Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene Expression and DNA Methylation of PPARGC1A in Muscle and Adipose Tissue From Adult Offspring of Women With Diabetes in Pregnancy

Prenatal exposure to maternal hyperglycemia is associated with an increased risk of later adverse metabolic health. Changes in the regulation of peroxisome proliferator–activated receptor-γ coactivator-1α (PPARGC1A) in skeletal muscle and subcutaneous adipose tissue (SAT) is suggested to play a role in the developmental programming of dysmetabolism based on studies of human subjects exposed to an abnormal intrauterine environment (e.g., individuals with a low birth weight). We studied 206 adult offspring of women with gestational diabetes mellitus (O-GDM) or type 1 diabetes (O-T1D) and of women from the background population (O-BP) using a clinical examination, oral glucose tolerance test, and gene expression and DNA methylation of PPARGC1A in skeletal muscle and SAT. Plasma glucose was significantly higher for both O-GDM and O-T1D compared with O-BP (P < 0.05). PPARGC1A gene expression in muscle was lower in O-GDM compared with O-BP (P = 0.0003), whereas no differences were found between O-T1D and O-BP in either tissue. PPARGC1A DNA methylation percentages in muscle and SAT were similar among all groups. Decreased PPARGC1A gene expression in muscle has previously been associated with abnormal insulin function and may thus contribute to the increased risk of metabolic disease in O-GDM. The unaltered PPARGC1A gene expression in muscle of O-T1D suggests that factors other than intrauterine hyperglycemia may contribute to the decreased PPARGC1A expression in O-GDM.
Encoding processes influence word-stem completion priming in Alzheimer's disease: A meta-analysis

Despite the numerous studies focused on priming performances in Alzheimer's disease (AD), the question of whether word-stem completion priming persists in AD is still prone to controversy. Methodological variations, such as encoding instructions, have been proposed to explain the discrepancy of word-stem completion priming results in AD. We conducted a meta-analysis on 678 AD patients and 640 controls to assess whether word-stem completion priming in AD differs according to instructions provided at encoding. When the data across the different encoding instructions were combined, the results showed that AD patients manifest significant completion priming, even though the magnitude of priming is reduced. Taking into account the different encoding conditions, the results suggested that whereas completion priming is impaired in AD when encoding conditions consist in reading or rating words, priming is equivalent to that of controls when encoding conditions require semantic judgments or generating words. In this latter condition in particular, self-generating a word at encoding may provide an aid to partially overcome conceptual deficits of the patients and increase the degree of adequacy between cognitive operations employed at encoding phase and those triggering implicit retrieval.
Social Desirability Bias in Self-Reporting of Hearing Protector Use among Farm Operators.

OBJECTIVE The purposes of this study were (i) to examine the relationship between reported hearing protector use and social desirability bias, and (ii) to compare results of the Marlowe-Crowne social desirability instrument when administered using two different methods (i.e. online and by telephone). METHODS A shortened version of the Marlowe-Crowne social desirability instrument, as well as a self-administered instrument measuring use of hearing protectors, was administered to 497 participants in a study of hearing protector use. The relationship between hearing protector use and social desirability bias was examined using regression analysis. The results of two methods of administration of the Marlowe-Crowne social desirability instrument were compared using t-tests and regression analysis. RESULTS Reliability (using Cronbach's alpha) for the shortened seven-item scale for this sample was 0.58. There was no evidence of a relationship between reported hearing protector use and social desirability reporting bias, as measured by the shortened Marlowe-Crowne. The difference in results by method of administration (i.e. online, telephone) was very small. CONCLUSIONS This is the first published study to measure social desirability bias in reporting of hearing protector use among farmers. Findings of this study do not support the presence of social desirability bias in farmers' reporting of hearing protector use, lending support for the validity of self-report in hearing protector use in this population.
Ethical Issues in the Use of Extracorporeal Membrane Oxygenation in Controlled Donation After Circulatory Determination of Death

The use of donor extracorporeal membrane oxygenation (ECMO) to improve graft outcomes by some controlled donation after circulatory determination of death (cDCDD) programs raises ethical issues. We reviewed cDCDD protocols using ECMO and the relevant ethics literature to analyze these issues. It is not obvious that ECMO in cDCDD improves graft outcomes. In our opinion, ECMO implemented before death can interfere with end‐of‐life care and damage bodily integrity. By restoring systemic circulation, ECMO risks invalidating the preceding declaration of death if brain and cardiac perfusion is not adequately excluded because of malfunction or misplacement of the supradiaphragmatic aortic occlusion balloon. The use of ECMO is not compatible with the acronym DCDD because circulation is restored after the determination of death. Because of these deficiencies, we concluded that other techniques are preferable, such as rapid recovery or in situ cold infusion. If ECMO is performed, it requires a specific informed consent and transparency.
Negative regulation of tumor-infiltrating NK cell in clear cell renal cell carcinoma patients through the exosomal pathway

Natural killer cells are the key components in tumor immunity and defects in function are necessary for tumor immune escape. Emerging studies on tumor cell-derived exosomes have shown the biological significance in tumor microenvironment, but the underlying role of exosomes in regulating natural killer cells functions in clear cell renal cell carcinoma patients remains unknown. Firstly, we precisely characterized the phenotype and function of natural killer cells in clear cell renal cell carcinoma patients vs healthy controls. With an inhibitory phenotype, tumor-infiltrating natural killer cells exhibited poor cytotoxic capacity and deficient potential to produce cytokines compared with natural killer cells from tumor margin tissue and non-tumor tissue. Next, we revealed that primary tumor cells trigged natural killer cell dysfunction in an exosome-dependent manner. Interestingly, exosomes from primary tumor cells were preferentially enriched with TGF-β1 which acted as important mediator of natural killer cell functional deficiency. In vitro culture of exosomes induced natural killer cell dysfunction mediated by activation of the TGF-β/SMAD signaling pathway, and abrogated by knockdown TGF-β. Our data indicate that exosomes from clear cell renal cell carcinoma induce natural killer cells dysfunction by regulating the TGF-β/SMAD pathway to evade innate immune surveillance.
Nebivolol in the management of essential hypertension: a review.

UNLABELLED Nebivolol is a lipophilic beta1-blocker. It is devoid of intrinsic sympathomimetic or membrane stabilising activity but appears to have nitric oxide-mediated vasodilatory effects. Nebivolol is administered as a racemic mixture of equal proportions of d- and l-enantiomers. The drug does not significantly influence glucose or plasma lipid metabolism and appears to have a protective effect on left ventricular function. At the recommended dosage (5 mg once daily) nebivolol reduces resting diastolic blood pressure as effectively as standard therapeutic dosages of atenolol, metoprolol, lisinopril and nifedipine, as shown in comparative trials. Nebivolol reduced blood pressure significantly more than enalapril 10 mg daily in the short but not the long term, although the enalapril dose may not have been optimal. Nebivolol has an additive effect in combination with hydrochlorothiazide. Standing blood pressure and/or mean 24-hour ambulatory blood pressure is significantly and similarly reduced with nebivolol, atenolol or nifedipine. Nebivolol tended to prevent increases in early morning blood pressure better than nifedipine. Overall response rates to nebivolol therapy (a decrease in sitting/supine diastolic blood pressure to < or = 90 mm Hg or a 10% or > or = 10 mm Hg fall in diastolic blood pressure) ranged from 58 to 81% after 4 to 52 weeks' treatment. In comparative studies, response rates were greater in nebivolol than in enalapril or metoprolol recipients, but not significantly different from those in atenolol or nifedipine recipients. Nebivolol 5 mg once daily is well tolerated in patients with hypertension. Adverse events are infrequent, transient and mild to moderate. Those reported most often include headache, fatigue, paraesthesias and dizziness. Several studies reported no signs of orthostatic hypotension with nebivolol. Comparative trials revealed no significant differences between the frequency and severity of adverse events in patients receiving nebivolol, atenolol, enalapril or placebo; however, the overall incidence of adverse events was greater with nifedipine or metoprolol. Some atenolol or enalapril, but not nebivolol, recipients reported impotence or decreased libido during therapy. CONCLUSION Current evidence indicates that nebivolol 5 mg once daily is a well tolerated beta-blocker, which is as effective as once daily atenolol and other classes of antihypertensive agents. It may therefore be recommended as a useful alternative first-line treatment option for the management of patients with mild to moderate uncomplicated essential hypertension.
Inhibitory effects of an anti-rheumatic agent T-614 on immunoglobulin production by cultured B cells and rheumatoid synovial tissues engrafted into SCID mice.

OBJECTIVE To clarify the pharmacological action of an anti-rheumatic agent T-614, we investigated its effects on immunoglobulin (Ig) production by cultured B cells and Ig secretion from synovial tissues of patients with rheumatoid arthritis (RA) using SCID mice engrafted with human RA tissue (SCID-HuRAg). METHODS Murine B cells were prepared from mouse spleen by a T-cell depletion method. The cells were cultured with lipopolysaccharide (LPS) and/or interleukin 4 (IL-4) in the absence or presence of T-614. Human B cells were isolated from peripheral blood of healthy donors and the Ig production was induced by co-culture with autologous T cells and anti-CD3 antibody. SCID-HuRAg was prepared according to our previous method. T-614 was orally administered to the mice once daily for 4 weeks starting on the fourth week after the implantation. Then, peripheral blood was obtained and the implanted tissues were removed. Igs in the culture media or the sera were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS In murine B-cell cultures, T-614 significantly decreased not only the IgM production stimulated with LPS but IgG1 production induced by LPS and IL-4. Regarding human B cells stimulated with T cells, it also inhibited IgM and IgG production. In SCID-HuRAg mice, high concentrations of polyclonal human IgG were detectable in the sera of all mice. A significant decrease in the IgG level was observed in the T-614-treated group compared with the control group. CONCLUSIONS We showed that T-614 inhibited Ig production by the cultured B cells and also decreased the high level of human IgG observed in SCID-HuRAg mice. These results may support its effect on plasma Ig in RA patients and provide insights into the mechanisms of its anti-rheumatic effect.
Antibiotic-Induced Cell Wall Fragments ofStaphylococcus aureus Increase Endothelial Chemokine Secretion and Adhesiveness for Granulocytes

ABSTRACT Antibiotics release inflammatory fragments, such as lipoteichoic acid (LTA) and peptidoglycan (PG), from the cell wall ofStaphylococcus aureus. In this study, we exposed S. aureus cultures to a number of β-lactam antibiotics (imipenem, flucloxacillin, and cefamandole) and protein synthesis-inhibiting antibiotics (erythromycin, clindamycin, and gentamicin) and investigated whether supernatants of these cultures differ in their capacity to stimulate endothelial cells (EC). After 24 h of incubation, endothelial adhesiveness for leukocytes, surface expression of various adhesion molecules, and secretion of the chemokines interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) were measured. Supernatants of β-lactam-exposed cultures (designated β-lactam supernatants) enhanced the adhesiveness of EC for granulocytes, whereas those of protein synthesis-inhibiting antibiotic-exposed cultures (designated protein synthesis-inhibitor supernatants) did not. This hyperadhesiveness coincided with a higher intercellular adhesion molecule-1 expression on the surface of the stimulated EC. In addition, EC stimulated with β-lactam supernatants secreted significantly higher concentrations of the chemokines IL-8 and MCP-1 than those stimulated with protein synthesis-inhibitor supernatants. The finding that the concentrations of LTA and PG in β-lactam supernatants were much higher than those in protein synthesis-inhibitor supernatants suggests that the observed differences in stimulatory effect between these supernatants are a result of differences in the release of cell wall fragments, although the presence of other stimulatory factors in the supernatants cannot be excluded. In conclusion, our results argue for a release of LTA and PG from S. aureus after exposure to β-lactam antibiotics that enhances the development of a systemic inflammatory response by stimulating EC such that adhesiveness for granulocytes is increased and large amounts of IL-8 and MCP-1 are secreted.
Optimization model for UV-riboflavin corneal cross-linking.

PURPOSE To develop a theoretical model for riboflavin ultraviolet-A cross-linking treatment that can predict the increase in stiffness of the corneal tissue as a function of the ultraviolet intensity and riboflavin concentration distribution, as well as the treatment time. METHODS A theoretical model for calculating the increase in corneal cross-linking (polymerization rate) was derived using Fick's second law of diffusion, Lambert-Beer's law of light absorption, and a photopolymerization rate equation. Stress-strain experiments to determine Young's modulus at 5% strain were performed on 43 sets of paired porcine corneal strips at different intensities (3-7 mW/cm²) and different riboflavin concentrations (0.0%-0.5%). The experimental results for Young's modulus increase were correlated with the simulated polymerization increase to determine a relationship between the model and the experimental data. RESULTS This model allows the calculation of the one-dimensional spatial and temporal intensity and concentration distribution. The total absorbed radiant exposure, defined by intensity, concentration distribution, and treatment time, shows a linear correlation with the measured stiffness increase from which a threshold value of 1.7 J/cm² can be determined. The relative stiffness increase shows a linear correlation with the theoretical polymer increase per depth of tissue, as calculated by the model. CONCLUSIONS This theoretical model predicts the spatial distribution of increased stiffness by corneal cross-linking and, as such, can be used to customize treatment, according to the patient's corneal thickness and medical indication.
Reliability of impairment and physical performance measures for persons with Parkinson's disease.

BACKGROUND AND PURPOSE Parkinson's disease (PD) is characterized by rigidity, postural instability, bradykinesia, and tremor, as well as other musculoskeletal impairments and functional limitations. The purpose of this investigation was to determine the reliability and stability of measures of impairments and physical performance for people in the early and middle stages of PD, Subjects. Thirteen men and 2 women in Hoehn and Yahr stages 2 and 3 of PD participated. Their mean age was 74.5 years (SD = 5.7, range = 64-84). METHODS Thirteen impairment-level variables and 8 physical performance variables were measured. Measurements were taken on two consecutive days and again a week later on the corresponding two consecutive days. Reliability and stability were assessed using analysis of variance and intraclass correlation coefficients (ICCs). RESULTS Test-retest reliability (ICCs) of variables ranged from . 69 (hamstring muscle length) to . 97 (lumbar flexion). Intraclass correlation coefficients were . 85 or greater for 10 of the variables. CONCLUSIONS AND DISCUSSION The results suggest that in the early and middle stages of PD, many of the measures of impairment and physical performance are relatively stable.
Bile acids induce monocyte differentiation toward interleukin‐12 hypo‐producing dendritic cells via a TGR5‐dependent pathway

Dendritic cells (DCs) are known as antigen‐presenting cells and play a central role in both innate and acquired immunity. Peripheral blood monocytes give rise to resident and recruited DCs in lymph nodes and non‐lymphoid tissues. The ligands of nuclear hormone receptors can modulate DC differentiation and so influence various biological functions of DCs. The role of bile acids (BAs) as signalling molecules has recently become apparent, but the functional role of BAs in DC differentiation has not yet been elucidated. We show that DCs derived from human peripheral blood monocytes cultured with a BA produce lower levels of interleukin‐12 (IL‐12) and tumour necrosis factor‐α in response to stimulation with commensal bacterial antigens. Stimulation through the nuclear receptor farnesoid X (FXR) did not affect the differentiation of DCs. However, DCs differentiated with the specific agonist for TGR5, a transmembrane BA receptor, showed an IL‐12 hypo‐producing phenotype. Expression of TGR5 could only be identified in monocytes and was rapidly down‐regulated during monocyte differentiation to DCs. Stimulation with 8‐bromoadenosine‐cyclic AMP (8‐Br‐cAMP), which acts downstream of TGR5 signalling, also promoted differentiation into IL‐12 hypo‐producing DCs. These results indicate that BAs induce the differentiation of IL‐12 hypo‐producing DCs from monocytes via the TGR5‐cAMP pathway.
The Effect of Religiosity and Campus Alcohol Culture on Collegiate Alcohol Consumption

Abstract Religiosity and campus culture were examined in relationship to alcohol consumption among college students using reference group theory. Participants and Methods: College students (N = 530) at a religious college and at a state university complete questionnaires on alcohol use and religiosity. Statistical tests and logistic regression were utilized to examine alcohol use, religiosity, and campus environment. Results: Alcohol consumption was significantly higher among students at the university (M = 26.9 drinks) versus students at the religious college (M = 11.9 drinks). University students also had lower religiosity scores (M = 23.8) than students at the religious college (M = 26.5). Students who attend a secular university are 4 times more likely to be moderate or heavy drinkers compared to students attending a religiously affiliated college. Students with the least religiosity were 27 times more likely to be a heavy alcohol user and 9 times more likely to be a moderate alcohol user compared to students with greater religiosity.
Observations on the doubling time of prostate cancer. The use of serial prostate‐specific antigen in patients with untreated disease as a measure of increasing cancer volume

Background. The serum marker prostate‐specific antigen (PSA) has been shown to be proportional to the volume of prostate cancer (Yang polyclonal assay). One gram of cancer on average produces 3.5 ng/ml of PSA elevation. Thus, changes in PSA in untreated patients should reflect tumor growth rate and the shape of the growth curve.
Control of body size by SMA-5, a homolog of MAP kinase BMK1/ERK5, in C. elegans

We have analyzed the sma-5(n678) mutant in C. elegans to elucidate mechanisms controlling body size. The sma-5 mutant is very small, grows slowly and its intestinal granules look abnormal. We found a 15 kb deletion in the mutant that includes a 226 bp deletion of the 3′ end of the W06B3.2-coding sequence. Based on this result, rescue experiments, RNAi experiments and a newly isolated deletion mutant of W06B3.2, we conclude that W06B3.2 is the sma-5 gene. The sma-5 mutant has much smaller intestine, body wall muscles and hypodermis than those of the wild type. However, the number of intestinal cells or body wall muscle cells is not changed, indicating that the sma-5 mutant has much smaller cells. In relation to the smaller cell size, the amount of total protein is drastically decreased; however, the DNA content of the intestinal nuclei is unchanged in the sma-5 mutant. The sma-5 gene is expressed in intestine, excretory cell and hypodermis, and encodes homologs of a mammalian MAP kinase BMK1/ERK5/MAPK7, which was reported to control cell cycle and cell proliferation. Expression of the sma-5 gene in hypodermis is important for body size control, and it can function both organ-autonomously and non-autonomously. We propose that the sma-5 gene functions in a MAP kinase pathway to regulate body size mainly through control of cell growth.
Molar Efficiency Study of Chlorinated NPG Substitutes in Dentin Bonding

This study evaluated and compared the contributions to dentin adhesive bonding of three N-phenylglycine analogues with electron-withdrawing substituents on the aromatic ring. These electron-deficient "N-compounds" included: N-(4-chlorophenyl)-glycine (NCPG), N-methyl-N-(4-chlorophenyl)-glycine (NMNCPG), and N-(3,4-dichlorophenyD-glycine (NDCPG). An experimental three-step dentin-bonding protocol that consisted of sequential application of acidic ferric oxalate solution, an N-compound in acetone, and a surface-active comonomer in acetone was used. The first and third steps were held constant throughout the study. EachN-compound (NCPG, NMNCPG, NDCPG) was used in step two at ten concentrations ranging from 0.0 mol/L (pure acetone) to 5 x 10-1 mol/L, depending on solubility. After overnight storage in distilled water, the dentin-to-composite bonds were broken in tension. The data were analyzed with ANOVA, and multiple comparisons were performed with Duncan's Multiple Range test. All statistical tests were controlled at α = 0.05. At 5 x 10-3 mol/L, the relative effectiveness of the three N-compounds (as measured by tensile bond strengths) was NMNCPG > NCPG > NDCPG. Of all concentrations studied, the mean bond strengths produced with NMNCPG were statistically as good as or better than those produced by the other two compounds, and NCPG was always as good as or better than NDCPG. Increased electron-withdrawing from the nitrogen of the amine group by the substituents narrowed the effective concentration range for dentin bonding and, in general, produced lower mean bond strengths between dentin and composite.