bluuebunny/crossref_metadata_2025 huggingface dataset:
P57 Filling the gap for children with heart failure: the EU-funded drug development program LENA (labeling of enalapril from neonates up to adolescents)
Authors: Laeer S , Breitkreutz J , Klingmann I , Lagler F , Dalinghaus M , Bajcetic M , de Wildt S , Clark AK , Breur H , Male C , Jovanovic I , Djukic M , Mir TS , Szatmári A , Vukomanović V , Ablonczy L , Burckhardt BB , Cawello W , Kleine K , Obarcanin E , Spatenkova L , Swoboda V , Van der Meulen M , Wagner P , Walsh J ,   on behalf of the LENA consortium
Published: May 2019

Background

ACE-inhibitors are first choice treatment for adult and paediatric patients with heart failure. Since there are no systematic data on pharmacokinetics and safety in the young heart failure population, the EU funded a drug development program1 to fill those gaps for the ACE-inhibitor enalapril. An age appropriate paediatric formulation was also required.

Methods

A paediatric patient cohort with heart failure was recruited to fulfil the paediatric investigation plan (PIP) requirements. The PIP required a total of 85 evaluable patients from birth to less than 12 years of age with a subset cohort of 25 patients with heart failure due to dilated cardiomyopathy and a subset of 60 heart failure patients of congenital heart disease. Out of these, 54% of patients must be aged below 12 months to provide a substantial amount of young patients.

Results

The LENA consortium recruited 102 children from birth to 12 years. Out of those, 89 patients fulfilled relevant protocol criteria and could be regarded as evaluable. Of these, 26 demonstrated heart failure due to cardiomyopathy and 63 due to congenital heart disease. Sixty five patients (73%) were below 12 months of age. Moreover, 22 patients were below 3 months of age, 26 patients from 3 months to less than 6 months and 17 patients from 6 months up to 12 months of age.

Conclusions

The LENA consortium had recruited the PDCO required number of paediatric patients for the drug development program LENA. As more than 2/3 of patients belong to the most vulnerable patient population below the age of 12 months, relevant data can be generated to fill gaps for the safe and reliable treatment with ACE-inhibitors of children with heart failure.

References

The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement n°602295 (LENA)

Disclosure(s)

Nothing to disclose
P60 Serum Creatinine is superior to Serum Cystatin C in explaining inter-individual variability of vancomycin clearance in neonates and young infants
Authors: Leroux S , Biran V , van den Anker J , Zhao W , Jacqz-Aigrain E , Pfister M
Published: May 2019

Background

Serum creatinine (SCr) is used as a surrogate marker of glomerular filtration rate to guide dosing of drugs eliminated by the kidney. Serum Cystatin C (S-CysC) has been suggested as a more reliable biomarker than SCr for monitoring kidney function in adults and children. Purpose of this study was to evaluate whether S-CysC is a more useful marker for estimating vancomycin clearance in neonates and young infants.

Methods

Pharmacokinetic (PK), Scr and S-CysC data were collected in patients undergoing continuous intravenous vancomycin treatment in the neonatal intensive care unit of Robert Debré Hospital - Paris. A population PK analysis was performed with the software package NONMEM, utilizing vancomycin therapeutic drug monitoring samples. S-CysC and SCr were compared in terms of usefulness to explain inter-individual variability (IIV) of vancomycin clearance. Statistical criteria were used for covariate selection.

Results

A total of 58 concentrations from 47 patients (gestational age [GA] ranging from 23 to 41 weeks and postmenstrual age [PMA] ranging from 26 to 46 weeks) were modeled with an allometric one-compartment model with first-order elimination. The median (range) values for SCr and S-CysC were 41.5 (12.0 to 102.0) µmol/L and 1.38 (0.95 to 2.32) mg/L, respectively. When tested individually, SCr and S-CysC explained 26.4% and 9.8% of IIV of vancomycin clearance, respectively. PMA was superior as a covariate on clearance, over the combination of GA and postnatal age. As such, bodyweight, PMA, and SCr were retained as significant covariates on clearance in the final model.

Conclusions

Serum Creatinine was found to be more useful than Serum Cystatin C to explain IIV of vancomycin clearance in this population. Further studies are needed to evaluate the utility of renal biomarkers to predict clearance and dosing of renally eliminated drugs in neonates.

Disclosure(s)

Nothing to disclose
How do patients from South Asian backgrounds experience life on haemodialysis in the UK? A multicentre qualitative study
Authors: Sharma Shivani , King Madeline , Mooney Roisin , Davenport Andrew , Day Clara , Duncan Neill , Modi Kirit , Da Silva-Gane Maria , Wellsted David , Farrington Ken
Published: May 2019

Objectives

End-stage kidney disease disproportionately affects people of South Asian origin. This study aimed to uncover the lived experiences of this group of patients on centre-based haemodialysis (HD), the most prevalent dialysis modality.

Design

The study utilised a qualitative focus group methodology. Seven focus groups were conducted across four NHS Trusts in the UK including three in Gujarati and two each in Punjabi and Urdu. This provided an inclusive opportunity for South Asian patients to contribute in their language of origin. A total of 24 patients participated. Focus groups were facilitated by bilingual project workers and data were forward translated and analysed using thematic analysis.

Results

Four themes were identified. This included (1) ‘treatment imposition’, which comprised of the restrictive nature of HD, the effects of treatment and the feeling of being trapped in an endless process. (2) The ‘patient–clinician relationship’ centred around the impact of a perceived lack of staff time, and inadequacies in the quality of interactions. (3) ‘Coping strategies’ highlighted the role of cognitive reappraisal, living in the moment and family support networks in facilitating adjustment. (4) ‘Pursuit of transplantation’ included equating this form of treatment with restoring normality, alongside cultural factors limiting hopefulness for receiving an organ.

Conclusions

In general, the experiences of South Asian patients receiving HD were not unique to this ethnic group. We did find distinct issues in relation to interactions with healthcare professionals, views on access to transplantation and the importance of family support networks. The study provides useful insights which may help enhance culturally tailored renal care.
Prevalence and impact of clinical violence towards nursing students in Hong Kong: a cross-sectional study
Authors: Cheung Kin , Ching Shirley SY , Cheng Samuel Hung Nam , Ho Simone Sin Man
Published: May 2019

Objectives

Studies of violence towards nursing students (NSs) have been scattered mainly in the West and Middle East, but to date there have been no studies in Eastern countries. Differences in nursing education systems and cultures might have contributed to variations in incidences of clinical violence. The purpose of this study was to investigate the prevalence, associated factors and impact of clinical violence to NSs.

Methods

This was a cross-sectional survey study. Convenience sampling was used to recruit university NSs from March to June 2012 in classroom settings in Hong Kong. A valid and reliable questionnaire was used to collect the data. 1297 questionnaires were distributed and 1017 NSs completed questionnaires, with a response rate of 78.41%.

Results

Of the 1017 NSs, 37.3% (n=379) reported having experienced clinical violence during their nursing studies. The prevalence of verbal abuse (30.6%) was significantly greater than that of physical violence (16.5%). The perpetrators of verbal abuse were predominantly patients (66.8%), hospital staff (29.7%), university supervisors (13.4%) and patients’ relatives (13.2%). Patients (91.0%) were the greatest source of physically violent assaults. Compared with those who had experienced physical violence, the NSs who had experienced verbal abuse were more likely not to take action, and not to stop or report the incident, but were also more likely to tell their friends/families. Although the negative effects on emotions, clinical performance and the extent to which they were disturbed by the violence were significantly greater for verbal abuse than that for physical violence, their intention to leave the nursing profession after experiencing either verbal or physical violence was significantly higher after than before the experience (p<0.001).

Conclusions

Our results found a moderately high prevalence of clinical violence among NSs. Provision and/or reinforcement of appropriate training about clinical violence in the nursing curricula is necessary.
Effectiveness of antitussives, anticholinergics or honey versus usual care in adults with uncomplicated acute bronchitis: a study protocol of an open randomised clinical trial in primary care
Authors: Cots Josep M , Moragas Ana , García-Sangenís Ana , Morros Rosa , Gomez-Lumbreras Ainhoa , Ouchi Dan , Monfà Ramon , Pera Helena , Pujol Jesus , Bayona Carolina , de la Poza-Abad Mariam , Llor Carl
Published: May 2019

Introduction

Despite the frequent use of therapies in acute bronchitis, the evidence of their benefit is lacking, since only a few clinical trials have been published, with low sample sizes, poor methodological quality and mainly in children. The objective of this study is to compare the effectiveness of three symptomatic therapies (dextromethorphan, ipratropium or honey) associated with usual care and the usual care in adults with acute bronchitis.

Methods and analysis

This will be a multicentre, pragmatic, parallel group, open randomised trial. Patients aged 18 or over with uncomplicated acute bronchitis, with cough for less than 3 weeks as the main symptom, scoring ≥4 in either daytime or nocturnal cough on a 7-point Likert scale, will be randomised to one of the following four groups: usual care, dextromethorphan 30 mg three times a day, ipratropium bromide inhaler 20 µg two puffs three times a day or honey 30 mg (a spoonful) three times a day, all taken for up to 14 days. The exclusion criteria will be pneumonia, criteria for hospital admission, pregnancy or lactation, concomitant pulmonary disease, associated significant comorbidity, allergy, intolerance or contraindication to any of the study drugs or admitted to a long-term residence. Sample: 668 patients. The primary outcome will be the number of days with moderate-to-severe cough. All patients will be given a paper-based symptom diary to be self-administered. A second visit will be scheduled at day 2 or 3 for assessing evolution, with two more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance and complications. Patients still with symptoms at day 29 will be called 6 weeks after the baseline visit.

Ethics and dissemination

The study has been approved by the Ethical Board of IDIAP Jordi Gol (reference number: AC18/002). The findings of this trial will be disseminated through research conferences and peer-review journals.

Trial registration number

NCT03738917; Pre-results.
Permanent cessation of nail growth using multiple nail plate avulsions and phenolisation in a dog
Authors: Carbonell Buj Elena , Farrell Michael
Published: May 2019

A two‐year‐old Yorkshire terrier was referred for treatment of abnormal growth of all nails of both thoracic limbs. Progressive fear aggression precluded nail clipping without the use of chemical restraint. Permanent cessation of nail growth was achieved by nail plate avulsion and phenolisation in all eight thoracic limb digits. After three years of follow‐up, there was no evidence of nail regrowth on any of the digits. To the authors’ knowledge, this is the first report of nail plate avulsion and phenolisation of multiple digits in the veterinary literature.
Neonatal line may develop after birth in the Indo-Pacific bottlenose dolphin (Tursiops aduncus)
Authors: Kemper C.M. , Milano S. , Ciraolo A.C.
Published: May 2019

Studies using teeth to estimate age in marine mammals presume that the neonatal line (NNL) develops at birth. This study of Indo-Pacific bottlenose dolphins (Tursiops aduncus (Ehrenberg, 1833)) is the first to investigate when the NNL appears in odontocete dentine. Two to four teeth were prepared by decalcification, thin-sectioning, and staining for 103 dolphins, including 7 dolphins of known age. Tooth length, prenatal and postnatal dentine and NNL widths were measured. Developmental class (foetus, young neonate, older neonate, <1-year-old calf, 1-year-old calf) was assigned using carcass external features. NNL presence or absence was categorised for individual dolphins. The NNL was absent in a near-term foetus and all except one young neonate and fully formed in 50% of older neonates, whose estimated ages were 1 week to 2 months. It was absent in a known-age dolphin aged 4–7 weeks. NNL width was greater in dolphins less than 1 year old compared with those that were 1 year old. Factors that trigger NNL development are unknown. The present study suggests that the NNL may not be related to birth per se in dolphins, as has been clearly demonstrated in humans. Physiological processes, driven by diet, and behavioural changes during the first few months of postnatal life may be important drivers for NNL formation in odontocetes.
Lower reproductive output of Mountain Bluebirds (Sialia currucoides) in clearcut versus grassland habitat is consistent with a passive ecological trap
Authors: Stalwick J.A. , Wiebe K.L.
Published: May 2019

Clearcutting of forests results in habitats that structurally resemble grasslands and so may act as ecological traps for grassland birds. Several studies have implicated predation as the factor that decreases the number of offspring, but few have examined performance at other breeding stages. Consistent with a passive ecological trap, Mountain Bluebirds (Sialia currucoides (Bechstein, 1798)) that settled in clearcuts in central British Columbia did not differ in age or quality from adults in grasslands. Nest building and laying date of the first egg did not differ between habitats, suggesting an equal propensity for settling in each habitat. In clearcuts, however, the body condition of female parents was lower, and they abandoned their nests more often in harsh weather. This higher total clutch loss in clearcuts meant that seasonal production of fledglings per female was 13% less in clearcuts. Furthermore, fledglings in grasslands weighed 4% more and female fledglings had plumage with shorter (UV-shifted) wavelengths (hence greater ornamentation) than those in clearcuts, suggesting that they were also of better quality. Thus, predation rates were not the cause of reduced reproduction in clearcuts; rather, our results suggest that lower prey abundance was linked to nest abandonment in harsh weather and reduced both the number and quality of offspring in those habitats.
Distributed impulsive consensus of nonlinear multi-agent systems with input saturation
Authors: Liu Xiaolu , Chen Duxin , Wang Yan-Wu
Published: May 2019

This paper investigates the leader-follower exponential consensus problem of a class of Lipschitz nonlinear multi-agent systems (MASs) with input saturation. Since each agent has nonlinear dynamics, the system is not asymptotically null controllable with bounded controls. Therefore, the widely-used low-gain feedback method for designing consensus protocols of MASs with input saturation can no longer work. Taking advantage of the stability theory of impulsive systems and features of the Laplacian matrix, and combining the properties of convex hull, a distributed impulsive consensus protocol is proposed. Still, the shape reference set is introduced to assess the attraction domain of leader–follower MASs. Finally, a numerical experiment validates the effectiveness of the proposed anti-saturation impulsive consensus algorithm.
Research on interpersonal relationship network of pyramid scheme organization based on social network: A case study
Authors: Feng Pihu , Gong Zaiwu , Sun Duoyong
Published: May 2019

As a form of organized crime, pyramid scheme has brought huge economic losses to many countries, especially China, and caused serious social problems. How to deeply analyze the structure of pyramid scheme organizations is a necessary topic to explore and combat pyramid scheme organizations. Social network analysis is an effective method to study organized crime. Among them, the motif and exponential random graph models are effective tools for studying organizational microstructure, endogenous process. For the first time, this paper uses the social network analysis to study the interpersonal relationship network of a specific pyramid scheme organization, the typical case of “5.03” in Hunan Province was taken as the research object, and the above model was used for modeling analysis. The results show that the interpersonal relationship network has a sparse density. The microstructure is not a pyramid structure that is generally considered, but presents more ternary closures. Cross-community links, cross-level links between core employees and surrounding employees are less. The pyramid scheme network of interpersonal relationships has obvious homogeneity characteristics.
The effects of the size and structure on magnetic behavior of core/shell nanoparticles
Authors: Le Long V. , Le Vinh V. , Ho Quy Q.
Published: May 2019

Molecular dynamics (MD) simulations have been employed to simulate the structure of Ni nanoparticles (NPs). These NPs consist of 500, 1372, 2916 and 5324 atoms. Various structures of these NPs, consisting of faced-centered cubic (fcc), hexagonal closed packed (hcp), icosahedral (ico) and amorphous states, have been simulated by changing the cooling rate from 2000 to 300 K. The models of mixed core/shell spin (1, 3/2) have been set based on the NPs. Monte Carlo (MC) simulation has been applied to investigate the magnetic behavior and phase diagrams of the models. We have found that the structure of the models plays important role on the characteristic phase diagrams. The effects of the atomic number as well as the exchange coupling J[Formula: see text]/J[Formula: see text] (J[Formula: see text] — the shell coupling and J[Formula: see text] — the core coupling) on the thermal and magnetic behaviors of the models have been presented and discussed. The phase diagrams in k[Formula: see text]T/J[Formula: see text]−J[Formula: see text]/J[Formula: see text] plane also have been observed by changing the structure and the number atoms of the models.
Influence of the counter-rotating terms on the quantum dynamics of the damped harmonic oscillator in a deformed bath
Authors: Daeimohammad Mohsen
Published: May 2019

The aim of the present study is to investigate the effect of the counter-rotating terms on the quantum dynamics of a harmonic oscillator in the presence of a deformed bath. We first obtain the Langevin equation of motion for damped oscillator with and without the rotating-wave approximation (RWA). Then, we study the effect of the counter-rotating terms on the diffusion coefficients. Then, we obtain the equation of motion for the harmonic oscillator correlation function with and without the RWA. Finally, we investigate the influence of the counter-rotating terms on the oscillator correlation function.
A comparative study of finite frequency scattering rate from Allen, Mitrović–Fiorucci, Shulga–Dolgov–Maksimov, Sharapov–Carbotte and memory function formalisms
Authors: Bhalla Pankaj , Singh Navinder
Published: May 2019

We report a comparative study of scattering rates which are calculated using different formalisms such as [P. B. Allen, Phys. Rev. B 3, 305 (1971); S. V. Shulga, D. V. Dolgov and E. G. Maksimov, Physica C 178, 266 (1991); B. Mitrović and M. A. Fiorucci, Phys. Rev. B 31, 2694 (1985); S. G. Sharapov and J. P. Carbotte, Phys. Rev. B 72, 134506 (2005)] and memory function formalism (MemF) [H. Mori, Prog. Theor. Phys. 33, 423 (1965)]. An advantage of this study is that it sheds light on the physical assumptions used in these formalisms. In this context, we consider a case of electron–phonon interaction and discuss frequency- and temperature-dependent behavior of scattering rates. Further, a comparative study of scattering rate proceeds for distinct phonon density of states (PDOS) and electron density of states (EDOS). From the detailed analysis, we observe that the MemF is the most general one and others are based on restrictive assumptions as discussed in this work.
Waveform control in generations of intense water window attosecond pulses via multi-color combined field
Authors: Li Liang , Zheng Mian , Feng R. Liqiang , Qiao Yan
Published: May 2019

The waveform control in the improvements of high-order harmonic generation (HHG) spectra and attosecond pulse signals driven by the two-color and three-color combined fields has been theoretically investigated. (a) The results show that by properly controlling the [Formula: see text]–2[Formula: see text] two-color laser beam (including the modulations of chirps, carrier envelope phases and delay time), either the harmonic cutoff can be extended, showing a water window spectral continuum, or the selective enhancement of the single-order and two-order harmonics can be found. Further, with the introduction of a third controlling field, the efficiency of spectral continuum can be enhanced by two orders of magnitude compared with that from the two-color field. Moreover, the enhancement of HHG is not very sensitive to the frequency of the third field (i.e., the frequency of the third field is chosen to be 3[Formula: see text], 4[Formula: see text] and 6[Formula: see text]). Thus, some water window attosecond pulses with the durations of 60 as can be obtained. (b) Furthermore, the harmonic cutoff can be further extended when using a half-cycle controlling pulse or introducing the inhomogeneous effect of the laser field. Moreover, the efficiency of HHG can be further improved when the initial state is prepared as the superposition state of the ground state and some excited state of He atom. Consequently, a much broader spectral continuum with an intensity enhancement of another two orders of magnitude can be found. Finally, through the Fourier transformation of some spectral continuum, the intense water window attosecond pulses with the durations of 60 as can be produced.
40 Years of Technological Innovation in China: A Review of the Four-Stage Climbing Track
Authors: Lei Jiasu , Liu Ying , Qi Yaoyuan , Zhang Qingzhi
Published: May 2019

This paper combs the landscapes of China’s technological innovation practice during the 40 years of reform and opening up, and describes it as “Four-Stage Climbing” that is, “Learning–Introducing–Supplying Stage” (LIS Stage), “Introducing–Imitating–Improving Stage” (III Stage), “Integrating–Boosting–Creating Stage” (IBC Stage), and the “Innovating–Iterating–Promoting Stage” (IIP Stage). It also explains the background of each stage and its specific innovation model. Furthermore, the paper emphasizes the main features, basic experiences and main lessons of China’s technological innovation practice during the past 40 years. This paper demonstrates that with the deepening of innovation-driven development, especially in the field of “Innovation Leads Development” which is valued by the country and industry, at this stage, it is urgent to pay closer attention to the following issues: first of all, the possible changes in mechanisms of international innovation competition and cooperation under the background of potential reconstruction for international governance; secondly, the occurrence and realization mechanism of Leading Scientific and Technological Innovation in the era of science and technology, as well as the structural and institutional mechanisms of the national innovation ecosystem, and also the ecological niche in which the future scientific innovation subject and technological innovation subject should be in the national innovation ecosystem; furthermore, the mechanism of innovation and development for “science-based industries”; last but not the least, the logical construction of innovation and development research under the Chinese context.
A Modal Intensity Distribution Estimation Algorithm Based on Horizontal Circular Array
Authors: Li Peng , Zhang Xinhua , Liu Bing , Li Lanrui , Li Jun
Published: May 2019

In shallow-water waveguide, the normal mode information of acoustic signals plays an important role in localization research. In this paper, an extraction algorithm of modal intensity distribution based on horizontal circular array is proposed. By using the horizontal wavenumber of each mode, the modal domain beamforming is used to estimate the modal intensity distribution of the acoustic signal. The theoretical derivation, data simulation and experimental data are used to verify the feasibility of the algorithm based on circular array and the superiority compared with the line array extraction algorithm. At the last part of the paper, an application based on modal intensity distribution is proposed: water surface interference suppression, and the effectiveness of the interference suppression algorithm is verified from theoretical derivation and simulation experiments.
Effect of acute high-phosphate intake on muscle metaboreflex activation and vascular function
Authors: Stephens Brandi Y. , Kaur Jasdeep , Vranish Jennifer R. , Barbosa Thales C. , Blankenship Jeanette K. , Smith Scott A. , Fadel Paul J.
Published: May 2019

Increased consumption of inorganic phosphate (Pi), an abundant ingredient in processed foods, has been associated with elevated cardiovascular disease risk; however, studies investigating underlying mechanisms are limited. Recently, high dietary Pi was shown to exaggerate the pressor response to static muscle contraction in rodents in part because of overactivation of metabolically sensitive skeletal muscle afferents. Whether acute high Pi consumption affects muscle metaboreflex activation in humans remains unknown. Furthermore, although acute high Pi consumption has been shown to impair vascular function in young healthy men, equivocal results have been reported. Therefore, we hypothesized that acute high Pi consumption augments mean arterial pressure (MAP) responses during muscle metaboreflex activation, impairs endothelial function, and increases arterial stiffness in young healthy men. Subjects performed 35% maximal voluntary contraction static handgrip (HG), followed by postexercise ischemia (PEI) to isolate muscle metaboreflex activation. Resting flow-mediated dilation (FMD) and arterial stiffness were assessed. Measures were made before (pre) and 60 min after (post) subjects consumed either a high-phosphate drink (2,000 mg phosphorus and 1,520 mg sodium) or a sodium drink (1,520 mg sodium; control). MAP responses during HG (preΔ = +23 ± 3 mmHg; postΔ = +21 ± 2 mmHg; P = 0.101) and PEI (preΔ = +21 ± 4 mmHg; postΔ = +18 ± 3 mmHg; P = 0.184) were similar before and after Pi consumption. In contrast, FMD was significantly attenuated following Pi (pre = 5.1 ± 0.5%; post = 3.5 ± 0.5%; P = 0.010), whereas arterial stiffness remained unchanged. There were no changes in any measured variable after control drink consumption. In summary, although the muscle metaboreflex remains unaffected following acute high Pi consumption in young healthy men, endothelial function is impaired.

NEW & NOTEWORTHY This study was the first to investigate the influence of acute high-phosphate consumption on the pressor response during isometric handgrip and isolated muscle metaboreflex activation during postexercise ischemia in young healthy humans. We demonstrated that a single high dose of phosphate (2,000 mg) did not augment blood pressure in response to exercise or isolated muscle metaboreflex activation, but endothelial function was blunted in young healthy men.
Phosphorylation of SOCS1 Inhibits the SOCS1–p53 Tumor Suppressor Axis
Authors: Saint-Germain Emmanuelle , Mignacca Lian , Huot Geneviève , Acevedo Mariana , Moineau-Vallée Karine , Calabrese Viviane , Bourdeau Véronique , Rowell Marie-Camille , Ilangumaran Subburaj , Lessard Frédéric , Ferbeyre Gerardo
Published: May 2019

Expression of the suppressor of cytokine signaling-1 (SOCS1) is inactivated in hematopoietic and solid cancers by promoter methylation, miRNA-mediated silencing, and mutations. Paradoxically, SOCS1 is also overexpressed in many human cancers. We report here that the ability of SOCS1 to interact with p53 and regulate cellular senescence depends on a structural motif that includes tyrosine (Y)80 in the SH2 domain of SOCS1. Mutations in this motif are found at low frequency in some human cancers, and substitution of Y80 by a phosphomimetic residue inhibits p53–SOCS1 interaction and its functional consequences, including stimulation of p53 transcriptional activity, growth arrest, and cellular senescence. Mass spectrometry confirmed SOCS1 Y80 phosphorylation in cells, and a new mAb was generated to detect its presence in tissues by IHC. A tyrosine kinase library screen identified the SRC family as Y80-SOCS1 kinases. SRC family kinase inhibitors potentiated the SOCS1–p53 pathway and reinforced SOCS1-induced senescence. Samples from human lymphomas that often overexpress SOCS1 also displayed SRC family kinase activation, constitutive phosphorylation of SOCS1 on Y80, and SOCS1 cytoplasmic localization. Collectively, these results reveal a mechanism that inactivates the SOCS1–p53 senescence pathway and suggest that inhibition of SRC family kinases as personalized treatment in patients with lymphomas may be successful.

Significance:

These findings show that SOCS1 phosphorylation by the SRC family inhibits its tumor-suppressive activity, indicating that patients with increased SOCS1 phosphorylation may benefit from SRC family kinase inhibitors.
Retinoblastoma Loss in Cancer: Casting a Wider Net
Authors: Choudhury Atish D. , Beltran Himisha
Published: May 2019

Capturing both genomic and nongenomic mechanisms of retinoblastoma gene dysfunction has potential to improve risk stratification and patient selection for biomarker-driven therapy. A 186-gene expression signature is capable of identifying Rb loss across cancer types, providing a new framework for assessing Rb dysfunction based on transcriptome data.

See related article by Chen et al., p. 4290
Human Endogenous Retrovirus-H and K Expression in Human Mesenchymal Stem Cells as Potential Markers of Stemness
Authors: Mareschi Katia , Montanari Paola , Rassu Marco , Galliano Ilaria , Daprà Valentina , Adamini Aloe , Castiglia Sara , Fagioli Franca , Bergallo Massimiliano
Published: May 2019

Objective: The human endogenous retroviruses (HERVs) are endogenous retroviruses that were inserted into the germ cell DNA of humans over 30 million years ago. Insertion of HERVs into the chromosomal DNA can influence a number of host genes in various modes during human evolution and their proviral long terminal repeats can participate in the transcriptional regulation of various cellular genes. Our aim was to evaluate the pol gene expression of HERV-K and HERV-H in mesenchymal stem cells (MSCs) in relation with the expression of stemness genes such as NANOG, OCT-4, and SOX-2. Methods: MSCs were isolated from bone marrow of healthy donors and expanded until the 5th passage in α-MEM with 10% fetal bovine serum. HERV-K, HERV-H pol gene, NANOG, OCT-4, SOX-2, and GAPDH expression was quantified by real-time PCR in MSCs during the expansion. Results: HERV-K and HERV-H expression was always higher at p1 compared to other passages and this difference reached a high statistical significance when passage p1 was compared with passage 3. In addition, NANOG, OCT-4, and SOX-2 expression at p1 was significantly higher than their expression at p3. Pearson’s test demonstrated a strong correlation between the expression of HERV-K and HERV-H and the expression of NANOG, OCT-4, and SOX-2. Conclusions: Our findings showed that HERV-K and H were concurrently expressed with pluripotency biomarkers NANOG, OCT-4, and SOX-2.
Distribution and Determinants of Dermatophagoides Mites Sensitization ofAllergic Rhinitis and Allergic Asthma in China
Authors: Chen Zhuang-Gui , Li Ya-Ting , Wang Wei-Hao , Tan Kai Sen , Zheng Rui , Yang Li-Fen , Guan Wei-Jie , Hong Hai-Yu , Yang Qin-Tai
Published: May 2019

Background: The implementation of allergen immunotherapy (AIT) requires extensive knowledge of allergen distribution in the region to identify high-risk regions for AIT utilization. However, the geographical distribution patterns of the major Dermatophagoides allergens in China remain unclear despite the increasing prevalence of these allergens. Methods: We performed comprehensive database searches of articles demonstrating the distribution patterns of Dermatophagoides-sensitized allergic rhinitis (AR) and allergic asthma (AA) in China, published between 1990 and 2017. Results: We retrieved 163 articles encompassing 114,302 allergen-positive cases to generate the distribution maps. The rate of sensitization to Dermatophagoides pteronyssinus(D. pteronyssinus)and Dermatophagoides farinae (D. farinae) was similar in patients with AR (75.1 vs. 75.2%, p > 0.05) but not in those with AA (78.5 vs. 77.7%, p = 0.041). Patients with AR and AA shared similar regional distribution patterns of both D. pteronyssinus and D. farinae sensitization, which were highest in the southern and central parts of China and lowest in the northern regions, especially in the Northwest. The overall rate of sensitization to D. pteronyssinus and D. farinae was significantly higher in patients with AA (p < 0.001). Additionally, the annual mean temperature and humidity were the 2 major determinants of D. pteronyssinus and D. farinae sensitization in AR and of D. pteronyssinus sensitization in AA, whereas the annual mean temperature was the sole determinant for D. farinae sensitization in AA. Conclusion: These findings may inform clinicians of the strategies for the prevention of Dermatophagoides sensitization and may be of benefit to the future clinical management of allergic diseasesassociated with sensitization to Dermatophagoides mites.
Correlation between Basal Macular Circulation and Following Glaucomatous Damage in Progressed High-Tension and Normal-Tension Glaucoma
Authors: Lee Chia-Yi , Liu Chin-Hsing  , Chen Hung-Chi , Sun Chi-Chin  , Yao Yen-Po , Chao Shih-Chun 
Published: May 2019

Objectives: Evaluate the correlation between basal macular circulation and late structural damage in progressed high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) via optical coherence tomography angiography (OCTA). Methods: Patients who received an OCTA examination were divided into progressed HTG, progressed NTG, and well-controlled HTG (control) groups. Superficial macular vessel density (SmVD), deep macular vessel density (DmVD), foveal avascular zone (FAZ), and flow area of the outer retina and choriocapillaris were obtained by one OCTA device. Associations between macular angiography and glaucoma parameters, including the visual field, retinal nerve fiber layer, and ganglion cell complex, were analyzed. Results: A total of 60 eyes from 60 patients were enrolled. The progressed HTG and NTG groups had lower SmVD than the control group, while the progressed NTG group had lower DmVD and a larger FAZ than the control group. The flow area of the outer retina in the progressed HTG group was lower than that of the control. A significant correlation between SmVD and glaucoma parameters was found in the progressed HTG group, while a similar correlation between SmVD and DmVD to glaucoma parameters was observed in the progressed NTG group. Conclusion: The progressed HTG and NTG patients showed an impaired vascular intake before significant disease development compared to well-controlled cases.
SCCA-IgM as a Potential Biomarker of Non-Alcoholic Fatty Liver Disease in Patients with Obesity, Prediabetes and Diabetes Undergoing Sleeve Gastrectomy
Authors: Bettini Silvia , Bordigato Emanuel , Milan Gabriella , Dal Pra’ Chiara , Favaretto Francesca , Belligoli Anna , Sanna Marta , Serra Roberto , Foletto Mirto , Prevedello Luca , Busetto Luca , Fassina Giorgio , Vettor Roberto , Fabris Roberto
Published: May 2019

Background: Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in obesity and its presence should be screened. Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for obesity, but its effects on NAFLD are still to be firmly established. The diagnosis of non-alcoholic steatohepatitis (NASH) is currently performed by liver biopsy, a costly and invasive procedure. Squamous cell carcinoma antigen-IgM (SCCA-IgM) is a biomarker of viral hepatitis to hepatocellular carcinoma development and its role in NAFLD to NASH progression has not yet been investigated. Objective: The aim of this study was to evaluate SCCA-IgM as a non-invasive biomarker of NAFLD/NASH in patients with different degrees of metabolic-complicated obesity before and after LSG. Method: Fifty-six patients with obesity were studied before and 12 months after LSG; anthropometric, biochemical, clinical, and imaging data were collected. Results: At baseline steatosis was strongly associated with the glycaemic profile (p = 0.016) and was already present in prediabetic patients with obesity (82%). Only 3 patients had an SCCA-IgM level above the normal cut-off. SCCA-IgM titre did not change according to glycaemic profile or steatosis. Metabolic and inflammatory factors and transaminases significantly reduced after LSG-induced weight loss, except for SCCA-IgM. The ALT/AST ratio decreased post-LSG correlated with BMI (r = 0.297, p = 0.031), insulin (r = 0.354, p = 0.014), and triglycerides (r = 0.355, p = 0.009) reduction. Conclusions: Our results confirm the tight link between NAFLD and metabolic complications, suggesting prediabetes as a new risk factor of steatosis. SCCA-IgM does not seem to have a role in the identification and prognosis of NAFLD.
The Effect of Vitamin D Supplement Consumption on Premenstrual Syndrome in Vitamin D-Deficient Young Girls: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Authors: Abdollahi Reihaneh , Abiri Behnaz , Sarbakhsh Parvin , Kashanian Maryam , Vafa Mohammadreza
Published: May 2019

Background: Premenstrual syndrome (PMS) alludes to a cyclic advent of somatic and psychiatric symptoms that affect some women of reproductive age. Some studies demonstrated that vitamin D was associated with premenstrual symptoms. Objective: The aim of this study was to evaluate the effect of vitamin D supplementation in the treatment of PMS in vitamin D-deficient young girls. Methods: In this randomized double-blind placebo-controlled trial, 130 vitamin D-deficient girls aged 18–30 years, with PMS, were randomly divided into 2 groups and received a 2,000 IU vitamin D tablet (n = 64) or a placebo (n = 66) every other day for 12 weeks. At the beginning and at the end of week 12, serum 25(OH)-D, premenstrual symptoms, anthropometric indices, dietary intake, physical activity level, and sun exposure were evaluated. Statistical analysis was performed using SPSS version 20. p < 0.05 was considered statistically significant. Results: Serum 25(OH)-D levels were significantly elevated in the vitamin D group in comparison to the placebo group after 12 weeks (p < 0.001). There was no significant difference between the 2 groups with regard to 14 symptoms of PMS after 12 weeks of intervention, even after adjustment for the baseline values of anxiety, weeping, and hypersomnia (for all symptoms, p > 0.05). However, in the vitamin D group, scores of nervousness (p < 0.001), job activity reduction (p = 0.01), social activity reduction (p = 0.01), fatigue (p < 0.001), and physical symptoms (p = 0.00) were reduced at the end of the intervention, and these changes were statistically significant compared to baseline. However, these alterations did not reach significance compared with the placebo group (p > 0.05). Conclusion: It seems that 2,000 IU vitamin D consumption in the vitamin D-deficient young girls with PMS every other day for 12 weeks had no significant impact on other PMS symptoms.
Comunicação, história e memória
Authors: Barbosa Marialva Carlos
Published: May 2019

O artigo reflete sobre os possíveis diálogos entre a comunicação, a história e a memória, tendo como fio condutor uma carta ditada por uma escrava no século XIX. Nota que esse documento representa um emblemático diálogo entre a comunicação e a história, sendo um ato de comunicação entre múltiplos atores. Discute as temporalidades na comunicação e na história, os atos narrativos que ambas produzem e o esfacelamento contemporâneo da articulação entre passado, presente e futuro, notando que a historicidade é governada hoje pela ação midiática. Ao fim, aborda a problemática da memória e sua presença no universo da comunicação e da história, refletindo sobre os múltiplos esquecimentos relacionados à escravidão no Brasil.
Por uma genealogia do ódio online
Authors: Ferraz Maria Cristina Franco , Saint Clair Ericson
Published: May 2019

Investiga-se, em perspectiva filosófica, o fenômeno da disseminação de ódio nas redes sociais, com ênfase em seus mecanismos de funcionamento. São convocados os conceitos de contágio e ressentimento na esteira de Gabriel Tarde e Friedrich Nietzsche. Tarde concebe a sugestibilidade de crenças e desejos (imitação) como força motriz de produção do socius. A viralização torna-se vetor de produção de homogeneidades instáveis, sob fundo móvel de diferenças. Nietzsche disseca a lógica de operação do ressentimento, enfatizando a invenção de relações dicotômicas regidas pela negatividade, criando tanto valores morais quanto a polarização nós e outros. Privilegia-se, assim, a análise do plano molecular em uma política dos afetos.
No jardim das delícias
Authors: Rocha Everardo , Lana Lígia
Published: May 2019

Neste artigo, analisamos os modos como a mídia noticiou a passagem de Brigitte Bardot pelo Rio de Janeiro, entre janeiro e abril de 1964, buscando compreender as relações entre o fenômeno da fama e a cultura. A visita da estrela francesa contribuiu para o desenvolvimento do turismo em Búzios. Investigamos os modos como a atriz se posicionou como celebridade, negociando sua presença na mídia carioca. Examinamos também os discursos que envolveram a caracterização de Brigitte Bardot como símbolo sexual feminino. As conclusões indicam três dualidades marcantes da vinda da atriz ao Brasil: o amor e o ódio com relação à mídia; a fama e o anonimato; as celebridades e a promoção do consumo.
Eles cresceram tão rápido:
Authors: Holzbach Ariane Diniz
Published: May 2019

A proposta deste artigo é entender de que maneira os canais transnacionais dialogam com conteúdos nacionais, tendo em vista, para isso, a consolidação do Cartoon Network Brasil e uma análise do desenho brasileiro Irmão do Jorel, produzido por uma produtora brasileira em parceria com o canal que o veicula. Os resultados mostram que o desenho incorpora variadas características locais, vinculadas ao lugar onde é produzido, ao mesmo tempo em que explora em sua narrativa elementos globais, reconhecidos internacionalmente. Todavia, a definição de global enfatizada pelo desenho perpassa especificamente o contexto midiático estadunidense, o que demarca um olhar autocentrado e autorreferente em torno do Cartoon Network.
Pesquisa e metapesquisa sobre comunicação na América Latina
Authors: Fuentes Navarro Raúl
Published: May 2019

Este artigo aborda e propõe a discussão, a partir de uma perspectiva comunicacional, das relações estratégicas e práticas entre a pesquisa e a metapesquisa da comunicação na América Latina. Para tanto, ressalta-se a importância da história como fator complementar essencial à estatística, bem como algumas reflexões controversas sobre postulados que parecem indispensáveis para retomar o debate na comunidade acadêmica e perante os órgãos responsáveis pela avaliação e orientação da ciência.
Moisés de Lemos Martins
Authors: Carvalho Carlos Alberto
Published: May 2019

Entrevista com o professor Catedrático da Universidade do Minho, Moisés de Lemos Martins, doutor em Sociologia pela Universidade de Estrasburgo, França, é o fundador e o diretor do único centro de excelência em investigação nas áreas da comunicação e dos estudos culturais, em Portugal, segundo a avaliação da Fundação para a Ciência e a Tecnologia (FCT).
Prevalence and factors associated to chronic kidney disease in older adults
Authors: Amaral Thatiana Lameira Maciel , Amaral Cledir De Araújo , Vasconcellos Maurício Teixeira Leite de , Monteiro Gina Torres Rego
Published: May 2019

OBJECTIVE: To verify the prevalence of chronic kidney disease and the factors associated to it in older adults (≥ 60 years). METHODS: This is a population-based research conducted in 2014, involving 1,016 older adults living in urban and rural areas of the municipality of Rio Branco, Acre. Chronic kidney disease was defined by glomerular filtration rate < 60 ml/min/1.73 m², estimated by the equations of the Chronic Kidney Disease Epidemiology Collaboration, and the presence of albuminuria > 29 mg/g. Association measure were estimated by gross and adjusted odds ratio (OR), with a confidence level of 95% (95%CI). RESULTS: The overall prevalence of chronic kidney disease was 21.4% in older adults, with the associated factors age, diabetes (OR = 3.39; 95%CI 2.13–5.40), metabolic syndrome (OR = 2.49; 95%CI 1.71–3.63), self-assessment of poor health (OR = 1.79; 95%CI 1.10–2.91), arterial hypertension (OR = 1.82; 95%CI 1.04–3.19) and obesity (OR = 1.69; 95%CI 1.02–2.80). CONCLUSIONS: The prevalence of chronic kidney disease was high in older adults, being associated with age, self-assessment of health as bad or very bad, obesity, diabetes and metabolic syndrome.
Health system financing paradigm in the state of São Paulo
Authors: Soares Adilson
Published: May 2019

OBJECTIVE: To analyze the allocation of financial resources in the Brazilian Unified Health System (SUS) in the state of São Paulo by level of care, health region, source of funds and level of government. METHODS: This is an exploratory study based on 2014 data extracted from the Public Health Budget Database, presented in absolute terms, relative terms and per capita. RESULTS: In 2014, R$52.1 bi were spent on public health, 58.0% having corresponded to the expenditures of the municipalities and 42.0% to those of the state government. Regional per capita spending varied from R$561.75 to R$824.85. As for the per capita spending on primary health care, which represented 37.5% of the municipalities’ total expenditure, the lowest value was found in the city of São Paulo and the highest, in Araçatuba. Campinas had the highest per capita expenditure on medium and high complexity care, while Presidente Prudente had the lowest. The highest regional percentage of the current net revenue spent on health was verified in Registro, and the lowest, in the city of São Paulo. CONCLUSIONS: The paradigm of the health sector’s financing in São Paulo revealed that the expenditure on primary health care, level elected by health policy as strategic because it depends on coordination and integral health care in the attention networks, was not considered a priority in relation to the expenditure with the medium and high complexity, exposing the iniquities in the state’s regions.