to hypogonadism in prostate cancer patients: a prospective randomized multicenter international study with denosumab vs. alendronate.

BACKGROUND Osteoporosis is a complication of androgen deprivation therapy (ADT) in men with prostate carcinoma. This is a multicenter, randomized, double-blind prospective study on use of denosumab versus alendronate in the therapy of secondary osteoporosis related to ADT. METHODS A total of 234 patients with diagnosis of osteoporosis underwent ADT for prostate cancer were enrolled. Patients were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months or alendronate (70 mg/week) for 2 years. All patient received supplemental vitamin D (600 IU/day) and supplemental calcium to maintain a calcium intake of 1200 mg per day. Effectiveness of therapy in both groups (denosumab group and alendronate group) was assessed by changes in bone turnover markers (BTMs), bone mineral density, fracture incidence, Visual Analogue Scale score for back pain, and Short Form-8 health survey score for health-related quality of life. RESULTS In the denosumab study group, level of BTMs for bone formation were significantly increased from baseline at all time points during the study (P<0.001); in the alendronate study group level of BTMs for bone formation were increased too (P>0.05). Mean changes in BMD at final follow-up differed significantly between two groups. BMD changes at the lumbar spine at 24 months were 5.6% with denosumab vs. -1.1% with alendronate (P<0.001). CONCLUSIONS Denosumab and alendronate showed similar clinical efficacy in the therapy of ADT-related osteoporosis in men with prostate carcinoma; both drugs provided significant improvements in back pain and general health conditions. Denosumab showed significant increase of BTMs and BMD than alendronate with lower rate of new vertebral fractures.
Coupling Short‐Term Changes in Ambient UV‐B levels with Induction of UV‐Screening Compounds †

A substantial number of studies have been conducted over the last several decades to assess the potential impacts of long‐term increases in ultraviolet‐B radiation (UV‐B between 280 and 320 nm) that will result from continued depletion of stratospheric ozone. However, seasonal changes, tropospheric chemistry and cloudiness are the dominant factors controlling ambient UV‐B levels on a short‐term or daily basis. The effects of short‐term changes in UV‐B on plant growth, phytochemistry and physiological processes have received relatively little attention. The USDA UV‐B Monitoring and Research Program provides an excellent network of stations that provide an opportunity to monitor long‐term changes in solar UV‐B radiation and evaluate the responses of plants to short‐term variation in UV‐B levels on a near‐real‐time basis. In this study barley (Hordeum vulgare L.) and soybean (Glycine max [L] Merr.) were used as model systems. Emerging seedlings of these species were grown under either near‐ambient levels of UV‐B or under reduced levels (ca 90% reduction) in the field. Periodic measurements of foliar UV‐screening compounds were made on separate groups of seedlings planted at intervals over the growing season during contrasting periods of ambient levels of UV radiation. The levels of UV‐screening compounds correlated with UV‐B levels in both species and with UV‐A in soybean but the sensitivity of the response differed between the two species and among the soybean cultivars. Response differences among species may be related to unique secondary chemistry of each species, so one response estimate or action spectrum may not be appropriate for all species.
Efficiency Evaluation of Fully Integrated On-Board EV Battery Chargers With Nine-Phase Machines

A fully integrated on-board battery charger for future electric vehicles (EVs) has been recently introduced. It reutilizes all the propulsion components of an EV in charging/vehicle-to-grid (V2G) modes, it does not require any additional components or hardware reconfiguration, and charging/V2G modes are realized with zero electromagnetic torque production. Both fast (three-phase) and slow (single-phase) chargings are possible, with unity power factor operation at the grid side. The solution is based on the use of a triple three-phase machine and a nine-phase inverter/rectifier. This paper reports on the results of efficiency evaluation for the said system. Testing is performed using both a nine-phase induction machine and a nine-phase permanent magnet machine for a range of operating conditions in charging/V2G modes, with both three-phase and single-phase grid connection. Additionally, the impact of converter interleaving on the losses and efficiency is also studied. Losses are separated for different subsystems, thus providing an insight into the importance of optimization of different EV power train components from the efficiency point of view. Promising efficiencies, in the order of 90%, are achieved although none of the system components have been optimized.
Patient Preference Clinical Trials: Why and When They Will Sometimes Be Preferred

In a preference clinical trial (PCT), two or more health-care interventions are compared among several groups of patients, at least some of whom have purposefully chosen the intervention to be administered to them. This stands in contrast to the randomized, controlled clinical trial (RCT), where patients are randomly assigned to receive one of the available test interventions. This article argues that when comparing two interventions, A and B, when blinding (or masking) the interventions is difficult or impossible and at least some of the potential participants prefer one or the other of the interventions, then the use of a PCT merits consideration. PCTs can be designed in several different ways, and the selection should be driven by the clinical question posed. PCTs also fall towards the pragmatic endpoint of the explanatory/pragmatic clinical trial continuum, suggesting that they may more favorably influence clinical decision-making in real-world contexts. Researchers often want to know not what is the best treatment irrespective of choice and compliance, but whether an intervention can work for the patients who choose it. If we want to answer the latter question, we must let patients choose.