bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of estradiol with sleep apnea in depressed perimenopausal and postmenopausal women: a preliminary study
Authors: Galvan Thania , Camuso Julia , Sullivan Kathryn , Kim Semmie , White David , Redline Susan , Joffe Hadine
Published: September 2016

Objective:

Women's risk of obstructive sleep apnea (OSA) increases substantially during and after the menopausal transition, when depression risk is also elevated, raising the possibility that estrogen withdrawal contributes to OSA vulnerability, in turn contributing to mood disturbance. We examined the association between estradiol levels and OSA in depressed peri- and postmenopausal women.

Methods:

Thirty depressed peri-/postmenopausal women (mean body mass index [BMI] 30.82 kg/m2) without known OSA completed routine polysomnography concurrent with serum estradiol levels. Estradiol in women with apnea-hypopnea indices (AHI) ≥15 indicating moderate-to-severe OSA was compared against those with AHI less than 15 using logistic regression adjusting for age and BMI.

Results:

Thirteen women (43%) had AHI ≥15 (median AHI 21.6). Estradiol levels were lower (P = 0.02) in those with OSA (median 19, interquartile range 9-25 pg/mL) than without OSA (median 29, interquartile range 19-66 pg/mL). On univariate analysis, higher estradiol was associated with reduced odds of OSA (odds ratio 0.95, 95% CI 0.90-0.99, P = 0.04). After adjusting for age and BMI, estradiol levels remained associated with lower odds of OSA (odds ratio 0.90), but the association was no longer statistically significant (95% CI 0.76-1.05, P = 0.18). Montgomery Åsberg Depression Rating Scale scores did not differ between those with and without OSA.

Conclusions:

These preliminary results suggest that, in addition to higher BMI and age, lower estradiol may be associated with increased OSA risk in depressed women during the peri- and postmenopause, raising the possibility that estradiol withdrawal associated with menopause influences upper-airway patency in women.
MYCOPLASMA PNEUMONIA-ASSOCIATED CHOROIDAL NEOVASCULARIZATION—BEVACIZUMAB INTRAVITREAL INJECTION AND LASER TREATMENT
Authors: Fiorentzis Miltiadis , Käsmann-Kellner Barbara , Meyer Sascha , Seitz Berthold , Viestenz Arne
Published: September 2016

Purpose:

To report a rare case of bilateral subretinal granulomas with choroidal neovascularization after Mycoplasma pneumoniae atypical pneumonia.

Methods:

Presentation of a 7-year-old girl, who showed bilateral atypical subretinal granulomas with choroidal neovascularization. Visual acuity was 20/20 oculus dexter and 20/200 oculus sinister. Evaluation revealed a systemic Mycoplasma pneumoniae infection with pulmonary involvement. Successful ocular treatment was performed by intravitreal injection of Bevacizumab and laser photocoagulation.

Results:

Visual acuity was unchanged 36 months after treatment. No further subretinal lesions were seen oculus uterque.

Conclusion:

To the best of their knowledge and according to literature this patient report is the first one of subretinal granuloma formation after pneumonia due to mycoplasma infection. Since Mycoplasma pneumoniae is a common pathogen, especially in children and young adults, it should be considered in the differential diagnosis of any febrile illness accompanied by ocular signs.
Current status of the influence of osteoporosis on periodontology and implant dentistry
Authors: Chambrone Leandro
Published: September 2016

Purpose of review

This review summarizes recent evidence on the impact of osteoporosis on periodontonlogy and implant dentistry, prevalence of diseases, pathophysiology and treatment outcomes.

Recent findings

Patients with osteoporosis should be advised about the importance of returning for periodical periodontal maintenance as inadequate oral care may lead to a faster development of periodontitis. There is no definitive information on the development of bisphosphonate-related osteonecrosis of the jaw associated with dental implant therapy. Patients presenting severe periodontitis, undergoing intravenous bisphosphonate therapy (for long-term periods) and submitted to more invasive periodontal/peri-implant surgical procedures (that can promote superior dentoalveolar surgical trauma) might be advised about the possibility of developing bisphosphonate-related osteonecrosis of the jaw following dental therapy. Thus, individualized risk evaluation must be undertaken by both the medical and dental teams prior to any dental treatment.

The most recent literature on the impact of osteoporosis on the periodontal and peri-implant tissues was reviewed to emphasize the importance of oral hygiene measures, and the combined medical/dental assessment of importance when osteoporotic patients are in need of dentoalveolar surgical procedures (e.g. tooth extraction and dental implant placement).
Nursing Professional Development Organizational Value Demonstration Project
Authors: Harper Mary G. , Aucoin Julia , Warren Joan I.
Published: September 2016

A common question nursing professional development (NPD) practitioners ask is, “How many NPD practitioners should my organization have?” This study examined correlations among facility size and structure, NPD practitioner characteristics and time in service, and organizational outcomes. Organizations with a higher rate of NPD full-time equivalents per bed had higher patient satisfaction with nurses’ communication and provision of discharge instruction on their HCAHPS (Hospital Consumer Assessment of Healthcare Provider and Systems) scores.
Defining Competence in Nursing and Its Relevance to Quality Care
Authors: Church Cory D.
Published: September 2016

A consistent definition of competence in nursing is needed considering the significance to nursing professional development. The author bridges the gap between previous concept analyses of competence by creating an overarching model, while discussing the relationship to quality of nursing care. Significance of competence and quality care to nursing professional development is explored. The author concludes with implications for nursing professional development practice and research, while highlighting the relevance to professional nursing.
Multifaceted Comparison of Two Cryotherapy Devices Used After Total Knee Arthroplasty
Authors: Schinsky Mark F. , McCune Christine , Bonomi Judith
Published: September 2016

BACKGROUND:

Some form of cryotherapy used after total knee arthroplasty is commonplace. However, various factors determine the specific device deployed.

PURPOSE:

This study aimed to answer the following questions:

Is an ice/gel pack cryotherapy wrap noninferior to a more elaborate circulating cold water therapy device in terms of patient outcomes, patient satisfaction, and hospital staff satisfaction?

What is the projected economic impact of using an ice/gel pack cryotherapy wrap versus a circulating cold water cryotherapy device?

METHODS:

A group of 100 patients undergoing primary total knee arthroplasty by a single surgeon were enrolled in an institutional review board–approved, prospective study and randomized to receive either a circulating cold water or ice/gel pack cryotherapy device postoperatively. Demographic, pain, swelling, blood loss, range of motion, compliance, satisfaction, and adverse event outcomes were recorded until 6 weeks after surgery. Hospital staff satisfaction and economic variables were examined.

RESULTS:

The ice/gel pack cryotherapy wrap was noninferior to the cold water cryotherapy device for any patient outcome measured. Average pain level at 6 weeks postoperative was significantly less in the ice/gel pack cryotherapy wrap group. Hospital staff satisfaction was higher with the ice/gel pack cryotherapy wrap.

Substantial economic savings can be realized at our institution by switching to the lower cost cryotherapy device.

CONCLUSION:

In this study, the lower cost ice/gel pack cryotherapy wrap was noninferior to the circulating ice water cryotherapy device with respect to objective patient outcomes and subjective patient satisfaction after total knee arthroplasty. Hospital staff satisfaction and economic considerations also favor the ice/gel pack compression cryotherapy wraps.
Association of Extracorporeal Membrane Oxygenation Support Adequacy and Residual Lesions With Outcomes in Neonates Supported After Cardiac Surgery*
Authors: Howard Taylor S. , Kalish Brian T. , Wigmore Daniel , Nathan Meena , Kulik Thomas J. , Kaza Aditya K. , Williams Kathryn , Thiagarajan Ravi R.
Published: September 2016

Objectives:

There is a paucity of data regarding the impact of extracorporeal membrane oxygenation support, adequacy of surgical repair, and timing of intervention for residual structural lesions in neonates cannulated to extracorporeal membrane oxygenation after cardiac surgery. Our goal was to determine how these factors were associated with survival.

Design:

Retrospective study.

Setting:

Cardiovascular ICU.

Subjects:

Neonates (≤ 28 d old) with congenital heart disease cannulated to extracorporeal membrane oxygenation after cardiac surgery during 2006–2013.

Interventions:

None.

Measurements and Main Results:

Eighty-four neonates were cannulated to venoarterial extracorporeal membrane oxygenation after cardiac surgery. Survival to discharge was 50%. There was no difference in survival based on surgical complexity and those with single or biventricular congenital heart disease. Prematurity (≤ 36 wk gestation; odds ratio, 2.33; p = 0.01), preextracorporeal membrane oxygenation pH less than or equal to 7.17 (odds ratio, 2.01; p = 0.04), need for inotrope support during extracorporeal membrane oxygenation (odds ratio, 3.99; p = 0.03), and extracorporeal membrane oxygenation duration greater than 168 hours (odds ratio, 2.04; p = 0.04) were all associated with increased mortality. Although preextracorporeal membrane oxygenation lactate was not significantly different between survivors and nonsurvivors, unresolved lactic acidosis greater than or equal to 72 hours after cannulation (odds ratio, 2.77; p = 0.002) was associated with increased mortality. Finally, many patients (n = 70; 83%) were noted to have residual lesions after cardiac surgery, and time to diagnosis or correction of residual lesions was significantly shorter in survivors (1 vs 2 d; p = 0.02).

Conclusions:

Our data suggest that clearance of lactate is an important therapeutic target for patients cannulated to extracorporeal membrane oxygenation. In addition, timely identification of residual lesions and expedient interventions on those lesions may improve survival.
Atypical Findings in Massive Bupropion Overdose: A Case Report and Discussion of Psychopharmacologic Issues
Authors: ZHU YUANJIA , KOLAWOLE TIWALOLA , JIMENEZ XAVIER F.
Published: September 2016

Bupropion is an atypical antidepressant that is structurally similar to amphetamines. Its primary toxic effects include seizure, sinus tachycardia, hypertension, and agitation; however, at higher amounts of ingestion, paradoxical cardiac effects are seen. We report the case of a 21-year-old woman who ingested 13.5 g of bupropion, a dose higher than any other previously reported. The patient presented with seizure, sinus tachycardia with prolonged QTc and QRS intervals, dilated pupils, and agitation. Four days after overdose, the patient’s sinus tachycardia and prolonged QTc and QRS intervals resolved with symptomatic management, but she soon developed sinus bradycardia, hypotension, and mild transaminitis. With continued conservative management and close monitoring, her sinus bradycardia resolved 8 days after the overdose. The transaminitis resolved 12 days after the overdose. Our findings are consistent with previously reported toxic effects associated with common overdose amounts of bupropion. In addition, we have observed transient cardiotoxicity manifesting as sinus bradycardia associated with massive bupropion overdose. These findings are less frequently reported and must be considered when managing patients with massive bupropion overdose. We review the psychopharmacologic implications of this and comment on previous literature.
Estimated HIV Incidence in the United States, 2003–2010
Authors: Xia Qiang , Teixeira-Pinto Armando , Forgione Lisa A. , Wiewel Ellen W. , Braunstein Sarah L. , Torian Lucia V.
Published: September 2016

Objective:

To estimate HIV incidence in the United States using a newly developed method.

Methods:

The analysis period (2002–2011) was broken down into 3-year periods with overlaps, and HIV incidence was estimated based on the relationship between number of new diagnoses and HIV incidence in each of these 3-year periods, by assuming that all HIV infections would eventually be diagnosed and within each 3-year period HIV incidence and case finding were stable.

Results:

The estimated HIV incidence in the United States decreased from 52,721 (range: 47,449–57,993) in 2003 to 39,651 (range: 35,686–43,617) in 2010, among males from 38,164 (range: 35,051–42,840) to 33,035 (range: 29,088–35,553), and among females from 13,557 (range: 12,133–14,830) to 6616 (range: 5825 to 7120).

Conclusions:

Using a simple and novel method based on the number of new HIV diagnoses, we were able to estimate HIV incidence and report a declining trend in HIV incidence in the United States since 2003.
Protein turnover measurement using selected reaction monitoring-mass spectrometry (SRM-MS)
Authors: Holman Stephen W. , Hammond Dean E. , Simpson Deborah M. , Waters John , Hurst Jane L. , Beynon Robert J.
Published: September 2016

Protein turnover represents an important mechanism in the functioning of cells, with deregulated synthesis and degradation of proteins implicated in many diseased states. Therefore, proteomics strategies to measure turnover rates with high confidence are of vital importance to understanding many biological processes. In this study, the more widely used approach of non-targeted precursor ion signal intensity (MS1) quantification is compared with selected reaction monitoring (SRM), a data acquisition strategy that records data for specific peptides, to determine if improved quantitative data would be obtained using a targeted quantification approach. Using mouse liver as a model system, turnover measurement of four tricarboxylic acid cycle proteins was performed using both MS1 and SRM quantification strategies. SRM outperformed MS1 in terms of sensitivity and selectivity of measurement, allowing more confident determination of protein turnover rates. SRM data are acquired using cheaper and more widely available tandem quadrupole mass spectrometers, making the approach accessible to a larger number of researchers than MS1 quantification, which is best performed on high mass resolution instruments. SRM acquisition is ideally suited to focused studies where the turnover of tens of proteins is measured, making it applicable in determining the dynamics of proteins complexes and complete metabolic pathways.

This article is part of the themed issue ‘Quantitative mass spectrometry’.
Towards quantitative mass spectrometry-based metabolomics in microbial and mammalian systems
Authors: Kapoore Rahul Vijay , Vaidyanathan Seetharaman
Published: September 2016

Metabolome analyses are a suite of analytical approaches that enable us to capture changes in the metabolome (small molecular weight components, typically less than 1500 Da) in biological systems. Mass spectrometry (MS) has been widely used for this purpose. The key challenge here is to be able to capture changes in a reproducible and reliant manner that is representative of the events that take place
in vivo
. Typically, the analysis is carried out
in vitro
, by isolating the system and extracting the metabolome. MS-based approaches enable us to capture metabolomic changes with high sensitivity and resolution. When developing the technique for different biological systems, there are similarities in challenges and differences that are specific to the system under investigation. Here, we review some of the challenges in capturing quantitative changes in the metabolome with MS based approaches, primarily in microbial and mammalian systems.

This article is part of the themed issue ‘Quantitative mass spectrometry’.
Quantitative mass spectrometry methods for pharmaceutical analysis
Authors: Loos Glenn , Van Schepdael Ann , Cabooter Deirdre
Published: September 2016

Quantitative pharmaceutical analysis is nowadays frequently executed using mass spectrometry. Electrospray ionization coupled to a (hybrid) triple quadrupole mass spectrometer is generally used in combination with solid-phase extraction and liquid chromatography. Furthermore, isotopically labelled standards are often used to correct for ion suppression. The challenges in producing sensitive but reliable quantitative data depend on the instrumentation, sample preparation and hyphenated techniques. In this contribution, different approaches to enhance the ionization efficiencies using modified source geometries and improved ion guidance are provided. Furthermore, possibilities to minimize, assess and correct for matrix interferences caused by co-eluting substances are described. With the focus on pharmaceuticals in the environment and bioanalysis, different separation techniques, trends in liquid chromatography and sample preparation methods to minimize matrix effects and increase sensitivity are discussed. Although highly sensitive methods are generally aimed for to provide automated multi-residue analysis, (less sensitive) miniaturized set-ups have a great potential due to their ability for in-field usage.

This article is part of the themed issue ‘Quantitative mass spectrometry’.
Gas-phase protein conformation/multimer ion formation by electrospray ion mobility-mass spectrometry: bovine insulin and ubiquitin
Authors: Gillig Kent J.
Published: September 2016

Ion mobility-mass spectrometry (IMMS) is a very attractive method for studies in structural biology because of the ability of rapid isolation by nearly simultaneous
m/z
characterization and size separation, leading to an emergence of IMMS as a complimentary biochemical tool. Earlier, we developed a method based on varying the protein concentration in solution prior to electrospray ionization (ESI) with subsequent
m/z
selection and dissociation of protein multimers by IMMS of cytochrome c. The focus of this work will be to correctly distinguish truly different ion conformations formed by ESI versus homomultimeric complexes with the same
m/z
for well-studied proteins bovine ubiquitin and insulin. These proteins were chosen due to their large difference in solution phase structures: insulin tightly bound by disulfide linkages, and ubiquitin—a protein that may adopt a range of states from compact to extended. Our preliminary results, as with cytochrome c reveal false negatives for protein oligomer formation and false positives for protein conformational states. In addition, these results will be couched in terms of the need for quantification of IMMS analysis of proteins given the total area under IMMS peaks can also distinguish conformation versus aggregation as higher order oligomers have more mass per ion.

This article is part of the themed issue ‘Quantitative mass spectrometry’.
Quantitative aspects of inductively coupled plasma mass spectrometry
Authors: Bulska Ewa , Wagner Barbara
Published: September 2016

Accurate determination of elements in various kinds of samples is essential for many areas, including environmental science, medicine, as well as industry. Inductively coupled plasma mass spectrometry (ICP-MS) is a powerful tool enabling multi-elemental analysis of numerous matrices with high sensitivity and good precision. Various calibration approaches can be used to perform accurate quantitative measurements by ICP-MS. They include the use of pure standards, matrix-matched standards, or relevant certified reference materials, assuring traceability of the reported results. This review critically evaluates the advantages and limitations of different calibration approaches, which are used in quantitative analyses by ICP-MS. Examples of such analyses are provided.

This article is part of the themed issue ‘Quantitative mass spectrometry’.
Mass spectrometry as a quantitative tool in plant metabolomics
Authors: Jorge Tiago F. , Mata Ana T. , António Carla
Published: September 2016

Metabolomics is a research field used to acquire comprehensive information on the composition of a metabolite pool to provide a functional screen of the cellular state. Studies of the plant metabolome include the analysis of a wide range of chemical species with very diverse physico-chemical properties, and therefore powerful analytical tools are required for the separation, characterization and quantification of this vast compound diversity present in plant matrices. In this review, challenges in the use of mass spectrometry (MS) as a quantitative tool in plant metabolomics experiments are discussed, and important criteria for the development and validation of MS-based analytical methods provided.

This article is part of the themed issue ‘Quantitative mass spectrometry’.
Identification of proteins from 4200-year-old skin and muscle tissue biopsies from ancient Egyptian mummies of the first intermediate period shows evidence of acute inflammation and severe immune response
Authors: Jones Jana , Mirzaei Mehdi , Ravishankar Prathiba , Xavier Dylan , Lim Do Seon , Shin Dong Hoon , Bianucci Raffaella , Haynes Paul A.
Published: September 2016

We performed proteomics analysis on four skin and one muscle tissue samples taken from three ancient Egyptian mummies of the first intermediate period, approximately 4200 years old. The mummies were first dated by radiocarbon dating of the accompany-\break ing textiles, and morphologically examined by scanning electron microscopy of additional skin samples. Proteins were extracted, separated on SDS–PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) gels, and in-gel digested with trypsin. The resulting peptides were analysed using nanoflow high-performance liquid chromatography–mass spectrometry. We identified a total of 230 unique proteins from the five samples, which consisted of 132 unique protein identifications. We found a large number of collagens, which was confirmed by our microscopy data, and is in agreement with previous studies showing that collagens are very long-lived. As expected, we also found a large number of keratins. We identified numerous proteins that provide evidence of activation of the innate immunity system in two of the mummies, one of which also contained proteins indicating severe tissue inflammation, possibly indicative of an infection that we can speculate may have been related to the cause of death.

This article is part of the themed issue ‘Quantitative mass spectrometry’.
Comprehensive evaluation of direct injection mass spectrometry for the quantitative profiling of volatiles in food samples
Authors: Lebrón-Aguilar R. , Soria A. C. , Quintanilla-López J. E.
Published: September 2016

Although qualitative strategies based on direct injection mass spectrometry (DIMS) have recently emerged as an alternative for the rapid classification of food samples, the potential of these approaches in quantitative tasks has scarcely been addressed to date. In this paper, the applicability of different multivariate regression procedures to data collected by DIMS from simulated mixtures has been evaluated. The most relevant factors affecting quantitation, such as random noise, the number of calibration samples, type of validation, mixture complexity and similarity of mass spectra, were also considered and comprehensively discussed. Based on the conclusions drawn from simulated data, and as an example of application, experimental mass spectral fingerprints collected by direct thermal desorption coupled to mass spectrometry were used for the quantitation of major volatiles in
Thymus zygis
subsp.
zygis
chemotypes. The results obtained, validated with the direct thermal desorption coupled to gas chromatography–mass spectrometry method here used as a reference, show the potential of DIMS approaches for the fast and precise quantitative profiling of volatiles in foods.

This article is part of the themed issue ‘Quantitative mass spectrometry’.
Quantitative metabolomics of photoreceptor degeneration and the effects of stem cell-derived retinal pigment epithelium transplantation
Authors: Wang Junhua , Westenskow Peter D. , Fang Mingliang , Friedlander Martin , Siuzdak Gary
Published: September 2016

Photoreceptor degeneration is characteristic of vision-threatening diseases including age-related macular degeneration. Photoreceptors are metabolically demanding cells in the retina, but specific details about their metabolic behaviours are unresolved. The quantitative metabolomics of retinal degeneration could provide valuable insights and inform future therapies. Here, we determined the metabolomic ‘fingerprint’ of healthy and dystrophic retinas in rat models using optimized metabolite extraction techniques. A number of classes of metabolites were consistently dysregulated during degeneration: vitamin A analogues, fatty acid amides, long-chain polyunsaturated fatty acids, acyl carnitines and several phospholipid species. For the first time, a distinct temporal trend of several important metabolites including DHA (4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid), all-
trans
-retinal and its toxic end-product
N
-retinyl-
N
-retinylidene-ethanolamine were observed between healthy and dystrophic retinas. In this study, metabolomics was further used to determine the temporal effects of the therapeutic intervention of grafting stem cell-derived retinal pigment epithelium (RPE) in dystrophic retinas, which significantly prevented photoreceptor atrophy in our previous studies. The result revealed that lipid levels such as phosphatidylethanolamine in eyes were restored in those animals receiving the RPE grafts. In conclusion, this study provides insight into the metabolomics of retinal degeneration, and further understanding of the efficacy of RPE transplantation.

This article is part of the themed issue ‘Quantitative mass spectrometry’.
On the preservation of non-covalent protein complexes during electrospray ionization
Authors: Chingin Konstantin , Barylyuk Konstantin , Chen Huanwen
Published: September 2016

The application range of electrospray ionization mass spectrometry for the quantitative determination of stoichiometries and binding constants for non-covalent protein complexes is broadly discussed. The underlying fundamental question is whether or not the original molecular equilibrium can be preserved during the ionization process and be revealed by subsequent mass spectrometry analysis. Here, we take a new look at this question by discussing recent studies in droplet chemistry.

This article is part of the themed issue ‘Quantitative mass spectrometry’.
Monitoring the synthesis of biomolecules using mass spectrometry
Authors: Miyagi Masaru , Kasumov Takhar
Published: September 2016

The controlled and selective synthesis/clearance of biomolecules is critical for most cellular processes. In most high-throughput ‘omics’ studies, we measure the static quantities of only one class of biomolecules (e.g. DNA, mRNA, proteins or metabolites). It is, however, important to recognize that biological systems are highly dynamic in which biomolecules are continuously renewed and different classes of biomolecules interact and affect each other's production/clearance. Therefore, it is necessary to measure the turnover of diverse classes of biomolecules to understand the dynamic nature of biological systems. Herein, we explain why the kinetic analysis of a diverse range of biomolecules is important and how such an analysis can be done. We argue that heavy water (
2
H
2
O) could be a universal tracer for monitoring the synthesis of biomolecules on a global scale.

This article is part of the themed issue ‘Quantitative mass spectrometry’.
The significance of petroleum bitumen in ancient Egyptian mummies
Authors: Clark K. A. , Ikram S. , Evershed R. P.
Published: September 2016

Mummification was practised in ancient Egypt for more than 3000 years, emerging from initial observations of buried bodies preserved by natural desiccation. The use of organic balms (and other funerary practices) was a later introduction necessitated by more humid burial environments, especially tombs. The dark colour of many mummies led to the assumption that petroleum bitumen (or natural asphalt) was ubiquitous in mummification; however, this has been questioned for more than 100 years. We test this by investigating 91 materials comprising balms, tissues and textiles from 39 mummies dating fromca3200 BC to AD 395. Targeted petroleum bitumen biomarker (steranes and hopanes) analyses by gas chromatography-mass spectrometry selected ion monitoring (GC-MS SIM,m/z217 and 191) showed no detectable bitumen use before the New Kingdom (ca1550–1070 BC). However, bitumen was used in 50% of New Kingdom to Late Period mummies, rising to 87% of Ptolemaic/Roman Period mummies. Quantitative determinations using14C analyses reveal that even at peak use balms were never more than 45%w/wbitumen. Critically, the dark colour of balms can be simulated by heating/ageing mixtures of fats, resins and beeswax known to be used in balms. The application of black/dark brown balms to bodies was deliberate after the New Kingdom reflecting changing funerary beliefs and shifts in religious ideology.

This article is part of the themed issue ‘Quantitative mass spectrometry’.
Discovery of flavivirus-derived endogenous viral elements in twoAnophelesmosquito genomes supports the existence ofAnopheles-associated insect-specific flaviviruses
Authors: Lequime Sebastian , Lambrechts Louis
Published: September 2016

TheFlavivirusgenus encompasses several arboviruses of public health significance such as dengue, yellow fever, and Zika viruses. It also includes insect-specific flaviviruses (ISFs) that are only capable of infecting insect hosts. The vast majority of mosquito-infecting flaviviruses have been associated with mosquito species of theAedesandCulexgenera in the Culicinae subfamily, which also includes most arbovirus vectors. Mosquitoes of the Anophelinae subfamily are not considered significant arbovirus vectors, however flaviviruses have occasionally been detected in field-caughtAnophelesspecimens. Whether such observations reflect occasional spillover or laboratory contamination or whetherAnophelesmosquitoes are natural hosts of flaviviruses is unknown. Here, we providein silicoandin vivoevidence of transcriptionally active, flavivirus-derived endogenous viral elements (EVEs) in the genome ofAnopheles minimusandAnopheles sinensis. Such non-retroviral endogenization of RNA viruses is consistent with a shared evolutionary history between flaviviruses andAnophelesmosquitoes. Phylogenetic analyses of the two newly described EVEs support the existence of a distinct clade ofAnopheles-associated ISFs.
Deriving robust biomarkers from multi-site resting-state data: An Autism-based example
Authors: Abraham Alexandre , Milham Michael , Martino Adriana Di , Craddock R. Cameron , Samaras Dimitris , Thirion Bertrand , Varoquaux Gael
Published: September 2016

Resting-state functional Magnetic Resonance Imaging (R-fMRI) holds the promise to reveal functional biomarkers of neuropsychiatric disorders. However, extracting such biomarkers is challenging for complex multi-faceted neuropathologies, such as autism spectrum disorders. Large multi-site datasets increase sample sizes to compensate for this complexity, at the cost of uncontrolled heterogeneity. This heterogeneity raises new challenges, akin to those face in realistic diagnostic applications. Here, we demonstrate the feasibility of inter-site classification of neuropsychiatric status, with an application to the Autism Brain Imaging Data Exchange (ABIDE) database, a large (N=871) multi-site autism dataset. For this purpose, we investigate pipelines that extract the most predictive biomarkers from the data. These R-fMRI pipelines build participant-specific connectomes from functionally-defined brain areas. Connectomes are then compared across participants to learn patterns of connectivity that differentiate typical controls from individuals with autism. We predict this neuropsychiatric status for participants from the same acquisition sites or different, unseen, ones. Good choices of methods for the various steps of the pipeline lead to 67% prediction accuracy on the full ABIDE data, which is significantly better than previously reported results. We perform extensive validation on multiple subsets of the data defined by different inclusion criteria. These enables detailed analysis of the factors contributing to successful connectome-based prediction. First, prediction accuracy improves as we include more subjects, up to the maximum amount of subjects available. Second, the definition of functional brain areas is of paramount importance for biomarker discovery: brain areas extracted from large R-fMRI datasets outperform reference atlases in the classification tasks.
Quantitative analysis of cryptic splicing associated with TDP-43 depletion
Authors: Humphrey Jack , Emmett Warren , Fratta Pietro , Isaacs Adrian M. , Plagnol Vincent
Published: September 2016

Reliable exon recognition is key to the splicing of pre-mRNAs into mature mRNAs. TDP-43 is an RNA-binding protein whose nuclear loss and cytoplasmic aggregation are a hallmark pathology in amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). TDP-43 depletion causes the aberrant inclusion of cryptic exons into a range of transcripts, but their extent, relevance to disease pathogenesis and whether they are caused by other RNA-binding proteins implicated in ALS/FTD are unknown. We developed an analysis pipeline to discover and quantify cryptic exon inclusion and applied it to publicly available human and murine RNA-sequencing data. We detected widespread cryptic splicing in TDP-43 depletion datasets but almost none in another ALS/FTD-linked protein FUS. Sequence motif and iCLIP analysis of cryptic exons demonstrated that they are bound by TDP-43. Unlike the cryptic exons seen in hnRNP C depletion, those linked to TDP-43 do not originate from a particular family of transposable element. Cryptic exons are poorly conserved and inclusion overwhelmingly leads to nonsense-mediated decay of the host transcript, with reduced transcript levels observed in differential expression analysis. RNA-protein interaction data on 73 different RNA-binding proteins showed that, in addition to TDP-43, 7 specifically bind TDP-43 linked cryptic exons.This suggests that TDP-43 competes with other splicing factors for binding to cryptic exons and can repress cryptic exon inclusion. Our quantitative analysis pipeline confirms the presence of cryptic exons during TDP-43 depletion and will aid investigation of their relevance to disease.
Towards an Open Data Framework for Body Sensor Networks Supporting Bluetooth Low Energy
Authors: Singh Ninoshka K. , Ricke Darrell O
Published: September 2016

Major companies, healthcare professionals, the military, and other scientists and innovators are now sensing that fitness and health data from wearable biosensors will likely provide new discoveries and insights into physiological, cognitive, and emotional health status of an individual. Having the ability to collect, process, and correlate data simultaneously from a set of heterogonous biosensor sources may be a key factor in informing the development of new technologies for reducing health risks, improving health status, and possibly preventing and predicting disease. The challenge in achieving this is getting easy access to heterogeneous data from a set of disparate sensors in a single, integrated wearable monitoring system. Often times, the data recorded by commercial biosensing devices are contained within each manufacturer’s proprietary platform. Summary data is available for some devices as free downloads or included only in annual premium memberships. Access to raw measurements is generally unavailable, especially from a custom developed application that may include prototype biosensors. In this paper, we explore key ideas on how to leverage the design features of Bluetooth Low Energy to ease the integration of disparate biosensors at the sensor communication layer. This component is intended to fit into a larger, multi-layered, open data framework that can provide additional data management and analytics capabilities for consumers and scientists alike at all the layers of a data access model which is typically employed in a body sensor network system.
Genomic profiling of multiple sequentially acquired tumor metastatic sites from an “exceptional responder” lung adenocarcinoma patient reveals extensive genomic heterogeneity and novel somatic variants driving treatment response
Authors: Biswas Romi , Gao Shaojian , Cultraro Constance M. , Maity Tapan K. , Venugopalan Abhilash , Abdullaev Zied , Shaytan Alexey K. , Carter Corey A. , Thomas Anish , Rajan Arun , Song Young , Pitts Stephanie , Chen Kevin , Bass Sara , Boland Joseph , Hanada Ken-Ichi , Chen Jinqiu , Meltzer Paul S. , Panchenko Anna R. , Yang James C. , Pack Svetlana , Giaccone Giuseppe , Schrump David S. , Khan Javed , Guha Udayan
Published: September 2016

We used next-generation sequencing to identify somatic alterations in multiple metastatic sites from an “exceptional responder” lung adenocarcinoma patient during his 7-yr course of ERBB2-directed therapies. The degree of heterogeneity was unprecedented, with ∼1% similarity between somatic alterations of the lung and lymph nodes. One novel translocation,PLAG1-ACTA2, present in both sites, up-regulated ACTA2 expression.ERBB2, the predominant driver oncogene, was amplified in both sites, more pronounced in the lung, and harbored an L869R mutation in the lymph node. Functional studies showed increased proliferation, migration, metastasis, and resistance to ERBB2-directed therapy because of L869R mutation and increased migration because of ACTA2 overexpression. Within the lung, a nonfunctional CDK12, due to a novel G879V mutation, correlated with down-regulation of DNA damage response genes, causing genomic instability, and sensitivity to chemotherapy. We propose a model whereby a subclone metastasized early from the primary site and evolved independently in lymph nodes.
PRISM-EM: template interface-based modelling of multi-protein complexes guided by cryo-electron microscopy density maps
Authors: Kuzu Guray , Keskin Ozlem , Nussinov Ruth , Gursoy Attila
Published: September 2016

The structures of protein assemblies are important for elucidating cellular processes at the molecular level. Three-dimensional electron microscopy (3DEM) is a powerful method to identify the structures of assemblies, especially those that are challenging to study by crystallography. Here, a new approach, PRISM-EM, is reported to computationally generate plausible structural models using a procedure that combines crystallographic structures and density maps obtained from 3DEM. The predictions are validated against seven available structurally different crystallographic complexes. The models display mean deviations in the backbone of <5 Å. PRISM-EM was further tested on different benchmark sets; the accuracy was evaluated with respect to the structure of the complex, and the correlation with EM density maps and interface predictions were evaluated and compared with those obtained using other methods. PRISM-EM was then used to predict the structure of the ternary complex of the HIV-1 envelope glycoprotein trimer, the ligand CD4 and the neutralizing protein m36.
Willingness to pay for innovations
Authors: Sadik-Rozsnyai Orsolya
Published: September 2016

Purpose

Whereas the impact of national culture on consumer innovativeness is widely discussed in the innovation literature, studies are scarce on consumer value and the related consumer willingness to pay (WTP) for innovations. Yet, innovative high-tech companies compete by enhancing their products with new attributes, and assessing consumer WTP for these innovative attributes in different countries is crucial to adapting the launching price and optimizing profits during the critical launch stage. To fill this gap, the purpose of this paper is to examine the impact of national culture and globalization on consumer value and the related WTP for technological innovations.

Design/methodology/approach

Data were collected in two culturally distinct but economically similar countries (France and Germany), using large representative and comparable consumer samples (n=642). Choice-based conjoint analysis was used as the principal method of data analysis.

Findings

This study reveals the significant impact of national culture on consumer value and the related WTP for technological innovations and the moderating effect of household income on this relationship.

Originality/value

This study is the first to reveal and provide strong empirical evidence of the impact of national culture on WTP for innovations. In addition, this study is the first to reveal the moderating effect of income on this relationship and to highlight an emerging European innovation adoption behavior.
Business model configurations: a five-V framework to map out potential innovation routes
Authors: Taran Yariv , Nielsen Christian , Montemari Marco , Thomsen Peter , Paolone Francesco
Published: September 2016

Purpose

Despite the common understanding that business model (BM) innovation is of vital importance for securing competitive positioning in the market place, managers still seem to lack appropriate frameworks and tools which can support them in renewing and rejuvenating their company’s existing BM. The purpose of this paper is to develop a structural and comprehensive toolbox of available BM configurations, from which companies can choose, to innovate their BM upon, and to design an appropriate BM innovation framework which can facilitate them in re-designing, selecting, and implementing new BM configuration possibilities.

Design/methodology/approach

A structured literature review is conducted to identify all the relevant BM configurations. Then, a value driver analysis is performed to group these BM configurations into appropriate categories. Finally, an ontological classification scheme and a structural and workable process, i.e. a BM innovation framework, are inductively developed.

Findings

The paper systematically develops a list of 71 BM configurations and groups them into an ontological classification scheme according to five groups: Value Proposition, Value Segment, Value Configuration, Value Network, and Value Capture. The paper illustrates how the BM innovation framework, enabled by this ontological classification scheme, provides a platform for identifying BM innovation routes for companies, allowing managers to envisage radical, disruptive, and new-to-the-world BM configuration ideas, or apply existing configurations from other industrial settings in what may be deemed new-to-the-industry innovation.

Originality/value

The paper enriches the amount of potential BM configurations available for managers to choose from when innovating their BMs, and extends the analysis to five core BM configuration categories. Moreover, the BM innovation framework suggested highlights the strong relationships among the value drivers, thus presenting the opportunity for managers to assess potential conflicts or synergies between various value drivers, and to align the BM management process as a whole.
Transformational leadership in leading young innovators – a subordinate’s perspective
Authors: Uusi-Kakkuri Piia , Brandt Tiina , Kultalahti Susanna
Published: September 2016

Purpose

The purpose of this paper is to investigate what kind of leadership young innovative people prefer and whether their level of innovativeness has an influence on those leadership preferences. It also asks specifically whether some leadership behaviours are preferred over others by young innovators, by comparing that group’s preferences to those of the majority of young people and an outlier group labelled laggards. Leadership preferences are studied in the context of transformational leadership covering transformational leadership, transactional leadership (including passive and active management by exception), rewarding, laissez-faire and authoritative leadership styles.

Design/methodology/approach

In total, 297 Finnish university students completed a voluntary leadership behaviour questionnaire and an innovativeness scale. A non-parametric independent samples median test was run to determine if there were differences in the leadership preference score between the innovativeness level groups.

Findings

Results indicate that the level of innovativeness influences leadership preferences. Receiving intellectual stimulation from their leader is more important to young innovators than it is to their peers but the former are also less comfortable with active management by exception.

Originality/value

Young innovators leadership preferences have not been studied. Harnessing the full power of this important talent pool is central to the future competitiveness of organizations and nations. This study intends to prompt discussion and studies on how to lead young innovators given their preferences.
Female entrepreneurs: motivations and constraints. An Italian regional study
Authors: Bianchi Marina , Parisi Valentino , Salvatore Renato
Published: September 2016

Purpose

This paper aims to identify the specific contextual constraints that women might face in becoming entrepreneurs; to correlate these constraints with the motivations that have determined this choice; and to ascertain how strongly constraints and motivations are correlated with individual rewards in terms of personal satisfaction and economic payoffs.

Design/methodology/approach

The empirical base is a survey that the authors conducted among female entrepreneurs in a Southern province of Italy in 2012. Data are analyzed through a correspondence and cluster analysis. The socio-economic context of the province within which these female-led firms operate is taken into account by means of a correspondence canonical analysis.

Findings

In terms of results: first, two-thirds of female entrepreneurs in the province are positively motivated, and this is a determining factor in their choice to become entrepreneurs. This translates into they also being satisfied with the choice they made. Second, contrary to the expectations, being positively motivated and satisfied holds both for firms operating in more dynamic and demanding sectors and for small firms using little financial or human capital.

Research limitations/implications

The chosen research approach has allowed to identify the most important decisional variables that affect female entrepreneurial choice. However, as most of the variables are categorical, the research’s results remain descriptive.

Practical implications

Positive motivations and personal rewards are clearly relevant for women making an entrepreneurial choice. However, they are not enough to stimulate fully the potential for growth of their enterprises: education and a social environment conducive to female creative expression are also necessary. To this end, the authors suggest that an important function of change could be played in particular by universities by fostering a culture of creativity and entrepreneurship.

Social implications

By stressing the connections between positive motivations and wellbeing, the authors suggest that the promotion of women’s entrepreneurial choices through networks and education generates more than purely economic benefits. It also has positive effects on their quality of life and on social welfare as well.

Originality/value

This paper responds to a need – not yet fulfilled in the literature – to better understand the relations between women’s motivation, satisfaction and the type of business selected.