Miracle-dz/UniFAR-FTUs huggingface dataset:
Maternal low-quality protein diet exerts sex-specific effects on plasma amino acid profile and alters hepatic expression of methyltransferases in adult rat offspring

Abstract Nutrition during pregnancy and lactation is a critical factor in the development of the offspring. Both protein content and source in maternal diet affect neonatal health, but the long-term effects of maternal low-quality protein diet on the offspring are less clear. This study aimed to examine the effects of maternal low-quality protein diet on offspring’s growth, development, circulating metabolites and hepatic expression of methyltransferases. Virgin Wistar rats were mated at 11 weeks of age. Dams were then maintained on either a chow diet with 20% casein as the control group (C), or a low-quality protein diet with 20% wheat gluten as the experimental group (WG) throughout gestation and lactation. After weaning, all offspring were fed a control chow diet until the age of 20 weeks. Male WG offspring had significantly lower body weight and energy intake, whereas female WG offspring had significantly higher body weight and energy intake when compared with controls. Early life exposure to WG diet had no significant effect on circulating metabolites. However, fasting insulin concentrations and homoeostasis model assessment-insulin resistance were decreased in WG male and female offspring. Maternal low-quality protein diet increased plasma aspartic acid, glutamic acid, histidine, cystathione and decreased lysine in male WG offspring. Conversely, the same amino acids were reduced in female WG offspring. Adult offspring exposed to WG diet had significantly upregulated hepatic DNMT3a and DNMT3b expressions. Our study showed that there were differential effects of maternal poor-quality protein diet upon adult offspring’s metabolism.
Synergistic antifungal activity and reduced toxicity of liposomal amphotericin B combined with gramicidin S or NF

Amphotericin B (AmpB) disrupts membrane integrity by binding to sterols in fungal and mammalian cell membranes. The gramicidins, which form pores in all membranes but exhibit poor antifungal activity, are too toxic to mammalian cells to be used systemically. This study demonstrated synergistic antifungal activity of free and liposomal forms of AmpB when combined with the free and liposomal forms of gramicidin S and gramicidin NF against five Candida strains. In vitro erythrocyte lysis was prevented by using the liposomal forms of all drugs tested alone or in combination. Presumably, AmpB increases accessibility of the fungal cell membrane to the gramicidins, while liposome encapsulation decreases the rate of transfer of the drugs to the mammalian cell membrane. Liposome encapsulation of inactive or toxic drugs, used in combination with liposomal AmpB, may give new life to drugs previously believed to be inactive or too toxic for therapeutic consideration.
Arabinosylation of recombinant human immunoglobulin-based protein therapeutics

ABSTRACT Protein glycosylation is arguably the paramount post-translational modification on recombinant glycoproteins, and highly cited in the literature for affecting the physiochemical properties and the efficacy of recombinant glycoprotein therapeutics. Glycosylation of human immunoglobulins follows a reasonably well-understood metabolic pathway, which gives rise to a diverse range of asparagine-linked (N-linked), or serine/threonine-linked (O-linked) glycans. In N-linked glycans, fucose levels have been shown to have an inverse relationship with the degree of antibody-dependent cell-mediated cytotoxicity, and high mannose levels have been implicated in potentially increasing immunogenicity and contributing to less favorable pharmacokinetic profiles. Here, we demonstrate a novel approach to potentially reduce the presence of high-mannose species in recombinant human immunoglobulin preparations, as well as facilitate an approximate 100% replacement of fucosylation with arabinosylation in Chinese hamster ovary cell culture through media supplementation with D-arabinose, an uncommonly used mammalian cell culture sugar substrate. The replacement of fucose with arabinose was very effective and practical to implement, since no cell line engineering or cellular adaptation strategies were required. Arabinosylated recombinant IgGs and the accompanying reduction in high mannose glycans, facilitated a reduction in dendritic cell uptake, increased FcγRIIIa signaling, and significantly increased the levels of ADCC. These aforementioned effects were without any adverse changes to various structural or functional attributes of multiple recombinant human antibodies and a bispecific DVD-Ig. Protein arabinosylation represents an expansion of the N-glycan code in mammalian expressed glycoproteins.
Assessing the release of copper from nanocopper‐treated and conventional copper‐treated lumber into marine waters I: Concentrations and rates

Little is known about the release of metal engineered nanomaterials (ENMs) from consumer goods, including lumber treated with micronized copper. Micronized copper is a recent form of antifouling wood preservative containing nanosized copper particles for use in pressure‐treated lumber. The present study investigated the concentrations released and the release rate of total copper over the course of 133 d under freshwater, estuarine, and marine salinity conditions (0, 1, 10, and 30‰) for several commercially available pressure‐treated lumbers: micronized copper azole (MCA) at 0.96 and 2.4 kg/m3, alkaline copper quaternary (ACQ) at 0.30 and 9.6 kg/m3, and chromated copper arsenate (CCA) at 40 kg/m3. Lumber was tested as blocks and as sawdust. Overall, copper was released from all treated lumber samples. Under leaching conditions, total release ranged from 2 to 55% of the measured copper originally in the lumber, with release rate constants from the blocks of 0.03 to 2.71 (units per day). Generally, measured release and modeled equilibrium concentrations were significantly higher in the estuarine conditions compared with freshwater or marine salinities, whereas rate constants showed very limited differences between salinities. Furthermore, organic carbon was released during the leaching and demonstrated a significant relationship with released copper concentrations as a function of salinity. The results indicate that copper is released into estuarine/marine waters from multiple wood treatments including lumber amended with nanoparticle‐sized copper. Environ Toxicol Chem 2018;37:1956–1968. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
Adipokine Profiling in Adult Women With Central Obesity and Hypertension

Central obesity and hypertension are common risk factors for the metabolic syndrome, cardiovascular and renal diseases. Studies have shown that it is more difficult to control blood pressure and prevent end-organ damage in obese individuals with hypertension compared to their non-obese counterparts, especially among women. Obese females have a 6 times higher risk of developing hypertension than non-obese females while obese males are at a 1.5 times higher risk of developing hypertension, compared to their non-obese counterparts. Indeed, the inter-relationship between obesity and hypertension is unclear. Adipokines have been proposed to play a mediating role in the relationship between obesity and hypertension and are involved in the pathogenesis of metabolic diseases. Therefore, this study sought to determine the role of adipokines (adiponectin, plasminogen activator inhibitor-1, leptin, and tumor necrosis factor-α) in hypertensive Hong Kong Chinese women with central obesity. A total of 387 women aged 58 ± 11 years who were examined with a 2 × 2 factorial design for central obesity (waist circumference ≥ 80 cm) and hypertension (blood pressure ≥ 140/90 mmHg), were recruited from a pool of 1,492 Hong Kong Chinese adults who were previously screened for metabolic syndrome. Subjects with hyperglycemia, hypertriglyceridemia, and dyslipidemia were excluded to eliminate confounding effects. Our findings revealed that hypertensive women with central obesity had a lower anti-inflammatory status (adiponectin) and a higher pro-inflammatory status (TNF-α) than obese alone or hypertensive alone women. Also, women with central obesity had higher circulatory PAI-1 and leptin concentrations than their non-obese counterparts. We conclude that obesity may shift toward a more pro-inflammatory state and may become more severe in the presence of hypertension or vice versa.
Respiratory consequences of targeted losses of Hoxa5 gene function in mice

ABSTRACT Fetal development of the respiratory tract and diaphragm requires strict coordination between genetically controlled signals and mechanical forces produced by the neural network that generates breathing. HOXA5, which is expressed in the mesenchyme of the trachea, lung and diaphragm, and in phrenic motor neurons, is a key transcription factor regulating lung development and function. Consequently, most Hoxa5−/− mutants die at birth from respiratory failure. However, the extensive effect of the null mutation makes it difficult to identify the origins of respiratory dysfunction in newborns. To address the physiological impact of Hoxa5 tissue-specific roles, we used conditional gene targeting with the Dermo1Cre and Olig2Cre mouse lines to produce specific Hoxa5 deletions in the mesenchyme and motor neurons, respectively. Hoxa5 expression in the mesenchyme is critical for trachea development, whereas its expression in phrenic motor neurons is essential for diaphragm formation. Breathing measurements in adult mice with whole-body plethysmography demonstrated that, at rest, only the motor neuron deletion affects respiration, resulting in higher breathing frequency and decreased tidal volume. But subsequent exposure to a moderate hypoxic challenge (FiO2=0.12; 10 min) revealed that both mutant mice hyperventilate more than controls. Hoxa5flox/flox;Dermo1+/Cre mice showed augmented tidal volume while Hoxa5flox/flox;Olig2+/Cre mice had the largest increase in breathing frequency. No significant differences were observed between medulla–spinal cord preparations from E18.5 control and Hoxa5flox/flox;Olig2+/Cre mouse embryos that could support a role for Hoxa5 in fetal inspiratory motor command. According to our data, Hoxa5 expression in the mesenchyme and phrenic motor neurons controls distinct aspects of respiratory development. Summary: HOXA5 is a transcription factor broadly expressed in the respiratory system; Hoxa5 expression in the mesenchyme and phrenic motor neurons controls distinct aspects of respiratory development.
The Importance of Spatial Visual Scene Parameters in Predicting Optimal Cone Sensitivities in Routinely Trichromatic Frugivorous Old-World Primates

Computational models that predict the spectral sensitivities of primate cone photoreceptors have focussed only on the spectral, not spatial, dimensions. On the ecologically valid task of foraging for fruit, such models predict the M-cone (“green”) peak spectral sensitivity 10–20 nm further from the L-cone (“red”) sensitivity peak than it is in nature and assume their separation is limited by other visual constraints, such as the requirement of high-acuity spatial vision for closer M and L peak sensitivities. We explore the possibility that a spatio-chromatic analysis can better predict cone spectral tuning without appealing to other visual constraints. We build a computational model of the primate retina and simulate chromatic gratings of varying spatial frequencies using measured spectra. We then implement the case study of foveal processing in routinely trichromatic primates for the task of discriminating fruit and leaf spectra. We perform an exhaustive search for the configurations of M and L cone spectral sensitivities that optimally distinguish the colour patterns within these spectral images. Under such conditions, the model suggests that: (1) a long-wavelength limit is required to constrain the L cone spectral sensitivity to its natural position; (2) the optimal M cone peak spectral sensitivity occurs at ~525 nm, close to the observed position in nature (~535 nm); (3) spatial frequency has a small effect upon the spectral tuning of the cones; (4) a selective pressure toward less correlated M and L spectral sensitivities is provided by the need to reduce noise caused by the luminance variation that occurs in natural scenes.
Carbonation of MSWI APCr for re-use as a light-weight aggregate

The incineration of municipal solid waste (MSW) is a more sustainable alternative to landfilling. Cleaning of flue gases from the incineration of MSW generates air pollution control residues (APCr). Carbon8 Systems, a spinout company from the University of Greenwich, UK has developed a treatment for APCr using accelerated carbonation technology (ACT). Accelerated carbonation enables carbonate-based solidification of an ash (or other suitable waste) using carbon dioxide gas. The solidified and stabilised products can be formed as pellets that are suitable for use as aggregate as a component in the manufacture of concrete building blocks. The result of this work is laying foundations for the construction of the world’s first full-scale commercial accelerated carbonation plant in the UK, with a capacity to produce 36,000 tonnes of APCr-derived annually.
Determination of Heavy Metals in of Fishes, Water and Sediment from the Demirköprü Dam Lake (Turkey)

In this study, concentrations of heavy metals were measured in the surface water, sediment and fi sh (Cyprinus carpio) from the Demirkopru Dam Lake (Manisa, Turkey). The obtained results showed that, in general, the heavy metal (Cd, Cr, Cu, Fe, Ni, Pb) concentrations in water did not exceed WHO (World Health Organization, 1999), EC (Europe Community, 1998), EPA (Environment Protection Agency, 2002) and TSE-266 (Turkish Standard, 1997), WPCL (Water Pollution Control Legistation, 2004), CIW (Criterions of the Irrigation Water, 1997) guidelines. Heavy metal concentrations were found decrease in sequence of the surface water Fe > Pb > Cu > Ni > Cr > Cd, the Cyprinus carpio samples, in the muscle Fe > Cu > Ni > Cr > Pb > Cd, in the gill Fe > Ni > Cu > Pb > Cr > Cd, in the stomach-intestine Fe > Cu > Pb > Ni > Cr > Cd, in the air sac Fe > Pb > Cu > Ni > Cr > Cd, in the heart Fe > Ni > Pb > Cu > Cr > Cd, in the liver Fe > Cu > Ni > Pb > Cr > Cd. These obtained results show that, the heavy metal concentrations exceded the tolerable values provided by the international institutions. Generally, heavy metal concentration of the sediments were found decrease in sequence of Fe > Ni > Cu > Cr > Pb > Cd.
Serum LL-37 Levels Associated With Severity of Bronchiolitis and Viral Etiology

Background LL-37 is a host defense peptide with antimicrobial and immunomodulatory properties. We examined the relation of serum LL-37 levels to the severity of bronchiolitis and viral etiology. Methods We performed a 17-center prospective cohort study in infants hospitalized with bronchiolitis over 3 winters (2011-2014). Site teams collected clinical data, nasopharyngeal aspirates and serum. We used real-time polymerase chain reaction to test nasopharyngeal aspirates for 16 viruses. We tested serum for LL-37. Severity of bronchiolitis was defined by intensive care use and hospital length of stay. Viral etiology was defined as respiratory syncytial virus (RSV) or rhinovirus (RV), including coinfections with other viruses. Results The median age of the 1005 enrolled infants was 3 months (interquartile range, 2-6 months). After adjustment for 12 variables, LL-37 levels in the lowest quartile, compared with the highest, were associated both with intensive care use (adjusted odds ratio [aOR], 1.97; P = .01) and longer hospital stay (1.34; P < .001). In separate multivariable models, infants with LL-37 levels in the lowest 3 quartiles, compared with the highest, were more likely to have RSV (eg, aOR, 2.6 [lowest quartile]; P < .001 [all quartiles]). By contrast, infants with the lowest 3 LL-37 quartiles were less likely to have RV (eg, aOR, 0.5 [lowest quartile]; Pall quartiles ≤ .03 [all quartiles]). Conclusions In a large multicenter study of infants hospitalized with bronchiolitis, lower levels of serum LL-37 were associated with increased severity of illness. There was also an inverse relationship between LL-37 levels and the most common virus causing bronchiolitis, RSV. These findings highlight the role of LL-37 in the pathogenesis of bronchiolitis.
Homogeneous flow of bulk metallic glass composites with a high volume fraction of reinforcement

We present a systematic study of homogeneous deformation in a La-based bulk metallic glass and two in situ composites based on the same glass. In contrast to prior investigations, which focused on relatively dilute composites, in this work the reinforcement volume percentages were more concentrated at 37% and 52%—near or above the percolation threshold (35–40%). Hot uniaxial compressive testing was conducted over a wide strain rate range from 10^-2 to 10^-5 s^-1 at a temperature near the glass transition. For such concentrated composites, the homogeneous deformation behavior appeared to be dominated by the properties of the reinforcement phase; in the present case the La reinforcements deformed by glide-controlled creep. Post-deformation analysis suggested that bulk metallic glass matrix composites were susceptible to microstructural evolution, which appeared to be enhanced by deformation, in contrast with a stress-free anneal. Consequently, unreinforced bulk metallic glass appeared to be more structurally stable than its composites during deformation near the glass transition.
Professional Reimbursement by Medicaid for Cochlear Implants and Related Services.

HYPOTHESIS Medicaid reimbursement rates for cochlear implants and related services fall short of the federal benchmark set by Medicare. BACKGROUND The financial hardships of cochlear implant centers around the United States may be a repercussion of poor Medicaid reimbursement. In time, these reimbursement discrepancies could force additional Otolaryngologists and cochlear implant centers to not provide these crucial services due to financial limitations. METHODS Based on Medicare (MCR) claims data, current procedural terminology (CPT) codes used for cochlear implantation and related services were selected. Medicaid (MCD) and Medicare (MCR) payment schemes were queried for the same services in 49 states and Washington, D.C. The difference in MCD and MCR payment in dollars and percent was determined and reimbursement per relative value of work (RVU) calculated. MCD reimbursement differences (by dollar amount and by percentage) were qualified as a shortfall or excess as compared with the MCR benchmark. RESULTS Marked differences in MCD and MCR reimbursement exist for all cochlear implant related services, most commonly as a substantial shortfall. The MCD shortfall varied in amount between states and great variability in reimbursement exists within and between audiology, surgery, and speech services. Shortfalls and excesses were not consistent between procedures or states. CONCLUSIONS The variation in MCD payment models reflects marked differences in the value of the same work provided, which in many cases is far less than federal benchmarks. These results question the fairness of the MCD reimbursement scheme in cochlear implantation with potential serious implications on access to care for this underserved patient population.
Fabrication of 3D Microfluidic Devices by Thermal Bonding of Thin Poly(methyl methacrylate) Films

Fabrication of 3D Microfluidic Devices by Thermal Bonding of Thin Poly(methyl methacrylate) Films Paul Said Ehrlich Pérez The use of thin-film techniques for the fabrication of microfluidic devices has gained attention over the last decade, particularly for three-dimensional channel structures. The reasons for this include effective use of chip volume, mechanical flexibility, dead volume reduction, enhanced design capabilities, integration of passive elements, and scalability. Several fabrication techniques have been adapted for use on thin films: laser ablation and hot embossing are popular for channel fabrication, and lamination is widely used for channel enclosure. However, none of the previous studies have been able to achieve a strong bond that is reliable under moderate positive pressures. The present work aims to develop a thin-film process that provides design versatility, speed, channel profile homogeneity, and the reliability that others fail to achieve. The three building blocks of the proposed baseline were fifty-micron poly(methyl methacrylate) thin films as substrates, channel patterning by laser ablation, and device assembly by thermal-fusion bonding. Channel fabrication was characterized and tuned to produce the desired dimensions and surface roughness. Thermal bonding 5 was performed using an adapted mechanical testing device and optimized to produce the maximum bonding strength without significant channel deformation. Bonding multilayered devices, incorporating conduction lines, and integrating various types of membranes as passive elements demonstrated the versatility of the process. Finally, this baseline was used to fabricate a droplet generator and a DNA detection chip based on micro-bead agglomeration. It was found that a combination of low laser power and scanning speed produced channel surfaces with better uniformity than those obtained with higher values. In addition, the implemented bonding technique provided the process with the most reliable bond strength reported, so far, for thin-film microfluidics. Overall, the present work proved to be versatile, reliable, and fast, making it a good candidate to reproduce several on-chip functions. Future work includes implementing thick-substrate bonding techniques to further improve the process and decrease energy requirements.
Parents' preferences for the organisation of long‐term follow‐up of childhood cancer survivors

Parents take an important role in follow-up of young cancer survivors. We aimed to investigate (1) parents' preferences for organisation of follow-up (including content, specialists involved and models of care), and (2) parents' and children's characteristics predicting preference for generalist vs. specialist-led follow-up. We sent a questionnaire to parents of childhood cancer survivors aged 11-17 years. We assessed on a 4-point Likert scale (1-4), parents' preferences for organisation of long-term follow-up. Proposed models were: telephone/questionnaire, general practitioner (GP) (both categorised as generalist for regression analysis); and paediatric oncologist, medical oncologist or multidisciplinary team (MDT) (categorised as specialists). Of 284 contacted parents, 189 responded (67%). Parents welcomed if visits included checking for cancer recurrence (mean = 3.89), late effects screening (mean = 3.79), taking patients seriously (mean = 3.86) and competent staff (mean = 3.85). The preferred specialists were paediatric oncologists (mean = 3.73). Parents valued the paediatric oncologist model of care (mean = 3.49) and the MDT model (mean = 3.14) highest. Parents of children not attending clinic-based follow-up (OR = 2.97, p = .009) and those visiting a generalist (OR = 4.23, p = .007) favoured the generalist-led model. Many parents preferred a clinic-based model of follow-up by paediatric oncologists or a MDT. However, parents also valued the follow-up care model according to which their child is followed up.