Miracle-dz/UniFAR-FTUs huggingface dataset:
An update on antidepressant use and suicidality in pediatric depression

Introduction: In 2003, public health advisories in North America and Europe regarding suicidality associated with selective serotonin reuptake inhibitors (SSRIs) led to the addition of black box warnings to antidepressant package inserts in 2004. Subsequently, a series of events appeared to result from these regulatory actions. Areas covered: This review provides an overview of the temporal associations of regulatory agencies' actions in North America and Europe with rates of depression diagnoses, pediatric antidepressant prescription rates, follow-up visits to physicians prescribing antidepressants, and rates of completed suicide and suicidal ideation in children and adolescents. In addition, evidence-based predictors of suicidal behavior and suicide risk, as provided by large, multisite studies of depressed children and adolescents, are outlined. Finally, this review considers key advancements in the study of young patients at risk for suicide and describes innovations in current research methodology, to more accurately identify suicidality and the relationship to antidepressant use within this vulnerable patient population. Expert opinion: Evaluating the role of antidepressants in those youths who do not respond to evidence-based psychotherapeutic interventions may be a useful future research direction. Until more data are available, however, closely monitored antidepressant treatment in combination with CBT may provide the most benefit.
The two-component sensor kinase KinB acts as a non-canonical switch between acute and chronic infection

P. aeruginosa is an opportunistic pathogen that occupies diverse environmental niches and is capable of causing a range of infections in humans. This versatility suggests that it has sophisticated mechanisms to sense and respond to the surrounding microenvironment. Two-component sensors are commonly used by bacteria to sense and respond to environmental stimuli and Pseudomonas aeruginosa has one of the largest sets of two-component sensors known in bacteria. We took advantage of a non-redundant transposon library and a recently characterized vertebrate model host, Danio rerio, that is amenable to higher throughput analysis than mammalian models, to systematically test the role of 60 two-component sensors that are required for P. aeruginosa virulence in acute infection. We found that the sensor kinase KinB is required for acute infection in zebrafish embryos and regulates a number of virulence related phenotypes in a manner independent of its kinase activity and its known response regulator, AlgB. Thus, the regulation of virulence by KinB highlights the increasing recognition of non-canonical two-component signaling mechanisms.
[Toll-like receptor 4 expression and function of respiratory syncytial virus-infected airway epithelial cells].

OBJECTIVE To observe the epithelial Toll like receptor (TLR)4 expression changes and the signaling pathway function after respiratory syncytial virus (RSV) infection and to explore the mechanisms of RSV-induced airway inflammation. METHODS 9HTEo-human tracheal epithelial cell line was infected by RSV (MOI = 10), and TLR1-10 mRNA were detected by RT-PCR assay at 3 h post RSV infection. TLR4 mRNA was detected by real time Q-PCR assay at 3 h, 6 h and 9 h post RSV infection, and TLR4 protein expression and cell apoptosis were determined by flow cytometry at 24 h post RSV infection. IL-8 in supernatant was detected by ELISA after RSV-infected cells exposed to lipopolysaccharide (LPS). A normal control group and a RSV infection group were set up for the RT-PCR and flow cytometry experiments, and the data were analyzed by paired t test using GraphPad 4.0 software. A normal group, a RSV group and a UV-inactivated RSV group were set up for the real time Q-PCR, experiments, and the data were analyzed by Kruskal-Wallis test. The ELISA experiments were divided into 4 groups including a normal control, a RSV, a LPS stimulation, and a RSV plus LPS co-stimulation groups, and the data were analyzed by One-way ANOVA test. RESULTS (1) TLR2-10 mRNA level was significantly up-regulated (t value of TLR2-10: 3.49 -14.47, P < 0.05), especially TLR-2, 6 enhanced expression, compared with the normal epithelial cells. Real time Q-PCR assay showed that TLR4 mRNA started to increase at 3hr (Kruskal-Wallis test value = 8.82, P < 0.05, n = 6) and significantly elevated at 9 hour (Kruskal-Wallis test value = 6.62, P < 0.05, n = 6). UV inactivated-RSV had no effect on the TLR4 mRNA level. (2) Flow cytometry showed that membrane TLR4 mean fluorescence intensity (MFI) increased (RSV: 1.27 +/- 0.48, normal: 0.97 +/- 0.25; t = 2.39, P > 0.05, n = 10) while cytoplasmic TLR4 MFI simultaneously decreased (RSV: 3.08 +/- 1.38, normal: 3.36 +/- 1.31, t = 2.92, P = 0.225, n = 10). Percentage of membrane TLR4-positive cells was higher in RSV infected population [RSV: (11.99 +/- 7.74)%, normal: (1.16 +/- 0.47)%, Mann-Whitney t value = 0.001, P < 0.01, n = 8], most (93.32 +/- 1.7)% of which were Annexin V positive. IL-8 was significantly induced in the RSV plus LPS costimulation group compared with RSV group (F = 59.29, P < 0.01, n = 3). CONCLUSIONS RSV induced epithelial TLR4 up-regulation, localization changes from cytoplasm to membrane, IL-8 secretion through TLR4 signaling pathway and epithelial cell apoptosis in membrane TLR4 positive population. These results indicate TLR4 is involved in RSV-induced acute or chronic epithelial-dependent inflammation, which might contribute to acute or chronic airway inflammation.
The benefits of early jejunal hyperalimentation in the head-injured patient.

To determine the efficacy of early jejunal hyperalimentation as nutritional support in the head-injured patient, 32 head-injured patients with Glasgow Coma Scale scores less than 10 were studied for the first 7 days after injury. The experimental (E) group had nasojejunal feeding tubes placed fluoroscopically. Within 36 hours of injury, they received nutritional support equal to their measured resting energy expenditure. The control (C) group was fed gastrically when bowel sounds returned. There were no significant differences (P greater than 0.05) in age, Glasgow Coma Scale score, type of neurological injury, or associated injuries between the two groups. The mean resting energy expenditure, serum albumin, glucose, lymphocyte count, body weight, and total nitrogen loss were nearly identical for both groups. With the jejunal feedings, daily caloric (E = 2102 kcal versus C = 1100 kcal) and nitrogen intake (E = 11.1 g versus C = 5.6 g) and daily nitrogen balance (E = -4.3 g versus C = -11.8 g) improved. The incidence of bacterial infections (E = 3 versus C = 14) and days of intensive care unit hospitalization (E = 6 versus C = 10) were significantly reduced (P less than .05). Head-injured patients will tolerate early jejunal hyperalimentation despite the presence of a clinically silent abdomen, and the cost and complications of total parenteral nutrition are avoided. The increased caloric and nitrogen intake and improved nitrogen retention markedly reduced infections and days of stay in the intensive care unit.
A hybrid innovation management model for emerging technology: Bibliometrics, qualitative methodology, and empirical study

Compared with traditional technologies, emerging technology presents some new features, e.g. uncertainty. Corresponding, technological innovation for emerging technologies faces many kinds of risks that dramatically affect their development paths. This paper illustrates how quantitative methods (Science, Technology & Innovation (ST&I) information resources) and qualitative approaches (experts input and technology assessment) could support the decision making through the different stages of technological innovation for the public or private sector in the emerging technology industry. It uses dye-sensitized solar cells (DSSCs) as a case example. The combination of qualitative and quantitative approaches should yield robust assessment and should facilitate communication of results. It is useful for technology managers and policy-makers to grasp the development process and prospects for a specific emerging technology to facilitate innovation management.
High Histone Acetylation and Decreased Polycomb Repressive Complex 2 Member Levels Regulate Gene Specific Transcriptional Changes During Early Embryonic Stem Cell Differentiation Induced by Retinoic Acid

Histone modifications play a crucial role during embryonic stem (ES) cell differentiation. During differentiation, binding of polycomb repressive complex 2 (PRC2), which mediates trimethylation of lysine 27 on histone H3 (K27me3), is lost on developmental genes that are transcriptionally induced. We observed a global decrease in K27me3 in as little as 3 days after differentiation of mouse ES cells induced by retinoic acid (RA) treatment. The global levels of the histone K27 methyltransferase EZH2 also decreased with RA treatment. A loss of EZH2 binding and K27me3 was observed locally on PRC2 target genes induced after 3 days of RA, including Nestin. In contrast, direct RA‐responsive genes that are rapidly induced, such as Hoxa1, showed a loss of EZH2 binding and K27me3 after only a few hours of RA treatment. Following differentiation induced by leukemia inhibitor factor (LIF) withdrawal without RA, Hoxa1 was not transcriptionally activated. Small interfering RNA‐mediated knockdown of EZH2 resulted in loss of K27me3 during LIF withdrawal, but the Hoxa1 gene remained transcriptionally silent after loss of this repressive mark. Induction of histone hyperacetylation overrode the repressive K27me3 modification and resulted in Hoxa1 gene expression. Together, these data show that there are multiple temporal phases of derepression of PRC2 target genes during ES cell differentiation and that other epigenetic marks (specifically, increased acetylation of histones H3 and H4), in addition to derepression, are important for gene‐specific transcriptional activation. This report demonstrates the temporal interplay of various epigenetic changes in regulating gene expression during early ES cell differentiation.
MtDNA and Y‐chromosome Variation in Kurdish Groups

In order to investigate the origins and relationships of Kurdish‐speaking groups, mtDNA HV1 sequences, eleven Y chromosome bi‐allelic markers, and 9 Y‐STR loci were analyzed among three Kurdish groups: Zazaki and Kurmanji speakers from Turkey, and Kurmanji speakers from Georgia. When compared with published data from other Kurdish groups and from European, Caucasian, and West and Central Asian groups, Kurdish groups are most similar genetically to other West Asian groups, and most distant from Central Asian groups, for both mtDNA and the Y‐chromosome. However, Kurdish groups show a closer relationship with European groups than with Caucasian groups based on mtDNA, but the opposite based on the Y‐chromosome, indicating some differences in their maternal and paternal histories. The genetic data indicate that the Georgian Kurdish group experienced a bottleneck effect during their migration to the Caucasus, and that they have not had detectable admixture with their geographic neighbours in Georgia. Our results also do not support the hypothesis of the origin of the Zazaki –speaking group being in northern Iran; genetically they are more similar to other Kurdish groups. Genetic analyses of recent events, such as the origins and migrations of Kurdish‐speaking groups, can therefore lead to new insights into such migrations.
Low Earth Orbit objects tracking and orbit determination from ground-based phased array radar systems

Ground-based phased array radar observations of Low Earth Orbit objects are addressed in this paper. Radar resources and radar data processing techniques are analysed with the aim of assessing the overall accuracy in orbit determination and propagation as a function of radar design trade-off parameters. The presented analysis is based on end-to-end simulation of both radar and orbital data processing components: measurement data and final data products are generated in accordance with current objectives of future European space surveillance sensors in the framework of space situational awareness (SSA).
Psychosocial factors associated with levels of metabolic control in youth with type 1 diabetes.

This study sought to determine the relationship between Youth Self Report (YSR) scores for behavior problems, YSR scores for social competence, and metabolic control in children and adolescents with Type 1 diabetes. Using a cross sectional design, 234 individuals between 11 and 18 years old were given the YSR at regular clinic appointments; glycosylated hemoglobin (GHb) was also measured. More than 50% of subjects showed GHb levels above 9%; the normal GHb level is 4.2% to 5.8%. Individuals reporting a greater number of behavior problems, though not in the pathological range on the aggression, delinquent behaviors, and attention problems subscales of the YSR, were more than twice as likely to have GHb levels above 9%. Using logistic regression the externalizing scale (aggression and delinquent behaviors combined) predicted elevated GHb at 2.41, p =. 003. Youth in this study were middle-class and were receiving subspecialty care. Yet, over half of them had GHb levels above the recommended 9%. The psychological health of youth should be monitored at regular intervals. Longitudinal studies are needed to determine whether aggression, delinquent behaviors, and attention problems in children and adolescents with Type 1 diabetes result later in depression and elevated levels of GHb in these same individuals or whether these elevations are transient. Interviews could be supplemented with instruments such as the YSR and care given for those with a higher number of self-reported problems.
The State of the World's Children 1997

Each year, The State of the World's Children closely examines a key issue affecting children. The 1997 Report focuses on the controversial and emotional, as well as complex and challenging issue of child labour. It asserts that thoughtful and comprehensive attempts at solutions must be guided by the best interests of the child and the Convention on the Rights of the Child. The Report urges an immediate end to hazardous and exploitative child labour and advocates urgent support for education so that children may acquire knowledge and skills to improve their lives.
Characterization of a voltage‐dependent potassium channel in quid Schwann cells reconstituted in planar lipid bilayers

An affinity column prepared with noxiustoxin (NTx), a K+ channel blocker from the venom of the Mexican scorpion Centruroides noxius, was used to purify a functional channel from a detergent extract of Schwann cell membrane of the giant axon of the squid Loligo vulgaris. The purified protein was reconstituted as a functional unit in a planar lipid bilayer and tested with a sequence of potentials to obtain information about single‐channel amplitude and kinetics. The reconstituted channel showed delayed rectifier behavior with a slope conductance of 10 pS under 5:1 asymmetric KCl concentrations and a clear tendency to open under negative potentials. The zero‐current potential was +36 mV, which fitted well with the Nernst equation for the CIS/TRANS K+‐concentration ratio of 5:1. The channel also showed a strong sensitivity to tetraethylammonium and its activity was inhibited by NTx, as expected from the purification procedure. The behavior of this protein in the presence of 0.5 mM ATP (cis side) was also tested, significantly increasing current fluctuations across the membrane. In order to compare the modulation of the Schwann cell K+ channel with that of the axonal K+ channel, a purified protein from the squid axon membrane was also tested in the presence of ATP. This 10–11 pS, delayed rectifier channel from the squid giant axon (Prestipino et al., FEBS Lett. 250:570–574, 1989) was also tested in the presence of ATP and showed a similar rise in activity. © 1995 Wiley‐Liss, Inc.
Changes in the electrical properties of chick ciliary ganglion neurones during embryonic development.

1. Whole‐cell recording techniques were used to examine the expression of ionic currents in chick ciliary ganglion neurones dissociated acutely at various stages of embryonic development. Currents were also examined in dissociated cells that had been maintained in vitro for several days. 2. Voltage‐activated, tetrodotoxin (TTX)‐sensitive Na+ currents (INa) could be detected in all cells tested between stage 25 and stage 40 (embryonic days 4.5‐14). INa increased in both amplitude and density throughout development, but no obvious changes in kinetics or sensitivity to TTX were observed. 3. High‐threshold Ca2+ currents (ICa) were also detectable between stage 25 and stage 40. ICa increased in both amplitude and density throughout this time. No obvious changes in kinetics or voltage dependence were observed. 4. Delayed rectifier K+ currents (IDR) and A‐currents (IA) could be detected in Ca(2+)‐free salines, and distinguished on the basis of differences in kinetics, voltage dependence, and sensitivity to tetraethylammonium (TEA). IA was either absent, or present at very low densities at stages 26‐30, but showed a sharp increase in density thereafter. In contrast, IDR was detectable as early as stage 25, and did not display a significant increase in density during development. 5. Ca(2+)‐activated K+ currents (IK(Ca)) were either undetectable or present at very low density between stage 26 and stage 30 (embryonic days 5‐9) but showed a large increase in amplitude and density thereafter. 6. Ionic currents were examined in age‐matched cells dissociated acutely on embryonic day 13, or isolated on embryonic day 9 and maintained in vitro for an additional 4 days. Most of the cells maintained in culture for 4 days did not express detectable IK(Ca), and had significantly reduced IA compared to acutely isolated controls. The cultured cells expressed normal densities of IDR, ICa and INa. 7. All ionic currents increased in amplitude during normal embryonic development, and all but IDR increased in density. The largest change in density generally occurred between stages 30 and 40, during which time ciliary ganglion neurones form synapses with target tissues. 8. Isolation of ciliary neurones from the in ovo environment prevented the normal development of IA and IK(Ca), suggesting that the expression of these channels is controlled by one or more extrinsic environmental factors. In contrast, the normal expression of INa, ICa and IDR is not dependent upon extrinsic factors.
Predictive Value of Nuclear Factor κB Activity and Plasma Cytokine Levels in Patients with Sepsis

ABSTRACT The relationship between fluctuating cytokine concentrations in plasma and the outcome of sepsis is complex. We postulated that early measurement of the activation of nuclear factor κB (NF-κB), a transcriptional regulatory protein involved in proinflammatory cytokine expression, may help to predict the outcome of sepsis. We determined NF-κB activation in peripheral blood mononuclear cells of 34 patients with severe sepsis (23 survivors and 11 nonsurvivors) and serial concentrations of inflammatory cytokines (interleukin-6, interleukin-1, and tumor necrosis factor) and various endogenous antagonists in plasma. NF-κB activity was significantly higher in nonsurvivors and correlated strongly with the severity of illness (APACHE II score), although neither was related to the cytokine levels. Apart from NF-κB activity, the interleukin-1 receptor antagonist was the only cytokine tested whose level in plasma was of value in predicting mortality by logistic regression analysis. These results underscore the prognostic value of early measurement of NF-κB activity in patients with severe sepsis.
Autoregulation of Epstein-Barr virus putative lytic switch gene BZLF1

Expression of the Epstein-Barr virus (EBV) BZLF1 gene in latently infected lymphocytes is sufficient to trigger the viral lytic cycle. As shown in the accompanying report (E. Flemington and S.H. Speck, J. Virol. 64:1217-1226, 1990), the promoter for the BZLF1 gene (Zp) contains two distinct types of elements (ZI and ZII [an AP-1-like domain]) which are responsive to the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), an inducer of the viral lytic cycle. Although Zp can be activated with TPA in an EBV-negative Burkitt's lymphoma cell line (Ramos), its activity is considerably lower than in EBV-positive cell lines which can be induced with TPA. Here we show that the protein product of the BZLF1 gene (ZEBRA) can transactivate its own promoter by a mechanism which involves direct binding to a region distinct from the ZI and ZII element. Moreover, we show that this region is composed of two distinct ZEBRA-binding-transactivation domains. Interestingly, these two domains are not homologous, and while one domain (ZIIIA) is similar to previously described ZEBRA-binding domains, the second (ZIIIB) is a higher-affinity site which bears no detectable homology to the consensus ZEBRA recognition sequence. We also show that transactivation is independent of the otherwise essential ZII domain, suggesting that ZEBRA binding may functionally replace or supercede the need for a functional ZII domain. This observation supports a model for activation of the lytic cycle whereby synthesis of a critical level of ZEBRA signals commitment to BZLF1 transcription and initiation of the lytic cascade.
Identification of host proteins modulated by the virulence factor AC2 of Tomato chlorotic mottle virus in Nicotiana benthamiana

Tomato, one of the most important crops cultivated worldwide, has been severely affected by begomoviruses such as the Tomato chlorotic mottle virus (ToCMoV). Virulence factor AC2 is considered crucial for a successful virus–plant interaction and is known to act as a transcriptional activator and in some begomoviruses to function as an RNA silencing suppressor factor. However, the exact functions of the AC2 protein of the begomovirus ToCMoV are not yet established. The aim of the present study was to identify differentially expressed proteins of the model plant Nicotiana benthamiana in response to the expression of the AC2 gene, isolated from ToCMoV. N. benthamiana plants were inoculated with Agrobacterium tumefaciens containing the viral vector Potato virus X (PVX) and with the PVX‐AC2 construction. 2DE was performed and proteins were identified by MS. The results showed that the expression of ToCMoV AC2 alters the levels of several host proteins, which are important for normal plant development, causing an imbalance in cellular homeostasis. This study highlights the effect of AC2 in the modulation of plant defense processes by increasing the expression of several oxidative stress‐related and pathogenesis‐related proteins, as well as its role in modulating the proteome of the photosynthesis and energy production systems.