Miracle-dz/UniFAR-FTUs huggingface dataset:
Impairment of the Plasmin Activation System in Primary Pulmonary Hypertension: Evidence for Gender Differences

Summary Primary pulmonary hypertension (PPH) is a rare disorder, with marked in-situ thrombosis of small pulmonary vessels occurring primarily in adult women. We investigated whether differences in the plasmin- and thrombin activation system are associated with the predominate affection of females. Plasma levels of plasminogen activator inhibitor type 1 (PAI-1), tissue-type plasminogen activator (t-PA), fibrinogen, thrombin-antithrombin (TAT) complexes, and prothrombin fragments (F1.2) were measured at baseline and after standardized venous occlusion (VO) in patients with PPH (24 female, 9 male). At baseline, females showed significant higher TAT levels (p = 0.05), higher t-PA antigen levels (p = 0.01) and higher fibrinogen levels (p = 0.03) with positive correlation to mean pulmonary artery pressure (mPAP), as well as nonsignificant lower t-PA activity, higher PAI-1 antigen and activity and F1.2 levels. After VO, females showed a significantly blunted increase in t-PA antigen (p = 0.01) and t-PA activity (p = 0.001), correlating with mPAP, as well as increased PAI-1 activity (p = 0.05). We hypothesize, that the observed presence of gender differences in the plasmin- and thrombin activation system in PPH leading to an antifibrinolytic/prothrombotic state might, in part, explain the female predominant incidence of this disease.
Vegetable Business and Smallholders’ Food Security: Empirical Findings from Northern Ethiopia

In Ethiopia, there have been increased efforts to promote market-oriented vegetable production. Given that food security is a crucial issue in Ethiopia, the question is whether market-oriented vegetable production will actually help farmers to become more food secure. Using a mixed methods approach, the present research gathered empirical evidence on the determinants of participation in the vegetable business and its food security impacts in the Raya Azebo district. The Heckman two-stage selection model was used to identify factors affecting participation in the vegetable business and its effects on several food security outcomes. A thematic analysis was applied to the qualitative data. The results show that a farmer’s participation in the vegetable business increased significantly with adequate household productive resources (e.g., land size and access to irrigation), cooperative memberships and access to extension services. On the other hand, the age of the head of household, the market distance and risk perceptions significantly decreased participation. Additionally, the results indicate participation in the vegetable business results not only in higher food availability and access but also in lower food variety and diet diversity scores. Participation has less of an impact on per capita kilocalorie consumption and child anthropometric measures of food security. The policy implication is that, while Ethiopia is going ahead with inclusive market-driven approaches to food security, alternative mechanisms must be put in place to address the negative impacts and to empower those living in the most vulnerable conditions.
Early virologic rebound in a pilot trial of ritonavir-boosted atazanavir as maintenance monotherapy.

OBJECTIVE To investigate the feasibility of ritonavir-boosted atazanavir monotherapy in HIV-1-infected patients with stable antiretroviral therapy (ART). DESIGN Single-armed single-center pilot trial. METHODS Adult HIV-1-infected patients, without protease inhibitor (PI) experience, were eligible if they had maintained a viral load <20 copies/mL for a minimum of 12 months on conventional ART. The trial regimen was atazanavir/ritonavir at a dose of 300/100 mg once daily. The atazanavir dose could be adjusted if plasma concentrations showed a low exposure. The study was intended to recruit 30 patients to be followed over 72 weeks. If 5 cases of virologic failure occurred during this period, the study was to be terminated. RESULTS The study was terminated according to protocol when 15 of the planned 30 patients had been recruited, because 5 cases of virologic failure had occurred. In patients failing therapy, viral rebound was seen at weeks 12 through 16. Plasma atazanavir concentrations were not associated with the outcome. The median serum bilirubin concentration was significantly lower in the patients failing therapy, however. No PI resistance was found in samples from patients failing therapy. CONCLUSIONS Ritonavir-boosted atazanavir as maintenance monotherapy in HIV-1 infection might not be as potent as conventional ART. Serum bilirubin should be further studied as a biomarker of adequate atazanavir exposure.
Lipoprotein Candidate Genes for Multivariate Factors of the Insulin Resistance Syndrome: A Sib-pair Linkage Analysis in Women Twins

Abstract The insulin resistance syndrome (IRS) is characterized by a combination of interrelated coronary heart disease risk factors, including low high-density lipoprotein cholesterol (HDLC) levels, obesity and increases in triglyceride (TG), systolic and diastolic blood pressure (BP), small low-density lipoprotein particles (LDL-size), and fasting and postload plasma insulin and glucose. Using factor analysis, we previously identified multivariate factors based on data from women participating in the Kaiser Permanente Women Twins Study: 1) Weight/Fat, 2) Insulin/Glucose, 3) Lipids, and 4) BP. The purpose of this study is to evaluate evidence for genetic linkage between the multivariate factors and candidate genes. Quantitative sib-pair analysis based on the factor scores with markers for 9 candidate genes was carried out based on data from 126 pairs of dizygotic (DZ) women twins from the second exam of the Kaiser Permanente Women Twins study. Suggestive evidence for linkage was found for the Weight/fat factor and the Apo E gene (p = 0.01), and stronger evidence for linkage with the Lipid factor and the cholesterol ester transfer protein (p = 0.002) gene. Therefore, the CETP gene appears to influence covariation in LDL size, TG, and HDL, and may account for a portion of the well-established statistical and metabolic associations observed between these risk factors.
The effect of oxygen tension on the in vitro assay of human osteoblastic connective tissue progenitor cells

Connective tissue progenitors (CTPs) are defined as the heterogeneous set of stem and progenitor cells that reside in native tissues and are capable of proliferation and differentiation into one or more connective tissue phenotypes. CTPs play important roles in tissue formation, repair, and remodeling. Therefore, in vitro assays of CTP prevalence and biological potential have important scientific and clinical relevance. This study evaluated oxygen tension as an important variable in optimizing in vitro conditions for quantitative assays of human CTPs. Bone marrow aspirates were collected from 20 human subjects and cultured using established medium conditions at ambient oxygen tensions of 1, 5, 10, and 20%. Colony‐forming efficiency (CFE), proliferation, and colony density were assessed. CFE and proliferation were greatest at 5% O2. Traditional conditions using atmospheric oxygen tension (20% O2) reduced CFE by as much as 32%. CFE and proliferation at 1% O2 were less than 5% O2 but comparable to that seen at 20% O2, suggesting that CTPs are relatively resilient under hypoxic conditions, a fact that may be relevant to their function in wound repair and their potential use in tissue engineering applications involving transplantation into settings of moderate to severe hypoxia. These data demonstrate that optimization of quantitative assays for CTPs will require control of oxygen tension. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1390–1397, 2008
Clinical review of mania, hostility and suicide-related events in children and adolescents treated with antidepressants.

BACKGROUND Recent controversy surrounding the use of non-tricyclic antidepressants and the emergence of suicide-related events, hostility/behavioural activation and mania in youth with depression warrants an exploration of the results from randomized controlled trials (RCTs) and published case reports for the emergence of these adverse events. OBJECTIVE To provide a clinical review of the available evidence from RCTs and case reports regarding the safety of nontricyclic anti-depressants in youth with depression. METHODS Seven RCTs of antidepressant use in youth with depression, four case reports of suicide-related adverse events, three case reports of hostility/behavioural activation, and 12 case reports of precipitation of mania were reviewed. RESULTS The majority of patients with suicide-related adverse events from both RCTs and published case reports were suicidal before the start of antidepressant treatment. Hostility/behavioural activation generally developed within days to weeks after the start of antidepressant treatment; in the majority of cases, symptoms resolved within four weeks of dosage lowering or discontinuation of the medication alone. Rates for precipitation of mania from RCTs ranged from 0% to 6%. In approximately 60% of published case reports, manic symptoms resolved with the discontinuation or lowering of the dosage of medication alone. CONCLUSIONS Several trends were observed in the association between adverse events and the use of nontricyclic antidepressants in youth. When prescribing antidepressants to youth, clinicians should closely monitor patients and fully inform them and their families of the risks and benefits of treatment with antidepressants.
Can glomerular mRNAs in human type 1 diabetes be used to predict transition from normoalbuminuria to microalbuminuria?

BACKGROUND mRNAs of pathogenetic importance in the development of diabetic nephropathy were measured in subjects with type 1 diabetes to determine whether these might be used to predict progression from normoalbuminuria to microalbuminuria. We proposed that conversion from normoalbuminuria to microalbuminuria would be most likely in subjects whose connective tissue growth factor (CTGF) and collagen mRNAs were above the 95% confidence interval (CI) for live renal donors and within the 95% CI for subjects with abnormal albuminuria. METHODS Glomerular CTGF, collagen alpha2(IV), and control glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNAs were measured in microdissected glomeruli from living renal donors (n = 10), and subjects with normoalbuminuria (n = 12), microalbuminuria (n = 5), and overt proteinuria (n = 6). RESULTS After 44 +/- 2 months of follow-up, one subject converted from normoalbuminuria to microalbuminuria. Although the data are limited, progression from normoalbuminuria to microalbuminuria occurred in the only normoalbuminuric subject whose mRNA levels were above the live renal donors' 95% CI for CTGF and collagen alpha2(IV) and within the 95% CI of subjects with abnormal albuminuria. No clinical or histopathologic finding distinguished the progressor from the nonprogressors at the time of biopsy. CONCLUSION This case report provides proof-of-principle that a panel of glomerular mRNA markers chosen because of their pathogenetic relevance may be useful adjuncts to albuminuria and histology in predicting clinical stability or clinical progression in diabetic nephropathy.
Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis

Silicosis is an occupational lung disease with no effective treatment. We hypothesized that dasatinib, a tyrosine kinase inhibitor, might exhibit therapeutic efficacy in silica-induced pulmonary fibrosis. Silicosis was induced in C57BL/6 mice by a single intratracheal administration of silica particles, whereas the control group received saline. After 14 days, when the disease was already established, animals were randomly assigned to receive DMSO or dasatinib (1 mg/kg) by oral gavage, twice daily, for 14 days. On day 28, lung morphofunction, inflammation, and remodeling were investigated. RAW 264.7 cells (a macrophage cell line) were incubated with silica particles, followed by treatment or not with dasatinib, and evaluated for macrophage polarization. On day 28, dasatinib improved lung mechanics, increased M2 macrophage counts in lung parenchyma and granuloma, and was associated with reduction of fraction area of granuloma, fraction area of collapsed alveoli, protein levels of tumor necrosis factor-α, interleukin-1β, transforming growth factor-β, and reduced neutrophils, M1 macrophages, and collagen fiber content in lung tissue and granuloma in silicotic animals. Additionally, dasatinib reduced expression of iNOS and increased expression of arginase and metalloproteinase-9 in silicotic macrophages. Dasatinib was effective at inducing macrophage polarization toward the M2 phenotype and reducing lung inflammation and fibrosis, thus improving lung mechanics in a murine model of acute silicosis.
Does Liquidity Matter on Bank Profitability Evidence from a Nonlinear Framework for a Large Sample

The aim of this paper is to define the optimal level of liquidity and to investigate its impact on the overall bank profitability. To achieve these goals, we use a large sample of 127 countries over the period 2005-2015. The whole sample is divided in two sub-samples. The first covers 46 high income countries and the second includes 81 low and middle income countries. We performed the Panel Smooth Transition Regression (PSTR) as econometric approach. Empirical results show that the optimal level of liquidity that affects bank profitability is 24.18% for high income countries and 40.45% for low and middle income countries. Findings also indicate that credit risk decreases significantly the level of profitability of the two groups of countries.
Current indications and results of orthotopic ileal neobladder for bladder cancer

During the past three decades, the reconstructive aspects of urologic surgery emerged and became a major component of our surgical specialty, and the most relevant developments have been observed in the field of urinary diversions. Health-related quality of life and self esteem have been improved following orthotopic bladder substitutions, which are actually the preferred method for continent urinary diversion. Patients with neobladders have enhanced cosmesis and the potential for normal voiding function with no abdominal stoma. Patient’s selection for orthotopic neobladder formation is mandatory as most of the surgical complications or consequences associated with a neobladder are correlated not only with surgical technique or management after surgery, but also with wrong patient’s selection. The principles of intestinal detubularization and reconfiguration to obtain spherical reservoir are the basis of continent urinary diversions and ileum seems to be preferable over any other segment. Nowadays, ileal neobladder is a widely adopted solution after cystectomy with a neobladder rate of 9–19% for population-based data with an increase to 39.1–74% for high-volume centers. However, controversies still exist in this urological field about the best candidates for neobladder construction, the best type of neobladder to offer, whether or not an antireflux uretero intestinal anastomosis should be used, the future of minimally invasive approaches, that is, robotic assisted cystectomy plus extracorporeal or intracorporeal neobladder, and last but very important, the functional results and the level of symptoms-induced distress and quality of life in the long term in patients with bladder cancer receiving an orthotopic bladder substitution. All these issues are discussed on the basis of the most recent published data.
Effects of Austerity: Expenditure- and Tax-Based Approaches

We review the debate surrounding the macroeconomic effects of deficit reduction policies (austerity). The discussion about "austerity" in general has distracted commentators and policymakers from a very important result, namely the enormous difference, on average, between expenditure- and tax-based austerity plans. Spending-based austerity plans are remarkably less costly than tax-based plans. The former have on average a close to zero effect on output and lead to a reduction of the debt/GDP ratio. Tax-based plans have the opposite effect and cause large and long-lasting recessions. These results also apply to the recent episodes of European austerity, which in this respect were not especially different from previous cases.
Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: A light and electron microscopic study of the thalamostriatal projection in relation to striatal heterogeneity

The organization of the thalamostriatal projections arising from the centromedian (CM) and parafascicular (Pf) thalamic nuclei in the squirrel monkey (Saimiri sciureus) was studied at both light and electron microscopic levels. Following selective injections of the anterograde axonal tracer Phaseolus vulgaris‐leucoagglutinin (PHA‐L) into the CM or Pf, patterns of terminal arborization within the striatum were compared to the biochemical heterogeneity of the striatum as revealed by immunohistochemical staining for the calcium‐binding protein calbindin D‐28k (CaBP), and histochemical staining for the enzymes acetylcholinesterase (AChE) and nicotinamide adenine dinucleotide phosphate‐diaphorase (NADPH‐diaphorase). The PHA‐L‐labeled axon terminals within the striatum were further analyzed at the ultrastructural level to characterize their pattern of synaptic organization. Dense and heterogeneous terminal fields occur in the „sensorimotor”︁ territory of the striatum after CM injections, or in the „associative”︁ striatal territory following Pf injections. In the associative territory labeled axons arborize in a diffuse manner predominantly within areas enriched with CaBP, AChE, or NADPH‐diaphorase, representing the matrix compartment, and tend to avoid areas poor in these substances, corresponding to the patch/striosome compartment. In the sensorimotor territory labeled axons form bands that occupy a subregion of the NADPH‐diaphorase‐rich zone in the putamen. The terminal pattern of the CM‐striatal projection suggests the existence of a more complex mosaic organization within the sensorimotor territory. Ultrastructural analysis of PHA‐L‐labeled elements within the striatum reveals that both CM and Pf projections form asymmetric synapses upon dendrites and spines of striatal cells. A total of 339 PHA‐L‐labeled boutons were examined after CM injections and compared to 293 boutons following Pf injections. After CM injections, 29% of PHA‐L‐labeled terminals form synapses on dendritic spines and 66% on dendritic shafts, whereas after Pf injections only 12% of synapses occur on dendritic spines compared to 81% on dendritic shafts. Labeled terminals forming axosomatic or axoaxonic synapses were not seen within the striatum following either CM or Pf injections. It is concluded that in the squirrel monkey: (1) Pf‐striatal fibers profusely arborize within the matrix compartment of the associative territory, (2) CM‐striatal fibers form bands that occupy a subregion of the NADPH‐diaphorase‐rich zone within the sensorimotor territory, and (3) that both Pf‐ and CM‐striatal projections establish asymmetric synapses with dendrites and spines of medium‐sized spiny cells. These results suggest that the complementary CM and Pf projections to the striatum are in a crucial position to exert a powerful and highly ordered excitatory influence upon the output neurons of the striatum in primates.
From dualization to continuum. Exploring dimensions of Outsiderness in Southern Europe.

In this paper we advance an original theoretical proposal for analysing the consequence of deregulation in Southern Europe labour markets. Instead of conceptualizing dualization as a binary combination of insiders/outsiders, we propose a model that explores different dimensions of outsiderness along a continuum of positions from the core to the margins of the labour market. Assuming an intersectional perspective, we analyse these trends in six Southern European countries characterised by different timing of labour market reforms, different welfare regimes, and different economic performances along the crisis (Spain, Italy, France, Austria, Croatia, Greece). Our main source will be the European Labour Force Survey microdata (2000-2016), aiming at identifying involuntary non-standard work characterised by a potential risk of contractual misuse.
Recovery from experimental autoimmune uveitis promotes induction of antiuveitic inducible Tregs

The recovery of EAU, a mouse model of endogenous human autoimmune uveitis, is marked with the emergence of autoantigen‐specific regulatory immunity in the spleen that protects the mice from recurrence of EAU. This regulatory immunity is mediated by a melanocortin‐driven suppressor APC that presents autoantigen and uses adenosine to activate an antigen‐specific CD4+ Tregs through the A2Ar. These cells are highly effective in suppressing uveitis, and they appear to be inducible Tregs. In this study, we determined whether they are inducible or natural Tregs and identified the dependent mechanism for the function of these post‐EAU Tregs. The post‐EAU spleen CD25+CD4+ T cells were sorted for NRP‐1 expression and transferred to recipient mice immunized for EAU. The sorted NRP‐1−, but not the NRP‐1+, Tregs suppressed EAU. These NRP‐1− Tregs coexpress PD‐1 and PD‐L1. Treatment of naive APCs with α‐MSH promoted a regulatory APC that induced CD25+ CD4+ Tregs in a CD73‐dependent manner. These Tregs were PD‐L1+ PD‐1+ NRP‐1− FOXP3+ HELIOS− and suppressed EAU when transferred to recipient mice. In contrast, PD‐1− T cells did not suppress EAU, indicating that PD‐1 is necessary for the suppressive activity of iTregs. Moreover, these Tregs did not suppress effector T cells when the PD/‐1/PD‐L1 pathway was blocked. These results demonstrate that post‐EAU Tregs are inducible Tregs, which use a PD‐1/PD‐L1 mechanism to suppress disease.
PROLIFERATIVE, PRESACCULAR STAGES OF TETRACAPSULOIDES BRYOSALMONAE (MYXOZOA: MALACOSPOREA) WITHIN THE INVERTEBRATE HOST FREDERICELLA SULTANA (BRYOZOA: PHYLACTOLAEMATA)

Proliferative kidney disease (PKD), caused by the malacosporean parasite, Tetracapsuloides bryosalmonae, is a major disease of salmonid culture both in western Europe and North America. The fish are infected from spores that develop within freshwater bryozoans and are released into the water column. Although sporogenesis has been studied in the bryozoan host and occurs within sacs, the formation of these sacs from presaccular stages has only been hypothesized. Examination of infected bryozoans by using a range of techniques identified proliferating, presaccular amoeboid stages of T. bryosalmonae on the body wall of the bryozoan Fredericella sultana. These stages possessed unique electron-dense bodies and were observed as aggregating within the bryozoan metacoel, differentiating to form spore sacs. Spore sac growth was associated with the assimilation of the presaccular parasites rather than through cryptomitosis of sac mural cells. This sac formation through aggregation and assimilation suggests an intriguing mechanism by which T. bryosalmonae can cross-fertilize.