bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Effect of CYP2B6 Genotype and Other Candidate Genes on a Steady-State Serum Concentration of Methadone in Opioid Maintenance Treatment
Authors: Kringen Marianne K. , Chalabianloo Fatemeh , Bernard Jean-Paul , Bramness Jørgen G. , Molden Espen , Høiseth Gudrun
Published: July 2017

Background:

A considerable interindividual variability in methadone pharmacokinetics is seen in patients on methadone maintenance treatment. The aim of this study was to clarify the impact of the reduced function CYP2B6*6 variant allele together with variants in other candidate genes on a steady-state methadone concentration in a naturalistic setting.

Methods:

Information of methadone serum concentration, dose, age, sex, and CYP2C9, CYP2C19, and CYP2D6 genotypes were collected from a routine therapeutic drug monitoring database, whereas variant alleles in CYP2B6 and CYP3A5 were retrospectively genotyped. Linear mixed model analyses were used to study the impact of gene variants on methadone serum concentration/dose (C/D) ratios, including age, sex, and time since the last dose intake as covariates.

Results:

Overall, 155 serum samples from 62 patients were included in this study. The estimated mean methadone C/D ratios was 17.8 nmol·L−1·mg−1 for homozygous carriers of CYP2B6*6, which was significantly (P < 0.001) higher than noncarriers (9.2 nmol·L−1·mg−1). There was no difference in C/D ratios between heterozygous carriers of CYP2B6*6 (9.1 nmol·L−1·mg−1) and noncarriers. An increase in mean methadone C/D ratios was also seen for homozygous carriers of CYP3A5*3 and heterozygous carriers of CYP2C9*2 or *3 and CYP2C19*2 or *3.

Conclusions:

Patients homozygous for CYP2B6*6 had a >90% higher methadone C/D ratio. Genotyping of CYP2B6 may therefore be of value when assessing dose requirements in methadone maintenance treatment.
INDOCYANINE GREEN ANGIOGRAPHY OF PACHYCHOROID PIGMENT EPITHELIOPATHY
Authors: Ersoz M. Giray , Arf Serra , Hocaoglu Mumin , Sayman Muslubas Isil , Karacorlu Murat
Published: July 2017

Purpose:

To compare choroidal hyperpermeability and vessel density between eyes with central serous chorioretinopathy (CSC), those with pachychoroid pigment epitheliopathy (PPE) and those with uncomplicated pachychoroid (UCP).

Methods:

We retrospectively reviewed indocyanine green angiography images of 60 patients with unilateral active CSC who had PPE (36 eyes) or UCP (24 eyes) in their fellow eyes. We used color thresholding of indocyanine green angiography images to determine choroidal vessel density.

Results:

The mean choroidal thickness of eyes with CSC was greater than that of eyes with PPE or UCP, but this difference was not statistically significant (P = 0.46). There was no significant difference between the PPE (92%) and CSC (93%) groups regarding choroidal hyperpermeability (P = 0.76), but both of these groups had higher choroidal permeability than the UCP group (50%) (both P < 0.001). In 30 (90%) of 33 eyes with PPE who had choroidal hyperpermeability, retinal pigment epithelium alterations were in the region of hyperpermeability. Choroidal vessel density did not differ between the PPE and UCP groups (P = 0.57).

Conclusion:

Pachychoroid pigment epitheliopathy is forme fruste of CSC. There is no difference between complicated and UCP regarding subfoveal choroidal thickness and choroidal vessel density. The main difference between these groups is choroidal hyperpermeability.
BLINDNESS RELATED TO PRESUMED RETINAL TOXICITY AFTER USING PERFLUOROCARBON LIQUID DURING VITREORETINAL SURGERY
Authors: Méndez-Martínez Silvia , Calvo Pilar , Rodriguez-Marco Nelson Arturo , Faus Fernando , Abecia Emilio , Pablo Luis
Published: July 2017

Purpose:

To describe the presumed retinal toxicity after using specific batches of perfluorocarbon liquid ALA OCTA (Alamedics, Dornstadt, Germany) in pars plana vitrectomy.

Methods:

This is an observational retrospective consecutive case series analyses of patients operated on pars plana vitrectomy for retinal detachment or intraocular lens subluxation, using the 150141 or 200114 batches of perfluorocarbon liquid ALA OCTA as assistance during the surgery in a single center. Patients were included in this report if they manifested retinal toxicity signs throughout the follow-up, such as retinal and retinal pigment epithelium atrophy, disk paleness, and intensive macular fibrosis. Spectral domain optical coherence tomography (Spectralis; Heidelberg Engineering, Heidelberg, Germany) and Ultra-Wide Field 200° retinal camera (Optos P200Tx; Optos, Scotland, United Kingdom) images, electrophysiological tests, and visual fields were performed to analyze the retinal structure and functionality.

Results:

Seven of 80 patients showed all the described signs of toxicity, after a mean follow-up of 34.29 days (range: 10–87) since surgery. Four patients needed a second pars plana vitrectomy because of tractional retinal detachment and proliferative vitreoretinopathy, and two of them underwent a third surgery because of redetachment. All patients experienced amaurosis or central scotoma, with a final best-corrected visual acuity ranging from 20/200 to light perception.

Conclusion:

Presumed toxic batches of perfluorocarbon liquid may cause massive retinal toxicity. A rapid suspicion, a correct traceability of surgical products, and informing health authorities are fundamental to prevent further cases of toxicity.
Serologic Responses in Childhood Pulmonary Tuberculosis
Authors: Nonyane Bareng A. S. , Nicol Mark P. , Andreas Nicholas J. , Rimmele Stefanie , Schneiderhan-Marra Nicole , Workman Lesley J. , Perkins Mark D. , Joos Thomas , Broger Tobias , Ellner Jerrold J. , Alland David , Kampmann Beate , Dorman Susan E. , Zar Heather J.
Published: July 2017

Background:

Identification of the Mycobacterium tuberculosis immunoproteome and antigens associated with serologic responses in adults has renewed interest in developing a serologic test for childhood tuberculosis (TB). We investigated IgG antibody responses against M. tuberculosis antigens in children with well-characterized TB.

Methods:

We studied archived sera obtained from hospitalized children with suspected pulmonary TB, and classified as having confirmed TB (culture-confirmed), unlikely TB (clinical improvement without TB treatment), or unconfirmed TB (all others). A multiplexed bead-based assay for IgG antibodies against 119 M. tuberculosis antigens was developed, validated and used to test sera. The area under the curves (AUCs) of the empiric receiver–operator characteristic curves were generated as measures of predictive ability. A cross-validated generalized linear model was used to select the most predictive combinations of antigens.

Results:

For the confirmed TB versus unlikely TB comparison, the maximal single antigen AUC was 0.63, corresponding to sensitivity 0.60 and specificity 0.60. Older (age: 60+ months old) children’s responses were better predictive of TB status than younger (age: 12–59 months old) children’s, with a maximal single antigen AUC of −0.76. For the confirmed TB versus unlikely TB groups, the most predictive combinations of antigens assigned TB risk probabilities of 0.33 and 0.33, respectively, when all ages were considered, and 0.57 (interquartile range: 0.48–0.64) and 0.35 (interquartile range: 0.32–0.40) when only older children were considered.

Conclusion:

An antigen-based IgG test is unlikely to meet the performance characteristics required of a TB detection test applicable to all age groups.
Subjective Versus Objective Estimated Cardiovascular Disease Risk and Adherence to Physical Activity in African American Women
Authors: Robinson Nadia , Miller Arlene , Wilbur JoEllen , Fogg Louis
Published: July 2017

Background:

Cardiovascular disease (CVD) is the leading cause of death for African American (AA) women in the United States. Despite high prevalence of CVD risk factors, AA women perceive their CVD risk as low.

Objective:

Our objectives were to (1) identify relationships between subjective (self-reported perceived) CVD risk and objective CVD risk estimated by the American College of Cardiology/American Heart Association atherosclerotic CVD (ASCVD) risk estimator, (2) identify demographic and psychosocial factors associated with subjective perceived risk and discrepancy with objective estimated CVD risk, and (3) determine whether subjective perceived CVD risk was associated with physical activity (PA) adherence.

Methods:

This was a secondary data analysis of data collected from a 12-month lifestyle PA intervention conducted with 281 AA women. Subjective perceived CVD risk was measured by 1 question; objective estimated CVD risk was calculated using the ASCVD score. Women were categorized by congruence or discrepancy between subjective perceived and objective estimated CVD risk.

Results:

Subjective perceived CVD risk and objective ASCVD risk scores were both low. Approximately 20% subjectively perceived their risk as lower than objective ASCVD scores. Atherosclerotic CVD risk discrepancy groups differed by depressed mood symptoms. Participants reported many perceived barriers to PA. Perceived CVD risk was not related to PA adherence.

Conclusions:

The significance of associated CVD risk factors may be underestimated by AA women, leading to discrepancy between subjective and objective risk estimates. Research is needed to clarify relationships among perceived risk, estimated risk using risk calculators such as ASCVD, and health behavior.
Dietary guidelines in type 2 diabetes: the Nordic diet or the ketogenic diet?
Authors: Magnusdottir Ola K. , Gunnarsdottir Ingibjorg , Birgisdóttir Bryndís E.
Published: July 2017

Purpose of review

To highlight recent developments in research regarding nutrition therapies for type 2 diabetes mellitus (T2DM) with a focus on the different approaches of the Nordic diet and the ketogenic diet.

Recent findings

Recent short-term studies have revealed that similar beneficial outcomes are seen after different dietary treatments for T2DM, with different approaches resulting in comparable weight loss and impacts on metabolic factors.

More individualized approaches in nutrition therapy should be considered for T2DM patients and clinical guidelines should reflect this. More studies, especially long-term studies, are urgently needed on the impacts of the diets on different health parameters. Such studies should be prioritized because of the high and increasing prevalence of T2DM and because dietary changes may have greater benefits than previously thought. Furthermore, studies that focus on patient compliance to different types of diets, and personal and environmental factors that may affect compliance, are needed.
Gait analysis on force treadmill in children: comparison with results from ground-based force platforms
Authors: Tesio Luigi , Malloggi Chiara , Portinaro Nicola M. , Catino Luigi , Lovecchio Nicola , Rota Viviana
Published: July 2017

Gait analysis (GA) typically includes surface electromyographic (sEMG) recording from several lower limb muscles, optoelectronic measurement of joint rotations, and force recordings from ground-based platforms. From the latter two variables, the muscle power acting on the lower limb joints can be estimated. Recently, gait analysis on a split-belt force treadmill (GAFT) was validated for the study of adult walking. It showed high reliability of spatiotemporal, kinematic, dynamic, and sEMG parameters, matching those obtainable with GA on the basis of ground walking. GAFT, however, still needs validation in children. Potential differences with respect to adult GAFT relate to (a) possible high signal-to-noise ratio, given the lower forces applied; (b) higher differences between treadmill and over-ground walking; and (c) limited compliance with the experimental setup. This study aims at investigating whether GAFT provides results comparable with those obtainable from ground walking in children and consistent with results from GAFT in adults. GAFT was applied to three groups of healthy children aged 5–6 years (n=6), 7–8 years (n=6), and 9–13 years (n=8) walking at the same average speed spontaneously adopted overground. The results were compared with those obtained from another study applying GA to an age-matched and speed-matched sample of 47 children, and with those obtained from GAFT in adults. The reliability (as indicated by the SD) of both spatiotemporal and dynamic parameters was higher in GAFT compared with GA. In the 5–6-, 7–8-, and 9–13-year-old groups, at average speeds of 0.83, 1.08, and 1.08 m/s, step length was shorter by 9.19, 3.57, and 2.30% compared with GA in controls at comparable speeds, respectively. For the youngest group, a lower power generation from the plantar flexors (peak power: 1.35±0.32 vs. 2.11±1.02 W/kg) and a slightly more flexed posture of the hip, knee, and ankle joints were observed during GAFT compared with GA in controls. The other gait parameters were very similar between the GAFT and the GA groups. The shortening of step length during GAFT, relative to GA at superimposable speed, was on average of all children 6.8%, in line with the 8% decrease found in adults. The profiles of sEMG and joint rotations, and all of the weight-standardized joint power parameters, matched those recorded in adults. The entire experimental session lasted about 1 h. All children complied with the experimental setting and easily completed the requested tests. In conclusion, GAFT seems to be a promising alternative to conventional GA in children.
Determinants of Human Papillomavirus Vaccination Intention Among Female Sex Workers in Amsterdam, the Netherlands
Authors: Marra Elske , van Dam Laura , Kroone Niki , Craanen Marianne , Zimet Gregory D. , Heijman Titia , Hogewoning Arjan A. , Sonder Gerard J.B. , de Vries Henry J.C. , Alberts Catharina J. , Paulussen Theo G.W.M. , Schim van der Loeff Maarten F.
Published: July 2017

Introduction

Female sex workers (FSWs) are at risk for human papillomavirus (HPV)–induced diseases but are currently not targeted by the HPV vaccination program in the Netherlands. We explored determinants of their intention to get vaccinated against HPV in case vaccination would be offered to them.

Methods

In 2016, FSWs 18 years and older having a sexually transmitted infection consultation with the Prostitution & Health Center (P&G292) in Amsterdam, either at the clinic or at their working location, were invited to complete a questionnaire assessing sociopsychological determinants of HPV vaccination intention (scale ranging from −3 to +3). Determinants of HPV vaccination intention were assessed with univariable and multivariable linear regression. In addition, we explored the effect of out-of-pocket payment on intention.

Results

Between May and September 2016, 294 FSWs participated. The median age was 29 years (interquartile range, 25–37 years). Human papillomavirus vaccination intention was high (mean, 2.0; 95% confidence interval [CI], 1.8–2.2). In multivariable analysis, attitude (β = 0.6; 95% CI, 0.5–0.7), descriptive norm (β = 0.2; 95% CI, 0.1–0.3), self-efficacy (β = 0.2; 95% CI, 0.1–0.3), beliefs (β = 0.1; 95% CI, 0.0–0.2), and subjective norm (β = 0.1; 95% CI, 0.0–0.2) seemed to be the strongest predictors of HPV vaccination intention (R
2 = 0.54). Human papillomavirus vaccination intention decreased significantly to a mean of 0.2 when vaccination would require out-of-pocket payment of €350.

Conclusions

The HPV vaccination intention among FSWs seems relatively high and is most strongly constituted in attitudinal, normative, and self-efficacy beliefs. Out-of-pocket payment will probably have a negative impact on their HPV vaccination acceptability.
Comparison of Different Antibody Clones for Immunohistochemistry Detection of Programmed Cell Death Ligand 1 (PD-L1) on Non–Small Cell Lung Carcinoma
Authors: Parra Edwin R. , Villalobos Pamela , Mino Barbara , Rodriguez-Canales Jaime
Published: July 2017

Programmed cell death ligand 1 (PD-L1) is a major immune checkpoint protein that mediates antitumor immune suppression and response. Preliminary data suggest that its detection using immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded tissues may predict clinical response to PD-1/PD-L1 therapy. In diagnostic pathology, it is essential to count with a validated IHC that can reliably detect PD-L1-positive cases. The present study was conducted to compare and validate different PD-L1 commercial clones and identify which ones can be reliably used by surgical pathologist to detect PD-L1 expression in human cancer tissues. Eight commercial available PD-L1 clones were tested and compared with a noncommercial PD-L1 antibody clone 5H1. Western blot and IHC using cell lines and human tissues were used to validate these clones. From all PD-L1 antibodies, only the clones E1L3N, E1J2J, SP142, 28-8, 22C3, and SP263 passed the Western blot and IHC validation, providing similar pattern than the clone 5H1 and then they were tested in 259 non–small cell lung cancer cases placed in 9 tissue microarrays. Among all cases, only those with ≥2 cores were included (185 cases). Positive and significant correlation was found between the median PD-L1 H-score in tumor and stroma compartments, for all selected antibodies. Overall, 56 of 185 cases were detected as positive cases in malignant cells expressing membranous PD-L1 by all the clones. However, the clone SP263 identified more PD-L1-positive cases compared with the other clones. Our results show that clones E1L3N, E1J2J, SP142, 28-8, 22C3, and SP263 provide positive membrane staining pattern comparable with clone 5H1. These commercial clones are comparable, but a careful evaluation by the pathologist is necessary to minimize error of positive misinterpretations.
Spindle Cell Lipomas in Women
Authors: Ko Jennifer S. , Daniels Brianne , Emanuel Patrick O. , Elson Paul , Khachaturov Vadim , McKenney Jesse K. , Goldblum John R. , Billings Steven D.
Published: July 2017

Spindle cell lipomas (SCL) are typically tumors of the upper back/neck (shawl region) of men (80% to 90%). In general, there is a frequent tendency to restrict the diagnosis to this specific clinical scenario and a hesitancy to diagnose SCL in women. We hypothesized that SCL in women have a more varied presentation. A total of 395 SCL were diagnosed at our institution over the last 11 years. The diagnosis of SCL in women was confirmed by re-review. Immunohistochemical stains for CD34, desmin, estrogen receptor, and p16 were performed. In a subset, fluorescence in situ hybridization to detect Retinoblastoma1 (RB1) gene deletion was performed. Of 395 SCLs, 331 (86%) occurred in men; 53 (14%) occurred in women (11 cases excluded). Of the 64 SCL in women, 58 had available material. In total, 53 of 58 were confirmed as SCL. Women were younger at diagnosis (median, 51 y; range, 5 to 76 y) compared with men (64 y; range, 23 to 98 y), P<0.0001, t test. SCL in women typically occurred outside the shawl distribution (36/53, 68%) compared with men (95/331, 29%) (P<0.001), including extremities (16/53, 30% vs. 32/331, 10%) and face (11/53, 21% vs. 47/331, 14%). Dermal SCL in women were also relatively common (16/53, 30%). The cases demonstrated varying proportions of bland spindled cells, ropey collagen, myxoid matrix, and adipocytes. By immunohistochemistry, 46/46 were CD34+, 48 of 48 were desmin negative, 33 of 42 were estrogen receptor negative, and 29 of 42 had loss of p16 expression. In total, 12 of 14 showed RB1 loss by fluorescence in situ hybridization. SCL in women frequently occurs in unconventional locations and in at a slightly younger patient age.
Do Nonseminomatous Germ Cell Tumors of the Testis With Lymphovascular Invasion of the Spermatic Cord Merit Staging as pT3?
Authors: Gordetsky Jennifer , Sanfrancesco Joseph , Epstein Jonathan I. , Trevino Karen , Xu Huiping , Osunkoya Adeboye , Xiao Guang Q. , Kao Chia-Sui , Unger Pamela , Hashemi-Sadraei Neda , Albany Constantine , Jorns Julie M. , Lu David Y. , Matoso Andres , Rais-Bahrami Soroush , Schwartz Lauren E. , Ulbright Thomas M. , Idrees Muhammad T.
Published: July 2017

The staging of testicular nonseminomatous germ cell tumors (NSGCTs) with lymphovascular invasion (LVI) of the spermatic cord in the absence of cord parenchymal involvement remains controversial. Our previous study showed that tumors with spermatic cord LVI present at a higher clinical stage than tumors with LVI confined to the testis (pT2). We compared NSGCTs with LVI of the spermatic cord without direct involvement of the spermatic cord soft tissues to pT3 tumors to help clarify the appropriate staging of this histologic finding. A retrospective, multi-institutional review was performed to identify cases of NSGCTs with LVI in the spermatic cord without soft tissue invasion of the cord. The clinical-pathologic findings were compared with NSGCTs with spermatic cord soft tissue invasion (pT3). We identified 38 pT2 NSGCTs with LVI in the spermatic cord without soft tissue invasion of the cord and 89 pT3 tumors. There were no significant differences in patient age, tumor size, or clinical stage at presentation between the 2 groups. There were no significant differences in dominant histologic subtype, rete testis invasion, hilar soft tissue invasion, or margin status. There were no significant differences in disease recurrence/progression (P=0.63), recurrence/progression after chemotherapy (P=0.35), or death (P=0.51) between patients with only spermatic cord LVI versus patients with cord soft tissue invasion. In patients with pT2 NSGCTs according to the current staging, LVI in the spermatic cord without cord soft tissue invasion is comparable with pT3 tumors in terms of clinical stage at presentation as well as disease recurrence and survival.
A Simulation-Based Quality Improvement Initiative Improves Pediatric Readiness in Community Hospitals
Authors: Whitfill Travis , Gawel Marcie , Auerbach Marc
Published: July 2017

Background

The National Pediatric Readiness Project Pediatric Readiness Survey (PRS) measured pediatric readiness in 4149 US emergency departments (EDs) and noted an average score of 69 on a 100-point scale. This readiness score consists of 6 domains: coordination of pediatric patient care (19/100), physician/nurse staffing and training (10/100), quality improvement activities (7/100), patient safety initiatives (14/100), policies and procedures (17/100), and availability of pediatric equipment (33/100). We aimed to assess and improve pediatric emergency readiness scores across Connecticut’s hospitals.

Objective

The aim of this study was to compare the National Pediatric Readiness Project readiness score before and after an in situ simulation–based assessment and quality improvement program in Connecticut hospitals.

Methods

We leveraged in situ simulations to measure the quality of resuscitative care provided by interprofessional teams to 3 simulated patients (infant septic shock, infant seizure, and child cardiac arrest) presenting to their ED resuscitation bay. Assessments of EDs were made based on a composite quality score that was measured as the sum of 4 distinct domains: (1) adherence to sepsis guidelines, (2) adherence to cardiac arrest guidelines, (3) performance on seizure resuscitation, and (4) teamwork. After the simulation, a detailed report with scores, comparisons to other EDs, and a gap analysis were provided to sites. Based on this report, a regional children’s hospital team worked collaboratively with each ED to develop action items and a timeline for improvements. The National Pediatric Readiness Project PRS scores, the primary outcome of this study, were measured before and after participation.

Results

Twelve community EDs in Connecticut participated in this project. The PRS scores were assessed before and after the intervention (simulation-based assessment and gap analysis/report-out). The average time between PRS assessments was 21 months. The PRS scores significantly improved 12.9% from the first assessment (mean ± SEM = 64 ± 4.4) to the second assessment (77 ± 4.0, P = 0.022). The PRS score domains also showed improvements in coordination of pediatric patient care (median improvement, 50%), quality improvement activities (median improvement, 79%), patient safety initiatives (mean improvement, 7%), policies and procedures (mean improvement, 17%), and availability of pediatric equipment (mean improvement, 7%).

Conclusions

Participation in a simulation-based quality improvement collaborative was associated with improvements in pediatric readiness.
Opioid Prescribing Practices in Pediatric Acute Care Settings
Authors: DePhillips Michelle , Watts Jennifer , Lowry Jennifer , Dowd M. Denise
Published: July 2017

Objectives

Deaths due to prescription opioid overdoses are at record-high levels. Limiting the amount of opioid prescribed has been suggested as a prevention strategy. The purpose of this study was to describe the opioid prescribing practices in the emergency departments and urgent care sites of a Midwestern tertiary care children’s hospital system.

Methods

This retrospective medical record review examined the visits from the 2 pediatric emergency departments and 2 pediatric urgent care sites in the system from June 1, 2012, to May 31, 2013, during which an outpatient opioid prescription was written. The primary outcome was number of days of opioid prescribed. Other data collected included patient demographics, diagnosis, and prescriber information; factors associated with prescriptions written for more than 5 days were identified.

Results

A total of 4075 opioid prescriptions were included in the 1-year study period, and 3991 of these had complete data for analysis. The median amount prescribed was 3.3 days with an interquartile range of 2.5 days. Odds of receiving a prescription of more than 5 days’ duration were higher for children younger than 1 year (odds ratio [OR], 12.3; 95% confidence interval [CI], 7.3–21.0), 1 to 4 years of age (OR, 7.7; 95% CI, 5.5–10.8), and 5 to 9 years of age (OR, 2.4; 95% CI, 1.7–3.4); for children with noninjury diagnoses (OR, 1.4; 95% CI, 1.2–1.7); or if prescribed by a resident physician (OR, 1.4; 95% CI, 1.1–1.8) or from the urgent care (OR, 1.4; 95% CI, 1.1–1.7).

Conclusions

Opioid prescriptions of more than 5 days were more frequently prescribed for younger patients, noninjury diagnoses, or if prescribed by a resident physician or from the urgent care. We need to focus on medical student, resident, and provider education as well as further opioid research in order to decrease unnecessary prescribing.
Response of CO
2
-starved diatom
Phaeodactylum tricornutum
to light intensity transition
Authors: Heydarizadeh Parisa , Boureba Wafâa , Zahedi Morteza , Huang Bing , Moreau Brigitte , Lukomska Ewa , Couzinet-Mossion Aurélie , Wielgosz-Collin Gaëtane , Martin-Jézéquel Véronique , Bougaran Gaël , Marchand Justine , Schoefs Benoît
Published: July 2017

In this study, we investigated the responses of
Phaeodactylum tricornutum
cells acclimated to 300 µmol m
−2
s
−1
photon flux density to an increase (1000 µmol m
−2
s
−1
) or decrease (30 µmol m
−2
s
−1
) in photon flux densities. The light shift occurred abruptly after 5 days of growth and the acclimation to new conditions was followed during the next 6 days at the physiological and molecular levels. The molecular data reflect a rearrangement of carbon metabolism towards the production of phosphoenolpyruvic acid (PEP) and/or pyruvate. These intermediates were used differently by the cell as a function of the photon flux density: under low light, photosynthesis was depressed while respiration was increased. Under high light, lipids and proteins accumulated. Of great interest, under high light, the genes coding for the synthesis of aromatic amino acids and phenolic compounds were upregulated suggesting that the shikimate pathway was activated.

This article is part of the themed issue ‘The peculiar carbon metabolism in diatoms’.
Intracellular metabolic pathway distribution in diatoms and tools for genome-enabled experimental diatom research
Authors: Gruber Ansgar , Kroth Peter G.
Published: July 2017

Diatoms are important primary producers in the oceans and can also dominate other aquatic habitats. One reason for the success of this phylogenetically relatively young group of unicellular organisms could be the impressive redundancy and diversity of metabolic isoenzymes in diatoms. This redundancy is a result of the evolutionary origin of diatom plastids by a eukaryote–eukaryote endosymbiosis, a process that implies temporary redundancy of functionally complete eukaryotic genomes. During the establishment of the plastids, this redundancy was partially reduced via gene losses, and was partially retained via gene transfer to the nucleus of the respective host cell. These gene transfers required re-assignment of intracellular targeting signals, a process that simultaneously altered the intracellular distribution of metabolic enzymes compared with the ancestral cells. Genome annotation, the correct assignment of the gene products and the prediction of putative function, strongly depends on the correct prediction of the intracellular targeting of a gene product. Here again diatoms are very peculiar, because the targeting systems for organelle import are partially different to those in land plants. In this review, we describe methods of predicting intracellular enzyme locations, highlight findings of metabolic peculiarities in diatoms and present genome-enabled approaches to study their metabolism.

This article is part of the themed issue ‘The peculiar carbon metabolism in diatoms’.
A High HIV-1 Strain Variability in London, UK, Revealed by Full-Genome Analysis: Results from the ICONIC Project
Authors: Yebra Gonzalo , Frampton Dan , Cassarino Tiziano Gallo , Raffle Jade , Hubb Jonathan , Ferns R Bridget , Kozlakidis Zisis , Hayward Andrew , Kellam Paul , Pillay Deenan , Clark Duncan , Nastouli Eleni , Leigh Brown Andrew J. ,   on behalf of the ICONIC consortium
Published: July 2017

Background & Methods

The ICONIC project has developed an automated high-throughput pipeline to generate HIV nearly full-length genomes (NFLG, i.e. fromgagtonef) from next-generation sequencing (NGS) data. The pipeline was applied to 420 HIV samples collected at University College London Hospital and Barts Health NHS Trust (London) and sequenced using an Illumina MiSeq at the Wellcome Trust Sanger Institute (Cambridge). Consensus genomes were generated and subtyped using COMET, and unique recombinants were studied with jpHMM and SimPlot. Maximum-likelihood phylogenetic trees were constructed using RAxML to identify transmission networks using the Cluster Picker.

Results

The pipeline generated sequences of at least 1Kb of length (median=7.4Kb) for 375 out of the 420 samples (89%), with 174 (46.4%) being NFLG. A total of 365 sequences (169 of them NFLG) corresponded to unique subjects and were included in the down-stream analyses. The most frequent HIV subtypes were B (n=149, 40.8%) and C (n=77, 21.1%) and the circulating recombinant form CRF02_AG (n=32, 8.8%). We found 14 different CRFs (n=66, 18.1%) and multiple URFs (n=32, 8.8%) that involved recombination between 12 different subtypes/CRFs. The most frequent URFs were B/CRF01_AE (4 cases) and A1/D, B/C, and B/CRF02_AG (3 cases each). Most URFs (19/26, 73%) lacked breakpoints in the PR+RTpolregion, rendering them undetectable if only that was sequenced. Twelve (37.5%) of the URFs could have emerged within the UK, whereas the rest were probably imported from sub-Saharan Africa, South East Asia and South America. For 2 URFs we found highly similarpolsequences circulating in the UK. We detected 31 phylogenetic clusters using the full dataset: 25 pairs (mostly subtypes B and C), 4 triplets and 2 quadruplets. Some of these were not consistent across different genes due to inter- and intra-subtype recombination. Clusters involved 70 sequences, 19.2% of the dataset.

Conclusions

The initial analysis of genome sequences detected substantial hidden variability in the London HIV epidemic. Analysing full genome sequences, as opposed to only PR+RT, identified previously undetected recombinants. It provided a more reliable description of CRFs (that would be otherwise misclassified) and transmission clusters.
Collective membrane dynamics emerging from curvature-dependent spatial coupling
Authors: Wu Zhanghan , Su Maohan , Tong Cheesan , Wu Min , Liu Jian
Published: July 2017

Membrane curvature has been recognized as an active participant of fundamental biological processes including vesicular transport and organelle biogenesis, but its effects on membrane remodeling are typically local. Here we show membrane curvature plays a critical role in propagating cortical waves and modulating mesoscale dynamics in living cells. We employ a membrane shape-dependent mechanochemical feedback model to account for the observed oscillatory travelling waves of Cdc42, F-BAR proteins and actin. We demonstrate that oscillatory membrane shape changes accompany and are required for such spatiotemporal patterns. In addition, modulating the curvature preference of the F-BAR proteins or membrane tension perturbs wave propagation. Our findings identify a distinct role of membrane curvature in mediating collective dynamics of cortical proteins and provide a molecular framework for integrating membrane mechanics and biochemical signaling in the context of subcellular pattern formation.
Meta-analysis of exome array data identifies six novel genetic loci for lung function
Authors: Jackson Victoria E , Latourelle Jeanne C , Wain Louise V , Smith Albert V. , Grove Megan L. , Bartz Traci M , Obeidat Maen , Province Michael A , Gao Wei , Qaiser Beenish , Porteous David J , Cassano Patricia A , Ahluwalia Tarunveer S. , Grarup Niels , Li Jin , Altmaier Elisabeth , Marten Jonathan , Harris Sarah E , Manichaikul Ani , Pottinger Tess D , Li-Gao Ruifang , Lind-Thomsen Allan , Mahajan Anubha , Lahousse Lies , Imboden Medea , Teumer Alexander , Prins Bram , Lyytikäinen Leo-Pekka , Eiriksdottir Gudny , Franceschini Nora , Sitlani Colleen M , Brody Jennifer A , Bossé Yohan , Timens Wim , Kraja Aldi , Loukola Anu , Tang Wenbo , Liu Yongmei , Bork-Jensen Jette , Justesen Johanne M. , Linneberg Allan , Lange Leslie A. , Rawal Rajesh , Karrasch Stefan , Huffman Jennifer E , Smith Blair H , Davies Gail , Burkart Kristin M , Mychaleckyj Josyf C , Bonten Tobias N. , Enroth Stefan , Lind Lars , Brusselle Guy G , Kumar Ashish , Stubbe Beate , Kähönen Mika , Wyss Annah B. , Psaty Bruce M , Heckbert Susan R , Hao Ke , Rantanen Taina , Kritchevsky Stephen B , Lohman Kurt , Skaaby Tea , Pisinger Charlotta , Hansen Torben , Schulz Holger , Polasek Ozren , Campbell Archie , Starr John M , Rich Stephen S , Mook-Kanamori Dennis O. , Johansson Åsa , Ingelsson Erik , Uitterlinden André G , Weiss Stefan , Raitakari Olli T. , Gudnason Vilmundur , North Kari E. , Gharib Sina A , Sin Don D , Taylor Kent D , O’Connor George T , Kaprio Jaakko , Harris Tamara B , Pedersen Oluf , Vestergaard Henrik , Wilson James G. , Strauch Konstantin , Hayward Caroline , Kerr Shona , Deary Ian J , Barr R Graham , de Mutsert Renée , Gyllensten Ulf , Morris Andrew P , Ikram M. Arfan , Probst-Hensch Nicole M , Gläser Sven , Zeggini Eleftheria , Lehtimäki Terho , Strachan David P , Dupuis Josee , Morrison Alanna C. , Hall Ian P , Tobin Martin D , London Stephanie J
Published: July 2017

Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease (COPD). We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. We identified significant (P<2·8x10-7) associations with six SNPs: a nonsynonymous variant inRPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17andUQCC1) and two intergenic SNPs near toLY86andFGF10. eQTL analyses found evidence for regulation of gene expression at three signals and implicated several genes includingTYRO3andPLAU. Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
Exact graph-based analysis of scientific articles on clinical trials
Authors: Levin Ilya
Published: July 2017

This article describes Amorpha, a software package based on new concept of exact graph-based linguistic analysis. Analytical capabilities of Amorpha are demonstrated using analysis of scientific abstracts on clinical trials from PubMed. Current trends in therapy of breast cancer and psoriatic arthritis were analyzed using 400 abstracts on breast cancer and 131 abstracts on psoriatic arthritis. The spectrum of diseases that currently treated with paclitaxel was extracted from 400 most recent abstracts on paclitaxel.

In addition to text representation, analytical results are presented as graph images showing essential concepts of a text. Amorpha is not designed specifically to analyze clinical trials and will be also useful for analysis of biological scientific articles and regulatory documents. Amorpha does not require any preliminary knowledge base, ensures full coverage of target text and 100% accuracy of obtained results.
Resolving systematic errors in widely-used enhancer activity assays in human cells enables genome-wide functional enhancer characterization
Authors: Muerdter Felix , Boryń Łukasz M. , Woodfin Ashley R. , Neumayr Christoph , Rath Martina , Zabidi Muhammad A. , Pagani Michaela , Haberle Vanja , Kazmar Tomáš , Catarino Rui R. , Schernhuber Katharina , Arnold Cosmas D. , Stark Alexander
Published: July 2017

The identification of transcriptional enhancers in the human genome is a prime goal in biology. Enhancers are typically predicted via chromatin marks, yet their function is primarily assessed with plasmid-based reporter assays. Here, we show that two previous observations relating to plasmid-transfection into human cells render such assays unreliable: (1) the function of the bacterial plasmid origin-of-replication (ORI) as a conflicting core-promoter and (2) the activation of a type I interferon (IFN-I) response. These problems cause strongly confounding false-positives and -negatives in luciferase assays and genome-wide STARR-seq screens. We overcome both problems by directly employing the ORI as a core-promoter and by inhibiting two kinases central to IFN-I induction. This corrects luciferase assays and enables genome-wide STARR-seq screens in human cells. Comprehensive enhancer activity profiles in HeLa-S3 cells uncover strong enhancers, IFN-I-induced enhancers, and enhancers endogenously silenced at the chromatin level. Our findings apply to all episomal enhancer activity assays in mammalian cells, and are key to the characterization of human enhancers.
Estimating encounter rates as the first step of sexual selection in the lizardAnolis sagrei
Authors: Kamath Ambika , Losos Jonathan B.
Published: July 2017

How individuals move through their environment dictates which other individuals they encounter, determining their social and reproductive interactions and the extent to which they experience sexual selection. Specifically, females rarely have the option of mating with all males in a population—they can only choose among the males they encounter. Further, quantifying phenotypic differences between the males that females encounter and those that sire females’ offspring lends insight into how social and reproductive interactions shape male phenotypes. We used an explicitly spatiotemporal Markov chain model to estimate the number of potential mates ofAnolis sagreilizards from their movement behavior, and used genetic paternity assignments to quantify sexual selection on males. Females frequently encountered and mated with multiple males, offering ample opportunity for female mate choice. Sexual selection favored males that were bigger and moved over larger areas, though the effect of body size cannot be disentangled from last-male precedence. Our approach corroborates some patterns of sexual selection previously hypothesized in anoles based on describing them as territorial, whereas other results, including female multiple mating itself, are at odds with territorial polygyny, offering insight into discrepancies in other taxa between behavioral and genetic descriptions of mating systems.
The RacGAP βChimaerin is essential for cerebellar granule cell migration
Authors: Estep Jason A. , Wong Wenny , Wong Yiu-Cheung E. , Loui Brian M. , Riccomagno Martin M.
Published: July 2017

During mammalian cerebellar development, postnatal granule cell progenitors proliferate in the outer part of the External Granule Layer (EGL). Postmitotic granule progenitors migrate tangentially in the inner EGL before switching to migrate radially inward, past the Purkinje cell layer, to achieve their final position in the mature Granule Cell Layer (GCL). Here, we show that the RacGAP β-chimaerin is expressed by a small population of late-born, premigratory granule cells. β-chimaerin deficiency causes a subset of granule cells to become arrested in the EGL, where they differentiate and form ectopic neuronal clusters. These clusters of granule cells are able to recruit aberrantly projecting mossy fibers. Collectively, these data suggest a role for β-chimaerin as an intracellular mediator of Cerebellar Granule Cell radial migration.
Crystal structures of 4-methoxybenzoic acid–1,3-bis(pyridin-4-yl)propane (2/1) and biphenyl-4,4′-dicarboxylic acid–4-methoxypyridine (1/2)
Authors: Gotoh Kazuma , Ishida Hiroyuki
Published: July 2017

The crystal structures of two hydrogen-bonded compounds, namely 4-methoxybenzoic acid–1,3-bis(pyridin-4-yl)propane (2/1), C13H14.59N2·C8H7.67O3·C8H7.74O3, (I), and biphenyl-4,4′-dicarboxylic acid–4-methoxypyridine (1/2), C14H9.43O4·C6H7.32NO·C6H7.25NO, (II), have been determined at 93 K. In (I), the asymmetric unit consists of two crystallographically independent 4-methoxybenzoic acid molecules and one 1,3-bis(pyridin-4-yl)propane molecule. The asymmetric unit of (II) comprises one biphenyl-4,4′-dicarboxylic acid molecule and two independent 4-methoxypyridine molecules. In each crystal, the acid and base molecules are linked by short O—H...N/N—H...O hydrogen bonds, in which H atoms are disordered over the acid O-atom and base N-atom sites, forming a linear hydrogen-bonded 2:1 or 1:2 unit of the acid and the base. The 2:1 units of (I) are linked via C—H...π, π–π and C—H...O interactions into a tape structure along [101], while the 1:2 units of (II) form a double-chain structure along [-101] through π–π and C—H...O interactions.
Crystal structure of 2,3-diphenyl-2,3-dihydro-4H-1,3-benzothiazin-4-one 1-oxide
Authors: Yennawar Hemant P. , Fox Ryan , Moyer Quentin J. , Yang Ziwei , Silverberg Lee J.
Published: July 2017

In the racemic title compound, C20H15NO2S, the planes of the two phenyl substituents form dihedral angles of 48.97 (15) and 69.26 (15)° with that of the fused benzene ring of the parent benzothiazine ring, while the heterocyclic thiazine ring exhibits a screw-boat pucker. The O atom on the S atom of the ring is pseudo-axial on the thiazine ring and trans to the 2-phenyl group. In the crystal, molecules are arranged in layers in the ac plane, the layers being linked across b through intermolecular C—H...O hydrogen-bonding interactions.
1,4-Bis(4-bromobutoxy)benzene
Authors: Maragatham Gunasekaran , Selvarani Sivasamy , Rajakumar Perumal , Lakshmi Srinivasakannan
Published: July 2017

The complete molecule of the title compound, C14H20Br2O2, is generated by crystallographic inversion symmetry and the 4-bromobutoxy side chain adopts an extended conformation. In the crystal, weak C—H...π interactions are observed, which help to consolidate a herringbone packing motif.
Work role transitions – expert nurses to novice preceptors
Authors: Miller Janice , Vivona Brian , Roth Gene
Published: July 2017

Purpose

Several issues are reported in the literature regarding the preparation and training of nurses for the preceptor role. The purpose of this study is to explore the experiences, growth and development of nurses transitioning to the preceptor role in allied health contexts.

Design/methodology/approach

A basic interpretive qualitative research method was used for this study. In total, 20 preceptors who were practicing in a variety of healthcare settings participated in in-depth interviews.

Findings

The preceptors of this study found meaning through their teaching and learning encounters with novice nurses. Their meaning making led to identity development and new perspectives on both the nursing and preceptor roles.

Research limitations/implications

This study extends the literature on informal learning and training by focusing on the unique work role of nurse precepting. Conclusions of this study call for additional research that examines other occupational areas in which workers have transitioned from expert to novice again, and how training can enhance these transitions

Practical implications

Participants described several areas of improvement for preceptorships: additional administrative support, guidelines and standards for preceptor training and preparation and additional time and support for transitioning to the preceptor role

Originality/value

Work role transition theory was used in this study to examine the preparation and training of preceptors. This study features the voices of nursing preceptors who have experienced changes in their employment status and major shifts in their work roles transitioning from expert to novice to expert again.
Developing entrepreneurial resilience: implications for human resource development
Authors: Lee Jin , Wang Jia
Published: July 2017

Purpose

Leadership development has attracted much research attention within the human resource development (HRD) community. However, little scholarly effort has been made to study a special group of leaders – entrepreneurs. This paper aims to fill in this knowledge gap by taking a close look at entrepreneurial resilience, a key ability of entrepreneurs to overcome challenges and adapt to uncertainties.

Design/methodology/approach

This paper conducted an extensive literature review using conceptual analysis as the primary method. Enablers and inhibitors affecting entrepreneurial resilience development were identified from the selected empirical studies.

Findings

From the analysis of empirical studies, a set of enablers and inhibitors was identified, and the effects on entrepreneur resilience were explored. Based on identified enablers and inhibitors, an integrative model of entrepreneurial resilience that serves as a building block for entrepreneurial resilience theory building was proposed.

Originality/value

Findings from this research and the newly proposed model will not only contribute to the much-needed entrepreneurial resilience theory building but also serve as a useful guide for human resource professionals and trainers in designing leadership development interventions.