bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Measurement of Low‐Energy Electron Foreshock Beams
Authors: Soucek Jan , Píša David , Santolík Ondrej
Published: April 2019

Electrostatic plasma waves above and below the local electron plasma frequency represent a characteristic feature of the foreshock region. These waves are known to be generated by electron beams originating from the bow shock and their spectrum varies from narrowband intense waves close to foreshock edge to weaker broadband emissions further downstream. We present a statistical analysis of electron beams observed in the terrestrial foreshock by the Cluster spacecraft. We compared the energy of foreshock electron beams with the spectrum of electrostatic waves and established a clear correspondence between beam energy and spectrum of the waves. The broadband emissions are correlated with low‐energy beams, while high‐energy electron beams are associated with narrowband Langmuir waves. Next we solved the linear dispersion relation for a subset of observed electron plasma distributions. We discovered that while the observed electron distributions often exhibit a “bump on tail” feature necessary for an instability, the observed combination of beam energy, density, and temperature typically corresponds to a stable situation. This indicates that strongly unstable electron beams are quickly dissipated by the quasi‐linear processes and only stable or marginally stable beams persist long enough to be observed by the instrument.
Three dimensional printing of metamaterial embedded geometrical optics (MEGO)
Authors: Sadeqi Aydin , Rezaei Nejad Hojatollah , Owyeung Rachel E. , Sonkusale Sameer
Published: April 2019

Three-dimensional printers have revolutionized many scientific fields with its low-cost, accessibility and ease of printing. In this paper, we show how stereolithography (SLA) based 3D printers can enable realization of innovative 3D optical devices formed through the fusion of metamaterials with geometrical optics or MEGO. It utilizes a combination of desktop SLA 3D printer and metal deposition/coating systems. Using this approach, we present innovative metamaterial embedded optical components such as mushroom-type metamaterials, curved wide-angle metamaterial absorbers/reflectors and a frequency selective moth eye hemispherical absorber. Finally a unique MEGO device formed through the fusion of a frequency selective metamaterial with an optical parabolic reflector has been demonstrated that combines their individual properties in a single device. The fabricated MEGO devices operate in the millimeter wave frequency range. Simulation and measurement results using terahertz continuous-wave spectrometer validate their functionality and performance. With improving resolution in 3D printing, MEGO devices will be able to reach Terahertz and optical frequencies in the near future.
Reaction-based fluorometric analysis ofN-bromosuccinimide by oxidative deprotection of dithiane
Authors: Lee Yu Jeong , Choi Myung Gil , Park Tae Jung , Chang Suk-Kyu
Published: April 2019

A fluorescent probe based on the oxidative hydrolysis of the dithiane moiety has been developed for the first time for the assay ofN-bromosuccinimide.
Systematic analysis of enoxaparins from different sources with online one- and two-dimensional chromatography
Authors: Ouyang Yilan , Zhu Meng , Wang Xin , Yi Lin , Fareed Jawed , Linhardt Robert J. , Zhang Zhenqing
Published: April 2019

Enoxaparin, one of the most important low-molecular-weight heparins (LMWHs), is widely used as a clinical anticoagulant.
Electrochemical reduction of CO2 using palladium modified boron-doped diamond electrodes: enhancing the production of CO
Authors: Jiwanti Prastika Krisma , Einaga Yasuaki
Published: April 2019

Electrochemical reduction of CO2 produced CO on PdBDD electrode at potential −1.6 V (vs. Ag/AgCl) in NaCl aqueous solution.
Synthesis and self-assembly of biobased poly(limonene carbonate)-block-poly(cyclohexene carbonate) diblock copolymers prepared by sequential ring-opening copolymerization
Authors: Bailer Janina , Feth Stefan , Bretschneider Felix , Rosenfeldt Sabine , Drechsler Markus , Abetz Volker , Schmalz Holger , Greiner Andreas
Published: April 2019

Diblock copolymers with a biobased PLimC block, showing well-defined bulk morphologies ranging from cylinders to HPL and lamellae, were prepared by sequential ROCOP.
Detection and identification ofO-GlcNAc-modified proteins using 6-azido-6-deoxy-N-acetyl-galactosamine
Authors: Guo Jianshuang , Zhang Guoqiang , Ma Jing , Zhao Caili , Xue Qingqing , Wang Jiyan , Liu Wenjie , Liu Kaihui , Wang Haifeng , Liu Ning , Song Qitao , Li Jing
Published: April 2019

Ac36AzGalNAc, as a metabolic probe, can robustly labelO-GlcNAc-modified proteins in cells with high selectivity.
Low‐altitude UAV air‐ground propagation channel measurement and analysis in a suburban environment at 3.9 GHz
Authors: Cui Zhuangzhuang , Briso César , Guan Ke , Matolak David W. , Calvo‐Ramírez César , Ai Bo , Zhong Zhangdui
Published: April 2019

Unmanned aerial vehicles (UAVs) have been applied to various promising applications because of their features of high‐mobility, portability, rapid deployment, and modest power consumption. Small UAVs fly at low altitudes and typically short distances from the ground controller. It is of interest and value to model the propagation channel between low‐altitude UAVs and ground stations. This article presents results of channel measurements at 3.9 GHz carried out in a suburban environment with a small‐size UAV flying at low altitudes, up to 40 m. The authors also present comparative results from ray‐tracing simulations. Height‐dependent models for path loss, root mean square (RMS) delay spread, and the number of multipath components are provided. The results illustrate that although multipath effects exist at low altitudes in this environment, the two‐ray path loss model works reasonably well in describing the channel behaviour. Initial ray tracing simulations show reasonable agreement with measurements. In addition, RMS delay spread results indicate that distant scatterers have an appreciable effect on the UAV air‐ground (AG) propagation channels, which can be different from some terrestrial channels. Authors’ results should be of use in the modelling of low‐altitude AG propagation channels and in the performance analysis of UAV‐enabled AG communication systems.
Synthesis and Characterization of Two Chiral Pyrrolyl α-Nitronyl Nitroxide Radicals and Determination of their Cytotoxicity and Radioprotective Properties in C6 Cells and Mice under Ionizing Radiation
Authors: Tian Min , Lan Ting , Gao Min , Li Bo , Zhang Gai , Wang Hai-Bo
Published: April 2019

In this study, two chiral nitronyl nitroxyl radicals, L1 and D1, were synthesized and evaluated for their potential radioprotective properties invitro and invivo. We synthesized the new stable nitronyl nitroxide radicals, L1 and D1, according to Ullman’s method, and their chemical structures were characterized using UV-vis absorption, electron spin resonance (ESR), and circular dichroism (CD) spectra. The cytotoxicity of L1 and D1 on C6 glioma cells (C6 cells) was examined using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. To study the anti-radiation effects of L1 and D1 on C6 cells, we determined the optical density (OD) values of irradiated C6 cells using the MTT assay. The effects of L1 and D1 on the survival rate of mice after radiation exposure was evaluated. To demonstrate the influence of L1 and D1 pre-treatment on the antioxidant enzyme system, we studied the activities of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GSH) in mouse plasma after exposure to 6.5 Gy gamma radiation. The results showed that L1 and D1 did not have any obvious cytotoxicity at concentrations below 125μgmL−1. Moreover, L1 and D1 had the same cytotoxic effects on C6 cells. L1 and D1 significantly enhanced C6 cell survival after 8, 10, and 12 Gy radiation exposure, and there was no significant difference in the OD values between L1 and D1. The effects of these drugs on mouse survival rates were dose-dependent. Pre-treatment with different concentrations of L1, D1, or WR2721 significantly increased the activity of SOD, CAT, and GSH and significantly decreased the activity of MDA compared with radiation exposure only. In addition, the activities of SOD, CAT, and GSH in the L1 group were higher than those in the D1 group, whereas the activity of MDA was lower. Therefore, L1 and D1 have potential as safe and efficient therapeutic drugs against radiation damage.
Lipid Mini-On: mining and ontology tool for enrichment analysis of lipidomic data
Authors: Clair Geremy , Reehl Sarah , Stratton Kelly G , Monroe Matthew E , Tfaily Malak M , Ansong Charles , Kyle Jennifer E
Published: April 2019

Here we introduce Lipid Mini-On, an open-source tool that performs lipid enrichment analyses and visualizations of lipidomics data. Lipid Mini-On uses a text-mining process to bin individual lipid names into multiple lipid ontology groups based on the classification (e.g. LipidMaps) and other characteristics, such as chain length. Lipid Mini-On provides users with the capability to conduct enrichment analysis of the lipid ontology terms using a Shiny app with options of five statistical approaches. Lipid classes can be added to customize the user’s database and remain updated as new lipid classes are discovered. Visualization of results is available for all classification options (e.g. lipid subclass and individual fatty acid chains). Results are also visualized through an editable network of relationships between the individual lipids and their associated lipid ontology terms. The utility of the tool is demonstrated using biological (e.g. human lung endothelial cells) and environmental (e.g. peat soil) samples.

Availability and implementation

Rodin (R package: https://github.com/PNNL-Comp-Mass-Spec/Rodin), Lipid Mini-On Shiny app (https://github.com/PNNL-Comp-Mass-Spec/LipidMiniOn) and Lipid Mini-On online tool (https://omicstools.pnnl.gov/shiny/lipid-mini-on/).

Supplementary information

Supplementary data are available at Bioinformatics online.
Place as a Social Determinant of Health: Narratives of Trauma and Homeland among Palestinian Women
Authors: Sousa Cindy A , Kemp Susan P , El-Zuhairi Mona
Published: April 2019

Despite calls for greater social work attention to the centrality of place in human life, the profession has yet to hone frameworks that fully capture the role of place in individual–collective identity and well-being. To move this agenda forward, this article draws on data from a series of focus groups to explore the placed experiences of women in Palestine. Analytically, it is informed by critical place inquiry, which emphasises the deeply interactional relationships between people and places, views place-centred practice and research as catalysts for active responses to the spatialised nature of power and injustice, and focuses centrally on the geographic and spatial dynamics of colonisation, and particularly settler colonialism, as key determinants of individual and collective well-being. Women’s spatial narratives revolved around individual–collective identity and sovereignty, focusing in particular on three interdependent factors: freedom of movement; possession and dispossession; and continuity of place. Findings also illuminated spatial practices of resistance by which women defend and promote identity and sovereignty. We conclude with recommendations for more explicit, critically informed attention to place in social work practice, education and research.
Systematic Analysis of the Impact of Diagnostic Delay on Bowel Damage in Paediatric Versus Adult Onset Crohn’s Disease
Authors: Schoepfer Alain , Santos Jessica , Fournier Nicolas , Schibli Susanne , Spalinger Johannes , Vavricka Stephan , Safroneeva Ekaterina , Aslan Nurullah , Rogler Gerhard , Braegger Christian , Nydegger Andreas
Published: April 2019

Background and Aims

Length of diagnostic delay is associated with bowel strictures and intestinal surgery in adult patients with Crohn’s disease [CD]. Here we assessed whether diagnostic delay similarly impacts on the natural history of paediatric CD patients.

Methods

Data from the Swiss IBD Cohort Study were analysed. Frequency of CD-related complications [bowel stenosis, perianal fistula, internal fistula, any fistula, resection surgery, fistula/abscess surgery, any complication] at diagnosis and in the long term [up to 30 years after CD diagnosis] was compared between paediatric patients [diagnosed <18 years] and adult patients [diagnosed ≥18 years] using multivariate Cox proportional hazard regression modelling.

Results

From 2006 to 2016, 387 paediatric and 1163 adult CD patients were included. Median [interquartile range: IQR] diagnostic delay was 3 [1–9] for the paediatric and 6 [1–24] months for the adult group, respectively. Adult onset CD patients presented at diagnosis more frequently with bowel stenosis [p <0.001] and bowel surgery [p <0.001] compared with paediatric CD patients. In the long term, length of diagnostic delay was significantly associated with bowel stenosis [p = 0.001], internal fistula [p = 0.038], and any complication [p = 0.024] in the adult onset CD population. No significant association between length of diagnostic delay and CD-related outcomes in the long term was observed in the paediatric population.

Conclusions

Adult CD patients have longer diagnostic delay compared with paediatric CD patients and present at diagnosis more often with bowel stenosis and surgery. Length of diagnostic delay was found to be predictive for CD-related complications only in the adult but not in the paediatric CD population.
Artificial intelligence in healthcare: a critical analysis of the legal and ethical implications
Authors: Schönberger Daniel
Published: April 2019

Artificial intelligence (AI) is perceived as the most transformative technology of the 21st century. Healthcare has been identified as an early candidate to be revolutionized by AI technologies. Various clinical and patient-facing applications have already reached healthcare practice with the potential to ease the pressure on healthcare staff, bring down costs and ultimately improve the lives of patients. However, various concerns have been raised as regards the unique properties and risks inherent to AI technologies. This article aims at providing an early stage contribution with a holistic view on the ‘decision-making’ capacities of AI technologies. The possible ethical and legal ramifications will be discussed against the backdrop of the existing frameworks. I will conclude that the present structures are largely fit to deal with the challenges AI technologies are posing. In some areas, sector-specific revisions of the law may be advisable, particularly concerning non-discrimination and product liability.
No Correlation Between Nasopharyngeal Human Bocavirus 1 Genome Load and mRNA Detection or Serology in Adeno-/Tonsillectomy Patients
Authors: Ivaska Lotta E , Christensen Andreas , Waris Matti , Puhakka Tuomo , Vuorinen Tytti , Allander Tobias , Söderlund-Venermo Maria , Jartti Tuomas
Published: April 2019

Human bocavirus 1 (HBoV1) can persist in nasopharynx and tonsils. Using HBoV1 serology, reverse-transcription polymerase chain reaction (PCR) for detecting messenger RNA (mRNA) and quantitative PCR for HBoV1 genome load count, we studied to what extent the HBoV1 DNA loads in nasopharynx correlate with acute infection markers. Tonsillar tissue, nasopharyngeal aspirate, and serum were obtained from 188 elective adeno-/tonsillectomy patients. Relatively high loads of HBoV1 DNA were detected in the nasopharynx of 14 (7%) primarily asymptomatic subjects with negative mRNA and/or serodiagnostic results. Quantitative HBoV1 DNA PCR may have lower specificity than HBoV1 mRNA detection for diagnosing symptomatic infection.
Toxicities and Residual Effect of Spinosad and Alpha-Cypermethrin-Based Baits to Replace Malathion for Ceratitis capitata (Diptera: Tephritidae) Control
Authors: Baronio Cléber Antonio , Schutze Inana Xavier , Nunes Marcelo Zanelato , Bernardi Daniel , Machota Ruben , Bortoli Ligia Caroline , Arioli Cristiano João , Garcia Flávio Roberto Mello , Botton Marcos
Published: April 2019

Ceratitis capitata (Wiedemann, 1824) is the main insect pest of fruits worldwide. The objective of this study was to evaluate the toxicity and residual effects of the ready-to-use toxic baits Success 0.02CB (0.24 g of active ingredient [a.i.] per liter of spinosad) and Gelsura (6 g of a.i./liter of alpha-cypermethrin) and to compare them with other food lures containing spinosad and malathion mixed with hydrolyzed protein (Biofruit 5% and Flyral 1.25%), Anamed without dilution or sugarcane molasses (7%) against adult C. capitata in laboratory and greenhouse trials. Ceratitis capitata adults were highly susceptible to all toxic bait formulations (mortality > 80%) until 96 h after exposure. The lowest LT50 (hours) of toxic baits were 2.32 (Gelsura at 4,000 mg/liter), 4.26 (Gelsura at 2,000 mg/liter), 4.28 (Anamed + malathion) and 4.89 (sugarcane molasses + malathion), while formulations containing spinosad (Biofruit, Flyral, Anamed and Success 0.02CB) showed LT50 of approximately 11 h. Without rain, Gelsura (2,000 mg/liter) and all spinosad formulations provided mortality superior to 80% 14 d after application. Gelsura and Anamed + spinosad showed higher resistance to a 5-mm simulated rain, similar to Anamed + malathion, while the other formulations had its efficacy decreased. All toxic baits were effective on adult C. capitata in residual experiments without rain while Anamed + spinosad caused high adult mortality after 5 to 25 mm rains. Gelsura and Anamed + spinosad can be used to replace toxic baits containing malathion for C. capitata population management.
The combination of histone deacetylase and p53 expressions and histological subtype has prognostic implication in uterine leiomyosarcoma
Authors: Baek Min-Hyun , Park Jeong-Yeol , Park Yangsoon , Kim Kyu-Rae , Kim Dae-Yeon , Suh Dae-Shik , Kim Jong-Hyeok , Kim Yong-Man , Kim Young-Tak , Nam Joo-Hyun
Published: April 2019

Objective

To investigate the expression of different histone deacetylases and their association with disease characteristics and survival outcomes in uterine leiomyosarcoma patients.

Methods

The immunohistochemical expression of different histone deacetylases and p53 by tissue microarray and histological subtypes were assessed in tumor tissue samples of 42 eligible patients.

Results

Histone deacetylases 1–4, 6 and 8 showed prevalent and strong (3+) expression (88.1, 90.5, 95.2, 92.9, 83.3 and 100%, respectively). Histone deacetylases 5, 7 and 9 showed infrequent strong expression (33.3, 50 and 38.1%, respectively). There were trends of higher disease-free survival rates according to the combination of weaker expression of histone deacetylase 5, 7 or 9 with positive p53 expression or with non-epithelial subtype. The patients with triple-positive favorable prognostic factors (any of weaker histone deacetylase 5, 7 and 9 expression, p53 positive, and non-epithelioid subtype) had the better survival outcomes while the patients with other combinations had the worse survival outcomes. In multivariate analysis, histone deacetylase 5 in combination with epithelioid subtype was an independent predictor for disease-free survival.

Conclusions

Expression of histone deacetylase 5, 7 and 9 is a potential prognostic marker in uterine leiomyosarcoma when combined with pathologically relevant prognostic factors (p53 and histological subtype). This prevalent and strong histone deacetylase expression warrants further study in well-designed investigations of histone deacetylases as therapeutic targets in uterine leiomyosarcoma.
Linalool modulates dermatophyte susceptibility to azole drugs
Authors: Ponte Hellen Aparecida Silva , Lima Maria Islaine de Oliveira , Lima Edeltrudes de Oliveira , Pereira Fillipe de Oliveira
Published: April 2019

This study investigated the monoterpene linalool and its resistance modulating activity involving ergosterol biosynthesis inhibitors (ketoconazole, fluconazole, and itraconazole) in strains of Microsporum spp. and Trichophyton spp. The minimum inhibitory concentration (MIC) of test-drugs were determined by microdilution. The modulating effect of linalool was evaluated by determining the MIC of the antifungals in the presence of subinhibitory concentrations of linalool. We also investigated the association effect (checkerboard) of linalool together with ketoconazole and itraconazole. The fungi became more sensitive to ketoconazole and itraconazole in the presence of linalool. The linalool and azole drug associations presented synergism.
A survey of current audit practice in occupational health
Authors: Cashman C
Published: April 2019

Background

In the 1990s, challenges were identified in relation to the quality of practice in occupational medicine, including a limited evidence-base and the need to translate good evidence into high-quality practice. Audit has been identified as having an important role to play in addressing the determinants of variations and quality in practice.

Aims

To explore current practice of occupational health (OH) audit and outcome measures.

Methods

A survey of 30 OH conference participants who were affiliated with an OH service or a professional body, from ~2000 attendees at the Triennial Congress of the International Commission on Occupational Health (ICOH) in Dublin, Ireland, over 2 days in May 2018.

Results

Of the 30 participants, 1 was lost at follow-up and 29 participants gave verbal consent to answer questions in relation to carrying out audit and outcomes. Overall, 25 participants undertook regular audit, 19 on an annual basis, 4 on a monthly basis and 2 every 2 years. Twelve participants confirmed multiple audit outcomes and 13 used audits for internal training purposes only. Four participants did not undertake any audit. Less than 50% confirmed multiple audit outcomes that included internal feedback for training purposes and external publication such as conference poster presentations and peer-reviewed publications.

Conclusions

This limited observational study underscores conclusions of previous research that development of clinical audit guidance and measurement of outcomes in occupational medicine is mostly unpublished.
COMPARATIVE STUDY ON PERFORMANCE OF VARIOUS ENVIRONMENTAL RADIATION MONITORS
Authors: Tamakuma Y , Yamada R , Suzuki T , Kuroki T , Saga R , Mizuno H , Sasaki H , Iwaoka K , Hosoda M , Tokonami S
Published: April 2019

After the Fukushima Daiichi Nuclear Power Plant accident, the radiation dose for first responders was not evaluated accurately due to lack of the monitoring data. It has been important to evaluate a radiation dose for workers in emergency response at a nuclear accident. In this study, a new device which can evaluate both of external and internal exposure doses was developed and the performance of various environmental radiation monitors including commercially available monitors were tested and compared from the viewpoint of an environmental monitoring at emergency situation. Background counts of the monitors and the ambient dose equivalent rate were measured in Fukushima Prefecture. The detection limit for beta particles was evaluated by the method of ISO11929. The sensitivity for gamma-rays of the dust monitor using a ZnS(Ag) and a plastic scintillator was high, but that of the external exposure monitor using a silicon photodiode with CsI(Tl) crystal was relatively low. The detection limit ranged 190–280 Bq m−3 at 100 μSv h−1, exceeding the detection limit of 100 Bq m−3 in the minimum requirement by the National Regulation Authority in Japan. Use of the shielding with lead is necessary to achieve the minimum requirement. These results indicate that the dust monitor using a ZnS(Ag) scintillator and a plastic scintillator is suitable for the external exposure monitor and the developed internal exposure monitor is for the internal exposure monitor at emergency situation among the evaluated monitors. In the future study, the counting efficiency, the relative uncertainty and the performance of the detection for alpha particles will be evaluated, and it will be considered which type of a monitor is suitable after taking the portability into account.
Head Circumference of Babies at Birth in Nigeria
Authors: Pam Victor Chung , Yilgwan Christopher Sabo , Shwe David Danjuma , Abok IbrahimIshaya , Shehu Nathan , Gomerep Simji Samuel , Ejiji Isa Samson , Ocheke Amaka , Ajang Francis Magaji , Mutihir Josiah Tul , Gurumdimma Nentawe , Egah Daniel , Oguche Stephen
Published: April 2019

Background and Objectives

Measuring head circumference (HC) of newborns is an important tool for evaluating intra-uterine brain development. HC reference charts currently in use in Nigeria are not representative of the local population. We thus present locally derived HC reference data for Nigerian infants at birth.

Subjects and Methods

We reviewed birth records of all infants at the Jos University Teaching Hospital (JUTH) over a 10 year period from January 2006. JUTH is a tertiary care center offering obstetric services to a large population of women in Jos and its environs. All births with gestational age between 28 and 42 weeks were included in the study. STATA version 14 was used to calculate gestational age associated HC percentile measurements.

Results

We included 18 282 babies to generate the reference values. The mean HC value was 34.4 ± 2.1 cm (M = 34.6 ± 2.16 cm, F = 34.1 ± 2.02 cm, p < 0.001). Our HC reference values significantly differ from the USA and INTERGROWTH-21 charts currently in use in our country. Mean HC was higher in male infants compared with female infants. This difference was uniformly so across all gestational age groups.

Conclusions

The use of our locally derived HC reference values could be more appropriate in defining normal head growth in Nigerian infant populations thereby improving newborn care.
Drug induced methaemoglobinaemia
Authors: Hutton William , Pucci Mark
Published: April 2019

Acquired methaemoglobinaemia can be caused by the oxidising effect of a number of different drugs. Prescribed drugs that cause methaemoglobinaemia include local anaesthetics, dapsone, sulphonamides and primaquine. Recreational drugs such as amyl and isobutyl nitrite (‘poppers’) and adulterants in cocaine are also well known to cause methaemoglobinaemia. Low concentrations of methaemoglobin do not require treatment, but higher concentrations can be fatal. When indicated, methylthioninium chloride is the treatment of choice. More complicated cases should be discussed with a local poisons centre.
Preliminary Validation of an Unannounced Telephone Pill Count Protocol to Measure Medication Adherence Among Young Adults With Perinatal HIV Infection
Authors: Bucek Amelia , Raymond Jeannette , Leu Cheng-Shiun , Warne Patricia , Abrams Elaine J. , Dolezal Curtis , Wiznia Andrew , Kalichman Seth , Kalichman Moira , Mellins Claude A.
Published: April 2019

Unannounced telephone pill counts are an objective antiretroviral therapy adherence measurement tool, but this method has not been validated in young adults (YA) living with perinatal HIV infection. Perinatally infected YA, recruited from the Child and Adolescent Self-Awareness and Health Study, agreed to unannounced telephone pill counts to measure medication adherence over 4 months and phlebotomy to measure viral load (VL). Differences in pill count adherence scores among YA with a VL of ≤20 versus >20, and demographic differences were assessed. Participants (N = 62) were, on average, 24 years old; 57% were African American, and 40% were Latino. Participants with VL of ≤20 (60%) had significantly higher adherence scores (85% versus 62%; p = .004). Associations were not significant among older YA (range, 25–28 years) or Latinos. Unannounced telephone pill counts are a valid measure of antiretroviral therapy adherence in YA with perinatal HIV infection. Studies with larger samples are needed.
What Are the Barriers at Home and School to Healthy Eating?: Overweight/Obese Child and Parent Perspectives
Authors: KIM Hee Soon , PARK Jiyoung , MA Yumi , IM Mihae
Published: April 2019

Background:

Most studies that have investigated factors influencing eating habits among obese children have focused mainly on individual or interpersonal factors and applied quantitative research methods.

Purpose:

This study was undertaken to identify the barriers in home and school settings that hamper healthy eating in overweight and obese children in South Korea.

Methods:

Focus group interviews were conducted with 15 overweight/obese children and 15 parents. A standard manual with open-ended questions was developed. Content analysis was used to identify key findings.

Results:

Participants were aware of the importance of home and school environments in shaping children's eating habits. Five major barriers, respectively, at home and at school emerged from the data. At home, the food preferences of parents affected the eating habits of their children. Moreover, parents worried about providing differentiated diets for siblings and about the permissiveness of grandparents toward grandsons. Furthermore, working parents preferred easy-to-prepare instant foods and said that their children ate overly quickly. At school, children cited time pressures, poor cafeteria environments, and ineffective nutrition education as barriers, whereas parents worried about inconsistent management by teachers and the unsafe food environment around the school.

Conclusions:

These environment-related barriers may be resolved through changes in the behavior of children, parents, and teachers as well as through the continued efforts of schools, community stakeholders, and policymakers, all of whose cooperation is essential to fostering a healthy food environment for children.
Improving IBD Transition, Self‐management, and Disease Outcomes With an In‐clinic Transition Coordinator
Authors: Gray Wendy N. , Holbrook Erin , Dykes Dana , Morgan Pamela J. , Saeed Shehzad A. , Denson Lee A.
Published: April 2019

Objectives:

Deficits in the preparation of patients with inflammatory bowel disease (IBD) who are transitioning to adult care are known yet studies presenting outcome data of transition interventions in IBD are lacking. We present data evaluating the impact of a transition coordinator on behavioral and clinical transition outcomes.

Methods:

A retrospective chart review identified 135 patients who had met with our transition coordinator and completed the Transition Readiness Assessment Questionnaire before, and 1 year after, the intervention. Changes in transition readiness, self‐management skill acquisition, and clinical outcomes (eg, number of patients transferred vs “bounced back” to pediatrics, percentage of patients over age 21, changes in disease remission) were examined and compared with patients who received no intervention.

Results:

Intervention participants demonstrated a significant increase in transition readiness, F(1, 134) = 24.34, P < 0.001, and self‐management skill acquisition, F(1, 134) = 5.61, P < 0.05. The percentage of patients in remission significantly increased from pre‐ to post‐intervention, χ2(134) = 9.03, P < 0.01. There were no significant changes in the comparison population (Ps > 0.05). Following implementation of our programming, the percentage of patients over age 21 decreased by 33.07%.

Conclusions:

A 1‐time transition coordinator‐led intervention improved adolescent transition readiness and acquisition of self‐management skills. The proportion of young adult patients retained in pediatric care was reduced. Benefits of hiring a transition coordinator are discussed.
Inflammatory Bowel Disease Serological Immune Markers Anti‐Saccharomyces cerevisiae Mannan Antibodies and Outer Membrane Porin C are Potential Biomarkers for Hirschsprung‐associated Enterocolitis
Authors: Frykman Philip K. , Patel Deven C. , Kim Sungjin , Cheng Zhi , Wester Tomas , Nordenskjöld Agneta , Kawaguchi Akemi , Hui Thomas T. , Ehrlich Peter F. , Granström Anna L. , Benliyan Filip ,   HAEC Collaborative Research Group (HCRG)
Published: April 2019

Objective:

Hirschsprung‐associated enterocolitis (HAEC) is the most frequent complication in Hirschsprung disease (HSCR) patients. Currently HAEC is diagnosed clinically, leaving uncertainty in the diagnosis thereby potentially leading to over‐ or undertreatment of patients. The aim of this study was to identify immune biomarkers to aid in the diagnosis of HAEC.

Methods:

From 2012 to 2017, 43 children with HSCR enrolled in a multicenter study, underwent retrospective evaluation of their medical records, and questionnaire‐directed parent interviews. HAEC status was determined using HAEC score with cutoff ≥4. Plasma was collected and analyzed by ELISA for the inflammatory bowel disease–associated antibodies: anti‐Saccharomyces cerevisiae mannan antibodies (ASCA), outer membrane porin C (OmpC), CBir1, antineutrophil cytoplasmic antibodies. Data were analyzed using t test, univariate, multivariable, and binomial regression models.

Results:

Eighteen patients had at least 1 episode of HAEC, 25 had no history of HAEC. The HAEC and NO HAEC groups had similar median ages (3 years) and family histories of HSCR. The HAEC group showed markedly elevated ASCA IgA and OmpC antibody levels compared with the NO HAEC group, whereas CBir1 and antineutrophil cytoplasmic antibodies were similar between the groups. Both univariate and multivariable analysis revealed higher OmpC antibody levels associated with HAEC (odds ratio 1.39, confidence interval 1–1.92, P = 0.048), whereas univariate analysis identified a trend toward elevated IgA and immunoglobulin G ASCA levels with HAEC.

Conclusions:

We identified elevated OmpC and ASCA serum antibody levels in HAEC patients, and that increased OmpC antibody levels correlated with HAEC occurrence, suggesting HAEC and Crohn disease share gut microbial‐host immune responses. These antibodies may serve as potential biomarkers for HAEC, although prospective study with larger sample size is needed.
Brief Report: Hazardous Cannabis Use and Monocyte Activation Among Methamphetamine Users With Treated HIV Infection
Authors: Vidot Denise C. , Manuzak Jennifer A. , Klatt Nichole R. , Pallikkuth Suresh , Roach Margie , Dilworth Samantha E. , Pahwa Savita , Carrico Adam W.
Published: April 2019

Background:

The use of stimulants, such as methamphetamine, has been associated with greater immune activation in treated HIV infection. However, relatively little is known about whether concomitant cannabis use is associated with lower immune activation among HIV-positive stimulant users.

Setting:

HIV-positive, sexual minority men with biologically confirmed, recent methamphetamine use were enrolled in San Francisco, CA.

Methods:

In total, 78 methamphetamine-using sexual minority men with an undetectable HIV viral load (<40 copies/mL) completed self-report measures of cannabis use and substance use disorder severity. Plasma biomarkers of monocyte activation (ie, sCD14 and sCD163) and intestinal barrier integrity (iFABP) were measured. The associations of hazardous cannabis use with these measurements were examined after adjusting for substance use disorder severity, age, antiretroviral therapy regimen, CD4+ T-cell count, and interleukin-6.

Results:

Hazardous cannabis users had the highest mean sCD14 levels (2181 ng/mL) compared with nonhazardous users (1991 ng/mL) and nonusers (1859 ng/mL; P = 0.05). In adjusted analyses, greater cannabis use severity was associated with higher sCD14 compared with nonusers (unstandardized beta = 133.6 ng/mL, P = 0.03). Cannabis use severity was not significantly associated with sCD163 or iFABP.

Conclusions:

Hazardous cannabis use is independently associated with elevations in a clinically relevant marker of immune activation in methamphetamine users with treated HIV.
Multiplexed Analysis of the Secretin-like GPCR-RAMP Interactome
Authors: Lorenzen Emily , Dodig-Crnković Tea , Kotliar Ilana B. , Pin Elisa , Ceraudo Emilie , Vaughan Roger D. , Uhlèn Mathias , Huber Thomas , Schwenk Jochen M. , Sakmar Thomas P.
Published: April 2019

Although receptor activity-modifying proteins (RAMPs) have been shown to modulate the functions of several different G protein-coupled receptors (GPCRs), potential direct interactions among the three known RAMPs and hundreds of GPCRs has never been investigated. We engineered three epitope-tagged RAMPs and 23 epitope-tagged GPCRs, focusing on the secretin-like family of GPCRs, and developed a suspension bead array (SBA) immunoassay designed to detect RAMP-GPCR complexes. We then used 64 antibodies raised against native RAMPs and GPCRs, along with four antibodies targeting the epitope tags, to multiplex the SBA assay to detect and measure all possible combinations of interaction among the 23 GPCRs and three RAMPs. The results of the SBA assay provide a complete interactome of secretin-like GPCRs with RAMPs. We demonstrate direct interaction of previously reported secretin-like GPCRs whose functions are modulated by RAMPs. We also discovered novel sets of GPCR-RAMP interacting pairs, and found additional secretin-like GPCRs, chemokine receptors and orphan receptors that interact with RAMPs. Using in situ roximity ligation assay, we verified a subset of these novel GPCR-RAMP interactions in cell membranes. In total, we found GPCR-RAMP interactions for the majority of the 23 GPCRs tested. Each GPCR interacted with either all three RAMPs or with RAMP2 and RAMP3, with the exception of one GPCR that interacted with just RAMP3. In summary, we describe an SBA strategy that will be useful to search for GPCR-RAMP interactions in cell lines and tissues, and conclude that GPCR-RAMP interactions are more common than previously appreciated.
Deep transcriptome sequencing of subgenual anterior cingulate cortex reveals disorder-specific expression changes in major psychiatric disorders
Authors: Akula Nirmala , Marenco Stefano , Johnson Kory , Feng Ningping , Cross Joanna , England Bryce , Detera-Wadleigh Sevilla , Xu Qing , Auluck Pavan K. , Ahn Kwangmi , Kramer Robin , Apud Jose , Harris Brent T. , Rhodes C. Harker , Lipska Barbara K. , McMahon Francis J.
Published: April 2019

How do differences in onset, symptoms, and treatment response arise between various mental illnesses despite substantial overlap of genetic risk factors? To address this question, we carried out deep RNA sequencing of human postmortem subgenual anterior cingulate cortex, a key component of limbic circuits linked to mental illness. Samples were obtained from 200 individuals diagnosed with bipolar disorder, schizophrenia, or major depression, and controls. Differential expression analysis in cases versus controls detected modest differences that were similar across disorders, although transcript-level differences were more pronounced. Case-case comparisons revealed greater expression differences between disorders, including many genes and transcripts that were expressed in opposite directions in each diagnostic group, compared to controls. Relative transcript abundances were associated with common genetic variants that accounted for disproportionate fractions of diagnosis-specific heritability. Inherited genetic risk factors shape the brain transcriptome and contribute to diagnostic differences between broad classes of mental illness.
A decrease in transcription capacity limits growth rate upon translation inhibition
Authors: Zhang Qing , Brambilla Elisa , Li Rui , Shi Hualin , Lagomarsino Marco Cosentino , Sclavi Bianca
Published: April 2019

In bacterial cells, inhibition of ribosomes by sublethal concentrations of antibiotics leads to a decrease in growth rate despite an increase in ribosome content. The limitation of ribosomal activity results in an increase in the level of expression from ribosomal promoters; this can deplete the pool of RNA polymerase (RNAP) that is available for the expression of non-ribosomal genes. However, the magnitude of this effect remains to be quantified. Here, we use the change in the activity of constitutive promoters with different affinities for RNAP to quantify the change in the concentration of free RNAP. The data are consistent with a significant decrease in the amount of RNAP available for transcription of both ribosomal and non ribosomal genes. Results obtained with different reporter genes reveal an mRNA length dependence on the amount of full-length translated protein, consistent with the decrease in ribosome processivity affecting more strongly the translation of longer genes. The genes coding for the β and β’ subunits of RNAP are amongst the longest genes in theE. coligenome, while the genes coding for ribosomal proteins are among the shortest genes. This can explain the observed decrease in transcription capacity that favors the expression of genes whose promoters have a high affinity for RNAP, such as ribosomal promoters.

Importance

Exposure of bacteria to sublethal concentrations of antibiotics can lead to bacterial adaptation and survival at higher doses of inhibitors, which in turn can lead to the emergence of antibiotic resistance. The presence of sublethal concentrations of antibiotics targeting translation results in an increase in the amount of ribosomes per cell and a decrease in the cells’ growth rate. In this work, we have found that inhibition of ribosome activity can result in a decrease in the amount of free RNA polymerase available for transcription, thus limiting the protein expression rate via a different pathway than what was expected. This result can be explained by our observation that long genes, such as those coding for RNA polymerase subunits, have a higher probability of premature translation termination in the presence of ribosome inhibitors, while expression of short ribosomal genes is affected less, consistent with their increased concentration.
Deciphering the protein dynamics and molecular determinants of iPSC-derived neurons
Authors: Varderidou-Minasian Suzy , Schätzle Philipp , Hoogenraad Casper. C. , Pasterkamp R. Jeroen , Altelaar Maarten
Published: April 2019

Neuronal development is a multistep process with different regulatory programs that shapes neurons to form dendrites, axons and synapses. To date, knowledge on neuronal development is largely based on murine data and largely restricted to the genomic and transcriptomic level. Advances in stem cell differentiation now enable the study of human neuronal development, and here we provide a mass spectrometry-based quantitative proteomic signature, at high temporal resolution, of human stem cell-derived neurons. To reveal proteomic changes during neuronal development we make use of two differentiation approaches, either by expression of neurogenin-2 (Ngn2) leading to glutamatergic induced neurons (iN) or via small molecule manipulations, leading to patterned motor neurons. Our analysis revealed key proteins that show significant expression changes (FDR <0.001) during neuronal differentiation. We overlay our proteomics data with available transcriptomic data during neuronal differentiation and show distinct, datatype-specific, signatures. Overall, we provide a rich resource of information on proteins associated with human neuronal development, and moreover, highlight several signaling pathways involved, such as Wnt and Notch.
Differences in GluN2B-containing NMDA receptors result in opposite long-term plasticity and dopaminergic modulation at ipsilateralvs. contralateral cortico-striatal synapses
Authors: Li Wei , Pozzo-Miller Lucas
Published: April 2019

Excitatory neurons in the primary motor cortex project bilaterally to the striatum. However, whether synaptic structure and function in ipsilateral and contralateral cortico-striatal pathways is identical or different remains largely unknown. Here, we describe that excitatory synapses in the contralateral pathway have higher levels of NMDA-type of glutamate receptors (NMDARs) than those in the ipsilateral pathway, although both synapses utilize the same presynaptic vesicular glutamate transporter. We also show that NMDARs containing the GluN2B subunit, but not GluN2A, contribute to this difference. The altered NMDAR subunit composition in these two pathways results in opposite synaptic plasticity: long-term depression in the ipsilateral pathway and long-term potentiation in the contralateral pathway. Furthermore, we demonstrate that activation of D1 and D2 dopamine (DA) receptors by either selective pharmacological agonists or light-induced release of endogenous DA have no effect on NMDAR-mediated neurotransmission in either pathway. However, blocking basal DAergic tone with either D1 or D2 with selective antagonists revealed that GluN2B-containing NMDARs are modulated by D1 receptors in the contralateral pathway and by D2 receptors in the ipsilateral pathway. Such distinct modulatory actions seem to be permissive rather than sufficient for the induction of long-term synaptic plasticity. Altogether, our results provide novel and unexpected evidence for the lack of bilaterality of NMDAR-mediated synaptic transmission at cortico-striatal pathways due to differences in the expression of GluN2B subunits, which results in differences in bidirectional synaptic plasticity and modulation by dopaminergic inputs.
Perturbation of the human gut microbiome by a non-antibiotic drug contributes to the resolution of autoimmune disease
Authors: Nayak Renuka R. , Alexander Margaret , Stapleton-Grey Kye , Ubeda Carles , Scher Jose U. , Turnbaugh Peter J.
Published: April 2019

The trillions of microorganisms (microbiota) found within the human gut play a critical role in shaping the immune system, yet these complex microbial communities are also highly sensitive to numerous environmental factors. While much of the focus to date has been on dietary intake, emerging data has begun to suggest that the use of pharmaceutical drugs, even those that are not considered to be antibiotics, can alter the human gut microbiota with unknown consequences for treatment outcomes. Here, we use a combination ofin vitro, in vivo, andex vivomethods to demonstrate that the first-line therapy for rheumatoid arthritis (RA), methotrexate (MTX), has off-target effects on the human gut microbiota, resulting in a significant growth advantage for drug-resistant Firmicutes over the Bacteroidetes, which tend to be more sensitive. Longitudinal analyses of the gut microbiotas of RA patients revealed that MTX-induced shifts in bacterial relative abundance are associated with improved drug response and transplant experiments in gnotobiotic mice show that these shifts lead to reduced inflammation. Together, these results suggest that the mechanism-of-action of non-antibiotic drugs may be due in part to off-target effects on the gut microbiota, while providing a critical first step towards explaining long-standing differences in drug response between patients.