Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolic Reprogramming Regulates the Proliferative and Inflammatory Phenotype of Adventitial Fibroblasts in Pulmonary Hypertension Through the Transcriptional Corepressor C-Terminal Binding Protein-1

Background: Changes in metabolism have been suggested to contribute to the aberrant phenotype of vascular wall cells, including fibroblasts, in pulmonary hypertension (PH). Here, we test the hypothesis that metabolic reprogramming to aerobic glycolysis is a critical adaptation of fibroblasts in the hypertensive vessel wall that drives proliferative and proinflammatory activation through a mechanism involving increased activity of the NADH-sensitive transcriptional corepressor C-terminal binding protein 1 (CtBP1). Methods: RNA sequencing, quantitative polymerase chain reaction,13C–nuclear magnetic resonance, fluorescence-lifetime imaging, mass spectrometry–based metabolomics, and tracing experiments with U-13C-glucose were used to assess glycolytic reprogramming and to measure the NADH/NAD+ ratio in bovine and human adventitial fibroblasts and mouse lung tissues. Immunohistochemistry was used to assess CtBP1 expression in the whole-lung tissues. CtBP1 siRNA and the pharmacological inhibitor 4-methylthio-2-oxobutyric acid (MTOB) were used to abrogate CtBP1 activity in cells and hypoxic mice. Results: We found that adventitial fibroblasts from calves with severe hypoxia-induced PH and humans with idiopathic pulmonary arterial hypertension (PH-Fibs) displayed aerobic glycolysis when cultured under normoxia, accompanied by increased free NADH and NADH/NAD+ ratios. Expression of the NADH sensor CtBP1 was increased in vivo and in vitro in fibroblasts within the pulmonary adventitia of humans with idiopathic pulmonary arterial hypertension and animals with PH and cultured PH-Fibs, respectively. Decreasing NADH pharmacologically with MTOB or genetically blocking CtBP1 with siRNA upregulated the cyclin-dependent genes (p15 and p21) and proapoptotic regulators (NOXA and PERP), attenuated proliferation, corrected the glycolytic reprogramming phenotype of PH-Fibs, and augmented transcription of the anti-inflammatory gene HMOX1. Chromatin immunoprecipitation analysis demonstrated that CtBP1 directly binds the HMOX1 promoter. Treatment of hypoxic mice with MTOB decreased glycolysis and expression of inflammatory genes, attenuated proliferation, and suppressed macrophage numbers and remodeling in the distal pulmonary vasculature. Conclusions: CtBP1 is a critical factor linking changes in cell metabolism to cell phenotype in hypoxic and other forms of PH and a therapeutic target.
Graphene Oxide–Silver Nanoparticles Nanocomposite Stimulates Differentiation in Human Neuroblastoma Cancer Cells (SH-SY5Y)

Recently, graphene and graphene related nanocomposite receive much attention due to high surface-to-volume ratio, and unique physiochemical and biological properties. The combination of metallic nanoparticles with graphene-based materials offers a promising method to fabricate novel graphene–silver hybrid nanomaterials with unique functions in biomedical nanotechnology, and nanomedicine. Therefore, this study was designed to prepare graphene oxide (GO) silver nanoparticles (AgNPs) nanocomposite (GO-AgNPs) containing two different nanomaterials in single platform with distinctive properties using luciferin as reducing agents. In addition, we investigated the effect of GO-AgNPs on differentiation in SH-SY5Y cells. The synthesized GO-AgNPs were characterized by ultraviolet-visible absorption spectroscopy (UV-vis), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Raman spectroscopy. The differentiation was confirmed by series of cellular and biochemical assays. The AgNPs were distributed uniformly on the surface of graphene oxide with an average size of 25 nm. As prepared GO-AgNPOs induces differentiation by increasing the expression of neuronal differentiation markers and decreasing the expression of stem cell markers. The results indicated that the redox biology involved the expression of various signaling molecules, which play an important role in differentiation. This study suggests that GO-AgNP nanocomposite could stimulate differentiation of SH-SY5Y cells. Furthermore, understanding the mechanisms of differentiation of neuroblastoma cells could provide new strategies for cancer and stem cell therapies. Therefore, these studies suggest that GO-AgNPs could target specific chemotherapy-resistant cells within a tumor.
Assessment of performance of lithium iron phosphate oxide, nickel manganese cobalt oxide and nickel cobalt aluminum oxide based cells for using in plug-in battery electric vehicle applications

This paper represents a comprehensive comparison of three battery chemistries for use in plug-in battery electric vehicles: lithium iron phosphate oxide, lithium nickel manganese cobalt oxide and nickel cobalt aluminum oxide anodes. The battery characteristics at different temperature conditions have been investigated, using test procedures as defined in the standard IEC 62660–1/2 and introducing new load profiles. Main focus key parameters are the energy density, power capabilities, rate performances during charge and discharge as well as the energy efficiency, thermal behaviour and life cycle. The results indicate that the lithium iron phosphate based cells have good performances at low temperatures (such as down to −18° C). However, the situation regarding the nickel cobalt aluminum oxide and nickel manganese cobalt oxide anodes demonstrates less favorable performances, especially at low temperatures where the power and energy capabilities are considerably poor. In addition, the cycle life properties are discussed in order to evaluate the long-term performances, and battery parameters such as cost and thermal behaviors are compared. Finally, this study contains a new definition for the well-known Peukert relationship during the discharge phase. Furthermore, an adapted equation during the charge phase is presented based on the charge characteristics of the proposed batteries at different environmental conditions.
Board of directors and financial transparency and disclosure. Evidence from Italy

The purpose of this paper is to examine the link between board of directors’ composition (independent directors’ ratio, board size, CEO-duality) and financial transparency and disclosure (T&D). ,The paper analyzes board composition and financial T&D of Italian listed companies using multiple linear regression analysis. ,The results of this paper show a significant link between board composition and the level of financial T&D. In particular, the authors found a positive and significant relationship between the independent directors’ ratio and the level of financial T&D and a negative relationship between board size and the level of financial T&D. ,While this paper focuses on a sample of 100 Italian listed companies, the authors acknowledge the importance of extending the results to other national context and to other type of firms (e.g. non-listed firms or SMEs). Moreover, while this paper concerns the amount of information disclosed by firms, it does not look at the quality or accuracy of disclosure. ,This paper reveals the importance of evaluating the effectiveness of corporate governance mechanisms (such as board composition) in enhancing the level of financial T&D. Indeed, the authors provide some indications to firms to improve their internal governance mechanisms (e.g. the importance of high proportion of independent directors and of small- and medium-sized boards of directors). ,This paper provides interesting insights to firms which are under pressure to improve the level of information to stakeholders. Moreover, has the level of information that is not legally required vary among companies and countries, the authors shed light on a context characterized by high level of ownership concentration, where firms can experience different types of conflict of interests.
Inflexibility and Stock Returns

Investment-based asset pricing research highlights the role of irreversibility as a determinant of firms' risk and expected return. In a neoclassical model of a firm with costly scale adjustment options, we show that the effect of scale flexibility (i.e., contraction and expansion options) is to determine the relation between risk and operating leverage: risk increases with operating leverage for inflexible firms, but decreases for flexible firms. Guided by theory, we construct easily reproducible proxies for inflexibility and operating leverage. Empirical tests provide support for the predicted interaction of these characteristics in stock returns and risk. Received October 28, 2015; editorial decision May 1, 2017 by Editor Andrew Karolyi.
Increasing prevalence of overweight among US adults. The National Health and Nutrition Examination Surveys, 1960 to 1991.

OBJECTIVE To examine trends in overweight prevalence and body mass index of the US adult population. DESIGN Nationally representative cross-sectional surveys with an in-person interview and a medical examination, including measurement of height and weight. SETTING/PARTICIPANTS Between 6000 and 13,000 adults aged 20 through 74 years examined in each of four separate national surveys during 1960 to 1962 (the first National Health Examination Survey [NHES I]), 1971 to 1974 (the first National Health and Nutrition Examination Survey [NHANES I]), 1976 to 1980 (NHANES II), and 1988 to 1991 (NHANES III phase 1). RESULTS In the period 1988 to 1991, 33.4% of US adults 20 years of age or older were estimated to be overweight. Comparisons of the 1988 to 1991 overweight prevalence estimates with data from earlier surveys indicate dramatic increases in all race/sex groups. Overweight prevalence increased 8% between the 1976 to 1980 and 1988 to 1991 surveys. During this period, for adult men and women aged 20 through 74 years, mean body mass index increased from 25.3 to 26.3; mean body weight increased 3.6 kg. CONCLUSIONS These nationally representative data document a substantial increase in overweight among US adults and support the findings of other investigations that show notable increases in overweight during the past decade. These observations suggest that the Healthy People 2000 objective of reducing the prevalence of overweight US adults to no more than 20% may not be met by the year 2000. Understanding the reasons underlying the increase in the prevalence of overweight in the United States and elucidating the potential consequences in terms of morbidity and mortality present a challenge to our understanding of the etiology, treatment, and prevention of overweight.
The bacterial community of entomophilic nematodes and host beetles

Insects form the most species‐rich lineage of Eukaryotes and each is a potential host for organisms from multiple phyla, including fungi, protozoa, mites, bacteria and nematodes. In particular, beetles are known to be associated with distinct bacterial communities and entomophilic nematodes. While entomopathogenic nematodes require symbiotic bacteria to kill and reproduce inside their insect hosts, the microbial ecology that facilitates other types of nematode–insect associations is largely unknown. To illuminate detailed patterns of the tritrophic beetle–nematode–bacteria relationship, we surveyed the nematode infestation profiles of scarab beetles in the greater Los Angeles area over a five‐year period and found distinct nematode infestation patterns for certain beetle hosts. Over a single season, we characterized the bacterial communities of beetles and their associated nematodes using high‐throughput sequencing of the 16S rRNA gene. We found significant differences in bacterial community composition among the five prevalent beetle host species, independent of geographical origin. Anaerobes Synergistaceae and sulphate‐reducing Desulfovibrionaceae were most abundant in Amblonoxia beetles, while Enterobacteriaceae and Lachnospiraceae were common in Cyclocephala beetles. Unlike entomopathogenic nematodes that carry bacterial symbionts, insect‐associated nematodes do not alter the beetles' native bacterial communities, nor do their microbiomes differ according to nematode or beetle host species. The conservation of Diplogastrid nematodes associations with Melolonthinae beetles and sulphate‐reducing bacteria suggests a possible link between beetle–bacterial communities and their associated nematodes. Our results establish a starting point towards understanding the dynamic interactions between soil macroinvertebrates and their microbiota in a highly accessible urban environment.
A theoretical framework for determining cerebral vascular function and heterogeneity from dynamic susceptibility contrast MRI

Mapping the complex heterogeneity of vascular tissue in the brain is important for understanding cerebrovascular disease. In this translational study, we build on previous work using vessel architectural imaging (VAI) and present a theoretical framework for determining cerebral vascular function and heterogeneity from dynamic susceptibility contrast magnetic resonance imaging (MRI). Our tissue model covers realistic structural architectures for vessel branching and orientations, as well as a range of hemodynamic scenarios for blood flow, capillary transit times and oxygenation. In a typical image voxel, our findings show that the apparent MRI relaxation rates are independent of the mean vessel orientation and that the vortex area, a VAI-based parameter, is determined by the relative oxygen saturation level and the vessel branching of the tissue. Finally, in both simulated and patient data, we show that the relative distributions of the vortex area parameter as a function of capillary transit times show unique characteristics in normal-appearing white and gray matter tissue, whereas tumour-voxels in comparison display a heterogeneous distribution. Collectively, our study presents a comprehensive framework that may serve as a roadmap for in vivo and per-voxel determination of vascular status and heterogeneity in cerebral tissue.
Network theory in autoimmunity. In vitro suppression of serum anti-DNA antibody binding to DNA by anti-idiotypic antibody in systemic lupus erythematosus.

Regulation of serum anti-DNA antibody in systemic lupus erythematosus (SLE) by an antiidiotypic antibody was evaluated. Various sera from SLE patients in active and inactive states of their disease, as well as sera from normal individuals, were first completely depleted of anti-DNA and of DNA by affinity chromatography. The suppressive capacity of equimolar concentrations of the various depleted sera (blocking sera) on target lupus sera were determined. The target sera were from lupus patients with known DNA-binding capacity. Blocking sera from inactive SLE suppressed the binding of autologous anti-DNA antibody to [(3)H]DNA (n = 19,P < 0.01). Blocking sera from active SLE (n = 19), as well as human serum albumin, did not suppress. Sera from normal donors who had no contact with lupus patients or with lupus sera did not suppress (n = 14, P > 0.5), whereas those from normal donors who had contact with lupus patients or sera did suppress the binding (n = 5,P < 0.02). The anti-anti-DNA antibody suppressive activity in the inactive lupus serum was shown to be localized within the F(ab')(2) portion of immunoglobulin (Ig)G and could not be removed upon adsorption by normal human gammaglobulin. Furthermore, immune complexes could be detected by a Clq binding assay when the inactive lupus blocking sera were incubated with the anti-DNA antibody containing target sera. The specificity of the suppressive serum factor was shown by its inability to block the binding of tetanus toxoid to antitetanus antibody and its ability to block the binding of DNA to F(ab')(2) fragments of active lupus IgG. Regulation of serum anti-DNA antibody levels by anti-antibodies could induce and maintain disease remission in lupus patients and prevent disease expression in normals.
Reduced folate transport to the CNS in female Rett patients

Background: Previous CSF studies in Rett syndrome suggest reduced turnover of the biogenic monoamines serotonin and dopamine. Because diminished turnover may result from CNS folate depletion, the authors studied transport of folate across the blood–brain barrier. Methods: In four patients with Rett syndrome, the authors measured CSF values of 5-methyltetrahydrofolate (5MTHF), biogenic monoamine end-metabolites, and pterins together with serum and red blood cell folate. In CSF, the overall folate binding capacity by the two soluble folate-binding proteins FBP1 and FBP2 (sFBP) was measured using a radioligand binding method for H3-labeled folate. A specific immunoreactive test (ELISA) detected sFBP1, which normally contributes to 30 to 35% of the total folate binding capacity. Genetic analysis included DNA sequencing of the MECP2, FBP1, and FBP2 genes. Empirical treatment with oral folinic acid was evaluated. Results: Two patients without and two with mutations of the MECP2 gene had normal values for red blood cell folate, serum folate, homocysteine, and methionine. In CSF, all patients had low values for 5MTHF, neopterin, and the serotonin end-metabolite 5-hydroxyindoleacetic acid (5-HIAA). Genetic analysis of FBP1 and FBP2 genes had normal results. Compared to controls, patients with Rett syndrome had normal immunoreactive sFBP1 in CSF, whereas the total folate binding capacity was disproportionately lowered. Empirical treatment with oral folinic acid normalized 5-MHTF and 5-HIAA levels in CSF, and led to partial clinical improvement. Conclusion: Irrespective of the MECP2 genotype, 5MTHF transfer to the CNS is reduced in Rett syndrome. Folinic acid supplementation restores 5MTHF levels and serotoninergic turnover. The lowered folate binding capacity of FBP is not explained by a defect of the FBP1 or FBP2 gene, but most likely occurs as a secondary phenomenon in Rett syndrome.
Sexually transmitted diseases among adolescents in developed countries.

CONTEXT Sexually transmitted diseases (STDs) are responsible for a variety of health problems, and can have especially serious consequences for adolescents and young adults. An international comparison of levels and trends in STDs would be useful to identify countries that are relatively successful in controlling the incidence of STDs, as a first step toward improving policies and programs in countries with high or growing STD incidence. METHODS Incidence data for the past decade on three common bacterial STDs--syphilis, gonorrhea and chlamydia--were obtained for as many as 16 developed countries from official statistics, published national sources or scientific articles, and unpublished government data. Rates of incidence per 100,000 were calculated for adolescents, for young adults and for the total population. (These estimates should be considered conservative, because STDs commonly are underreported.) RESULTS The incidence of these three STDs has generally decreased over the last decade, both in the general population and among adolescents. However, the Russian Federation is an important exception: Syphilis has risen dramatically in the 1990s. Except in the Russian Federation and Romania, the syphilis rate in the mid-1990s was quite low, with rates of less than seven reported cases per 100,000 teenagers in most developed countries. Gonorrhea incidence is many times higher than that of syphilis in several countries, and this disease disproportionately affects adolescents and young adults. Gonorrhea rates among adolescents can be as high as 600 per 100,000 (in the Russian Federation and the United States), although in many countries the reported rate among teenagers is below 10 per 100,000. In all countries with good reporting, chlamydia incidence is extremely high among adolescents (between 563 and 1,081 cases per 100,000). The reported incidence of all three STDs is generally higher among female teenagers than among males of the same age; this is especially true for chlamydia. CONCLUSION Prevention programs, active screening strategies and better access to STD diagnosis and treatment services, especially for adolescents and young adults, are necessary to reduce the incidence and the burden of STDs among young people.
High-Resolution Molecular Spectroscopy of van der Waals Clusters in Liquid Helium Droplets

Small van der Waals clusters of sulfur hexafluoride (SF6) and mixed SF6-rare gas clusters were prepared inside large droplets of helium-4, with each droplet consisting of about 4000 helium atoms. A diode laser was used to measure the high-resolution infrared spectra of these clusters in the vicinity of the ν3 vibrational mode. In all cases rotational structure was observed, indicating that the embedded species rotate nearly freely, although they had been cooled to a temperature of 0.37 kelvin. The results indicate that helium droplets are probably superfluid and thereby provide a uniquely cold yet gentle matrix for high-resolution spectroscopy.
Brief screening for family psychiatric history: the family history screen.

BACKGROUND Brief screens to collect lifetime family psychiatric history are useful in clinical practice and for identifying potential families for genetic studies. METHODS The Family History Screen (FHS) collects information on 15 psychiatric disorders and suicidal behavior in informants and their first-degree relatives. Since each question is posed only once about all family members as a group, the administrative time is 5 to 20 minutes, depending on family size and illness. Data on the validity against best-estimate (BE) diagnosis based on independent and blind direct interviews on 289 probands and 305 relatives and test-retest reliability across 15 months in 417 subjects are presented. RESULTS Agreement between FHS and BE diagnosis for proband and relative self-report had median sensitivity (SEN) of 67.6 and 71.1 respectively; median specificity (SPC) was 87.6 and 89.4, respectively. Marked decrease in SEN occurred when a single informant (the proband) reported on a relative (median, 37.5); however, median SPC was 95.8. Use of more than 1 informant substantially improved SEN (median, 68.2), with a modest reduction in SPC (median, 86.8). Test-retest reliability across 15 months resulted in a median kappa of 0.56. CONCLUSIONS The FHS is a promising brief screen for collecting lifetime psychiatric history on an informant and/or first-degree relatives. Its validity is best demonstrated for major depression, anxiety disorders, substance dependence (alcohol and drug dependence), and suicide attempts. It is not a substitute for more lengthy family history if more detail on diagnosis is required.
Fabry disease mimicking hypertrophic cardiomyopathy: genetic screening needed for establishing the diagnosis in women

Fabry disease, an X‐linked storage disorder caused by defective lysosomal enzyme alpha‐galactosidase A activity, may resemble sarcomere‐gene‐associated hypertrophic cardiomyopathy (HCM). The ‘cardiac variant’ of Fabry disease which only affects the heart may be missed unless specifically tested for.