Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictive value of urine interleukin-18 in the evolution and outcome of acute kidney injury in critically ill adult patients.

BACKGROUND Interleukin-18 (IL-18) is a pro-inflammatory protein, which mediates ischaemic tubular injury, and has been suggested to be a sensitive and specific biomarker for acute kidney injury (AKI). The predictive value of IL-18 in the diagnosis, evolution, and outcome of AKI in critically ill patients is still unclear. METHODS We measured urine IL-18 from critically ill patients at intensive care unit (ICU) admission and 24 h. We evaluated the association of IL-18 with developing new AKI, renal replacement therapy (RRT), and 90-day mortality. We calculated areas under receiver operating characteristics curves (AUCs), best cut-off values, and positive likelihood ratios (LR+) for IL-18 concerning these endpoints. Additionally, we compared the predictive value of IL-18 at ICU admission to that of urine neutrophil gelatinase-associated lipocalin (NGAL). RESULTS In this study population of 1439 patients the highest urine IL-18 during the first 24 h in the ICU associated with the development of AKI with an AUC [95% confidence interval (CI)] of 0.586 (0.546-0.627) and with the development of Stage 3 AKI with an AUC (95% CI) of 0.667 (0.591-0.774). IL-18 predicted the initiation of RRT with an AUC (95% CI) of 0.655 (0.572-0.739), and 90-day mortality with an AUC (95% CI) of 0.536 (0.497-0.574). CONCLUSIONS IL-18 had poor-to-moderate ability to predict AKI, RRT, or 90-day mortality in this large cohort of critically ill patients. Thus, it should be used with caution for diagnostic or predictive purposes in the critically ill.
Cation binding and conformational changes in VILIP and NCS-1, two neuron-specific calcium-binding proteins.

VILIP and NCS-1, neural-specific, 22-kDa Ca(2+)-binding proteins possessing four EF-hands, were expressed in Escherichia coli to study their divalent cation properties. Flow dialysis (Ca2+ binding) and equilibrium gel filtration (Mg2+ binding) revealed that both recombinant proteins possess only two active metal-binding sites, which can accommodate either Ca2+ or Mg2+. VILIP binds cations without cooperativity with intrinsic affinity constants K'Ca of 1.0 x 10(6) M-1 and K'Mg of 4.8 x 10(3) M-1.Mg2+ antagonizes Ca2+ binding by shifting the isotherms to higher free Ca2+ concentrations without changing their shape. The competition equation yields a K'Mg, comp value of 180 M-1 for both sites. NCS-1 binds two Mg2+ without cooperativity with K'Mg of 8.3 x 10(4) M-1 and two Ca2+ with very strong positive cooperativity (nH = 1.96). In the absence of Mg2+ the K'Ca1 and K'Ca2 values are 8.9 x 10(4) and 1.4 x 10(8) M-1, respectively, which represent an allosteric increase of 1600-fold. Mg2+ shifts the Ca(2+)-binding isotherms to higher Ca2+ concentrations, yielding a K'Mg, comp value of 800 M-1 for both sites. Thus VILIP and NCS-1 show three remarkable differences in the Ca2+/Mg2+ binding parameters: 1) VILIP binds Ca2+ with much lower affinity than NCS-1; 2) VILIP binds Ca2+ in a noncooperative way, whereas NCS-1 shows maximal positive cooperativity; 3) in VILIP the Mg2+/Ca2+ antagonism is much weaker than in NCS-1. Conformational changes monitored by Trp fluorescence indicate that the metal-free forms already are highly structured. Ca2+ binding promotes a 20-30% increase of fluorescence in both proteins, but whereas the Mg2+ form of VILIP has the same fluorescence properties as the metal-free form, Mg(2+)-saturated NCS-1 has those of the Ca2+ form. Near UV difference spectra confirmed that in VILIP the Mg2+ form is very similar to the metal-free form; in NCS-1 it is different, especially in the Tyr region. NCS-1 possesses one unique Cys-38 in EF-hand site I. Its reactivity (kSH) toward 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) is the same for the Ca(2+)- and Mg(2+)-loaded protein, but kSH is 4-fold higher in metal-free NCS-1. VILIP possesses two additional thiols, one of which is inaccessible to DTNB in the native protein. The reactivity of the two accessible thiols is identical in the metal-free and Mg2+ forms and 5-fold higher than in the Ca2+ form. (ABSTRACT TRUNCATED AT 400 WORDS)
H∞ model reduction for positive systems

This paper is concerned with the model reduction of positive systems. For a given stable positive system, our attention is focused on the construction of a reduced-order model in such a way that the positivity of the original system is preserved and the error system is stable with a prescribed H∞ performance. Based upon a system augmentation approach, a novel characterization on the stability with H∞ performance of the error system is first obtained in terms of linear matrix inequality (LMI). Then, a necessary and sufficient condition for the existence of a desired reduced-order model is derived accordingly. A significance of the proposed approach is that the reduced-order system matrices can be parametrized by a positive definite matrix with flexible structure, which is fully independent of the Lyapunov matrix; thus, the positivity constraint on the reduced-order system can be readily embedded in the model reduction problem. Finally, a numerical example is provided to show the effectiveness of the proposed techniques.
MGMT promoter hypermethylation in a series of 104 glioblastomas.

AIM To evaluate MGMT promoter hypermethylation as prognostic factor in a retrospective study of 104 cases of glioblastoma multiforme (GBM). MATERIALS AND METHODS The O(6)-methylguanine-DNA methyltransferase (MGMT) status was evaluated by methylation-specific PCR (MSP), immunohistochemistry and Western blotting analysis in formalin-fixed paraffin-embedded surgical samples. RESULTS The MGMT gene was found to be methylated in 29 of 101 tumors (28.7%) by MSP, according to the evaluation methods employed. By immunohistochemistry, different categories were identified on the basis of reaction intensity, percentage of positive cells and homogeneous or heterogeneous distribution. MSP did not correlate with immunohistochemistry, with the exception of the category with the highest percentage of positive cells and homogeneity of immunostaining. Western blotting analysis correlated with immunohistochemical findings (Pearson's correlation coefficient r=0.268, p=0.0211), but not with MSP. By Kaplan-Meier survival analysis, radiotherapy was a significant prognostic factor (p=0.0001). When uncensored patients alone were considered, MGMT methylation status showed a significant correlation with survival (p=0.026). Temozolomide therapy correlated with survival (p=0.022), but not with MGMT methylation. After multivariate Cox regression analysis, only radiotherapy remained as an independent prognostic factor (p=0.0001). CONCLUSION Correlation was inconclusive among MSP, immunohistochemistry and Western blotting analysis, despite the sophisticated score system for the immunohistochemical quantitative evaluation. MGMT expression is a complex event in which many factors beside epigenetic silencing are implicated.
Antigenic and molecular analysis of influenza A (H3N2) virus strains isolated from a localised influenza outbreak in South Africa in 2003

A severe acute institutional influenza outbreak occurred in a police residential college in Pretoria amongst new recruits and staff members at the end of May 2003. The outbreak was characterised by marked illness which affected a total of 648 students, 26 of whom were admitted to hospital. Symptoms included pyrexia, severe headache, and myalgia. The attack rate per dormitory building ranged from 20 to 47%, with an overall attack rate of 34%. Throat swabs and bronchoalveolar lavage specimens were sent to the National Institute for Communicable Diseases (NICD) from 20 patients. All were positive for influenza A by multiplex PCR and/or indirect immunofluorescence, and were further identified as subtype H3N2. Additional specimens from sporadic influenza cases in Johannesburg and surrounding areas were collected through the NICD active viral surveillance programme for respiratory viral testing and were also positive for influenza A H3N2 viruses. Viruses isolated from patients from both the institutional outbreak as well as from sporadic cases were analysed both antigenically and at the molecular level to determine the characteristics of the influenza strain responsible for the epidemic. The results showed clearly that the outbreak was caused by the introduction in 2003 into South Africa of the novel A/Fujian/411/02‐like H3N2 influenza strain, which is antigenically distinct from the A/Panama/2007/99 vaccine strain. The rapid spread of these variant viruses to the southern hemisphere indicates that the H3N2 component of the influenza vaccine needs to be updated for the 2004 southern hemisphere winter. J. Med. Virol. 73:71–78, 2004. © 2004 Wiley‐Liss, Inc.
Human papillomavirus 16 load in normal and abnormal cervical scrapes: An indicator of CIN II/III and viral clearance

The relation between human papillomavirus type 16 (HPV 16) viral load in cervical scrapes and development of high‐grade cervical intraepithelial neoplasia (CIN II or III) was studied in a nested case‐control study of women with normal cytology (group A) and in a cohort of women with abnormal cytology (group B). HPV 16 DNA load was determined using a quantitative real‐time PCR assay. In group A, case women (women with CIN II/III, n = 12) had a significantly higher viral load than control women (women with CIN ≤ I, n = 47). This resulted in an increased relative risk of women with the 50% highest viral load for development of CIN II/III (OR 7.7; CI 1.6–33). In group B, women with CIN II/III (n = 38) had a significantly higher viral load than women with CIN ≤ I (n = 25). Women with the 50% highest viral load had an increased relative risk of CIN II/III (OR 3.2; CI 1.1–9.3) and a decreased chance of both viral clearance and cytologic regression. Our data suggest that in women with normal cytology an increased HPV 16 load confers an increased risk of developing a CIN lesion. A sustained high viral load is subsequently informative for progression to a high‐grade CIN lesion. © 2002 Wiley‐Liss, Inc.
Partial Agonism of Taprostene at Prostanoid IP Receptors in Vascular Preparations from Guinea-Pig, Rat, and Mouse

This study investigates whether incomplete relaxation of vascular smooth muscle preparations induced by the prostacyclin analogue taprostene is due to partial agonism at prostanoid IP receptors. In the presence of the prostanoid EP4 receptor antagonist AH 23848, 3 μM taprostene induced 45% relaxation of phenylephrine-contracted guinea-pig saphenous vein rings and displaced log concentration-response curves for the prostacyclin analogues AFP-07, TEI-9063, and cicaprost to the right, parallel to their predicted addition curves. In contrast, taprostene interacted additively with prostaglandin E2 (PGE2), ONO-AE1-259 (selective EP2 agonist), and acetylcholine. Similarly, on rat tail artery contracted with phenylephrine, 3 μM taprostene (20% relaxation) opposed AFP-07– but not PGE2–induced relaxation. However, under U-46619-induced tone (AH 23848 absent), taprostene antagonized AFP-07 and cicaprost more than TEI-9063, suggesting that the latter has more than one relaxation mechanism. The presence of a sensitive EP3 contractile system in mouse aorta interfered with IP receptor-mediated relaxation. By generating tone with phenylephrine and the potent EP3 agonist sulprostone, it was possible to show that 3 μM taprostene (15% relaxation) selectively opposed relaxations induced by AFP-07, TEI-9063, and cicaprost. Our experiments indicate that taprostene is a partial agonist at prostanoid IP receptors, and may be a lead to an IP receptor antagonist.
A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease. North American Crohn's Study Group Investigators.

BACKGROUND Patients with Crohn's disease often have relapses. Better treatments are needed for the maintenance of remission. Although methotrexate is an effective short-term treatment for Crohn's disease, its role in maintaining remissions is not known. METHODS We conducted a double-blind, placebo-controlled, multicenter study of patients with chronically active Crohn's disease who had entered remission after 16 to 24 weeks of treatment with 25 mg of methotrexate given intramuscularly once weekly. Patients were randomly assigned to receive either methotrexate at a dose of 15 mg intramuscularly once weekly or placebo for 40 weeks. No other treatments for Crohn's disease were permitted. We compared the efficacy of treatment by analyzing the proportion of patients who remained in remission at week 40. Remission was defined as a score of 150 or less on the Crohn's Disease Activity Index. RESULTS Forty patients received methotrexate, and 36 received placebo. At week 40, 26 patients (65 percent) were in remission in the methotrexate group, as compared with 14 (39 percent) in the placebo group (P=0.04; absolute reduction in the risk of relapse, 26.1 percent; 95 percent confidence interval, 4.4 percent to 47.8 percent). Fewer patients in the methotrexate group than in the placebo group required prednisone for relapse (11 of 40 [28 percent] vs. 21 of 36 [58 percent], P=0.01). None of the patients who received methotrexate had a severe adverse event; one patient in this group withdrew because of nausea. CONCLUSIONS In patients with Crohn's disease who enter remission after treatment with methotrexate, a low dose of methotrexate maintains remission.
Increased Alcohol Use in a Treatment Sample of Oklahoma City Bombing Victims

Abstract Research examining alcohol use in disaster victims has yielded conflicting results. This study of 43 acknowledged alcohol users, taken from a nonrandom volunteer sample of Oklahoma City bombing victims receiving support services, revealed relationships between increased alcohol use and a number of variables—injury, retrospectively reported initial reaction to the explosion, grief, and posttraumatic stress symptomatology. The findings suggest that if alcohol use was motivated by an attempt to alleviate symptoms, it was not effective, as evidenced by an association between increased alcohol use and functional impairment. Increased alcohol consumption may present a problem in disaster victims months after exposure to trauma. Therefore, the use of alcohol should be routinely assessed in those who remain symptomatic over time.
Causal precedent relations among messages in object-based systems

Distributed applications are realized by cooperation of a group of multiple objects. In the group cooperation, a message is multicast and multiple kinds of messages are in parallel sent to multiple destinations. The object waits for multiple messages in conjunctive and disjunctive ways from multiple objects. We newly define a novel precedent relation of messages exchanged among objects in presence of multicast and parallel-cast and conjunctive-receipt and disjunctive-receipt of messages.
Signal Peptide and Helical Bundle Domains of Virulent Canine Distemper Virus Fusion Protein Restrict Fusogenicity

ABSTRACT Persistence in canine distemper virus (CDV) infection is correlated with very limited cell-cell fusion and lack of cytolysis induced by the neurovirulent A75/17-CDV compared to that of the cytolytic Onderstepoort vaccine strain. We have previously shown that this difference was at least in part due to the amino acid sequence of the fusion (F) protein (P. Plattet, J. P. Rivals, B. Zuber, J. M. Brunner, A. Zurbriggen, and R. Wittek, Virology 337:312-326, 2005). Here, we investigated the molecular mechanisms of the neurovirulent CDV F protein underlying limited membrane fusion activity. By exchanging the signal peptide between both F CDV strains or replacing it with an exogenous signal peptide, we demonstrated that this domain controlled intracellular and consequently cell surface protein expression, thus indirectly modulating fusogenicity. In addition, by serially passaging a poorly fusogenic virus and selecting a syncytium-forming variant, we identified the mutation L372W as being responsible for this change of phenotype. Intriguingly, residue L372 potentially is located in the helical bundle domain of the F1 subunit. We showed that this mutation drastically increased fusion activity of F proteins of both CDV strains in a signal peptide-independent manner. Due to its unique structure even among morbilliviruses, our findings with respect to the signal peptide are likely to be specifically relevant to CDV, whereas the results related to the helical bundle add new insights to our growing understanding of this class of F proteins. We conclude that different mechanisms involving multiple domains of the neurovirulent A75/17-CDV F protein act in concert to limit fusion activity, preventing lysis of infected cells, which ultimately may favor viral persistence.
Six degree-of-freedom analysis of hip, knee, ankle and foot provides updated understanding of biomechanical work during human walking

ABSTRACT Measuring biomechanical work performed by humans and other animals is critical for understanding muscle–tendon function, joint-specific contributions and energy-saving mechanisms during locomotion. Inverse dynamics is often employed to estimate joint-level contributions, and deformable body estimates can be used to study work performed by the foot. We recently discovered that these commonly used experimental estimates fail to explain whole-body energy changes observed during human walking. By re-analyzing previously published data, we found that about 25% (8 J) of total positive energy changes of/about the body's center-of-mass and >30% of the energy changes during the Push-off phase of walking were not explained by conventional joint- and segment-level work estimates, exposing a gap in our fundamental understanding of work production during gait. Here, we present a novel Energy-Accounting analysis that integrates various empirical measures of work and energy to elucidate the source of unexplained biomechanical work. We discovered that by extending conventional 3 degree-of-freedom (DOF) inverse dynamics (estimating rotational work about joints) to 6DOF (rotational and translational) analysis of the hip, knee, ankle and foot, we could fully explain the missing positive work. This revealed that Push-off work performed about the hip may be >50% greater than conventionally estimated (9.3 versus 6.0 J, P=0.0002, at 1.4 m s−1). Our findings demonstrate that 6DOF analysis (of hip–knee–ankle–foot) better captures energy changes of the body than more conventional 3DOF estimates. These findings refine our fundamental understanding of how work is distributed within the body, which has implications for assistive technology, biomechanical simulations and potentially clinical treatment. Highlighted article: Six degree-of-freedom (6DOF) analysis of hip–knee–ankle–foot better captures energy changes of the body during gait than conventional 3DOF joint work estimates, revealing increased work contributions from the hip.
Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures

The retinal and cerebral microvasculatures share many morphological and physiological properties. Assessment of the cerebral microvasculature requires highly specialized and expensive techniques. The potential for using non‐invasive clinical assessment of the retinal microvasculature as a marker of the state of the cerebrovasculature offers clear advantages, owing to the ease with which the retinal vasculature can be directly visualized in vivo and photographed due to its essential two‐dimensional nature. The use of retinal digital image analysis is becoming increasingly common, and offers new techniques to analyse different aspects of retinal vascular topography, including retinal vascular widths, geometrical attributes at vessel bifurcations and vessel tracking. Being predominantly automated and objective, these techniques offer an exciting opportunity to study the potential to identify retinal microvascular abnormalities as markers of cerebrovascular pathology. In this review, we describe the anatomical and physiological homology between the retinal and cerebral microvasculatures. We review the evidence that retinal microvascular changes occur in cerebrovascular disease and review current retinal image analysis tools that may allow us to use different aspects of the retinal microvasculature as potential markers for the state of the cerebral microvasculature.
Elimination of the enhanced Simon effect for older adults in a three-choice situation: Ageing and the Simon effect in a go/no-go Simon task

In a Simon task, participants show better performance when the irrelevant stimulus location corresponds with the response location than when it does not, and this effect is typically greater for older adults than for younger adults. To study the effect of cognitive ageing in the Simon task, we compared young and old adults using two versions of the Simon task: (a) a standard visual Simon task, for which participants respond with left and right key-presses to the red and green colours of stimuli presented in left and right locations; (b) a go/no-go version of the Simon task, which was basically the same, except that the shape of the stimulus in one third of the trials indicates that no response is to be made. In both tasks, both age groups showed the Simon effect. The magnitude of the effect for the standard Simon task was greater for the older adults than for the younger adults. Nevertheless, the two groups showed an equivalent Simon effect in the go/no-go version of the Simon task. Reaction time distribution analyses revealed basically similar functions for both age groups: a decreasing pattern of the Simon effect in the standard task and an increasing pattern of the effect in the go/no-go version of the task. The results suggest that older adults find it more difficult to suppress an automatic activation of the corresponding response, though this automatic activation was reduced in situations where the response was frequently inhibited.
Smoking during consecutive pregnancies among primiparous women in the population-based Norwegian Mother and Child Cohort Study.

INTRODUCTION This study investigated changes in smoking behavior across pregnancies in a sample of 10,890 primiparous women participating in the prospective population-based Norwegian Mother and Child Cohort Study (MoBa) in order to identify risk factors that may inhibit smoking cessation and promote smoking during a woman's second pregnancy. METHODS Registry information regarding smoking, age, marital status, parity, and year of birth was applied, in addition to questionnaire assessments of own and partner's smoking behavior, educational attainment, and symptoms of anxiety and depression at weeks 17 and 30 of gestation from both pregnancies. RESULTS The vast majority did not smoke in either of the pregnancies, and more women quit smoking than relapsed to smoking in their second pregnancy. Among smokers in the first pregnancy, 30.9% quit smoking by their second pregnancy. Women living with a nonsmoking partner or a partner who quit between pregnancies were more likely to quit smoking, as were women smoking occasionally in their first pregnancy. Symptoms of psychological distress and increasing number of years between pregnancies were negatively associated with smoking cessation. Among women not smoking in their first pregnancy, 2.3% did smoke during their second. Living with a smoking partner, low educational attainment, symptoms of psychological distress, and increasing number of years between pregnancies were all associated with smoking during the second pregnancy. CONCLUSIONS These findings, linking smoking behavior to changes taking place between pregnancies, offer new and additional insight into modifiable risk factors that may help facilitate more targeted smoking cessation interventions for women at the highest risk.