Miracle-dz/UniFAR-FTUs huggingface dataset:
Oral Sildenafil in Infants With Persistent Pulmonary Hypertension of the Newborn: A Pilot Randomized Blinded Study

BACKGROUND. Persistent pulmonary hypertension (PPHN) occurs in as many as 6.8 of 1000 live births. Mortality is ∼10% to 20% with high-frequency ventilation, surfactant, inhaled nitric oxide, and extracorporeal membrane oxygenation but is much higher when these therapies are not available. Sildenafil is a phosphodiesterase inhibitor type 5 that selectively reduces pulmonary vascular resistance. OBJECTIVE. Our goal was to evaluate the feasibility of using oral sildenafil and its effect on oxygenation in PPHN. DESIGN. This study was a proof-of-concept, randomized, masked study in infants >35.5 weeks' gestation and <3 days old with severe PPHN and oxygenation index (OI) >25 admitted to the NICU (Hospital Niño Jesús, Barranquilla, Colombia). The sildenafil solution was prepared from a 50-mg tablet. The first dose (1 mg/kg) or placebo was given by orogastric tube <30 minutes after randomization and every 6 hours. Preductal saturation and blood pressure were monitored continuously. OI was calculated every 6 hours. The main outcome variable was the effect of oral sildenafil on oxygenation. Sildenafil or placebo was discontinued when OI was <20 or if there was no significant change in OI after 36 hours. RESULTS. Six infants with an OI of >25 received placebo, and 7 received oral sildenafil at a median age of 25 hours. All infants were severely ill, on fraction of inspired oxygen 1.0, and with similar ventilatory parameters. Intragastric sildenafil and placebo were well tolerated. In the treatment group, OI improved in all infants within 6 to 30 hours, all showed a steady improvement in pulse oxygen saturation over time, and none had noticeable effect on blood pressure; 6 of 7 survived. In the placebo group, 1 of 6 infants survived. CONCLUSIONS. Oral sildenafil was administered easily and tolerated as well as placebo and improved OI in infants with severe PPHN, which suggests that oral sildenafil may be effective in the treatment of PPHN and underscores the need for a large, controlled trial.
Role of K+ATP Channels, Endothelin A Receptors, and Effect of Angiotensin II on Blood Flow in Oral Tissues

K+ATP channels are involved in CGRP-mediated vasodilation and in the vasoconstriction induced by endothelin or angiotensin II. In this study, we examined the effects of a K+ATP channel antagonist and an ET(A) receptor antagonist on resting blood flow in the pulp and gingiva, and observed their role in the vasodilation induced by tooth stimulation. We also investigated whether receptors for angiotensin II exist in the pulp and gingiva. Blood flow was measured with laser-Doppler flowmetry. Under control conditions, the K+ATP channel antagonist and angiotensin II caused a significant drop in blood flow in both target tissues. Blocking of ET(A) receptor did not change basal blood flow. The vasodilation observed after tooth stimulation remained unchanged following blockade of K+ATP channels and ET(A) receptors. Analysis of the data shows that open K+ATP channels exist during resting conditions in the pulp and gingiva, but that CGRP seems to induce vasodilation mainly via mechanisms other than K+ATP channels. ET(A) and AT1 receptors are found in the pulp and gingiva, but ET(A) receptors are not involved in modulation of a basal vascular tone in these tissues or in the vasodilation observed after tooth stimulation. Open K+ATP channels exist during resting conditions in both the dental pulp and gingiva, but calcitonin gene-related peptide seems to induce vasodilation via mechanisms other than the K+ATP channels.
Evaluation of D-isomers of O-11C-methyl tyrosine and O-18F-fluoromethyl tyrosine as tumor-imaging agents in tumor-bearing mice: comparison with L- and D-11C-methionine.

UNLABELLED The aim of this study was to investigate whether D-amino acid isomers of O-(11)C-methyl tyrosine ((11)C-CMT) and O-(18)F-fluoromethyl tyrosine ((18)F-FMT) were better than the corresponding L-isomers as tumor- detecting agents with PET in comparison with the difference between L- and D-methyl-(11)C-methionine ((11)C-MET). METHODS L- and D-(11)C-MET, (11)C-CMT, and (18)F-FMT were injected intravenously into BALB/cA Jcl-nu mice bearing HeLa tumor cells. At 5, 15, 30, and 60 min after injection, normal abdominal organs and xenotransplanted HeLa cells were sampled, and the uptake of each ligand was determined. Metabolic analyses of these compounds in the plasma were also performed. Accumulation of the d-isomers of (11)C-MET, (11)C-CMT, and (18)F-FMT in turpentine-induced inflammatory tissue was assayed in comparison with (18)F-FDG. The whole-body distribution of each tracer was imaged with a planar positron imaging system (PPIS). RESULTS Although the tumor uptake (standardized uptake value [SUV]) levels of the D-isomers of (11)C-MET, (11)C-CMT, and (18)F-FMT were 261%, 72%, and 95% of each L-isomer 60 min after administration, the tumor-to-blood ratios of these D-isomers were 130%, 140%, and 182% of the corresponding L-isomers. In the blood, the D-isomers of these labeled compounds revealed a relatively faster elimination rate compared with their L-isomers, with a high peak uptake in the blood and kidney 5 min after administration. Compared with the natural amino acid ligand l-(11)C-MET, the uptake of L-isomers of (11)C-CMT and (18)F-FMT was relatively low and stable in the abdominal organs, whereas D-isomers revealed much lower levels and faster clearance rates compared with corresponding L-isomers. Among the abdominal organs, the pancreas showed a relatively high uptake of (11)C-CMT and (18)F-FMT; the uptake of these D-isomers was much lower than that of L-isomers. Pretreatment with cycloheximide, a protein synthesis inhibitor, resulted in a marked reduction of L-(11)C-MET uptake and a slight reduction of D-(11)C-MET uptake into protein fractions, whereas no significant changes were detected with L- and D-(11)C-CMT and (18)F-FMT. D-Isomers of (11)C-MET, (11)C-CMT, and (18)F-FMT did not accumulate in turpentine-induced inflammatory tissue, where (18)F-FDG revealed a high uptake. Whole-body imaging with a PPIS provided consistent distribution data obtained from the tissue dissection analysis. CONCLUSION These results suggest that D-isomers of (11)C-CMT and (18)F-FMT could be potentially better tracers than L- and D-(11)C-MET for tumor imaging with PET.
A Case–Control Study of Social Risk Factors for Depression in American Patients

Objective To describe the social risk factors for depression and their interaction with recent life events in depressed American patients. Methods Forty patients with a major depressive episode were compared with 40 normal controls. Risk factors for depression were assessed, recent life events recorded, and their interaction examined. Results Significantly more depressed patients than controls had a poor marriage before the onset of depression and were unemployed. The depressed patients had also recently experienced significantly more life events. The only significant interaction was that employed depressed patients had experienced more recent life events than unemployed depressed patients. Conclusion In addition to recent life events, having a poor marriage and being unemployed may be social risk factors for depression in American patients.
GABA, glutamate and substance P‐like immunoreactivity release: effects of novel GABAB antagonists

1 The effects of various GABA receptor ligands on the electrically‐evoked release of endogenous GABA, glutamate and substance P‐like immunoreactivity from the dorsal horn of rat isolated spinal cord were examined. 2 Exogenous GABA (10–300 μm) significantly decreased the evoked, but not basal, release of endogenous glutamate in a concentration‐dependent manner. The GABAA agonist, isoguvacine (1–100 μm), failed to decrease the release of glutamate although it did reduce the release of GABA. Baclofen (0.1–1000 μm), the GABAB agonist, reduced the release of GABA and glutamate in a stereospecific and concentration‐dependent manner. 3 The actions of five GABAB antagonists on these release systems were compared. CGP36742, CGP52432, CGP55845A and CGP57250A significantly increased the evoked release of GABA and glutamate. They also reversed the effects of (−)−baclofen in a concentration‐dependent manner. On the other hand, while CGP56999A had no effect on glutamate release, it was an effective antagonist of the baclofen‐induced inhibition of GABA and substance P release. 4 These results suggest that GABAB receptors on nerve terminals within the dorsal horn spinal cord may be heterogeneous. However, this is based solely on the data obtained with CGP56999A which affected only GABA and substance P, but not glutamate, release.
Crop seed oil bodies: From challenges in protein identification to an emerging picture of the oil body proteome

Oleaginous seeds store lipids in specialized structures called oil bodies (OBs). These organelles consist of a core of neutral lipids bound by proteins embedded in a phospholipid monolayer. OB proteins are well conserved in plants and have long been grouped into only two categories: structural proteins or enzymes. Recent work, however, which identified other classes of proteins associated with OBs, clearly shows that this classification is obsolete. Proteomics‐mediated OB protein identification is facilitated in plants for which the genome is sequenced and annotated. However, it is not clear whether this knowledge can be dependably transposed to less well‐characterized plants, including the well‐established commercial sources of seed oil as well as the many others being proposed as novel sources for biodiesel, especially in Africa and Asia. Toward an update of the current data available on OB proteins this review discusses (i) the specific difficulties for proteomic studies of organelles; (ii) a 2012 census of the proteins found in seed OBs from various crops; (iii) the oleosin composition of OBs and their role in organelle stability; (iv) PTM of OB proteins as an emerging field of investigation; and finally we describe the emerging model of the OB proteome from oilseed crops.
A Nonlinear Dynamics Perspective of Wolfram's New Kind of Science Part IX: Quasi-ergodicity

Our scientific odyssey through the theory of 1-D cellular automata is enriched by the definition of quasi-ergodicity, a new empirical property discovered by analyzing the time-1 return maps of local rules. Quasi-ergodicity plays a key role in the classification of rules into six groups: in fact, it is an exclusive characteristic of complex and hyper Bernoulli-shift rules. Besides introducing quasi-ergodicity, this paper answers several questions posed in the previous chapters of our quest. To start with, we offer a rigorous explanation of the fractal behavior of the time-1 characteristic functions, finding the equations that describe this phenomenon. Then, we propose a classification of rules according to the presence of Isles of Eden, and prove that only 28 local rules out of 256 do not have any of them; this result sheds light on the importance of Isles of Eden. A section of this paper is devoted to the characterization of Bernoulli basin-tree diagrams through modular arithmetic; the formulas obtained allow us to shorten drastically the number of cases to take into consideration during numerical simulations. Last but not least, we present some theorems about additive rules, including an analytical explanation of their scale-free property.
Lobbying and welfare in a representative democracy

This paper studies the impact of lobbying on political competition and policy outcomes in a framework which integrates the citizen-candidate model of representative democracy with the menu-auction model of lobbying. Positive and normative issues are analysed. On the positive side, lobbying need have little or no effect on policy outcomes because voters can restrict the influence of lobbyists by supporting candidates with offsetting policy preferences. On the normative side, coordination failure among lobbyists can result in Pareto inefficient policy choices. In addition, by creating rents to holding office, lobbying can lead to "excessive" entry into electoral competition.
Puberty and Physical Self-Perceptions of Competitive Female Figure Skaters

This study considered the interrelationships among biological maturation and its physical correlates, social physique anxiety, and appearance-related physical self-perceptions in 113 adolescent female figure skaters participating in solo (n = 73) or partner contexts (n = 40). Participants were interviewed about their menarcheal status, underwent a battery of anthropometric measurements, and completed the Physical Self Description Questionnaire and the Social Physique Anxiety Scale. Menarcheal status was a stronger correlate of physical self-perceptions than age. A combination of biological and psychological characteristics accounted for 25% of the variance in appearance-related physical self-perceptions. Younger, premenarcheal, ectomorphic skaters reporting lower social physique anxiety were more satisfied with their body fat and sport competence but reported lower self-esteem, global physical self-concept, and appearance scores. Skating context did not predict physical self-perceptions.
A bcr-v-abl oncogene induces lymphomas in transgenic mice

In chronic myeloid leukemia and some cases of acute lymphoblastic leukemia, a 9;22 chromosome translocation has fused most of the c-abl oncogene to a gene designated bcr. To explore in vivo the biological effects of the chimeric gene, we introduced a facsimile of the translocation product, a bcr-v-abl gene, into the mouse germ line under the control of the immunoglobulin heavy-chain enhancer or a retroviral long terminal repeat. Some transgenic mice bearing either construct developed clonal lymphoid tumors. T lymphomas predominated, but some pre-B lymphomas developed. The transgenes were expressed in the tumors but not detectably in the lymphoid tissues of nontumorous transgenic animals, implying that transcription is activated by a low-frequency somatic event. These results demonstrate that bcr-v-abl is tumorigenic in vivo and provide a new animal model for lymphomagenesis.
Characteristics of tinnitus induced by head injury.

OBJECTIVE To determine if the characteristics of tinnitus produced by head trauma are specific and exclusive when compared with other origins of tinnitus. DESIGN Retrospective study using clinic test results and data from the Tinnitus Data Registry compiled from questionnaires, interviews, and testing. Tinnitus produced by head injury was compared with tinnitus of mixed origins, including no known origin. SETTING A tinnitus referral clinic where all patients must see an otologist or an ear, nose, and throat physician prior to attending the clinic. PATIENTS All patients had severe to moderately severe constant tinnitus and presented with tinnitus as the primary symptom. RESULTS No exclusive characteristics were found to describe head injury-induced tinnitus. The tinnitus for the group with head injury was statistically significantly (P = .004) louder and occurred with greater incidence of continuing pain in the ears. The group with head injury also had more episodes of dizziness and a more severe form of tinnitus. However, no marked difference was noted in pitch of tinnitus, complexity (number of sounds) of tinnitus, or the minimum masking level. CONCLUSIONS This retrospective study found that tinnitus induced by head injury was significantly (P = .004) louder than tinnitus induced from other causes but, interestingly, did not require higher levels of masking. The patients with head injury-induced tinnitus more frequently (P = .0003) displayed residual inhibition although the duration of residual inhibition was not different from that of the comparison group. Other symptoms associated with the tinnitus onset were more frequently mentioned by the group with head trauma-induced tinnitus, except for the condition of pressure sensation in the ears. Using a severity questionnaire, the group with head trauma-induced tinnitus rated their tinnitus as being more severe than did the comparison group. However, such things as pitch of the tinnitus, masking level, acceptance of wearable maskers, general hearing level, and complexity of the tinnitus did not distinguish the two groups.
Disruption of the Zinc Finger Motifs in the Leishmania tarentolae LC-4 (=TbMP63) L-complex Editing Protein Affects the Stability of the L-complex*

The uridine insertion/deletion editing complex, which we have termed the L-complex, is composed of at least 16 polypeptides stabilized entirely by protein-protein interactions. Three L-complex proteins contain zinc finger motifs that could be involved in these interactions. In Leishmania these proteins are labeled LC-1, LC-4, and LC-7b, and the orthologs in Trypanosoma brucei are labeled MP81, MP63, and MP42. Overexpression of TAP-tagged LC-4 in Leishmania tarentolae led to a partial localization of the protein in the L-complex together with the endogenous LC-4 protein, suggesting at least a dimeric organization. Disruption of zinc fingers 1 or 2 (ZnF-1 and ZnF-2) in the tagged LC-4 protein was performed by mutation of the two zinc-binding cysteines to glycines. Disruption of ZnF-1 led to a partial growth defect and a substantive breakdown of the L-complex, whereas disruption of ZnF-2 had no effect on cell growth and caused a partial breakdown of the L-complex. A close interaction of LC-4 with 2–4 proteins, including REL1 (RNA ligase) and LC-3, was suggested by chemical crosslinking and co-immunoprecipitation experiments. Our results suggest that both ZnF-1 and ZnF-2 in LC-4 play a role in protein-protein interactions and indicate that the LC-4 subcomplex may be required for formation or stability of the entire L-complex.
The Acute Box cis-Element in Human Heavy Ferritin mRNA 5′-Untranslated Region Is a Unique Translation Enhancer That Binds Poly(C)-binding Proteins*

Intracellular levels of the light (L) and heavy (H) ferritin subunits are regulated by iron at the level of message translation via a modulated interaction between the iron regulatory proteins (IRP1 and IRP2) and a 5′-untranslated region. Iron-responsive element (IRE). Here we show that iron and interleukin-1β (IL-1β) act synergistically to increase H- and L-ferritin expression in hepatoma cells. A GC-rich cis-element, the acute box (AB), located downstream of the IRE in the H-ferritin mRNA 5′-untranslated region, conferred a substantial increase in basal and IL-1β-stimulated translation over a similar time course to the induction of endogenous ferritin. A scrambled version of the AB was unresponsive to IL-1. Targeted mutation of the AB altered translation; reverse orientation and a deletion of the AB abolished the wild-type stem-loop structure and abrogated translational enhancement, whereas a conservative structural mutant had little effect. Labeled AB transcripts formed specific complexes with hepatoma cell extracts that contained the poly(C)-binding proteins, iso-αCP1 and -αCP2, which have well defined roles as translation regulators. Iron influx increased the association of αCP1 with ferritin mRNA and decreased the αCP2-ferritin mRNA interaction, whereas IL-1β reduced the association of αCP1 and αCP2 with H-ferritin mRNA. In summary, the H-ferritin mRNA AB is a key cis-acting translation enhancer that augments H-subunit expression in Hep3B and HepG2 hepatoma cells, in concert with the IRE. The regulated association of H-ferritin mRNA with the poly(C)-binding proteins suggests a novel role for these proteins in ferritin translation and iron homeostasis in human liver.
Neuronal Autoantibodies Call for Attention in Epilepsy.

1 The concept of autoimmune epilepsy has gained considerable interest over the last few years. After the detection of a plethora of antibodies in patients with acute and established epilepsy, prospective cohorts started investigating factors of inflammation. In a recent report, Dubey et al. reported neurological autoantibodies (NAAs) among patients with epilepsy of unknown etiology. They investigated 112 patients for various NAAs including anti-GAD and found NAAs in 34.8% of the cases (1). It is most notable that our recent studies showed very similar antibody prevalence and clinical associations as those of Dubey et al. We investigated identical patient groups, namely, focal epilepsy of unknown cause and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) 3 years ago, and published our results of 81 patients (2). We found antibodies to the glycine receptor (GLY-R) in 6.2% of our patients, CASPR2 in 4.9%, NMDAR in 2.5%, and VGKC-complex in 2.5% (2).
Chronotype, sport participation, and positive personality-trait-like individual differences

Chronotype and sport participation have been found to relate to positive personality-trait-like individual differences (PTLID). To date, research has focused exclusively on the morningness–eveningness dimension of chronotype, and little is known about the relationship between chronotype and various characteristics of sport participation (e.g. training time). This investigation had three primary objectives: (1) to extend the current evidence base by exploring how sport participation and PTLID relate to chronotype amplitude, (2) to explore how chronotype (morningness–eveningness and amplitude) relates to various characteristics of sport training and competition, and (3) to explore the independent and interrelated contribution of sport participation and chronotype to PTLID. The sample included 976 non-athletes (493 women and 483 men) and 974 athletes (478 women and 496 men). Participants completed a battery of questionnaires targeting sport participation characteristics, six positive PTLID (hope, optimism, perseverance, resilience, self-efficacy and trait emotional intelligence) and chronotype dimensions. Results showed that morningness–eveningness was negatively related to positive PTLID but was unrelated to sport participation. Greater diurnal fluctuations (amplitude dimension) were associated with lower positive PTLID values, lower sport participation, and shorter training durations. Positive PTLID were also associated with better sleep quality and a shorter sleep duration. Chronotype (morningness–eveningness and amplitude) and sport participation had independent associations with PTLID. These findings suggest that changes in sport participation and activity times might be a useful approach to developing positive PTLID.
The external costs of coal mining: the case of collieries supplying Kusile power station

The aim of this paper was to quantify the external costs of mining and transporting coal to the Kusile coal-fired power station in eMalahleni. Monetary values were estimated for a number of impacts including its contribution to climate change, human health effects of classic air pollutants, mortality and morbidity, impacts of water pollution and water consumption. The results of the study disclosed that coal mining and transportation will inflict costs to both the environment and humans of between R6 538 million and R12 690 million per annum, or between 20.24 c/kWh and 39.3 c/kWh sent out. The external effect of water consumption (opportunity costs of water) constitutes over 90% of the total cost, followed by global warming damage costs and ecosystem services lost due to coal mining. The estimated externality cost is approximately between 50% and 100% of the current average electricity price.
01-09 The Strategy of Professional Forecasting Marco Ottaviani

This paper develops and compares two theories of strategic behavior of professional forecasters. The first theory posits that forecasters compete in a forecasting contest with pre-specified rules. In equilibrium of a winner-take-all contest, forecasts are excessively differentiated. According to the alternative reputational cheap talk theory, forecasters aim at convincing the market that they are well informed. The market evaluates their forecasting talent on the basis of the forecasts and the realized state. If the market has naive views on forecasters’ behavior, forecasts are biased toward the prior mean. Otherwise, equilibrium forecasts are unbiased but imprecise.