Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeted Estimation of the Relationship Between Childhood Adversity and Fluid Intelligence in a US Population Sample of Adolescents

Many studies have shown inverse associations between childhood adversity and intelligence, although most are based on small clinical samples and fail to account for the effects of multiple co-occurring adversities. Using data from the 2001-2004 National Comorbidity Survey Adolescent Supplement, a cross-sectional US population study of adolescents aged 13-18 years (n = 10,073), we examined the associations between 11 childhood adversities and intelligence, using targeted maximum likelihood estimation. Targeted maximum likelihood estimation incorporates machine learning to identify the relationships between exposures and outcomes without overfitting, including interactions and nonlinearity. The nonverbal score from the Kaufman Brief Intelligence Test was used as a standardized measure of fluid reasoning. Childhood adversities were grouped into deprivation and threat types based on recent conceptual models. Adjusted marginal mean differences compared the mean intelligence score if all adolescents experienced each adversity to the mean in the absence of the adversity. The largest associations were observed for deprivation-type experiences, including poverty and low parental education, which were related to reduced intelligence. Although lower in magnitude, threat events related to intelligence included physical abuse and witnessing domestic violence. Violence prevention and poverty-reduction measures would likely improve childhood cognitive outcomes.
Deficits in emotion recognition are associated with depressive symptoms in youth with disruptive mood dysregulation disorder

Although severe irritability is a predictor of future depression according to recent meta‐analytic evidence, other mechanisms for this developmental transition remain unclear. In this study, we test whether deficits in emotion recognition may partially explain this specific association in youth with severe irritability, defined as disruptive mood dysregulation disorder (DMDD).
Stress-induced strain and brain region-specific activation of LINE-1 transposons in adult mice

Abstract Transposable elements (TEs) are conserved mobile genetic elements that are highly abundant in most eukaryotic genomes. Although the exact function of TEs is still largely unknown, it is increasingly clear that they are significantly modulated in response to stress in a wide range of organisms, either directly or indirectly through regulation of epigenetic silencing. We investigated the effect of repeated restraint stress (2 h a day, for 5 d) on transcription levels of LINE-1 (L1) retrotransposon in the brain of inbred BALB/c, DBA/2, C57BL/6N, and outbred CD1 mice. Repeated restraint stress induced strain and brain region-specific modulation of L1 activity. We observed a significant derepression of L1 transcription in the hippocampus (HIPP) of BALB/c mice and a significant downregulation in the hippocampus of C57BL/6N mice. No significant change in L1 expression was found in the other strains and brain regions. These findings indicate in mice the control of transposons expression as an additional mechanism in stress-induced pathophysiological responses, demonstrating that their regulation is highly dependent on the strain genetic background and the brain region. Lay summary Hippocampal expression of the transposon L1 is significantly altered by repeated restraint stress in mice. L1 modulation is not only region specific, but also strain dependent, suggesting that the genetic background is an important determinant of L1 response to environmental stimuli.
Acute Nitric Oxide Synthase Inhibition Accelerates Transendothelial Insulin Efflux In Vivo

Before insulin can stimulate glucose uptake in muscle, it must be delivered to skeletal muscle (SkM) through the microvasculature. Insulin delivery is determined by SkM perfusion and the rate of movement of insulin across the capillary endothelium. The endothelium therefore plays a central role in regulating insulin access to SkM. Nitric oxide (NO) is a key regulator of endothelial function and stimulates arterial vasodilation, which increases SkM perfusion and the capillary surface area available for insulin exchange. The effects of NO on transendothelial insulin efflux (TIE), however, are unknown. We hypothesized that acute reduction of endothelial NO would reduce TIE. However, intravital imaging of TIE in mice revealed that reduction of NO by l-NG-nitro-l-arginine methyl ester (l-NAME) enhanced the rate of TIE by ∼30% and increased total extravascular insulin delivery. This accelerated TIE was associated with more rapid insulin-stimulated glucose lowering. Sodium nitroprusside, an NO donor, had no effect on TIE in mice. The effects of l-NAME on TIE were not due to changes in blood pressure alone, as a direct-acting vasoconstrictor (phenylephrine) did not affect TIE. These results demonstrate that acute NO synthase inhibition increases the permeability of capillaries to insulin, leading to an increase in delivery of insulin to SkM.
Visual–Vestibular Integration During Self-Motion Perception in Younger and Older Adults

Younger adults integrate visual and vestibular cues to self-motion in a manner consistent with optimal integration; however, little is currently known about whether this process changes with older age. Our objective was to determine whether older adults, like younger adults, display evidence of optimal visual–vestibular integration, including reductions in bimodal variance (Visual + Vestibular) compared with unimodal variance (visual or vestibular alone), and reliability-based cue weighting. We used a motion simulator and a head-mounted display to introduce a 2-interval forced-choice heading estimation task. Older (65+ years) and younger adults (18–35 years) judged which of two movements was more rightward. Movements consisted of vestibular cues (passive movement in darkness), visual cues (optic flow), or both cues combined. The combined condition contained either congruent cues or incongruent cues (either a subtle 5° or larger 20° conflict). Results demonstrated that older adults had less reliable visual heading estimates than younger adults but comparable vestibular heading estimates. During combined, congruent conditions, both age groups exhibited reductions in combined variance, consistent with predicted optimal integration. During subtle cue conflicts, only younger adults exhibited combined variance consistent with predicted optimal integration, but both age groups displayed reliability-based cue weighting. During larger spatial conflicts, neither group demonstrated optimal reductions in variance. Younger adults displayed reliability-based cue weighting but older adults’ heading estimates were biased toward the less reliable visual estimate. Older adults’ tendency to incorporate spatially conflicting and unreliable visual cues into their self-motion percept may affect their performance on mobility-related tasks like walking and driving.
A Multidisciplinary Approach Reveals an Age-Dependent Expression of a Novel Bioactive Peptide, Already Involved in Neurodegeneration, in the Postnatal Rat Forebrain

The basal forebrain has received much attention due to its involvement in multiple cognitive functions, but little is known about the basic neuronal mechanisms underlying its development, nor those mediating its primary role in Alzheimer’s disease. We have previously suggested that a novel 14-mer peptide, ‘T14’, could play a pivotal role in Alzheimer’s disease, via reactivation of a developmental signaling pathway. In this study, we have characterized T14 in the context of post-natal rat brain development, using a combination of different techniques. Ex-vivo rat brain slices containing the basal forebrain, at different stages of development, were used to investigate large-scale neuronal network activity in real time with voltage-sensitive dye imaging. Subsequent Western blot analysis revealed the expression profile of endogenous T14, its target alpha7 nicotinic receptor and the familiar markers of Alzheimer’s: amyloid beta and phosphorylated Tau. Results indicated maximal neuronal activity at the earliest ages during development, reflected in a concomitant profile of T14 peptide levels and related proteins. In conclusion, these findings show that the peptide, already implicated in neurodegenerative events, has an age-dependent expression, suggesting a possible contribution to the physiological mechanisms underlying brain maturation.
Health Care in a Multi-Payer System: Spillovers of Health Care Service Demand among Adults under 65 on Utilization and Outcomes in Medicare

This paper examines, theoretically and empirically, how changes in the demand for health insurance and medical services in the non-Medicare population - coverage eligibility changes for parents and the firm size composition of employment - spill over and affect health insurance coverage and how these factors affect per beneficiary Medicare spending. We find that factors that increase coverage and hence demand for medical services in the non-Medicare population generate contemporaneous decreases in per beneficiary Medicare spending and utilization, particularly for high variation services. Moreover, these increases in the demand for medical services in the non-Medicare population are not associated with increases in the total quantity of physician services supplied. Finally, we find that the higher Medicare spending associated with lower insurance coverage rates in the non-Medicare population does not generate improvements in measures of Medicare patients' well-being, such as patient experience of care, ambulatory-care sensitive admissions, and mortality.
Induction of NAD (P)H: Quinone reductase 1 (QR1) and antioxidant activities in vitro of ‘Toranja Burarama’ (Citrus maxima [Burm.] Merr.)

Toranja ‘Burarama’, Citrus maxima (Burm.) Merr. (Citrus grandis), is a new citrus discovered in the State of Espírito Santo, Brazil. As several varieties of citrus are known to possess antioxidant and cancer chemopreventive properties, the aim of the study was to evaluate in vitro if this Toranja possess these properties. The antioxidant activity, the potential to induce quinone reductase 1, and the influence on cell viability were measured. ESI(‐)FT‐ICR MS analysis was also performed and identified flavonoids, coumarins, and fatty acids in the extract. The ethyl acetate and methanolic extracts of the peels presented the highest antioxidant activity in vitro by DPPH (IC50 = 298.3 ± 2.6 μg/ml and 303.8 ± 0.4 μg/ml), ABTS assay (IC50 = 298.2 ± 6.4 μg/ml and 296.4 ± 2.5 μg/ml), and FRAP (IC50 = 234.6 ± 1.8 μg/ml and 398.1 ± 3.8 μg/ml). The ethyl acetate extract of the peel induced quinone reductase 1 activity in Hepa1c1c7 cells, indicating that C. maxima exhibited cancer chemopreventive properties.
Heterogeneity of lipidomic profiles among lung cancer subtypes of patients

Lung cancer is a leading cause of cancer‐related deaths with an increasing incidence and poor prognoses. To further understand the regulatory mechanisms of lipidomic profiles in lung cancer subtypes, we measure the profiles of plasma lipidome between health and patients with lung cancer or among patients with squamous cell carcinomas, adenocarcinoma or small cell lung cancer and to correct lipidomic and genomic profiles of lipid‐associated enzymes and proteins by integrating the data of large‐scale genome screening. Our studies demonstrated that circulating levels of PS and lysoPS significantly increased, while lysoPE and PE decreased in patients with lung cancer. Our data indicate that lung cancer‐specific and subtype‐specific lipidomics in the circulation are important to understand mechanisms of systemic metabolisms and identify diagnostic biomarkers and therapeutic targets. The carbon atoms, dual bonds or isomerism in the lipid molecule may play important roles in lung cancer cell differentiations and development. This is the first try to integrate lipidomic data with lipid protein‐associated genomic expression among lung cancer subtypes as the part of clinical trans‐omics. We found that a large number of lipid protein‐associated genes significantly change among cancer subtypes, with correlations with altered species and spatial structures of lipid metabolites.
Parathyroid cysts

Background: Parathyroid cysts are lesions that represent 1–5% of neck masses. They are subdivided into two categories: functioning and non-functioning. The aim of the present review is to give a detailed account of all reported cases of parathyroid cysts in the literature and to analyze statistically the available data. Methods: A bibliographic research was performed from 1905 until 2016. A database with the patients’ characteristics was made and analyzed statistically. Results: A total of 218 articles were found, reporting 359 cases of cysts. Mean age of patients was 49.24 y/o and the male/female ratio was 1:1.85. The most common locations were left thyroid lobe (113/358 patients, 31.6%), and superior mediastinum (69/358 patients, 19.3%), while the most common symptoms were neck mass (148/355 patients, 41.7%), compressive symptoms (73/355 patients, 206%) and hyperparathyroidism (62/355 patients, 17.5%). Non-functioning cysts were more frequent (220/357 patients, 61.6%). Regarding dimensions, mean diameter was 4.88 cm. Ultrasound and FNA are used for their diagnosis, while cystic fluid analysis may help the differential diagnosis. Recurrences were mentioned in 27/97 patients (27.8%) with available data. No deaths due to parathyroid cysts were mentioned in the literature. Conclusion: Parathyroid cysts should be taken into consideration in case of parathyroid dysfunction or asymptomatic neck mass. The surgeon's careful manipulations on the cyst are crucial for a definitive treatment.
Three- to Four-Year-Old Children Rapidly Adapt Their Predictions and Use Them to Learn Novel Word Meanings.

Adults create and update predictions about what speakers will say next. This study asks whether prediction can drive language acquisition, by testing whether 3- to 4-year-old children (n = 45) adapt to recent information when learning novel words. The study used a syntactic context which can precede both nouns and verbs to manipulate children's predictions about what syntactic category will follow. Children for whom the syntactic context predicted verbs were more likely to infer that a novel word appearing in this context referred to an action, than children for whom it predicted nouns. This suggests that children make rapid changes to their predictions, and use this information to learn novel information, supporting the role of prediction in language acquisition.
Pharmacokinetics of colistin in patients with multidrug-resistant Gram-negative infections: A pilot study

Background & objectives: There is little information concerning intravenously (i.v.) administered colistin in patients with multidrug-resistant (MDR) Gram-negative infections. Thus, this pilot prospective study was undertaken to characterize efficacy and pharmacokinetics of colistin in patients with MDR Gram-negative infections. Methods: Nine patients with age >12 yr and MDR Gram-negative infections were included, of whom six were given colistin at the doses of 2 MU, while three patients were given 1 MU i.v. dose every 8 h. Blood samples were collected at different time intervals. Determination of colistin concentration was done by a ultra-high-performance liquid chromatography/mass spectrometry/selected reaction monitoring assay. Results: The area under the plasma concentration-versus-time curve over eight hours (AUC0-8) for colistin after the 1st dose ranged from 3.3 to 16.4 mg×h/l (median, 4.59). After the 5th dose, AUC0-8for colistin ranged from 4.4 to 15.8 mg×h/l (median, 6.0). With minimal inhibitory concentration (MIC) value of 0.125 mg/l, AUC0-8/MIC ranged from 26.7 to 131.4 (median, 36.7) and 35.5 to 126.0 (median, 48.0) after the 1st and the 5th doses of 2 MU every 8 h, respectively. Interpretation & conclusions: As there is a paucity of information on AUC/MIC for colistin, it may not be possible to conclude whether AUC/MIC values in our patients were adequate. There is a microbiological clearance of organism, which goes in favour of the dosing schedule being adequate. Further studies need to be done to understand the pharmacokinetics of colistin in patients with infections.
Demethylbelamcandaquinone B (Dmcq B) Is the Active Compound of Marantodes pumilum var. alata (Blume) Kuntze with Osteoanabolic Activities

Phytoestrogens have attracted considerable attention for their potential in the prevention of postmenopausal osteoporosis. Recently, a phytoestrogen-rich herbal plant, Marantodes pumilum var. alata (Blume) Kuntze was reported to protect against bone loss in ovariectomized rat. However, the bioactive compound responsible for these effects and the underlying mechanism were not known. Through bioassay-guided isolation, demethylbelamcandaquinone B (Dmcq B) was isolated and identified from Marantodes pumilum var. alata leaf extract. In terms of its bone anabolic effects, Dmcq B was at par with 17β-estradiol (E2), in promoting the proliferation, differentiation and mineralization of osteoblast cells. Dmcq-B increased early differentiation markers, collagen content and enzymatic ALP activity. It was demonstrated to regulate BMP2 signaling pathway which further activated the transcription factor, osterix. Subsequently, Dmcq B was able to increase the osteocalcin expression which promoted matrix mineralization as evidenced by the increase in calcium deposition. Dmcq B also reduced the protein level of receptor activator of NF-κβ ligand (RANKL) and promoted osteoprotegerin (OPG) protein expression by osteoblast cells, therefore hastening bone formation rate by decreasing RANKL/OPG ratio. Moreover, Dmcq B was able to increase ER expression, postulating its phytoestrogen property. As the conclusion, Dmcq B is the active compound isolated from Marantodes pumilum var. alata leaves, regulating osteoanabolic activities potentially through the BMP2 and ER signaling pathways.
Detection of the Potential Inactivation of Tetrodotoxin by Lactic Acid Bacterial Exopolysaccharide

Screening for compounds that can neutralize the toxicity of tetrodotoxin (TTX) or reduce its negative effects is necessary. Our study tested the TTX detoxification capacity of exopolysaccharide (EPS) extracted from lactic acid bacteria. EPS of Leuconostoc mesenteroides N3 isolated from the Vung Tau sea (Vietnam), Lactobacillus plantarum PN05, and Lactobacillus rhamnosus PN04 were used in the study. To more completely evaluate the importance of EPS in detoxification, EPS samples of Leuconostoc mesenteroides N3, Lactobacillus plantarum PN05 and Lactobacillus rhamnosus PN04 were also tested. The majority of EPS of these bacteria contained glucose; this was observed using thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) analysis. As observed with FTIR analysis, only EPS of Lactobacillus plantarum PN05 contained methyl groups. The results indicated that detoxification of TTX in mice could be obtained at an optimal dose of 248 µg EPS from Leuconostoc mesenteroides incubated with 54 µg cuprous oxide for 40 min or 148 µg EPS Lactobacillus rhamnosus incubated with 55 µg cuprous oxide for 40 min, while EPS from Lactobacillus plantarum showed TTX detoxification capacity without cuprous oxide combination. Consequently, EPS from Lactobacillus plantarum PN05 can be used in TTX prevention. This is the first report on the importance of lactic acid bacteria in TTX detoxification.
2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide Radical (PTIO•) Trapping Activity and Mechanisms of 16 Phenolic Xanthones

This study used the 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•) trapping model to study the antioxidant activities of 16 natural xanthones in aqueous solution, including garcinone C, γ-mangostin, subelliptenone G, mangiferin, 1,6,7-trihydroxy-xanthone, 1,2,5-trihydroxyxanthone, 1,5,6-trihydroxyxanthone, norathyriol, 1,3,5,6-tetrahydroxy-xanthone, isojacareubin, 1,3,5,8-tetrahydroxyxanthone, isomangiferin, 2-hydroxyxanthone, 7-O-methylmangiferin, neomangiferin, and lancerin. It was observed that most of the 16 xanthones could scavenge the PTIO• radical in a dose-dependent manner at pH 4.5 and 7.4. Among them, 12 xanthones of the para-di-OHs (or ortho-di-OHs) type always exhibited lower half maximal inhibitory concentration (IC50) values than those not of the para-di-OHs (or ortho-di-OHs) type. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) analysis revealed that most of these xanthones gave xanthone-xanthone dimers after incubation with PTIO•, except for neomangiferin. Based on these data, we concluded that the antioxidant activity of phenolic xanthone may be mediated by electron-transfer (ET) plus H+-transfer mechanisms. Through these mechanisms, some xanthones can further dimerize unless they bear huge substituents with steric hindrance. Four substituent types (i.e., para-di-OHs, 5,6-di-OHs, 6,7-di-OHs, and 7,8-di-OHs) dominate the antioxidant activity of phenolic xanthones, while other substituents (including isoprenyl and 3-hydroxy-3-methylbutyl substituents) play a minor role as long as they do not break the above four types.
Differentiated adipose‐derived stem cell cocultures for bone regeneration in RADA16‐I in vitro

Craniofacial defects can cause morbidness. Adipose‐derived stem cells (ADSCs) have shown great promise for osteogeneration and vascularization; therefore cocultures of differentiated ADSCs are explored to increase bone and vessel formation. In this study, ADSCs were induced into osteogenic ADSCs (os‐ADSCs) and endothelial ADSCs (endo‐ADSCs) cells, which were then cocultured in variable proportions (os‐ADSCs/endo‐ADSCs = 2:1, 1:1, 1:2). The os‐ADSCs in a ratio of 1:1 expressed more ALP, RUNX2 and COL‐I, whereas VEGF, vWF and CD31 were upregulated in the endo‐ADSCs of this group. Next generation RNA sequencing (RNA‐seq) was performed to evaluate the molecular mechanisms of cocultured ADSCs. The os‐ADSCs and endo‐ADSCs interacted with each other during osteogenic and angiogenic differentiation, especially at the ratio of 1:1, and were regulated by vascular‐related genes, cell‐mediated genes, bone‐related genes and the transforming growth factor β signaling pathway (TGF‐β), mitogen‐activated protein kinase signaling pathway (MAPK) and wnt signaling pathway (Wnt). Angptl4, apoe, mmp3, bmp6, mmp13 and fgf18 were detected to be up‐regulated, and cxcl12 and wnt5a were down‐regulated. The results showed that the gene expression levels were consistent with that in RNA‐seq. The cells were then seeded into self‐assembling peptide RADA16‐I scaffolds as cocultures (1:1) and monocultures (ADSCs, os‐ADSCs, endo‐ADSCs). The results showed that the cells of all groups grew and proliferated well on the scaffolds, and the cocultured group exhibited better osteogeneration and vascularization. In conclusion, cocultured os‐ADSCs and endo‐ADSCs at the ratio of 1:1 showed strong osteogenic and angiogenic differentiation. There is a great potential for osteogenesis and vascularization by 3D culturing cells in a 1:1 ratio in self‐assembling peptide RADA16‐I scaffolds, which requires evaluation for bone regeneration in vivo.