Miracle-dz/UniFAR-FTUs huggingface dataset:
GC-MS Based Metabolomics and NMR Spectroscopy Investigation of Food Intake Biomarkers for Milk and Cheese in Serum of Healthy Humans

The identification and validation of food intake biomarkers (FIBs) in human biofluids is a key objective for the evaluation of dietary intake. We report here the analysis of the GC-MS and 1H-NMR metabolomes of serum samples from a randomized cross-over study in 11 healthy volunteers having consumed isocaloric amounts of milk, cheese, and a soy drink as non-dairy alternative. Serum was collected at baseline, postprandially up to 6 h, and 24 h after consumption. A multivariate analysis of the untargeted serum metabolomes, combined with a targeted analysis of candidate FIBs previously reported in urine samples from the same study, identified galactitol, galactonate, and galactono-1,5-lactone (milk), 3-phenyllactic acid (cheese), and pinitol (soy drink) as candidate FIBs for these products. Serum metabolites not previously identified in the urine samples, e.g., 3-hydroxyisobutyrate after cheese intake, were detected. Finally, an analysis of the postprandial behavior of candidate FIBs, in particular the dairy fatty acids pentadecanoic acid and heptadecanoic acid, revealed specific kinetic patterns of relevance to their detection in future validation studies. Taken together, promising candidate FIBs for dairy intake appear to be lactose and metabolites thereof, for lactose-containing products, and microbial metabolites derived from amino acids, for fermented dairy products such as cheese.
Efficacy and Safety of Lamivudine Versus Entecavir for Treating Chronic Hepatitis B Virus–related Acute Exacerbation and Acute-on-Chronic Liver Failure: A Systematic Review and Meta-Analysis

Background: Oral nucleos(t)ide analogs are recommended for patients with chronic hepatitis B virus (HBV)-related acute exacerbation (AE) and acute-on-chronic liver failure (ACLF). The efficacy and safety of administering entecavir (ETV) and lamivudine (LAM) to such patients remain unclear. Methods: A comprehensive literature search was performed to select studies published before December 2015 on therapy involving ETV or LAM for chronic HBV-related AE with or without ACLF. The main outcomes were short-term (within 4 mo) and long-term (beyond 4 mo) mortality. The secondary outcomes were virological and biochemical responses, ACLF recurrence, and safety. Results: Three prospective and 8 retrospective cohort studies involving 1491 patients were selected. An overall analysis revealed comparable short-term and long-term mortality rates among all patients who received ETV or LAM [short term: risk ratio (RR)=0.99; 95% confidence interval (CI), 0.78-1.27; long term: RR=0.82; 95% CI, 0.45-1.52]. However, in patients with ACLF, ETV yielded a more favorable long-term outcome than did LAM (RR=0.60; 95% CI, 0.45-0.80). Furthermore, ETV resulted in more efficient virological and biochemical responses than did LAM regarding the HBV DNA undetectable rate (RR=1.34; 95% CI, 1.09-1.63), HBV DNA reduction rate (weighted mean difference=−0.41; 95% CI, −0.69 to −0.13), and serum alanine aminotransferase normalization rate (RR=1.13; 95% CI, 1.05-1.21). Conclusions: ETV and LAM treatments exerted similar effects on the mortality rate of patients with chronic HBV-related AE with or without ACLF. However, ETV yielded a more favorable long-term outcome than did LAM in patients with ACLF; ETV was associated with greater clinical improvements. Additional larger, long-term randomized controlled trials are required to confirm these conclusions.
Behaviour of carbon fibre–reinforced polymer-confined hollow circular concrete columns with inner polyvinyl chloride tube

Existing studies have shown that the use of an inner tube can significantly enhance the effectiveness of confinement in fibre-reinforced polymer-confined hollow columns. The inner tube used in the existing studies, however, generally had a large stiffness and also served as longitudinal reinforcement. The use of a stiff inner tube is inefficient in resisting bending for hollow columns with a relatively small void and may be unnecessary for constraining the inner surface of concrete. Against this background, this article presents the first experimental study on fibre-reinforced polymer-confined hollow columns with an inner polyvinyl chloride tube. The experimental program included a total of 18 specimens which were tested under axial compression. The test variables included the section configuration (i.e. solid specimens, hollow specimens and hollow specimens with a polyvinyl chloride tube) and the thickness of fibre-reinforced polymer. The test results showed that due to the beneficial effect of the polyvinyl chloride tube which provided constraints/confinement from inside, fibre-reinforced polymer-confined hollow columns with an inner polyvinyl chloride tube generally possessed good strength and ductility compared to their counterparts without a polyvinyl chloride tube.
Target-Site Investigation for the Plasma Prolactin Response: Mechanism-Based Pharmacokinetic-Pharmacodynamic Analysis of Risperidone and Paliperidone in the Rat

To understand the drivers in the biological system response to dopamine D2 receptor antagonists, a mechanistic semiphysiologically based (PB) pharmacokinetic-pharmacodymanic (PKPD) model was developed to describe prolactin responses to risperidone (RIS) and its active metabolite paliperidone (PAL). We performed a microdialysis study in rats to obtain detailed plasma, brain extracellular fluid (ECF), and cerebrospinal fluid (CSF) concentrations of PAL and RIS. To assess the impact of P-glycoprotein (P-gp) functioning on brain distribution, we performed experiments in the absence or presence of the P-gp inhibitor tariquidar (TQD). PK and PKPD modeling was performed by nonlinear mixed-effect modeling. Plasma, brain ECF, and CSF PK values of RIS and PAL were well described by a 12-compartmental semi-PBPK model, including metabolic conversion of RIS to PAL. P-gp efflux functionality was identified on brain ECF for RIS and PAL and on CSF only for PAL. In the PKPD analysis, the plasma drug concentrations were more relevant than brain ECF or CSF concentrations to explain the prolactin response; the estimated EC50 was in accordance with reports in the literature for both RIS and PAL. We conclude that for RIS and PAL, the plasma concentrations better explain the prolactin response than do brain ECF or CSF concentrations. This research shows that PKPD modeling is of high value to delineate the target site of drugs.
Can source code auditing software identify common vulnerabilities and be used to evaluate software security?

Software vulnerabilities are a growing problem (c.f. MITRE's CVE, http://eve.mitre.org). Moreover, many of the mistakes leading to vulnerabilities are repeated often. Source code auditing tools could be a great help in identifying common mistakes, or in evaluating the security of software. We investigated the effectiveness of the auditing tools we could access, using the following criteria: number of false positives, false negatives by comparison to known vulnerabilities, and time required to validate the warnings related to vulnerabilities. Some of the known vulnerabilities could not be found by any code auditor, because they were fairly unusual or involved knowledge not contained or codified in the source code. The coding problems that could be identified consisted of string format vulnerabilities, buffer overflows, race conditions, memory leaks, and symlink attacks. However, we found it extremely time-consuming to validate warnings related to the latter four types, because the number of false positives was very high, and because it was not easily apparent if they were real vulnerabilities. These required that the code be audited locally, by people familiar with the code, and carefully inspected to see if the values could be manipulated in such a way as to produce malicious effects. However, the string format vulnerabilities were much easier to recognize. In small and medium scale projects, the open source program Pscan was useful in finding a mix of coding style issues that could potentially enable string format vulnerabilities, as well as actual vulnerabilities. The limitations of Pscan were more obvious in large scale projects like OpenBSD, as more false positives occurred. Clearly, auditing source code for all vulnerabilities remains a time-consuming process, even with the help of the current tools, and more research is needed in identifying and avoiding other common mistakes.
Robust network oscillations during mammalian respiratory rhythm generation driven by synaptic dynamics

Significance The mechanism underlying mammalian respiratory rhythm generation in the preBötzinger complex is still under debate. Here, we developed a simulation model to show that a synaptic depression/facilitation mechanism sufficient for neurons to generate network rhythms, without the need for intrinsically rhythmic neurons. Simulations of the model under several normal or pathological conditions the living system experiences, together with critical electrophysiological experiments, converge to show that randomly connected neuronal networks with synaptic dynamics underlie rhythmic activity. This study provides a generally applicable mechanism for other central pattern generator systems that are less well understood. How might synaptic dynamics generate synchronous oscillations in neuronal networks? We address this question in the preBötzinger complex (preBötC), a brainstem neural network that paces robust, yet labile, inspiration in mammals. The preBötC is composed of a few hundred neurons that alternate bursting activity with silent periods, but the mechanism underlying this vital rhythm remains elusive. Using a computational approach to model a randomly connected neuronal network that relies on short-term synaptic facilitation (SF) and depression (SD), we show that synaptic fluctuations can initiate population activities through recurrent excitation. We also show that a two-step SD process allows activity in the network to synchronize (bursts) and generate a population refractory period (silence). The model was validated against an array of experimental conditions, which recapitulate several processes the preBötC may experience. Consistent with the modeling assumptions, we reveal, by electrophysiological recordings, that SF/SD can occur at preBötC synapses on timescales that influence rhythmic population activity. We conclude that nondeterministic neuronal spiking and dynamic synaptic strengths in a randomly connected network are sufficient to give rise to regular respiratory-like rhythmic network activity and lability, which may play an important role in generating the rhythm for breathing and other coordinated motor activities in mammals.
Association between postoperative hyponatremia and renal prognosis in major urologic surgery

Recent evidence for the clinical significance of postoperative hyponatremia after urologic surgeries remains scarce. We examined the incidence, risk factors, and outcomes of electrolyte imbalance in urologic surgery. Patients with newly developed hyponatremia, defined as a sodium level lower than 135 mEq/L within 7 days after surgery, were included in our study group. The primary outcome was progression to end-stage renal disease (ESRD). Secondary outcome was composition of progression to ESRD and creatinine doubling/eGFR halving from baseline. A survival analysis with a multivariable Cox proportional hazard model was performed. We included 9,206 cases of bladder, prostate, ureter, and kidney surgery. Incidence of new-onset postoperative hyponatremia was 15.4% (1,414/9,206). Postoperative hyponatremia mostly developed in patients with high-risk perioperative characteristics. The development of postoperative hyponatremia was independently associated with progression to ESRD (adjusted HR 1.343, 95% CI 1.082–1.680, P = 0.007). The secondary outcome was also related to the electrolyte imbalance in prostate (adjusted HR 1.729, 95% CI 1.145–2.612, P = 0.009) and kidney (adjusted HR 1.339, 95% CI 1.099–1.632, P = 0.004) surgery. Postoperative hyponatremia in urologic surgery was a common electrolyte imbalance in patients with high-risk perioperative status, and associated with worse renal prognosis.
Effects of Chronic Renal Failure on Brain Cytochrome P450 in Rats

Chronic renal failure (CRF) impedes renal excretion of drugs and their metabolism by reducing the expression of liver cytochrome P450 (P450). Uremic serum contains factors, such as parathyroid hormone (PTH), that decrease liver P450s. The P450s are also involved in the metabolism of xenobiotics in the brain. This study investigates: 1) the effects of CRF on rat brain P450, 2) the role of PTH in the downregulation of brain P450s in CRF rats, and 3) the effects of PTH on P450s in astrocytes. Protein and mRNA expression of P450s were assessed in the brain of CRF and control (CTL) rats, as well as from CTL or CRF rats that underwent parathyroidectomy (PTX) 1 week before nephrectomy. CYP3A activity was measured using 3-[(3, 4-difluorobenzyl) oxy]-5, 5-dimethyl-4-[4-methylsulfonyl) phenyl] furan-2(5H)-1 metabolism in brain microsomal preparation. CYP3A protein expression was assessed in primary cultured astrocytes incubated with serum obtained from CRF or CTL rats or with PTH. Significant downregulations (≥40%) of CYP1A, CYP2C11, and CYP3A proteins were observed in microsomes from CRF rat brains. CYP3A activity reduction was also observed. CYP3A expression and activity were unaffected in PTX-pretreated CRF rats. Serum of PTX-treated CRF rats had no impact on CYP3A levels in astrocytes compared with that of untreated CRF rats. Finally, PTH addition to normal calf serum induced a reduction in CYP3A protein similar to CRF serum, suggesting that CRF-induced hyperparathyroidism is associated with a significant decrease in P450 drug-metabolizing enzymes in the brain, which may have implications in drug response.
S-adenosylmethionine and methylthioadenosine inhibit cancer metastasis by targeting microRNA 34a/b-methionine adenosyltransferase 2A/2B axis

MicroRNA-34a (miR-34a) is down-regulated in colorectal cancers (CRC) and required for interleukin-6 (IL-6)-induced CRC metastasis. Mice lacking miR-34a developed more invasive cancer in a colitis-associated cancer model. In the same model, S-adenosylmethionine (SAMe) and methylthioadenosine (MTA) inhibited IL-6/STAT3 and lowered tumor burden. SAMe and MTA reduce the expression of methionine adenosyltransferase 2A (MAT2A) and there are consensus binding sites for miR-34a/b in the MAT2A 3’UTR. Here we examined whether SAMe/MTA influence miR-34a/b expression and cancer metastasis. We found SAMe and MTA raised miR-34a/b expression in CRC cell lines, inhibited migration and invasion in vitro and liver metastasis in vivo. Like CRC, MAT2A and MAT2B expression is induced in human pancreas and prostate cancers. Treatment with SAMe, MTA, miR-34a or miR-34b inhibited MAT2A expression mainly at the protein level. MAT2B protein level also fell because MAT2A and MAT2B enhance each other’s protein stability. Overexpressing miR-34a or miR-34b inhibited while MAT2A or MAT2B enhanced CRC migration and invasion. Co-expressing either miR-34a/b had minimal to no effect on MAT2A/MAT2B’s ability to increase migration, invasion and growth. Taken together, MAT2A and MAT2B are important targets of miR-34a/b and SAMe and MTA target this axis, suppressing MAT2A/MAT2B while raising miR-34a/b expression, inhibiting cancer metastasis.
The ModERN Resource: Genome-Wide Binding Profiles for Hundreds of Drosophila and Caenorhabditis elegans Transcription Factors

The model organism Encylopedia of Regulatory Elements (modERN) project was designed to generate genome-wide binding profiles for the majority of transcription. To develop a catalog of regulatory sites in two major model organisms, Drosophila melanogaster and Caenorhabditis elegans, the modERN (model organism Encyclopedia of Regulatory Networks) consortium has systematically assayed the binding sites of transcription factors (TFs). Combined with data produced by our predecessor, modENCODE (Model Organism ENCyclopedia Of DNA Elements), we now have data for 262 TFs identifying 1.23 M sites in the fly genome and 217 TFs identifying 0.67 M sites in the worm genome. Because sites from different TFs are often overlapping and tightly clustered, they fall into 91,011 and 59,150 regions in the fly and worm, respectively, and these binding sites span as little as 8.7 and 5.8 Mb in the two organisms. Clusters with large numbers of sites (so-called high occupancy target, or HOT regions) predominantly associate with broadly expressed genes, whereas clusters containing sites from just a few factors are associated with genes expressed in tissue-specific patterns. All of the strains expressing GFP-tagged TFs are available at the stock centers, and the chromatin immunoprecipitation sequencing data are available through the ENCODE Data Coordinating Center and also through a simple interface (http://epic.gs.washington.edu/modERN/) that facilitates rapid accessibility of processed data sets. These data will facilitate a vast number of scientific inquiries into the function of individual TFs in key developmental, metabolic, and defense and homeostatic regulatory pathways, as well as provide a broader perspective on how individual TFs work together in local networks and globally across the life spans of these two key model organisms.
The Effects of Laryngeal Activity on Articulatory Kinematics

The Effects of Laryngeal Activity on Articulatory Kinematics Katherine Marie Barber Department of Communication Disorders, BYU Master of Science The current study examined the effects of three speech conditions (voiced, whispered, mouthed) on articulatory kinematics at the sentence and word level. Participants included 20 adults (10 males, 10 females) with no history of speech, language, or hearing disorders. Participants read aloud six target utterances in the three different speaking conditions while articulatory kinematics were measured using the NDI Wave electromagnetic articulograph. The following articulators were examined: mid tongue, front of tongue, jaw, lower lip, and upper lip. One of the target utterances was chosen for analysis (It’s time to shop for two new suits) at the sentence level and then further segmented for more detailed analysis of the word time. Results revealed a number of significant changes between the voiced and mouthed conditions for all articulators at the sentence level. Significant increases in sentence duration, articulatory stroke count, and stroke duration as well as significant decreases in peak stroke speed, stroke distance, and hull volume were found in the mouthed condition at the sentence level when compared to the voiced condition. Peak velocity significantly decreased in the mouthed condition at the word level, but overall the sentence level measures were more sensitive to change. These findings suggest that both laryngeal activation and auditory feedback may be necessary in the production of normally articulate speech, and that the absence of these may account for the significant changes between the voiced and mouthed conditions.
Cognitively Engaging Activity Is Associated with Greater Cortical and Subcortical Volumes

As the population ages and dementia becomes a growing healthcare concern, it is increasingly important to identify targets for intervention to delay or attenuate cognitive decline. Research has shown that the most successful interventions aim at altering lifestyle factors. Thus, this study examined how involvement in physical, cognitive, and social activity is related to brain structure in older adults. Sixty-five adults (mean age = 71.4 years, standard deviation = 8.9) received the Community Healthy Activities Model Program for Seniors (CHAMPS), a questionnaire that polls everyday activities in which older adults may be involved, and also underwent structural magnetic resonance imaging. Stepwise regression with backward selection was used to predict weekly time spent in either social, cognitive, light physical, or heavy physical activity from the volume of one of the cortical or subcortical regions of interest (corrected by intracranial volume) as well as age, education, and gender as control variables. Regressions revealed that more time spent in cognitive activity was associated with greater volumes of all brain regions studied: total cortex (β = 0.289, p = 0.014), frontal (β = 0.276, p = 0.019), parietal (β = 0.305, p = 0.009), temporal (β = 0.275, p = 0.020), and occipital (β = 0.256, p = 0.030) lobes, and thalamus (β = 0.310, p = 0.010), caudate (β = 0.233, p = 0.049), hippocampus (β = 0.286, p = 0.017), and amygdala (β = 0.336, p = 0.004). These effects remained even after accounting for the positive association between cognitive activity and education. No other activity variable was associated with brain volumes. Results indicate that time spent in cognitively engaging activity is associated with greater cortical and subcortical brain volume. Findings suggest that interventions aimed at increasing levels of cognitive activity may delay cognitive consequences of aging and decrease the risk of developing dementia.
Nutrition and the homeless: the underestimated challenge

Abstract Homelessness is present in most societies and represents a situation in which the basic needs for survival including food are often limited. It is logical to surmise that the homeless person’s diet is likely to be nutritionally deficient and yet there is a relative paucity in research regarding this issue with studies varying in both their methodology and homeless population. Despite these differences, diets of the homeless are frequently characterised as high in saturated fat and deficient in fibre and certain micronutrients, all of which can have negative implications for the homeless individual’s health and/or mental state. The conclusion from intervention studies is that there is no consensus as to the most effective method for assessing dietary intake. In order to address this, the present review aims to provide a greater understanding of the existing literature surrounding nutrition and the homeless and to act as a foundation from which further research can be conducted. An evaluation of the main findings and challenges surrounding the assessment of the nutritional status of the homeless will be provided followed by a review of the physical and mental consequences of the homeless diet. Current and potential interventions aimed at increasing the nutritional quality of food consumed by the homeless will be addressed with a focus on the role of the nutritional science community in assisting in this endeavour.
Theoretical modulation of singlet/triplet chemiexcitation of chemiluminescent imidazopyrazinone dioxetanone via C_8-substitution

Coelenterazine, a member of the imidazopyrazinone class of chemiluminescent substrates, presents significant potential as a dynamic probe of reactive oxygen species in a biological environment, such as a superoxide anion, in which these species are important in cellular biology and pathology. The objective of the current study was to understand in what way the efficiency of singlet and triplet chemiexcitation could be modulated, towards a more efficient use of imidazopyrazinone-based compounds as dynamic chemiluminescent probes. To this end the thermolysis of imidazopyrazinone dioxetanone, substituted at the C_8-position with electron-donating or electron-withdrawing groups, was characterized with a theoretical approach based on density functional theory. Substituents with different electron-donating/withdrawing characters have only a limited effect on the singlet chemiexcitation of anionic dioxetanone. For neutral dioxetanone, both electron-withdrawing and weak electron-donating substituents increase singlet chemiexcitation, to the contrary of strong electron-donating groups. During their thermolysis reaction, all molecules presented regions of degeneracy with triplet states, thereby indicating the possibility of triplet chemiexcitation.