Miracle-dz/UniFAR-FTUs huggingface dataset:
Adaptation of iron transport and metabolism to acute high‐altitude hypoxia in mountaineers

Human iron homeostasis is regulated by intestinal iron transport, hepatic hepcidin release, and signals from pathways that consume or supply iron. The aim of this study was to characterize the adaptation of iron homeostasis under hypoxia in mountaineers at the levels of (1) hepatic hepcidin release, (2) intestinal iron transport, and (3) systemic inflammatory and erythropoietic responses. Twenty‐five healthy mountaineers were studied. Blood samples and duodenal biopsies were taken at baseline of 446 m as well as on day 2 (MG2) and 4 (MG4) after rapid ascent to 4559 m. Divalent metal‐ion transporter 1 (DMT‐1), ferroportin 1 (FP‐1) messenger RNA (mRNA), and protein expression were analyzed in biopsy specimens by quantitative reverse‐transcription polymerase chain reaction (RT‐PCR) and immunohistochemistry. Serum hepcidin levels were analyzed by mass spectrometry. Serum iron, ferritin, transferrin, interleukin (IL)−6, and C‐reactive protein (CRP) were quantified by standard techniques. Serum erythropoietin and growth differentiation factor 15 (GDF15) levels were measured by enzyme‐linked immunosorbent assay (ELISA). Under hypoxia, erythropoietin peaked at MG2 (P < 0.001) paralleled by increased GDF15 on MG2 (P < 0.001). Serum iron and ferritin levels declined rapidly on MG2 and MG4 (P < 0.001). Duodenal DMT‐1 and FP‐1 mRNA expression increased up to 10‐fold from baseline on MG2 and MG4 (P < 0.001). Plasma CRP increased on MG2 and MG4, while IL‐6 only increased on MG2 (P < 0.001). Serum hepcidin levels decreased at high altitude on MG2 and MG4 (P < 0.001). Conclusion: This study in healthy volunteers showed that under hypoxemic conditions hepcidin is repressed and duodenal iron transport is rapidly up‐regulated. These changes may increase dietary iron uptake and allow release of stored iron to ensure a sufficient iron supply for hypoxia‐induced compensatory erythropoiesis. (Hepatology 2013; 58:2153–2162)
Short-term Effects of EU Regional Policy on Employment and GDP Growth in the 2014-2020 Budgetary Cycle

The aim of this paper is to uncover early effects of EU regional policy on employment and GDP growth in the 2014-2020 budgetary cycle. EU regional policy distributes funds based on regions GDP per capita being below or above a certain threshold. This paper exploits two of these thresholds to uncover effects of EU regional policy with a Regression Discontinuity design. The estimated effect of the status of less developed region on average annual growth in the employment rate and GDP per capita (in PPS) is 1.4\\% and 2.1\\% respectively. No effects were found of the status of transition region on either growth in the employment rate or GDP.
Alginate and alginate/gelatin microspheres for human adipose-derived stem cell encapsulation and differentiation

Human adipose-derived stem cells (hADSC) encapsulated in alginate and alginate/gelatin microspheres with adjustable properties were fabricated via an improved microsphere generating device. The mechanism of the device, porous property, swelling behavior of the microspheres and hADSC proliferation as well as adipogenic differentiation were studied extensively. Microspheres with high-ratio evenly distributed adipocytes could be obtained by utilizing the proper matrix material and manufacturing parameters. The adipocyte/hADSC microspheres were a sound in vitro mimicking of a natural fat lobule and therefore a good candidate for adipose tissue engineering and regenerative medicine.
Regulatory T Cells Induced by 1α,25-Dihydroxyvitamin D3 and Mycophenolate Mofetil Treatment Mediate Transplantation Tolerance1

1α,25-Dihydroxyvitamin D3, the active form of vitamin D3, and mycophenolate mofetil, a selective inhibitor of T and B cell proliferation, modulate APC function and induce dendritic cells (DCs) with a tolerogenic phenotype. Here we show that a short treatment with these agents induces tolerance to fully mismatched mouse islet allografts that is stable to challenge with donor-type spleen cells and allows acceptance of donor-type vascularized heart grafts. Peritransplant macrophages and DCs from tolerant mice express down-regulated CD40, CD80, and CD86 costimulatory molecules. In addition, DCs from the graft area of tolerant mice secrete, upon stimulation with CD4+ cells, 10-fold lower levels of IL-12 compared with DCs from acutely rejecting mice, and induce a CD4+ T cell response characterized by selective abrogation of IFN-γ production. CD4+ but not CD8+ or class II+ cells from tolerant mice, transferred into naive syngeneic recipients, prevent rejection of donor-type islet grafts. Graft acceptance is associated with impaired development of IFN-γ-producing type 1 CD4+ and CD8+ cells and an increased percentage of CD4+CD25+ regulatory cells expressing CD152 in the spleen and in the transplant-draining lymph node. Transfer of CD4+CD25+ cells from tolerant but not naive mice protects 100% of the syngeneic recipients from islet allograft rejection. These results demonstrate that a short treatment with immunosuppressive agents, such as 1α,25-dihydroxyvitamin D3/mycophenolate mofetil, induces tolerance to islet allografts associated with an increased frequency of CD4+CD25+ regulatory cells that can adoptively transfer transplantation tolerance.
Ireland's Magdalen Laundries and the Nation's Architecture of Containment

The Magdalen laundries were workhouses in which many Irish women and girls were effectively imprisoned because they were perceived to be a threat to the moral fiber of society. Mandated by the Irish state beginning in the eighteenth century, they were operated by various orders of the Catholic Church until the last laundry closed in 1996. A few years earlier, in 1993, an order of nuns in Dublin sold part of their Magdalen convent to a real estate developer. The remains of 155 inmates, buried in unmarked graves on the property, were exhumed, cremated, and buried elsewhere in a mass grave. This triggered a public scandal in Ireland and since then the Magdalen laundries have become an important issue in Irish culture, especially with the 2002 release of the film "The Magdalene Sisters. " Focusing on the ten Catholic Magdalen laundries operating between 1922 and 1996, "Ireland's Magdalen Laundries and the Nation's Architecture of Containment" offers the first history of women entering these institutions in the twentieth century. Because the religious orders have not opened their archival records, Smith argues that Ireland's Magdalen institutions continue to exist in the public mind primarily at the level of story (cultural representation and survivor testimony) rather than history (archival history and documentation). Addressed to academic and general readers alike, James M. Smith's book accomplishes three primary objectives. First, it connects what history we have of the Magdalen laundries to Ireland's "architecture of containment" that made undesirable segments of the female population such as illegitimate children, single mothers, and sexually promiscuous women literally invisible. Second, it critically evaluates cultural representations in drama and visual art of the laundries that have, over the past fifteen years, brought them significant attention in Irish culture. Finally, Smith challenges the nation - church, state, and society - to acknowledge its complicity in Ireland's Magdalen scandal and to offer redress for victims and survivors alike.
Endothelial dysfunction in rat mesenteric artery after regional cardiac ischaemia–reperfusion

In most previous studies, ischaemia–reperfusion (I/R)‐induced vascular injury referred to injury in the tissue or blood vessel that was directly subjected to I/R. However, less attention has been focused on remote vascular injury that might be caused by cardiac I/R. In the present study, we aimed to assess whether cardiac I/R could affect vasoconstriction and vasodilatation in mesenteric arteries from Sprague–Dawley rats. Left anterior descending coronary arteries from adult male Sprague–Dawley rats were occluded (60 min) and then reperfused (120 min). Changes in haemodynamic parameters indicated that this procedure caused evident cardiac dysfunction. In mesenteric arteries isolated from the animals, cardiac I/R significantly increased the maximal contractions in response to KCl, 5‐hydroxytryptamine, phenylephrine and U46619 and decreased the maximal relaxation in response to acetylcholine, but not to sodium nitroprusside, compared with sham‐operated animals. The nitric oxide synthase inhibitor l‐NAME abolished differences of contractile responses to phenylephrine between sham‐operated and I/R rats. The antioxidant N‐acetyl‐l‐cysteine reversed the impairment of acetylcholine‐stimulated vasodilatation induced by regional cardiac I/R. However, l‐NAME caused a similar degree of inhibition of acetylcholine‐stimulated relaxation in mesenteric arteries from sham‐operated and I/R rats. Electron microscopy revealed that mesenteric arterial endothelial structure was degraded in the I/R group and that N‐acetyl‐l‐cysteine treatment prevented this structural damage. In conclusion, regional cardiac I/R caused by transient occlusion and reperfusion of the left anterior descending coronary artery results in peripheral vascular endothelial dysfunction.
Determinants of Intensity of Biomass Utilization: Evidence from Cassava Smallholders in Nigeria

The paradigm shift from value chains to value webs in the emerging bioeconomy has necessitated a review on how agricultural systems transit to value web production systems. This study examines how smallholders in the cassava system in Nigeria have been able to increase utilization of biomass in their production systems. Using a sample of 541 households, the study employed cluster analysis and ordered probit regression to examine the intensity of cassava utilization and the determinants of the intensity of utilization. The study found that over 50% of the respondents were classified as low-intensity utilization households, while ~13% were high-intensity utilization households. Land, social capital, farming experience, and asset ownership increased the probability of intensifying cassava utilization among smallholders. The study recommends strengthening assets acquisition, improving land quality and encouraging social capital development among smallholders.
Defining a Structural and Kinetic Rationale for Paralogous Copies of Phenylacetate-CoA Ligases from the Cystic Fibrosis Pathogen Burkholderia cenocepacia J2315*

The phenylacetic acid (PAA) degradation pathway is the sole aerobic route for phenylacetic acid metabolism in bacteria and facilitates degradation of environmental pollutants such as styrene and ethylbenzene. The PAA pathway also is implicated in promoting Burkholderia cenocepacia infections in cystic fibrosis patients. Intriguingly, the first enzyme in the PAA pathway is present in two copies (paaK1 and paaK2), yet each subsequent enzyme is present in only a single copy. Furthermore, sequence divergence indicates that PaaK1 and PaaK2 form a unique subgroup within the adenylate-forming enzyme (AFE) superfamily. To establish a biochemical rationale for the existence of the PaaK paralogs in B. cenocepacia, we present high resolution x-ray crystal structures of a selenomethionine derivative of PaaK1 in complex with ATP and adenylated phenylacetate intermediate complexes of PaaK1 and PaaK2 in distinct conformations. Structural analysis reveals a novel N-terminal microdomain that may serve to recruit subsequent PAA enzymes, whereas a bifunctional role is proposed for the P-loop in stabilizing the C-terminal domain in conformation 2. The potential for different kinetic profiles was suggested by a structurally divergent extension of the aryl substrate pocket in PaaK1 relative to PaaK2. Functional characterization confirmed this prediction, with PaaK1 possessing a lower Km for phenylacetic acid and better able to accommodate 3′ and 4′ substitutions on the phenyl ring. Collectively, these results offer detailed insight into the reaction mechanism of a novel subgroup of the AFE superfamily and provide a clear biochemical rationale for the presence of paralogous copies of PaaK of B. cenocepacia.
Amino‐acid interactions in psychrophiles, mesophiles, thermophiles, and hyperthermophiles: Insights from the quasi‐chemical approximation

We investigate the mechanisms used by proteins to maintain thermostability throughout a wide range of temperatures. We use the quasi‐chemical approximation to estimate interaction strengths for psychrophiles, mesophiles, thermophiles, and hyperthermophiles. Our results highlight the importance of core packing in thermophilic stability. Although we observed an increase in the number of charged residues, the contribution of salt bridges appears to be relatively modest by comparison. We observed results consistent with a gradual loosening of structure in psychrophiles, including a weakening of almost all types of interactions.
Bioinformatics in mass spectrometry data analysis for proteomics studies

Mass spectrometry is a technique widely employed for the identification and characterization of proteins. The role of bioinformatics is fundamental for the elaboration of mass spectrometry data due to the amount of data that this technique can produce. To process data efficiently, new software packages and algorithms are continuously being developed to improve protein identification and characterization in terms of high-throughput and statistical accuracy. However, many limitations exist concerning bioinformatics spectral data elaboration. This review aims to critically cover the recent and future developments of new bioinformatics approaches in mass spectrometry data analysis for proteomics studies.
Regulation of CREB signaling through L-type Ca2+ channels by Nipsnap-2

A recent study identified Nipsnap1 as an auxiliary protein inhibiting TRPV6 ion channel activity. Based upon this finding, we investigated the role of Nipsnap1, and the closely related Nipsnap2, in Ca2+ channel regulation. Here, we find that overexpression of Nipsnap2 caused a 45% increase in currents though L-type Ca2+ channels in a neuronal cell line, while siRNA knockdown of Nipsnap2 greatly reduced L-type currents. The increased influx through L-type Ca2+ channels due to Nipsnap2 overexpression led to increased phosphorylation of the transcription factor cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) along with enhanced expression of several transcription factors and CREB target genes. These experiments highlight a novel role of Nipsnap2 in transcriptional regulation via L-type Ca2+ channels.
Disaccharidase activities in Belgian children: reference intervals and comparison with non‐Belgian Caucasian children

Aim: To establish reference values for disaccharidase activities in Belgian children and to compare enzyme activities with those of non‐Belgian Caucasian children. Methods: Data from Belgian children who had undergone endoscopic jejunal biopsies (1994–2000) for suspected malabsorption were reviewed. The patients were divided into three groups based on histology: (A) normal (n= 201), (B) moderate changes (n= 58) and (C) (sub)total atrophy (n= 14). The 95% reference limits for disaccharidase activities (U/g protein) were calculated for group A after exclusion of patients with a positive hydrogen breath test, a history of lactose intolerance or coeliac disease (final population: n=151, 0.1–12 y). Values were compared with those of 34 non‐Belgian Caucasian children with normal histology (28 of Mediterranean origin). Results: The reference limits (90% confidence interval) were 86 (65–111)–423 (366–494) for maltase, 9 (6–12)–91 (78–122) for lactase and 24 (18–30)–155 (120–184) for sucrase. No gender‐related differences in enzyme activities were found. Lactase levels showed a slight decrease with increasing age. Disaccharidase activities of children with histologically confirmed mucosal injury were significantly lower than those of children with normal histology: median values for groups A, B and C were 208, 181 and 96, respectively, for maltase, 40, 28 and 7, respectively, for lactase and 69, 54 and 25, respectively, for sucrase. Median disaccharidase activities in biopsies with normal histology were lower in non‐Belgian children, the difference being only statistically significant for lactase, 33 versus 40.
Outcomes and Risk Prediction Model for Peripheral Arterial Disease in Patients with Stable Coronary Artery Disease

We used the National Heart, Lung, and Blood Institute Limited Access Dataset of Prevention of Events with Angiotensin-Converting Enzyme Inhibition (PEACE) Trial (n = 8290) which included patients with stable coronary artery disease (CAD) and preserved ejection fraction (>40%). We identified risk factors for the development of critical peripheral arterial disease (PAD; those needing angioplasty, bypass grafting, or aneurysm repair) and formulated a risk score by multivariate analyses. A total of 220 patients (2.8%) developed critical PAD over a mean follow-up of 4.7 years. Significant predictors of critical PAD were history of intermittent claudication, smoking, hypertension (HTN), coronary-artery bypass grafting (CABG), diabetes, age, serum cholesterol, and body mass index (BMI). Incident critical PAD was associated with increased composite outcome of cardiovascular death, myocardial infarction, percutaneous transluminal coronary angioplasty, or CABG (hazard ratio 1.82, 95% CI 1.50-2.22, P < .001). Risk assessment using our score may identify CAD patients at risk for critical PAD events.
The importance of indirect costs in primary cardiovascular disease prevention: can we save lives and money with statins?

BACKGROUND The losses in productivity due to cardiovascular disease (CVD) are substantial but rarely considered in health economic analyses. We compared the cost-effectiveness of lipid level modification in the primary prevention of CVD with and without these indirect costs. METHODS We used the Cardiovascular Life Expectancy Model to estimate the long-term benefits and cost-effectiveness of lipid level modification with atorvastatin calcium, including 28% and 38% reductions in total cholesterol and low-density lipoprotein cholesterol levels, respectively, and a 5.5% increase in high-density lipoprotein cholesterol level. The direct costs included all medical care costs associated with CVD. The indirect costs represented the loss of employment income and the decreased value of housekeeping services after different manifestations of CVD. All costs were expressed in 2000 Canadian dollars. RESULTS When only direct medical care costs were considered, the incremental cost-effectiveness ratios for lifelong therapy with atorvastatin calcium, 10 mg/d, were generally positive, ranging from a few thousand to nearly $20 000 per year of life saved. When the societal point of view was adopted and indirect costs were included, the total costs were generally negative, representing substantial cost savings (up to $50 000) and increased life expectancy for most groups of individuals. CONCLUSIONS Lipid therapy with statins can reduce CVD morbidity and mortality as demonstrated in a number of clinical trials. Adding the indirect CVD costs associated with productivity losses at work and home can result in forecasted cost savings to society as a whole such that lipid therapy could potentially save lives and money.
Directly Administered Antiretroviral Therapy for HIV-Infected Drug Users Does Not Have an Impact on Antiretroviral Resistance: Results From a Randomized Controlled Trial

Background:Directly administered antiretroviral therapy (DAART) is an effective intervention that improves clinical outcomes among HIV-infected drug users. Its effects on antiretroviral drug resistance, however, are unknown. Methods:We conducted a community-based, prospective, randomized controlled trial of DAART compared with self-administered therapy (SAT). We performed a modified intention-to-treat analysis among 115 subjects who provided serum samples for HIV genotypic resistance testing at baseline and at follow-up. The main outcomes measures included total genotypic sensitivity score, future drug options, number of new drug resistance mutations (DRMs), and number of new major International AIDS Society (IAS) mutations. Results:The adjusted probability of developing at least 1 new DRM did not differ between the 2 arms (SAT: 0.41 per person-year [PPY], DAART: 0.49 PPY; adjusted relative risk [RR] = 1.04; P = 0.90), nor did the number of new mutations (SAT: 0.76 PPY, DAART: 0.83 PPY; adjusted RR = 0.99; P = 0.99) or the probability of developing new major IAS new drug mutations (SAT: 0.30 PPY, DAART: 0.33 PPY; adjusted RR = 1.12; P = 0.78). On measures of GSS and FDO, the 2 arms also did not differ. Conclusion:In this trial, DAART provided on-treatment virologic benefit for HIV-infected drug users without affecting the rate of development of antiretroviral medication resistance.
Medicaid, hospital financial stress, and the incidence of adverse medical events for children.

OBJECTIVE To assess the association between Medicaid-induced financial stress of a hospital and the probability of an adverse medical event for a pediatric discharge. DATA SOURCES Secondary data from the Nationwide Inpatient Sample, Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project, and the American Hospital Association's Annual Survey of Hospitals. Study examines 985,896 pediatric discharges (children age 0-17), from 1,050 community hospitals in 26 states (representing 63 percent of the U.S. Medicaid population) between 2005 and 2007. STUDY DESIGN We estimate the probability of an adverse event, controlling for patient, hospital, and state characteristics, using an aggregated, composite measure to overcome rarity of individual events. PRINCIPAL FINDINGS Children in hospitals with relatively high proportions of pediatric discharges that are more reliant on Medicaid reimbursement are more likely than children in other hospitals (odds ratio = 1.62) to experience an adverse event. Medicaid pediatric inpatients are more likely than privately insured patients (odds ratio = 1.10) to experience an adverse event. CONCLUSIONS Hospital reliance on comparatively low Medicaid reimbursement may contribute to the problem of adverse medical events for hospitalized children. Policies to reduce adverse events should account for differences in underlying, contributing factors of these events.
On Optimality Conditions for Auto-Encoder Signal Recovery

Auto-Encoders are unsupervised models that aim to learn patterns from observed data by minimizing a reconstruction cost. The useful representations learned are often found to be sparse and distributed. On the other hand, compressed sensing and sparse coding assume a data generating process, where the observed data is generated from some true latent signal source, and try to recover the corresponding signal from measurements. Looking at auto-encoders from this signal recovery perspective enables us to have a more coherent view of these techniques. In this paper, in particular, we show that the true hidden representation can be approximately recovered if the weight matrices are highly incoherent with unit $ \ell^{2} $ row length and the bias vectors takes the value (approximately) equal to the negative of the data mean. The recovery also becomes more and more accurate as the sparsity in hidden signals increases. Additionally, we empirically also demonstrate that auto-encoders are capable of recovering the data generating dictionary when only data samples are given.