Miracle-dz/UniFAR-FTUs huggingface dataset:
COX-2 and the Kidney

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of pain and inflammation. Nonselective NSAIDs inhibit both cyclooxygenase (COX)-1 and COX-2. Nephrotoxicity of nonselective NSAIDs has been well documented. The effects of selective COX-2 inhibitors on renal function and blood pressure are attracting increasing attention. In the kidney, COX-2 is constitutively expressed and is highly regulated in response to alterations in intravascular volume. COX-2 metabolites have been implicated in the mediation of renin release, regulation of sodium excretion, and maintenance of renal blood flow. Similar to nonselective NSAIDs, inhibition of COX-2 may cause edema and modest elevations in blood pressure in a minority of subjects. COX-2 inhibitors may also exacerbate preexisting hypertension or interfere with other antihypertensive drugs. Occasional acute renal failure has also been reported. Caution should be taken when COX-2 inhibitors are prescribed, especially in high-risk patients (including elderly patients and patients with volume depletion).
PEGylation Confers Greatly Extended Half-Life and Attenuated Immunogenicity to Recombinant Methioninase in Primates

Methionine depletion by recombinant methioninase (rMETase) has been demonstrated previously to be highly effective in tumor-bearing mouse models. However, the therapeutic potential of rMETase has been limited by its short plasma half-life and immunologic effects, including high antibody production in mice and monkeys and anaphylactic reactions in monkeys. To overcome these limits of rMETase, the enzyme has been coupled to methoxypolyethylene glycol succinimidyl glutarate (MEGC-PEG-5000). In this study, we evaluated the pharmacokinetics, antigenicity and toxicity of MEGC-PEG-rMETase in Macaca fascicularis monkeys using an escalating-dose strategy. Dose ranging studies at 1,000, 4,000, and 8,000 units/kg i.v. determined that a single dose of 4,000 units/kg was sufficient to reduce plasma methionine to <5 μmol/L for 12 hours. Pharmacokinetic analysis with the single 4,000 units/kg dose showed that MEGC-PEG-rMETase holoenzyme activity was eliminated with a biological half-life of 1.3 hours, and the MEGC-PEG-rMETase apoenzyme was eliminated with a biological half-life of 90 hours, an ∼36-fold increase compared with non-PEGylated rMETase. A single dose at 2,000 units/kg of MEGC-PEG-rMETase resulted in an apoenzyme half-life of 143 hours. A seven-day i.v. administration of 4,000 units/kg every 12 hours resulted in a steady-state depletion of plasma methionine to <5 μmol/L. The only manifest toxicity was decreased food intake and slight weight loss. Red cell values and hemoglobin declined transiently during treatment but recovered after cessation of treatment. Subsequent challenges on days 29, 50 and, 71 did not result in any immunologic reactions. This result is in contrast to non-PEGylated rMETase, which elicited anaphylactic reactions in monkeys. Anti-MEGC-PEG-rMETase antibodies (at 10−2) were found on day 29, and these increased to 10−3 to 104 on day 71, 100 to 1,000-fold less than antibodies elicited by naked rMETase. Although anti-MEGC-PEG-rMETase antibodies were produced, no neutralizing antibody was identified, and each challenge dose was effective in depleting plasma methionine levels. The results of the present study demonstrate that PEGylation greatly prolongs serum half-life of the rMETase apoenzyme and eliminated anaphylactic reactions. The results indicate a profile with respect to serum half-life, toxicity, and antigenicity that suggest clinical potential of MEGC-PEG-rMETase.
Combined DC and AC Integration of Energy Sources in Hybrid 3-Phase Off-Grid Systems

Hybrid systems which incorporate more than one energy source face the challenge of integrating DC sources like PV and AC sources like wind turbines or diesel gensets at the same time. Currently, two main paradigms are pursued in order to supply off-grid AC loads: DC-coupled systems and AC-coupled systems. However, DC-coupled systems are normally not able to integrate AC sources like wind generators directly but via rectifiers. AC coupled systems have to invert the electricity generated by DC sources like PV and rectify them again to charge batteries. The result of these concepts is inefficient operation and high investment costs. Conergy ISA hybrid inverters are designed to integrate DC and AC sources in their natural way: direct integration of AC sources like in a grid and maximum efficiency with direct DC integration
Study on unnatural childhood deaths presented to North Colombo Teaching Hospital, Sri Lanka

Introduction Unnatural childhood deaths are not only associated with intense trauma and separation distress, but also relate to a sense of neglect to protect children from harm. Accurate information on causes and circumstances of such deaths through a process of medico-legal investigations is essential in creating an awareness among the policy makers and educators/caregivers, to prevent these tragic deaths. Objective The aim of the study was to determine the causes and the circumstances of unnatural deaths of children among the medico-legal autopsy population presented to North Colombo Teaching Hospital, Sri Lanka. Study design A retrospective descriptive study was carried out based on Reports of Postmortem Examination performed in a Tertiary Care Hospital, on children who died of unnatural causes during the period from 2009 to 2011. Results Out of 48 unnatural childhood deaths, 24 (50%) children were older than 10 years of age. The most frequent circumstance of death was accidental 39 (81%), while the most frequent cause of death was drowning 16 (33%). Fifteen died due to accidental drowning while one was a homicidal drowning. Suicidal deaths were found only among the children older than 16 years of age. Fifty-four percent of the accidental deaths had taken place at or around the home. Conclusion Accidents accounted for the majority (or greatest number) of tragic childhood deaths. The presence of drowning as the most common cause of death indicates that an immense responsibility lies with the parents and caregivers to prevent such deaths.
Theory of transition from the tunneling regime to point contact in scanning tunneling microscopy.

L'effet tunnel apparait a travers une barriere effective meme si la barriere de potentiel s'effondre. Apres cet effondrement le contact ponctuel est amorce et conduit a un transport ballistique. On observe des oscillations qu'on explique par un agrandissement irregulier de la surface de contact
Results From Portugal's 2016 Report Card on Physical Activity for Children and Youth.

BACKGROUND This article describes the procedures and development of the first Portuguese Report Card on Physical Activity in Children and Adolescents. METHODS Comprehensive searches for data related to indicators of physical activity (PA) were completed by a committee of physical activity and sports specialists. Grades were assigned to each indicator consistent with the process and methodology outlined by the Active Healthy Kids Canada Report Card model. RESULTS Nine indicators of PA were graded. The following grades were assigned: Overall Physical Activity Levels, D; Organized Sport Participation, B; Active Play, D; Active Transportation, C; Sedentary Behaviors, D; Family and Peers, C; Schools, B; Community and the Built Environment, D; and Government, C. CONCLUSIONS Portuguese children and adolescents do not reach sufficient physical activity levels and spend larger amounts of time spent in sedentary behaviors compared with recommendations. Effective policies of PA promotion and implementation are needed in different domains of young people's daily lives.
Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients before and after vitamin D supplementation

Background: Vitamin D could play a protective role in multiple sclerosis. Methods: In an observational, uncontrolled study, vitamin D3 supplementation (3010 IU/day on average) was given to 156 consecutive patients with relapsing–remitting multiple sclerosis, under first-line immunomodulatory therapy and with initial 25-OH-D serum level lower than 100 nmol/l (40 ng/ml). Relapses were determined for 29.1 ± 8.4 months during vitamin D and 29.8 ± 10.1 months before supplementation. The 25-OH-D level was measured before supplementation and several times during supplementation. The incidence rate of relapses before and during supplementation was estimated using negative binomial regression models with follow-up durations as offset terms. The incidence rate and incidence rate ratio of relapses at various 25-OH-D levels were also calculated using negative binomial regression models. Results: In 76 patients, immunomodulatory therapy preceded vitamin D supplementation (by 4.2 ± 2.7 years) and in 80 patients both treatments were started simultaneously. Under supplementation, the 25-OH-D level increased from 49 ± 22 nmol/l to 110 ± 26 nmol/l on average. Pooling data collected before and during supplementation, we found a significant strong inverse relationship between the relapse incidence rate and the 25-OH-D level (p < 0.0001), suggesting that vitamin D did indeed influence the relapse rate. Results of univariate, bivariate and multivariate analyses were analogous: in the multivariate model adjusted for age, disease duration and previous use of immunomodulatory therapy, every 10 nmol increase in 25-OH-D level was associated with a reduction in the relapse incidence rate of 13.7%. Dividing iteratively the population made up of pooled periods into two subgroups according to the 25-OH-D levels, the relapse incidence rate ratio decreased as the 25-OH-D level increased up to 110 nmol/l, but a plateau effect was observed beyond this limit. Conclusion: Further studies are warranted for accurate quantification of the vitamin D effect.
Calcium-induced conformational changes in the C-terminal half of gelsolin stabilize its interaction with the actin monomer.

The basic mechanism for the nucleating effect of gelsolin on actin polymerization is the formation of a complex of gelsolin with two actin monomers. Probably due to changes in the C-terminal part of gelsolin, a stable ternary complex is only formed at [Ca(2+)] >10(-5) M [Khaitlina, S. , and Hinssen, H. (2002) FEBS Lett. 521, 14-18]. Therefore, we have studied the binding of actin monomer to the isolated C-terminal half of gelsolin (segments 4-6) over a wide range of calcium ion concentrations to correlate the conformational changes to the complex formation. With increasing [Ca(2+)], the apparent size of the C-terminal half as determined by gel filtration was reduced, indicating a transition into a more compact conformation. Moreover, Ca(2+) inhibited the cleavage by trypsin at Lys 634 within the loop connecting segments 5 and 6. Though the inhibitory effect was observed already at [Ca(2+)] of 10(-7) M, it was enhanced with increasing [Ca(2+)], attaining saturation only at >10(-4) M Ca(2+). This indicates that the initial conformational changes are followed by additional molecular transitions in the range of 10(-5)-10(-4) M [Ca(2+)]. Consistently, preformed complexes of actin with the C-terminal part of gelsolin became unstable upon lowering the calcium ion concentrations. These data provide experimental support for the role of the type 2 Ca-binding sites in gelsolin segment 5 proposed by structural studies [Choe et al. (2002) J. Mol. Biol. 324, 691]. We assume that the observed structural transitions contribute to the stable binding of the second actin monomer in the ternary gelsolin-actin complex.
Re-operative abdominal predictive score: a prognostic model combining Acute Re-intervention Predictive Index and intra-abdominal pressure.

BACKGROUND The decision to re-operate after abdominal surgery is still difficult, especially in the setting of intraabdominal sepsis. Mathematical models provide a good aid to both diagnosis and decision-making. METHODS A prospective observational study was conducted with 300 patients consecutively admitted to the intensive care unit of an academic institution affiliated to Calixto García Medical Faculty following abdominal surgery from January 2008 to January 2010. The patients were randomly separated (2:1) into estimation and validation groups. Logistic regression analysis was used in the estimation group to develop three models for decision-making related to re-operation including related factors such as age, ARPI, IAP, type of surgery (elective or emergency), and the duration of surgery. The three models developed were validated on the other group. RESULTS The acute re-operation predictive index-intra-abdominal pressure (ARPI-IAP) model was the best of the three models, with an excellent calibration, using the Hossmer-Lemeshow goodness-of-fit statistical test (C = 9.976, P = 0.267), as well as discrimination (AUC = 0.989; 95% CI: 0.976-1.000). CONCLUSION The combination of IAP with ARPI in a mathematical model can add accuracy to the prediction of need for re-operation related to intra-abdominal infectious complications in patients following abdominal surgery. This may be useful in all medical settings, but especially those with limited resources.
Does age impact the obese asthma phenotype? Longitudinal asthma control, airway function, and airflow perception among mild persistent asthmatics.

BACKGROUND The relationship between obesity and asthma remains inadequately defined. Studies about how obesity affects asthma control and lung function show conflicting results. Additional focus on the effect of age as a modifier may make clearer the interaction between obesity and asthma phenotype. We sought to use a diverse and well-phenotyped cohort of asthmatic patients to determine how age impacts the relationship between obesity and spirometry, peak flow variability, airflow perception, and asthma control. METHODS The characteristics of 490 patients with mild persistent asthma taken from 2,794 study visits from a prospective trial studying strategies of step-down therapy were included in this post hoc analysis. A longitudinal mixed-effect model was used to determine if age affects the relationship between obesity and asthma characteristics, including spirometry, asthma control, airway pH, and perception of airflow changes. RESULTS The effect of obesity on asthma outcomes changes with age and gender. Obese 6- to 11-year-old children had the largest reduction in lung function but reported relatively fewer asthma symptoms than did similar nonobese asthmatics. Obese 12- to 17-year-olds showed a trend toward greater airflow obstruction and asthma symptoms compared with nonobese asthmatics. Adults in general displayed few obesity-related alterations in asthma phenotype. Female gender among 12- to 17- and 18- to 44-year-olds was associated with greater obesity-related asthma impairment. CONCLUSIONS Age is a significant effect modifier on the relationship between obesity and asthma phenotype. With increasing age, the influence of obesity on the asthma phenotype is generally reduced. The asthma phenotype may be most impacted by obesity among children and women. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT00156819; URL: www.clinicaltrials. gov.
The Big Picture: Effects of Surround on Immersion and Size Perception

Despite the fear of the entertainment industry that illegal downloads of films might ruin their business, going to the movies continues to be a popular leisure activity. One reason why people prefer to watch movies in cinemas may be the surround of the movie screen or its physically huge size. To disentangle the factors that might contribute to the size impression, we tested several measures of subjective size and immersion in different viewing environments. For this purpose we built a model cinema that provided visual angle information comparable with that of a real cinema. Subjects watched identical movie clips in a real cinema, a model cinema, and on a display monitor in isolation. Whereas the isolated display monitor was inferior, the addition of a contextual model improved the viewing immersion to the extent that it was comparable with the movie theater experience, provided the viewing angle remained the same. In a further study we built an identical but even smaller model cinema to unconfound visual angle and viewing distance. Both model cinemas produced similar results. There was a trend for the larger screen to be more immersive; however, viewing angle did not play a role in how the movie was evaluated.
[Value of the 'non-diagnostic' lung scan--further classification as to the risk of pulmonary embolism not reliable].

OBJECTIVE To determine to what extent the 'non-diagnostic' lung scans made because of a clinical suspicion of pulmonary embolism enable further determination of the risk of pulmonary embolism. DESIGN Retrospective. METHOD All non-diagnostic lung perfusion ventilation scans made in the Academic Medical Centre of Amsterdam in 1997 of 114 patients in succession (55 males and 59 females aged 27-85 years) were subjected to blind and independent re-evaluation by three observers (an experienced nuclear medicine expert, an experienced and an inexperienced intern) who, using a lung segment chart, estimated the risk of embolism as < 25%, 25-50%, 50-75% and > 75%. They did this first without and then with the chest X-ray. The findings were grouped on the basis of accordance or non-accordance with the pulmonary angiogram. The interobserver agreement was calculated by means of kappa statistics. RESULTS Of 58 patients the lung scan could be compared with a chest X-ray and a pulmonary angiogram. In 43 patients with a normal angiogram the observers in an average of 50% of the scans estimated the risk of pulmonary embolism as < 25%, as against 25-50% in 27%, 50-75% in 9% and > 75% in 5%. In 15 patients with a deviant pulmonary angiogram, these figures were 22%, 38%, 20%, and 12%, respectively. The interobserver kappa for evaluation without chest X-ray was < or = 0.16, as against < or = 0.41% with the chest X-ray. CONCLUSIONS A reliable classification of the risk of pulmonary embolism was not possible on the basis of non-diagnostic lung scans, regardless of whether the patient did or did not have pulmonary embolism. The interobserver variability was less when the lung scan was evaluated together with the chest X-ray, but even so it was unacceptably high.
Geometric Morphometric Investigation of Molar Shape Diversity in Modern Lemurs and Lorises

In the study of mammalian adaptation to the environment, teeth are of primary importance due to their role as one of the direct interaction points between an individual and its ecological surroundings. Here, molar shape and function are investigated through traditional multivariate statistics and Thin‐Plate Splines deformations to compare the relative location of lower first molar occlusal structures (protoconid, metaconid, hypoconid, entoconid, cristid obliqua, and protolophid) in modern lemurs, lorises, tarsiers, and a non‐primate outgroup taxon (Tupaia). Results suggest that shape is based both on tooth size and dietary patterns. Small teeth tend to be short (anteroposteriorally) with wide talonids, whereas larger teeth are generally characterized as being long and narrow. In considering non‐size related shape trends, frugivorous and graminivorous taxa generally exhibit a relatively buccal intersection of the cristid obliqua with the base of the protolophid, and a relatively “perpendicular” position of the protolophid in relation to the anteroposterior axis of the tooth (defined as the axis connecting the protolophid and hypoconid). Morphological trends of folivores include a central (midline) position of the cristid obliqua‐protolophid base intersection and an oblique angle of the protolophid. Insectivorous taxa (primate and non‐primate) generally exhibit a central placement of the cristid obliqua‐protolophid base intersection (as in folivores), along with a relatively perpendicular angle of the protolophid (as in frugivores). Omnivorous taxa exhibit shape patterns that are intermediate between these three former groups. This study provides a comparative baseline for the interpretation of morphological trends in fossil primate groups, particularly the Adapiformes. Anat Rec, 292:701–719, 2009. © 2009 Wiley‐Liss, Inc.
Myocarditis, Microbes and Autoimmunity

Acute and chronic myocarditis can be caused by a number of infectious agents, including viruses, bacteria and protozoa. These diseases are refractory to treatment, and the development of rational therapies will require a detailed understanding of the mechanisms that underlie the pathological inflammatory responses. Here, we review three infectious myocarditides that, despite the dissimilarity of the microorganisms, share several common features: (i) the microbes replicate in the heart; but (ii) are difficult to isolate, in infectious form, during chronic disease; (iii) autoreactive antibodies and T cells specific for cardiac antigens have been identified in infected animals; and (iv) these autoreactive responses have been proposed as the main effectors of cell death, and myocardial damage. We critically evaluate the data, and we suggest that the findings can be reconciled without invoking autoimmunity as an effector mechanism. Alternative hypotheses to explain the tissue destruction are proposed.
Synaptic transmission from splanchnic nerves to the adrenal medulla of guinea‐pigs.

1. Membrane potentials were recorded with conventional intracellular microelectrodes from chromaffin cells in isolated, bisected adrenal glands from guinea‐pigs. 2. All cells were electrically excitable and responded to depolarizing current with all‐or‐nothing action potentials that were blocked by tetrodotoxin. 3. Input resistance was 180 +/‐ 14 M omega and this was lower than that reported for isolated chromaffin cells using patch electrodes. 4. All cells responded to transmural stimulation with action potentials that arose from excitatory synaptic potentials in response to the excitation of one or more preganglionic fibres, many having strong synaptic action. Other fibres had weaker synaptic action but in all cases, maximal transmural stimulation caused depolarization well above threshold for action potential initiation. 5. Spontaneous excitatory synaptic potentials were observed whose frequency was greatly increased by repetitive stimulation at 10 or 30 Hz. 6. No evidence was found for the desensitization of nicotinic receptors in response to acetylcholine released from presynaptic nerve terminals. 7. These experiments show that there are many similarities between the responses to splanchnic nerve stimulation of guinea‐pig chromaffin cells in situ and sympathetic ganglion cells from the same species.
Rethinking Marketing Performance Measurement: Justification and Operationalisation of an Alternative Approach to Affiliate Marketing Performance Measurement in Tourism

A number of measurement frameworks have been developed to help organisations assess the effectiveness of their marketing activities. Yet, the approaches provided by these frameworks seem to be largely linear and outdated. Whilst effectively explaining cause-and-effect relationships between marketing efforts and performance in the offline domain, the existent marketing performance measurements frequently fail to capture a full spectrum of marketing influences online and, therefore, fail to portray the construct of marketing performance holistically. In opposition to the linear explanations of marketing performance, this study argues in favour of a more dynamic complex systems approach to the measurement of online marketing performance. In particular, it proposes a methodology for the development of a complexity-based performance measurement system for affiliate marketing in tourism.