Miracle-dz/UniFAR-FTUs huggingface dataset:
FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment.

BACKGROUND High levels of the phosphaturic hormone fibroblast growth factor 23 (FGF-23) predict mortality in haemodialysis patients. The prognostic relevance of increased plasma FGF-23 levels in patients with less advanced chronic kidney disease (CKD) who are not on dialysis therapy is presently unknown. METHODS We measured plasma c-terminal FGF-23 levels in 149 CKD patients not undergoing dialysis treatment. Patients were stratified by their baseline FGF-23 levels (>104 vs ≤ 104 rU/mL) and followed for a period of 4.8 ± 0.9 years. During the follow-up, the pre-specified combined clinical endpoint was the first occurrence of a cardiovascular event, e.g. myocardial infarction, coronary artery angioplasty/stenting/bypass surgery, stroke, carotid endarterectomy/stenting, non-traumatic lower extremity amputation, lower limb artery surgery/angioplasty/stenting or death. RESULTS At baseline, elevated FGF-23 levels >104 rU/mL were associated with more advanced CKD. Traditional cardiovascular risk factors and prevalent cardiovascular disease did not differ between CKD patients with high vs low FGF-23 levels. Fifty patients experienced a cardiovascular event during follow-up. Compared with CKD patients with FGF-23 ≤104 rU/mL, CKD patients with FGF-23 levels above the cut-off had worse event-free survival at univariate (log-rank test P = 0.012) and multivariate analysis [hazard ratio 2.49 (95% CI 1.40-4.39); P = 0.002]. CONCLUSIONS Elevated FGF-23 plasma levels predict cardiovascular events in CKD patients not on dialysis therapy. This finding complements two recent cohort studies in which incident and prevalent haemodialysis patients with highest FGF-23 levels had worst survival. Lowering FGF-23 levels (e.g. by oral phosphate binder medication) could emerge as a promising new therapeutic option to reduce cardiovascular morbidity in CKD patients.
An assessment of institutional influences on corporate governance in Nigeria : a multi-stakeholder perspective

Purpose: This study aims to achieve two objectives. First, to explore the main concerns of corporate governance stakeholders in Nigeria, focusing on three broad fields of institutionalisation: political, social and economic. Second, to examine the coverage accorded to the main institutional influences in the primary code of corporate governance in Nigeria. Design/methodology/approach: Employing an intrepretivist research philosophy, the study adopts a qualitative research strategy. Data was collected using semi-structured, face-to-face interviews from three groups of stakeholders (executives, regulators and corporate governance consultants). Their responses and views were analysed using a qualitative content analysis (QCA) technique. Findings: In highlighting the main institutional elements driving corporate governance in Nigeria, this study revealed that individuals wield the power to influence existing institutions in developing countries. This contradicts the position in developed economies where the robustness of institutional frameworks acts as a constraint on the behaviour of economic agents. This thesis also show that the recognition accorded to the main institutional frames in the primary code of corporate governance is inadequate. Based on these findings, a bottom-up approach to corporate governance is proposed where the concerns of economic agents are prioritised, as a strategy for building sustainable institutional frameworks. Originality/value: The study reinforced the need to re-examine the basis of agency and institutional theories in the context of developing economies. The study also made a case for the re-evaluation of the significance of executives in agency theory literature regarding developing economies, relying on the level of economic sophistication and the general lack of knowledge by shareholders with respect to their rights. This observation will enrich the scholarship on agency and institutional theories as this study draws attention to alternative strategies for understanding agency (human institutionalism) and institutional (bottom-up approach) theories.
Use of 11C-MPDX and PET to Study Adenosine A1 Receptor Occupancy by Nonradioactive Agonists and Antagonists

Adenosine A1 receptors (A1Rs) in human and rodent brains can be visualized with the radioligand 8-dicyclopropylmethyl-1-11C-methyl-3-propylxanthine (11C-MPDX) and PET. Here we investigated whether A1R occupancy by nonradioactive agonists and antagonists can be assessed with this technique. Methods: Small-animal PET scans with arterial blood sampling were obtained for 4 groups of isoflurane-anesthetized Wistar rats: controls (n = 7); pretreated with a centrally active A1R agonist, N6-cyclopentyladenosine (CPA; 0.25 mg/kg intraperitoneally; dissociation constant, 0.48 nM; n = 7); pretreated with a moderate dose of caffeine (antagonist for A1Rs and adenosine A2A receptors; 4 mg/kg intraperitoneally; dissociation constant, 11 μM; n = 6); and pretreated with a high dose of caffeine (40 mg/kg intraperitoneally; n = 6). Results: The administration of CPA resulted in a strong reduction (>50%) in the heart rate, and caffeine administration resulted in a small increase (10%–15%). A caffeine dose of 4 mg/kg (n = 6) resulted in 65.9% A1R occupancy, and a dose of 40 mg/kg (n = 6) resulted in 98.5% occupancy (calculated from a modified Lassen plot). However, the administration of CPA resulted in an increase in 11C-MPDX binding in the brain. Conclusion: Small-animal PET with 11C-MPDX can be used to assess antagonist but not agonist binding at A1Rs. Changes in tracer uptake after the administration of CPA resembled previously reported changes induced by treatment of rats with ethanol and an adenosine kinase inhibitor (ABT702). Thus, the administration of an exogenous agonist or increasing the level of an endogenous agonist have similar effects. Agonists and antagonists may bind to different sites on the A1R protein having allosteric interactions.
Anoxic Fibroblasts Activate a Replication Checkpoint That Is Bypassed By E1a

ABSTRACT Little is known about cell cycle regulation in hypoxic cells, despite its significance. We utilized an experimentally tractable model to study the proliferative responses of rat fibroblasts when rendered hypoxic (0.5% oxygen) or anoxic (<0.01% oxygen). Hypoxic cells underwent G1 arrest, whereas anoxic cells also demonstrated S-phase arrest due to suppression of DNA initiation. Upon reoxygenation, only those cells arrested in G1 were able to resume proliferation. The oncoprotein E1a induced p53-independent apoptosis in anoxic cells, which when suppressed by Bcl-2 permitted proliferation despite anoxia. E1a expression led to marked increases in the transcription factor E2F, and overexpression of E2F-1 allowed proliferation in hypoxic cells, although it had minimal effect on the anoxic suppression of DNA initiation. We thus demonstrate two distinct cell cycle responses to low oxygen and suggest that alterations that lead to increased E2F can overcome hypoxic G1 arrest but that additional alterations, promoted by E1a expression, are necessary for neoplastic cells to proliferate despite anoxia.
Development of an accuracy assessment phantom for surgical navigators

The objective of this study was to design a calibration phantom for a surgical navigator used in a hospital environment. It addresses two major issues: the design of an accuracy phantom and the accuracy analysis of the surgical navigator in a hospital setting. The designed phantom was used to assess the accuracy of the optical tracking modality of the surgical navigator used at Oulu University Hospital, Oulu, Finland. The phantom functioned according to the design criteria, it was easy to use and it had enough calibration points that were localized by the navigator according to the accuracy assessment protocol to assess the accuracy error. The distances measured from a fixed origin with the surgical navigator were compared to the known phantom calibration point coordinates. The mean error was within the manufacturer specifications of 1.00 mm. The analysis done using the designed phantom and accuracy assessment protocol showed that the error increased with the distance from the center of the phantom. The accuracy assessment protocol using the present phantom proved to be a suitable method for accuracy analysis of a surgical navigator in a hospital setting.
Neuroanatomical correlates of tube dependency and impaired oral intake after hemispheric stroke

Acute stroke patients with severely impaired oral intake are at risk of malnutrition and dehydration. Rapid identification of these patients is necessary to establish early enteral tube feeding. Whether specific lesion location predicts early tube dependency was analysed, and the neural correlates of impaired oral intake after hemispheric ischaemic stroke were assessed.
Effect of soil sorption and aquatic natural organic matter on the antibacterial activity of a fullerene water suspension

The present study investigated the association of a C60 water suspension (nC60) with natural organic matter, present as a soil constituent or dissolved in the water column, and its effect on the antibacterial activity of nC60. Sorption of nC60 to soil reduced its bioavailability and antibacterial activity, and the sorption capacity strongly depended on the organic content of the soil. Adsorption of aquatic dissolved humic substances onto nC60 and possible subsequent reactions also were found to eliminate nC60 toxicity at humic acid concentrations as low as 0.05 mg/L. These findings indicate that natural organic matter in the environment can mitigate significantly the potential impacts of nC60 on microbial activities that are important to ecosystem health.
Aiming Low and Achieving It: A Long-Term Equilibrium Analysis of a Renewable Policy in Chile

We develop a long-term equilibrium model of electricity and renewable energy certificate (REC) markets to assess the costs of meeting a 70% renewables target by 2050 in Chile. We consider different scenarios of demand growth, resource eligibility (i.e., large hydropower), and transmission system configuration. Our numerical results indicate that the sole characteristics of the available renewable resources in the country and reductions in technology costs will provide sufficient economic incentives for private investors to supply a fraction of renewables larger than 70% for a broad range of scenarios, meaning that the proposed target will likely remain a symbolic government effort. Increasing transmission capacity between the northern and central interconnected systems could reduce total system cost by $400 Million per year and increase the equilibrium share of nonconventional renewable energy (NCRE) in the system from 45% to 52%, without the need for any additional policy incentive. Surprisingly, imposing a 70% of NCRE by 2050 results in a REC price lower than the noncompliance fine used for the current target of 20% of NCRE by 2025, the latter of which represents the country’s maximum willingness to pay for the attributes of electricity supplied from NCRE resources.
Examining the Socialization of Physical Education Teachers: A Case Study.

In the last thirty years childhood obesity and inactivity rates in the United States have increased at alarming rates (Ogden, Carroll, Kit, & Flegal, 2014). In response to this, physical education curriculum is shifting to focus more on health promotion rather than competitive team sports and game play. This focus is reflected in the recently revised K-12 physical education national content standards and learning outcomes and is impacting how colleges are preparing future teachers (SHAPE America (Organization), Couturier, Chepko, & Holt/Hale, 2014). Changing how physical education is taught can be challenging for teacher educators, in part due to the fact that students’ deeply held beliefs about the purposes of physical education are often based on years of experience in traditional, PK-12, sports-based physical education programs (Placek et al., 1995). The purpose of this study was to explore how teacher candidates and recent graduates experience the process of occupational socialization into their profession as physical education teachers. Utilizing occupational socialization theory, this study examined factors that impacted participants’ teaching perspectives and explored the beliefs they held about the goals and purposes of PK-12 physical education. The adoption of the national physical education standards by the Vermont Agency of Education, along with recent legislation (Act 77) that is changing the way schools prepare PK-12 students for college and careers, make the Vermont context a rich setting. This phenomenological case study was set within a small public university located in Vermont in the United States during the summer and fall of 2016. The units of analysis included five freshman year physical education candidates, five junior year physical education candidates, and five recent graduates, also from the same institution, who were employed as Vermont physical education teachers. Three secondary participants included a Vermont principal and two physical education teacher education faculty members. Data collection methods included eighteen semi-structured interviews and document review of course syllabi and student assessments. Findings suggested that participants: 1) enter the field with teaching orientations rather than coaching orientations, 2) believe that the purpose of physical education is lifelong health and wellness, 3) develop innovative teaching perspectives during teacher education that persist into teaching careers, and 4) identify as agents of change in the field of physical education. Understanding how students are socialized into careers as physical education teachers may inform the decision-making for physical education teacher education faculty and PK-12 physical education teachers.
Structural Requirements for Sterol Regulatory Element-binding Protein (SREBP) Cleavage in Fission Yeast*

Background: Yeast sterol regulatory element-binding proteins (SREBPs) are proteolytically activated by a mechanism distinct from that of mammals. Results: Site-directed mutagenesis studies define structural requirements for yeast SREBP cleavage. Conclusion: Yeast SREBP cleavage requires a novel conserved glycine-leucine motif. Significance: Understanding SREBP structural requirements aids mechanistic dissection of SREBP cleavage essential for fungal pathogenesis. Sterol regulatory element-binding proteins (SREBPs) are central regulators of cellular lipid synthesis and homeostasis. Mammalian SREBPs are proteolytically activated and liberated from the membrane by Golgi Site-1 and Site-2 proteases. Fission yeast SREBPs, Sre1 and Sre2, employ a different mechanism that genetically requires the Golgi Dsc E3 ligase complex for cleavage activation. Here, we established Sre2 as a model to define structural requirements for SREBP cleavage. We showed that Sre2 cleavage does not require the N-terminal basic helix-loop-helix zipper transcription factor domain, thus separating cleavage of Sre2 from its transcription factor function. From a mutagenesis screen of 94 C-terminal residues of Sre2, we isolated 15 residues required for cleavage and further identified a glycine-leucine sequence required for Sre2 cleavage. Importantly, the glycine-leucine sequence is located at a conserved distance before the first transmembrane segment of both Sre1 and Sre2 and cleavage occurs in between this sequence and the membrane. Bioinformatic analysis revealed a broad conservation of this novel glycine-leucine motif in SREBP homologs of ascomycete fungi, including the opportunistic human pathogen Aspergillus fumigatus where SREBP is required for virulence. Consistent with this, the sequence was also required for cleavage of the oxygen-responsive transcription factor Sre1 and adaptation to hypoxia, demonstrating functional conservation of this cleavage recognition motif. These cleavage mutants will aid identification of the fungal SREBP protease and facilitate functional dissection of the Dsc E3 ligase required for SREBP activation and fungal pathogenesis.
Involvement of Clostridium botulinum ATCC 3502 Sigma Factor K in Early-Stage Sporulation

ABSTRACT A key survival mechanism of Clostridium botulinum, the notorious neurotoxic food pathogen, is the ability to form heat-resistant spores. While the genetic mechanisms of sporulation are well understood in the model organism Bacillus subtilis, nothing is known about these mechanisms in C. botulinum. Using the ClosTron gene-knockout tool, sigK, encoding late-stage (stage IV) sporulation sigma factor K in B. subtilis, was disrupted in C. botulinum ATCC 3502 to produce two different mutants with distinct insertion sites and orientations. Both mutants were unable to form spores, and their elongated cell morphology suggested that the sporulation pathway was blocked at an early stage. In contrast, sigK-complemented mutants sporulated successfully. Quantitative real-time PCR analysis of sigK in the parent strain revealed expression at the late log growth phase in the parent strain. Analysis of spo0A, encoding the sporulation master switch, in the sigK mutant and the parent showed significantly reduced relative levels of spo0A expression in the sigK mutant compared to the parent strain. Similarly, sigF showed significantly lower relative transcription levels in the sigK mutant than the parent strain, suggesting that the sporulation pathway was blocked in the sigK mutant at an early stage. We conclude that σK is essential for early-stage sporulation in C. botulinum ATCC 3502, rather than being involved in late-stage sporulation, as reported for the sporulation model organism B. subtilis. Understanding the sporulation mechanism of C. botulinum provides keys to control the public health risks that the spores of this dangerous pathogen cause through foods.
Translation-priming effects on tip-of-the-tongue states

Bilinguals experience more tip-of-the-tongue (TOT) states than monolinguals, but it is not known if this is caused in part dual-language activation (i.e., co-activation of representations from the bilinguals' two languages). In two translation-priming experiments, bilinguals were given three Spanish primes and produced either semantically- (Experiment 1) or phonologically-related Spanish words (Experiment 2) to each. They then named a picture in English. On critical trials, one of the primes was the Spanish translation of the English picture name. Translation primes significantly increased TOTs regardless of task, and also speeded correct retrievals but only with the semantic task. In both experiments translation-primed TOTs were significantly more likely to resolve spontaneously. These results illustrate an effect of non-dominant language activation on dominant-language retrieval, as well as imply that TOTs can arise during (not after) lexical retrieval, at a level of processing where translation equivalent lexical representations normally interact (possibly competing for selection, or mutually activating each other, or both depending on the locus of retrieval failure).
Establishment of Joint Attention in Dyads Involving Hearing Mothers of Deaf and Hearing Children, and Its Relation to Adaptive Social Behavior

Mounting evidence points to joint attention as a mediating variable in children's adaptive behavior development. Joint attention in interactions between hearing mothers and congenitally deaf (n = 27) and hearing (n = 29) children, ages 18–36 months, was examined. All deaf children had severe to profound hearing loss. Mother-child interactions were coded for maternally initiated and child-initiated success rates in establishing joint attention; mothers completed ratings of their children's adaptive behavior. Hearing mother–deaf child dyads had significantly lower maternally initiated success rates. No significant between-group differences on child-initiated success rates were shown. Maternal ratings of adaptive behavior were significantly lower for deaf children, and related positively and significantly to both child-initiated and maternally initiated success rates. The findings suggest that mother-child interactions that are low in successful establishment of joint attention might mediate the development of socioemotional problems evident in deaf children with hearing families.
Chordoma: A Clinicopathologic and Prognostic Study of a Swedish National Series

Chordoma is a rare tumor with slow growth developing from remnants of the notochord and thus appears in close relation to the axial skeleton. A Swedish national series collected over a period of 13 years, comprising 51 patients with a follow-up time of 8–20 years, was studied. Histologically all tumors had a typical appearance except two, which had the characteristics of “chondroid chordoma”. Fifty-seven per cent of the tumors were located in the sacrococcygeal region, 27 per cent in the spheno-occipital region and 16 per cent in the vertebrae. The peak age incidence was in the 6th and 7th decades. Male: female ratio was 1:1. The main symptoms were pain and neurologic disturbances. Skeletal destruction was noted radiographically in most instances. Intratumoral calcifications were rarely seen. The treatment was surgery, radiotherapy or a combination of these. There was only one long-term survivor without evidence of disease, a patient operated on for cervical chordoma 14 years earlier. Six other patients l.
Adaptive neural control of nonlinear time-delay systems with unknown virtual control coefficients

In this paper, adaptive neural control is presented for a class of strict-feedback nonlinear systems with unknown time delays. The proposed design method does not require a priori knowledge of the signs of the unknown virtual control coefficients. The unknown time delays are compensated for using appropriate Lyapunov-Krasovskii functionals in the design. It is proved that the proposed backstepping design method is able to guarantee semi-global uniformly ultimately boundedness of all the signals in the closed-loop. In addition, the output of the system is proven to converge to a small neighborhood of the origin. Simulation results are provided to show the effectiveness of the proposed approach.
A massive transfusion protocol to decrease blood component use and costs.

HYPOTHESIS A massive transfusion protocol (MTP) decreases the use of blood components, as well as turnaround times, costs, and mortality. DESIGN Retrospective before-and-after cohort study. SETTING Academic level I urban trauma center. PATIENTS AND METHODS Blood component use was compared in 132 patients during a 2-year period following the implementation of an MTP; 46 patients who were treated the previous year served as historical control subjects. INTERVENTION Introduction of an MTP that included recombinant factor VIIa for patients with exsanguinating hemorrhage. MAIN OUTCOME MEASURES The amount of each blood component transfused, turnaround times, blood bank and hospital charges, and mortality rates. RESULTS After introduction of the MTP, there was a significant decrease in packed red blood cells, plasma, and platelet use. The turnaround time for the first shipment was less than 10 minutes, and the time between the first and second shipments was reduced from 42 to 18 minutes, compared with historical controls. The decreased use of blood products represented a savings of $2270 per patient or an annual savings of $200, 000, despite increased costs for recombinant factor VIIa. There was no difference in mortality in either group; it remained around 50%. Thromboembolic complications did not increase, despite a significant increase in the use of recombinant factor VIIa. CONCLUSIONS The MTP resulted in a reduction in the use of blood components with improved turnaround times and significant savings. Mortality was unaffected. The use of recombinant factor VIIa did not increase thromboembolic complications in these patients.