Miracle-dz/UniFAR-FTUs huggingface dataset:
Is N,N-dimethylglycine N-oxide a choline and betaine metabolite?

Abstract Choline metabolism is by oxidation to betaine, which is demethylated to N,N-dimethylglycine; dimethylglycine is oxidatively demethylated to sarcosine. This pathway is important for osmoregulation and as a source of methyl groups. We asked whether another metabolite was involved. We synthesized the N-oxide of dimethylglycine (DMGO) by oxidizing dimethylglycine with peracetic acid, and measured DMGO in human plasma and urine by HPLC-MS/MS with positive ion detection, using two chromatography procedures, based on ion exchange and HILIC separations. The molecular ion DMGOH+ (m/z=120) yielded four significant fragments (m/z=103, 102, 58 and 42). The suspected DMGO peak in human body fluids showed all these fragments, and co-chromatographed with added standard DMGO in both HPLC systems. Typical plasma concentrations of DMGO are under 1 μmol/l. They may be lower in metabolic syndrome patients. Urine concentrations are higher, and DMGO has a higher fractional clearance than dimethylglycine, betaine and choline. It was present in all of over 80 human urine and plasma samples assayed. Plasma DMGO concentrations correlate with plasma DMG concentrations, with betaine and choline concentrations, with the osmolyte myo-inositol, and strongly with urinary DMGO excretion. We conclude that DMGO is probably a normal human metabolite.
Bayesian nonparametric density estimation under length bias

ABSTRACT A density estimation method in a Bayesian nonparametric framework is presented when recorded data are not coming directly from the distribution of interest, but from a length biased version. From a Bayesian perspective, efforts to computationally evaluate posterior quantities conditionally on length biased data were hindered by the inability to circumvent the problem of a normalizing constant. In this article, we present a novel Bayesian nonparametric approach to the length bias sampling problem that circumvents the issue of the normalizing constant. Numerical illustrations as well as a real data example are presented and the estimator is compared against its frequentist counterpart, the kernel density estimator for indirect data of Jones.
Urinary levels of interleukin-6 and disease activity in patients with IgA nephropathy.

We studied, using ELISA, 27 patients with IgA nephropathy to determine if levels of urinary interleukin-6 (IL-6) might reflect the disease activity. The levels of urinary IL-6 in patients with the advanced stage were significantly higher than those in patients with the mild stage of the disease or in healthy adults. The results showed a significant correlation between the levels of urinary IL-6 and the disease activity, i.e., levels of urinary cast and urinary protein. It was thus suggested that the measurement of urinary IL-6 is useful in evaluating the degree of glomerular injuries and/or prognosis in patients with IgA nephropathy.
Reliability of Standardized Echography before Vitreoretinal Surgery for Proliferative Diabetic Retinopathy

Standardized A- and B-scan echography was performed in 45 patients (68 eyes) affected by proliferative diabetic retinopathy, before vitreoretinal surgery, to evaluate the percentage of agreement between the ultrasonographic data and the surgical findings. The agreement was quite good for tractional retinal detachment (93%) and for posterior vitreous detachment (91%). The main cause of failure was the presence of vitreoschisis, while preretinal and vitreal membranes can easily be detected.
Effect of Cystic Fibrosis-associated Mutations in the Fourth Intracellular Loop of Cystic Fibrosis Transmembrane Conductance Regulator*

The cystic fibrosis transmembrane conductance regulator (CFTR) contains multiple membrane spanning sequences that form a Cl− channel pore and cytosolic domains that control the opening and closing of the channel. The fourth intracellular loop (ICL4), which connects the tenth and eleventh transmembrane spans, has a primary sequence that is highly conserved across species, is the site of a preserved sequence motif in the ABC transporter family, and contains a relatively large number of missense mutations associated with cystic fibrosis (CF). To investigate the role of ICL4 in CFTR function and to learn how CF mutations in this region disrupt function, we studied several CF-associated ICL4 mutants. We found that most ICL4 mutants disrupted the biosynthetic processing of CFTR, although not as severely as the most common ΔF508 mutation. The mutations had no discernible effect on the channel's pore properties; but some altered gating behavior, the response to increasing concentrations of ATP, and stimulation in response to pyrophosphate. These effects on activity were similar to those observed with mutations in the nucleotide-binding domains, suggesting that ICL4 might help couple activity of the nucleotide-binding domains to gating of the Cl− channel pore. The data also explain how these mutations cause a loss of CFTR function and suggest that some patients with mutations in ICL4 may have a milder clinical phenotype because they retain partial activity of CFTR at the cell membrane.
Trichostatin A decreases the levels of MeCP2 expression and phosphorylation and increases its chromatin binding affinity

ABSTRACT MeCP2 binds to methylated DNA in a chromatin context and has an important role in cancer and brain development and function. Histone deacetylase (HDAC) inhibitors are currently being used to palliate many cancer and neurological disorders. Yet, the molecular mechanisms involved are not well known for the most part and, in particular, the relationship between histone acetylation and MeCP2 is not well understood. In this paper, we study the effect of the HDAC inhibitor trichostatin A (TSA) on MeCP2, a protein whose dysregulation plays an important role in these diseases. We find that treatment of cells with TSA decreases the phosphorylation state of this protein and appears to result in a higher MeCP2 chromatin binding affinity. Yet, the binding dynamics with which the protein binds to DNA appear not to be significantly affected despite the chromatin reorganization resulting from the high levels of acetylation. HDAC inhibition also results in an overall decrease in MeCP2 levels of different cell lines. Moreover, we show that miR132 increases upon TSA treatment, and is one of the players involved in the observed downregulation of MeCP2.
Critical defining characteristics for nursing diagnosis about ineffective breastfeeding.

OBJECTIVE To investigate the Nursing diagnostic accuracy measures and to propose a model to use defining characteristics in order to judge the nursing diagnosis of ineffective breastfeeding. METHOD Cross-sectional study with a sample of 73 binomials mom-child hospitalized in a maternity ward of an University Hospital, from July to August of 2014. RESULTS The diagnostic predominance rate was 58.9%. The characteristics that best meet the needs of logistic regression model were: discontinuance of breast sucking; infant's inability of seizing the areola-nipple region correctly; infant's crying one hour after breastfeeding and inappropriate milk supply perceived. CONCLUSION Breastfeeding process is dynamic; diagnostic judgement may suffer some changes according to the time data are collected; the defining characteristics are the best predictors if associated with models and rules of use.
Statewide Intervention to Reduce Television Viewing in WIC Clients and Staff

Purpose. To evaluate a statewide campaign that was designed to reduce television viewing by clients and staff of the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Television reduction is frequently recommended as a strategy for preventing pediatric overweight. Methods. Data were collected from a convenience sample of 10,445 clients and staff who attended clinics during a 3-week period before the intervention and 9188 clients and staff who attended clinics after the intervention. Chi-square tests were used to compare the proportion of WIC clients watching television 2 or 3 hours per day before and after the intervention. Within the context of WIC, which is a large and complex public health program, it was not possible to measure individual exposures or response rates. Results. At baseline, 64.2% of WIC clients reported watching 2 or less hours of television per day. After the intervention, 70.5% limited television viewing to this recommended level. Conclusions. It is feasible to deliver television-reduction messages in large public health programs.
Effects of a 10,000 Steps per Day Goal in Overweight Adults

Purpose. This study was designed (1) to examine the effects of a 10,000 steps·d−1 exercise prescription on sedentary, overweight/obese adults, and (2) to examine the effects of adherence on body composition and cardiovascular risk factors. Methods. Fifty-six overweight/obese adults participated in the study. Body composition and cardiovascular risk factors were determined at baseline, 20 weeks, and 36 weeks. Adherence was defined as averaging ≥ 9500 steps·d−1 from week 4 to week 36. Results. 38 participants (68%) wore pedometers daily for 36 weeks and were available for posttesting. Significant improvements were noted in mean values for walking volume (3994 steps·d−1), body weight (–2.4 kg), body mass index (–0.8 kg·m−2), percentage body fat (–1.9%), fat mass (–2.7 kg), waist circumference (–1.8 cm), hip circumference (–1.9 cm) and high-density lipoprotein (3 mg/dl). The adherers had large improvements in body composition measures, whereas the nonadherers showed little or no change in these variables. Discussion. A 10,000 steps·d−1 exercise prescription resulted in weight loss over 36 weeks in previously sedentary, overweight/obese adults. Adherence to the step goal had a marked effect on the outcome.
Metabolic dynamics of Desulfovibrio vulgaris biofilm grown on a steel surface

Abstract In this study, a comparative metabolomics approach combining gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–mass spectrometry (LC-MS) was applied first between planktonic cells and biofilms and then between pure cultures and biofilms of Desulfovibrio vulgaris. The results revealed that the overall metabolic level of the biofilm cells was down-regulated, especially for metabolites related to the central carbon metabolism, compared to the planktonic cells and the pure culture of D. vulgaris. In addition, pathway enrichment analysis of the 58 metabolites identified by GC-MS showed that fatty acid biosynthesis in the biofilm cells was up-regulated, suggesting that fatty acids may be important for the formation, maintenance and function of D. vulgaris biofilm. This study offers a valuable perspective on the metabolic dynamics of the D. vulgaris biofilm.
The Impact of Adding Sentinel Node Biopsy to Extended Pelvic Lymph Node Dissection on Biochemical Recurrence in Prostate Cancer Patients Treated with Robot-Assisted Radical Prostatectomy

The benefit of adding sentinel node biopsy (SNB) to extended pelvic lymph node dissection (ePLND) remains controversial. The aim of our study was to evaluate biochemical recurrence (BCR) after robot-assisted radical prostatectomy and ePLND in prostate cancer patients, stratified by the application of SNB. The results were compared with the predictions of the updated Memorial Sloan Kettering Cancer Center nomogram. Methods: Between January 2006 and November 2016, 920 patients underwent robot-assisted radical prostatectomy and ePLND with or without SNB (184 and 736 patients, respectively). BCR was defined as 2 consecutive prostate-specific antigen rises of at least 0.2 ng/mL. The Kaplan–Meier method and Cox regression analyses were used to identify predictors of BCR. Results: Median follow-up was 28 mo (interquartile range, 13–56.7 mo). The 5-y BCR-free survival rate was 80.5% and 69.9% in the ePLND+SNB and ePLND groups, respectively. At multivariate analysis, prostate-specific antigen level, primary Gleason grade greater than 3, seminal vesicle invasion, and higher number of removed and positive nodes were independent predictors of BCR in the ePLND group. In the ePLND+SNB group, only the number of positive nodes was an independent predictor of BCR. The overall accuracy of the Memorial Sloan Kettering Cancer Center nomogram was higher in the ePLND+SNB than in the ePLND group. However, the nomogram was underestimating the probability of BCR-free status in the ePLND+SNB group, whereas the ePLND group was performing as predicted. Conclusion: Adding SNB to ePLND improves BCR-free survival, although the precise explanation of this observation remains speculative. Our results should be interpreted cautiously, given the nonrandomized nature and the selection bias of the study.
Incorporation of relative biological effectiveness uncertainties into proton plan robustness evaluation

Abstract Background: The constant relative biological effectiveness (RBE) of 1.1 is typically assumed in proton therapy. This study presents a method of incorporating the variable RBE and its uncertainties into the proton plan robustness evaluation. Material and methods: The robustness evaluation was split into two parts. In part one, the worst-case physical dose was estimated using setup and range errors, including the fractionation dependence. The results were fed into part two, in which the worst-case RBE-weighted doses were estimated using a Monte Carlo method for sampling the input parameters of the chosen RBE model. The method was applied to three prostate, breast and head and neck (H&N) plans for several fractionation schedules using two RBE models. The uncertainties in the model parameters, linear energy transfer and α/β were included. The resulting DVH error bands were compared with the use of a constant RBE without uncertainties. Results: All plans were evaluated as robust using the constant RBE. Applying the proposed methodology using the variable RBE models broadens the DVH error bands for all structures studied. The uncertainty in α/β was the dominant factor. The variable RBE also shifted the nominal DVHs towards higher doses for most OARs, whereas the direction of this shift for the clinical target volumes (CTVs) depended on the treatment site, RBE model and fractionation schedule. The average RBE within the CTV, using one of the RBE models and 2 Gy(RBE) per fraction, varied between 1.11–1.26, 1.06–1.16 and 1.14–1.25 for the breast, H&N and prostate patients, respectively. Conclusions: A method of incorporating RBE uncertainties into the robustness evaluation has been proposed. By disregarding the variable RBE and its uncertainties, the variation in the RBE-weighted CTV and OAR doses may be underestimated. This could be an essential factor to take into account, especially in normal tissue complication probabilities based comparisons between proton and photon plans.
Involvement of lateral septum in alcohol's dopamine‐elevating effect in the rat

Drugs of abuse share the ability to increase extracellular dopamine (DA) levels in the mesolimbic DA system. This effect has been linked to positive and reinforcing experiences of drug consumption and is presumed to be of importance for continued use, as well as for the development of dependence and addiction. Previous rat studies from our lab have implicated a neuronal circuitry involving glycine receptors in nucleus accumbens (nAc) and, secondarily, nicotinic acetylcholine receptors in the ventral tegmental area (VTA) in ethanol's (EtOH) DA‐elevating effect. The work presented here, performed in male Wistar rats, suggests that the lateral septum (LS), which has previously been associated with different aspects of EtOH‐related behaviour, is involved as well. In vivo microdialysis methodology demonstrated that blocking the generation of action potentials in LS using tetrodotoxin prevented a DA increase in nAc after accumbal EtOH perfusion. Retrograde tracing and polymerase chain reaction (PCR) were used to identify and characterize cells projecting to VTA from nAc/LS and from LS to nAc. Based on the PCR results, cells projecting from both LS/nAc to anterior VTA and from LS to nAc were mainly GABAergic neurons expressing glycine receptors, and these cells are presumed to be involved in mediating the DA‐elevating effect of EtOH. These results provide further evidence implicating LS in the reinforcing effects of EtOH. Additional studies are needed to investigate LS involvement in EtOH consumption behaviour and its potential role in the development of dependence and addiction.
A Domain Decomposition Scheme With Curvilinear Discretizations for Solving Large and Complex PEC Scattering Problems

A nonconformal and nonoverlapping domain decomposition (DD) scheme for surface integral equations is presented to analyze electromagnetic scattering from electrically large and complex perfect electric conducting objects. In this work, a discontinuous Galerkin approach is employed to avoid the introduction of artificial touching faces between adjacent subdomains. To weakly enforce the current continuity at the cutting contours of these subdomains, a novel interior penalty term is defined so that the error energy associated with the error charges can be minimized. Consequently, without the introduction of a stabilization term that relies on the line integral over interactions of nonmatching meshes, the proposed method provides an effective DD preconditioner and requires no effort to be extended to curvilinear elements for higher modeling accuracy. To show this, curvilinear Rao–Wilton–Glisson basis functions defined over curvilinear elements are employed in this work to demonstrate the accuracy and efficiency of the proposed DD scheme.
Prevalence and factors associated with xerostomia and hyposalivation among community-dwelling older people in Japan.

OBJECTIVE This study investigated the prevalence and factors associated with xerostomia and hyposalivation among community-dwelling older people. BACKGROUND Xerostomia and hyposalivation are common symptoms in the older population. MATERIALS AND METHODS This study included with 894 community-dwelling, Japanese older people (355 men, 539 women; age 65-84 years) who participated in a comprehensive geriatric health examination, which included questionnaires and interviews regarding medical history, medications, Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC), depressive condition. The Zung Self-Rating Depression Scale (SDS) was used to evaluate depression. Resting salivary flow rate was evaluated by the modified cotton roll method. RESULTS In this study, 34.8% of the participants (mean age, 73.5 ± 5.0 years) complained about xerostomia, while the prevalence of hyposalivation was 11.5%. Multiple regression analysis revealed hypnotics use [odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.13-2.61], SDS (OR = 1.05, CI = 1.04-1.07) and TMIG-IC total points (OR = 0.87, CI = 0.76-0.99) to be significantly associated with xerostomia. In contrast, female gender (OR = 2.59, CI = 1.55-4.31) and the use of agents affecting digestive organs (OR = 1.78, CI = 1.11-2.86) were associated with hyposalivation. CONCLUSION Our findings showed that the prevalence of xerostomia and hyposalivation were approximately 1 in 3 and 1 in 10 respectively. The factors associated with psychological factors and high-level functional competence, while hyposalivation was associated with medications and gender, as well as systemic and/or metabolic differences. It is important to consider these multidimensional factors associated with xerostomia and hyposalivation.
Choroidal thickness at age 66 years in the Danish high myopia study cohort 1948 compared with follow‐up data on visual acuity over 40 years: a clinical update adding spectral domain optical coherence tomography

A population‐based Copenhagen birth year 1948 cohort with high myopia recorded since age 14 years (spherical equivalent less than or equivalent to −6 D) has been followed over 50 years. Despite complications, current follow‐ups have outlined a better visual prognosis than usually drawn from selected clinical series in the literature. For the present status at age 66 years, focus was on visual ability and choroidal thickness.
Partitioning the Pleiotropy Between Coronary Artery Disease and Body Mass Index Reveals the Importance of Low Frequency Variants and Central Nervous System–Specific Functional Elements

Background: The objective of this study is to investigate the extent and nature of pleiotropy between coronary artery disease (CAD) and body mass index (BMI). Methods: We examined the contribution of genome-wide single-nucleotide polymorphisms (minor allele frequency ≥0.01) to co-occurrence of CAD and BMI in a sample of genetically unrelated 8041 subjects (genetic resemblance ⩽0.025) of European ancestry using mixed-linear-models. We further partitioned the estimated pleiotropy according to biological features to gain insight into the nature of pleiotropy between CAD and BMI. Results: We found significant (P<0.0001) positive genetic correlation between CAD and BMI (rg=0.60). The estimated pleiotropy explained 68% of phenotypic correlation, and it was not proportionally distributed across the chromosomes; notably, chromosome 10 contributed more; whereas, chromosomes 11 and 14 contributed less to pleiotropy than expected given their chromosomal length. We noted that a large proportion (63%; P=0.002) of the pleiotropy is attributed to single-nucleotide polymorphisms with low allele frequency (minor allele frequency <0.05). Of note, pleiotropy was enriched among central nervous system genes and genes of metabolic pathways. Further analyses revealed that these effects are more pronounced in the proopiomelanocortin pathway and genes involved in carbohydrate metabolism. After genome-wide association study meta-analysis, only single-nucleotide polymorphisms downstream of the MC4R gene were found concordantly associated with (P<5×10–8) BMI and CAD with lead single-nucleotide polymorphism being rs663129 (combined P=2.7×10–65). Finally, partitioning the pleiotropy according to functional elements pointed to the importance of superenhancers and notably brain-specific superenhancers. Conclusions: Genome-wide pleiotropy substantially contributes to co-occurrence of CAD and obesity, and it is highly enriched among low frequency variants and central nervous system–specific functional elements.
Depression impacts the physiological responsiveness of mother–daughter dyads during social interaction

Maternal depression is associated with increased risk of psychiatric illness in offspring. While risk may relate to depressed mothers’ difficulties regulating emotions in the context of interacting with offspring, physiological indicators of emotion regulation have rarely been examined during mother–child interactions—and never among mother–adolescent dyads in which both mother and adolescent have histories of major depressive disorder (MDD).
Urinary tract infection during pregnancy: current concepts on a common multifaceted problem

Abstract Urinary tract infections (UTIs) are the most common bacterial infection in pregnancy, increasing the risk of maternal and neonatal morbidity and mortality. Urinary tract infections may present as asymptomatic bacteriuria, acute cystitis or pyelonephritis. Escherichia coli is the most common pathogen associated with both symptomatic and asymptomatic bacteriuria. If asymptomatic bacteriuria is untreated, up to 30% of mothers develop acute pyelonephritis, with an increased risk of multiple maternal and neonatal complications, such as preeclampsia, preterm birth, intrauterine growth restriction and low birth weight. Urinary tract infection is a common, but preventable cause of pregnancy complications, thus urinary tests, such as urine culture or new technologies such as high-throughput DNA sequence-based analyses, should be used in order to improve antenatal screening of pregnant women.