bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the maternal vaginal microbiota play a role in seeding the microbiota of neonatal gut and nose?
Authors: Sakwinska O. , Foata F. , Berger B. , Brüssow H. , Combremont S. , Mercenier A. , Dogra S. , Soh S.-E. , Yen J.C.K. , Heong G.Y.S. , Lee Y.S. , Yap F. , Meaney M.J. , Chong Y.-S. , Godfrey K.M. , Holbrook J.D.
Published: October 2017

The acquisition and early maturation of infant microbiota is not well understood despite its likely influence on later health. We investigated the contribution of the maternal microbiota to the microbiota of infant gut and nose in the context of mode of delivery and feeding. Using 16S rRNA sequencing and specific qPCR, we profiled microbiota of 42 mother-infant pairs from the GUSTO birth cohort, at body sites including maternal vagina, rectum and skin; and infant stool and nose. In our study, overlap between maternal vaginal microbiota and infant faecal microbiota was minimal, while the similarity between maternal rectal microbiota and infant microbiota was more pronounced. However, an infant’s nasal and gut microbiota were no more similar to that of its own mother, than to that of unrelated mothers. These findings were independent of delivery mode. We conclude that the transfer of maternal vaginal microbes play a minor role in seeding infant stool microbiota. Transfer of maternal rectal microbiota could play a larger role in seeding infant stool microbiota, but approaches other than the generally used analyses of community similarity measures are likely to be needed to quantify bacterial transmission. We confirmed the clear difference between microbiota of infants born by Caesarean section compared to vaginally delivered infants and the impact of feeding mode on infant gut microbiota. Only vaginally delivered, fully breastfed infants had gut microbiota dominated by Bifidobacteria. Our data suggest that reduced transfer of maternal vaginal microbial is not the main mechanism underlying the differential infant microbiota composition associated with Caesarean delivery. The sources of a large proportion of infant microbiota could not be identified in maternal microbiota, and the sources of seeding of infant gut and nasal microbiota remain to be elucidated.
Pediatric Depression: The Latest in Diagnosis and Treatment
Authors: Malik Salma , Azeem Muhammad Waqar
Published: October 2017

Depressive disorders in children and adolescents constitute a significant burden on social and public health. The impairment can affect several domains of functioning including family, school, and social. Depression is also a significant risk factor in suicide and other psychiatric disorders. The prevalence of major depressive disorder is estimated to be 2% in children and 4% to 8% in adolescents. The rates are much higher in subsyndromal depression, which also affects the functioning of youth. Most youth do recover; however, recurrence is common, with 40% to 70% of youth experiencing relapse within 3 to 5 years. Biopsychosocial assessment of depression requires gathering information from multiple informants and synthesizing the information to diagnose depression. Treatment of pediatric depression consists of social, psychological, and pharmacological interventions.

[
Psychiatr Ann.
2017;47(10):502–506.]
Nurses' Communication of Safety Events to Nursing Home Residents and Families
Authors: Wagner Laura M. , Driscoll Lena , Darlington Jasmin L. , Flores Victoria , Kim Julee , Melino Katerina , Patel Hema Doshi , Spetz Joanne
Published: October 2017

Although communication is an essential part of the nursing process, nurses have little to no formal education in how to best communicate patient safety event (PSE) information to nursing home (NH) residents and their family members. The current mixed-methods study tested an intervention aimed at educating nurses on how to communicate a PSE to residents/family members using a structured communication tool. Nurse participants improved their knowledge of PSE communication, especially about the cause of the event, what they would say to the resident/family member, and future prevention of the PSE. Through qualitative subgroup analysis, an increased number of empathic statements were noted post-intervention. The tool tested in this study provides structure to an important care process that is necessary for improving the culture of safety in NH settings. [
Journal of Gerontological Nursing, 44
(2), 25–32.]
Preferences for Everyday Living: Understanding the Impact of Cognitive Status on Preference Importance Ratings in Nursing Homes
Authors: Carey Christopher J. , Heid Allison R. , Van Haitsma Kimberly
Published: October 2017

Assessing everyday living preferences for nursing home residents is a cornerstone of delivering person-centered care (PCC), yet little is known about how cognitive ability can influence the importance of reported preferences. The current study examined the effect of cognitive ability on the level and stability of reported importance of preferences for everyday living in a sample of 255 nursing home residents across 3 months. Participants were grouped by cognitive impairment status (none-to-low, mild, and moderate) at baseline and completed the Preferences for Everyday Living Inventory, Nursing Home version interview at baseline and 3 months. Repeated measures analyses of covariance revealed no significant differences (
p
> 0.001) between cognitive groups on their reported level of importance of preferences at baseline and no significant change over 3 months. These data highlight the value of assessing everyday care preferences to help support delivery of PCC for individuals with and without cognitive impairment. [
Journal of Gerontological Nursing, 44
(5), 9–17.]
Vitamin D Use and Health Outcomes After Surgery for Hip Fracture
Authors: Sprague Sheila , Slobogean Gerard P. , Bogoch Earl , Petrisor Brad , Garibaldi Alisha , O'Hara Nathan , Bhandari Mohit ,   FAITH Investigators
Published: October 2017

Daily administration of vitamin D is important for maintaining bone homeostasis. The orthopedic community has shown increased interest in vitamin D supplementation and patient outcomes after fracture. The current study used data from a large hip fracture trial to determine the proportion of patients who consistently used vitamin D after hip fracture surgery and to determine whether supplementation was associated with improved health-related quality of life and reduced reoperation rates. The FAITH study is a multicenter trial of elderly patients with femoral neck fracture treated with internal fixation. The current study asked a subset of patients included in the FAITH study about vitamin D supplementation and categorized them as consistent users, inconsistent users, or nonusers. This study also evaluated whether supplementation was associated with improved quality of life and reduced reoperation rates. The final analysis included 573 patients (mean age, 74.1 years; female, 66.3%; nondis-placed fractures, 72.4%). A total of 18.7% of participants reported no use of vitamin D, 35.6% reported inconsistent use, and 45.7% reported consistent use. Adjusted analysis found that consistent supplementation was associated with a 2.42 increase of the Short Form-12 physical component score 12 months postoperatively (
P
=.033). However, supplementation was not associated with reduced reoperation rates (
P
=.386). Despite guidelines recommending vitamin D supplementation, a low proportion of elderly patients with hip fracture use vitamin D consistently, suggesting a need for additional strategies to promote compliance. This study found that the use of vitamin D was associated with a statistically significant but not clinically significant improvement in health-related quality of life after hip fracture. Further research is needed to confirm these findings. [
Orthopedics.
2017; 40(5):e868–e875.]
Surgical Outcome of Congenital Cataract in Eyes With Microcornea
Authors: Matalia Jyoti , Shirke Sheetal , Shetty K. Bhujang , Matalia Himanshu
Published: October 2017

Purpose:

To report the intraoperative and postoperative outcomes of congenital cataract surgery in eyes with microcornea.

Methods:

In this retrospective, interventional, comparative case series, the authors reviewed 47 eyes of 26 children with microcornea and congenital cataract (21 bilateral and 5 unilateral) who underwent lens aspiration with primary posterior capsulectomy and anterior vitrectomy between 2008 and 2014 with a minimum follow-up period of 6 months. Demographic profiles and systemic and ocular features were documented. Intraoperative and postoperative complications were studied separately for bilateral and unilateral cases. Patients were also divided into two groups on the basis of their ages at surgery (early surgery group: 3 months or younger; late surgery group: older than 3 months) and postoperative complications were compared. Visual outcome was analyzed in those with a follow-up period of more than 1 year.

Results:

Early surgery was performed in 24 eyes of 13 patients (11 bilateral and 2 unilateral) and late surgery in 23 eyes of 13 patients (10 bilateral and 3 unilateral). Intraoperatively, all eyes had poor pupillary dilatation and 6 (12.8%) eyes needed iris hooks. Postoperatively, the most common early complication was transient corneal edema observed in 22 (46.8%) eyes (13 and 8 eyes in the early and late surgery groups, respectively). Late complications included visual axis opacification in 6 (12.76%) eyes (3 in each group), and secondary glaucoma in 5 (10.64%) eyes (2 and 3 eyes in the early and late surgery groups, respectively). Vision was normal for age in 18 (60%) of the bilateral cases with a follow-up period of more than 1 year.

Conclusions:

Early surgical intervention for congenital cataract in eyes with microcornea can result in favorable outcomes with an acceptable rate of postoperative complications.

[
J Pediatr Ophthalmol Strabismus
. 2018;55(1):30–36.]
Inferior Oblique Belly Transposition for Small Angle Hypertropia With Inferior Oblique Overaction: A Pilot Study
Authors: Yang Shiqiang , Guo Xin , Tien David Robbins
Published: October 2017

Purpose:

To evaluate the efficacy of transposition of the belly of the inferior oblique muscle in treating inferior oblique overaction with small angle hypertropia.

Methods:

The medical records of 10 patients who underwent inferior oblique belly transposition from March 2014 to July 2016 were reviewed. Transposition of the inferior oblique muscle belly consisted of suturing the entire body of the muscle to the sclera 5 mm posterior to the temporal insertion of the inferior rectus muscle. All patients had small hypertropias (< 5 prism diopters) in the primary gaze position with associated inferior oblique overaction. Deviations in both primary and lateral gazes, compensatory face turns or head tilts, and the degree of inferior oblique overaction were evaluated preoperatively and postoperatively.

Results:

Nine of the 10 patients had a complete resolution of inferior oblique overaction. In the remaining patient, the inferior oblique overaction improved from +3 to +1. None of the patients had any residual vertical deviation. There was elimination of compensatory head tilting in 5 patients and correction of compensatory face turns in 4 patients. One patient with mild up drifting of the involved eye also improved after the procedure. All patients expressed subjective satisfaction with the surgical outcome.

Conclusions:

Transposition of the inferior oblique muscle belly effectively weakened mild to moderate inferior oblique overaction and corrected small primary position hypertropias. This procedure may be a useful addition to surgical treatment options in patients with small hypertropias associated with inferior oblique overaction.

[
J Pediatr Ophthalmol Strabismus
. 2018;55(1):43–46.]
Asymptomatic Leukemic Optic Nerve Infiltration as Presentation of Acute Lymphoblastic Leukemia Relapse
Authors: Caty Jane , Grigorian A. Paula , Grigorian Florin
Published: October 2017

The authors report a case of asymptomatic leukemic optic neuropathy as the first sign of acute lymphoblastic leukemia relapse in a 4-year-old boy. Routine ophthalmologic examination showed normal visual acuity and pupillary function in the presence of a tumoral mass covering the left optic disc. The mass resolved with preservation of vision after intrathecal chemotherapy. A routine ophthalmological examination is recommended for all patients with a history of acute lymphoblastic leukemia to exclude optic nerve involvement without systemic symptoms or signs. Vision can be preserved and radiation avoided by using targeted chemotherapy.

[
J Pediatr Ophthalmol Strabismus
. 2017;54:e60–e62.]
Customized Corneal Cross-linking Using Different UVA Beam Profiles
Authors: Shetty Rohit , Pahuja Natasha , Roshan Thimmarayappa , Deshmukh Rashmi , Francis Mathew , Ghosh Arkasubhra , Sinha Roy Abhijit
Published: October 2017

PURPOSE:

To evaluate the performance of different customized corneal cross-linking (CXL) methods.

METHODS:

This was a single-center interventional, prospective, longitudinal case series. Four different customized CXL methods were evaluated in keratoconic eyes: (1) uniform (uniform intensity ultraviolet-A [UVA] beam [9 mW/cm
2
] for 10 minutes) (n = 12 eyes); (2) sector axial map (sector-based UVA irradiation) (n = 12 eyes); (3) ring axial map (concentric rings of UVA beam intensity centered at the steepest curvature of the anterior axial map) (n = 12 eyes); and ring tangential map (same as the ring axial map but centered at the steepest curvature of the anterior tangential map) (n = 14 eyes). Peak UVA energy density in the sector and ring axial map (and ring tangential map) protocols did not exceed 15.0 and 10.8 J/cm
2
, respectively. A 0.1% riboflavin solution was applied after epithelium removal. Corneal tomography and visual acuity were assessed before and 6 months after CXL.

RESULTS:

Average and peak energy density was lowest in the ring tangential protocol and highest in the sector axial map group (
P
< .001). Treated area was lowest in the ring tangential map group and highest in the uniform group (
P
< .001). Decrease in curvature was similar among the uniform, sector axial map, and ring axial map groups (
P
< .05). The ring tangential map group had the greatest decrease in curvature per unit energy dose to the cornea (
P
< .05). Improvement in uncorrected (0.081 ± 0.056 logMAR) and corrected (0.041 ± 0.026 logMAR) distance visual acuity per unit energy density was greatest in the ring tangential map group (
P
> .05).

CONCLUSIONS:

When normalized to the average energy density, the ring tangential map protocol appeared to provide maximum flattening and improvement in visual acuity. Further studies with larger sample sizes are needed to validate the findings of this pilot study.

[
J Refract Surg.
2017;33(10):676–682.]
Accuracy of a New Swept-Source Optical Coherence Tomography Biometer for IOL Power Calculation and Comparison to IOLMaster
Authors: Savini Giacomo , Hoffer Kenneth J. , Shammas H. John , Aramberri Jaime , Huang Jinhai , Barboni Piero
Published: October 2017

PURPOSE:

To investigate the accuracy of the measurements provided by a new optical biometer (OA-2000, Tomey Corporation, Nagoya, Japan) for calculating the intraocular lens (IOL) power and to compare the refractive outcomes to those obtained with the IOLMaster 500 (Carl Zeiss Meditec, Jena, Germany).

METHODS:

In this interventional multicenter study, consecutive patients having cataract surgery were enrolled. Only the IOL model used in the largest sample of patients was selected and the eyes implanted with that IOL were subsequently analyzed. The OA-2000, an optical biometer based on swept-source optical coherence tomography (SS-OCT), was used to measure axial length and corneal power in all eyes. IOL power was calculated with the Hoffer Q, Holladay 1, and SRK/T formulas. In a subsample of eyes, the IOL power was also calculated with measurements obtained by partial coherence interferometry (IOLMaster 500). The median absolute error and percentage of eyes with a prediction error of ±0.50 diopters (D) or less were calculated.

RESULTS:

Two hundred forty-nine eyes were analyzed. Using SS-OCT, the median absolute error ranged between 0.33 (Holladay 1) and 0.35 (SRK/T) D. The rate of eyes with a prediction error of ±0.50 D or less ranged between 71.5% (Hoffer Q) and 67.1% (SRK/T). In the subsample of 87 eyes with measurements by both devices, the median absolute error was lower with the OA-2000 (Hoffer Q:
P
= .0377; Holladay 1:
P
= .0191; SRK/T:
P
= .0087).

CONCLUSIONS:

The SS-OCT–based optical biometer investigated in the current study provides accurate measurements for IOL power calculation and seems to offer more predictable refractive results compared to the partial coherence interferometry IOLMaster.

[
J Refract Surg.
2017;33(10):690–695.]
Visualizing Patterns and Trends of 25 Years of Published Health Literacy Research
Authors: Massey Philip M. , Kim Meen Chul , Dalrymple Prudence W. , Rogers Michelle L. , Hawthorne Kisha H. , Manganello Jennifer A.
Published: October 2017

Background:

With an increase in the number of disciplines contributing to health literacy scholarship, we sought to explore the nature of interdisciplinary research in the field.

Objective:

This study sought to describe disciplines that contribute to health literacy research and to quantify how disciplines draw from and contribute to an interdisciplinary evidence base, as measured by citation networks.

Methods:

We conducted a literature search for health literacy articles published between 1991 and 2015 in four bibliographic databases, producing 6,229 unique bibliographic records. We employed a scientometric tool (CiteSpace [Version 4.4.R1]) to quantify patterns in published health literacy research, including a visual path from cited discipline domains to citing discipline domains.

Key Results:

The number of health literacy publications increased each year between 1991 and 2015. Two spikes, in 2008 and 2013, correspond to the introduction of additional subject categories, including information science and communication. Two journals have been cited more than 2,000 times—the
Journal of General Internal Medicine
(
n
= 2,432) and
Patient Education and Counseling
(
n
= 2,252). The most recently cited journal added to the top 10 list of cited journals is the
Journal of Health Communication
(
n
= 989). Three main citation paths exist in the health literacy data set. Articles from the domain “medicine, medical, clinical” heavily cite from one domain (health, nursing, medicine), whereas articles from the domain “psychology, education, health” cite from two separate domains (health, nursing, medicine and psychology, education, social).

Conclusions:

Recent spikes in the number of published health literacy articles have been spurred by a greater diversity of disciplines contributing to the evidence base. However, despite the diversity of disciplines, citation paths indicate the presence of a few, self-contained disciplines contributing to most of the literature, suggesting a lack of interdisciplinary research. To address complex and evolving challenges in the health literacy field, interdisciplinary team science, that is, integrating science from across multiple disciplines, should continue to grow.

[
Health Literacy Research and Practice
. 2017;1(4):e182–e191.]

Plain Language Summary:

The addition of diverse disciplines conducting health literacy scholarship has spurred recent spikes in the number of publications. However, citation paths suggest that interdisciplinary research can be strengthened. Findings directly align with the increasing emphasis on team science, and support opportunities and resources that incentivize interdisciplinary health literacy research.
The Theoretical Foundations and Historical Development of Interdisciplinarity
Authors: Al-Suqri Mohammed Nasser , AlKindi Salim Said
Published: October 2017

The concept of interdisciplinarity has a long history but interpretations of this term and the importance of interdisciplinarity in research and education have varied over time. This chapter traces the theoretical understanding and historical development of interdisciplinarity to provide background and context for the book. First it examines the ways in which interdisciplinarity and similar phenomena have been conceptualized in the literature. A roughly chronological account of the main theoretical and empirical developments in interdisciplinarity is then set out, divided into three main periods dating from the early 20th century to the present day.
Interdisciplinary Relationships Between Medicine and Social Sciences
Authors: Al-Busaidi Said Saud
Published: October 2017

The aim of medical science is treating and preventing diseases. The development of medical sciences has been influenced by developments taking place in other sciences including social sciences. Sciences including physical sciences, biological sciences or social sciences interact with each other. The interaction takes place between sciences in each category and between sciences from different categories. However, there are very few studies that deal specifically with the interaction of medicine with social sciences. As both have to work together because of the human complex nature as a result some authors considered medicine itself as a social science, thus creating an interdisciplinary environment that hosts both medicine and social sciences. This chapter reviews the complex interdisciplinarity between medicine and a number of social sciences, including anthropology, psychology, sociology, political sciences and economy.
A New Data Mining-Based Framework to Test Case Prioritization Using Software Defect Prediction
Authors: Alsukhni Emad , Saifan Ahmad A. , Alawneh Hanadi
Published: October 2017

Test cases do not have the same importance when used to detect faults in software; therefore, it is more efficient to test the system with the test cases that have the ability to detect the faults. This research proposes a new framework that combines data mining techniques to prioritize the test cases. It enhances fault prediction and detection using two different techniques: 1) the data mining regression classifier that depends on software metrics to predict defective modules, and 2) the k-means clustering technique that is used to select and prioritize test cases to identify the fault early. Our approach of test case prioritization yields good results in comparison with other studies. The authors used the Average Percentage of Faults Detection (APFD) metric to evaluate the proposed framework, which results in 19.9% for all system modules and 25.7% for defective ones. Our results give us an indication that it is effective to start the testing process with the most defective modules instead of testing all modules arbitrary arbitrarily.
Social Media Usage in E-Government
Authors: Vakeel Khadija Ali , Panigrahi Prabin Kumar
Published: October 2017

When citizens are actively engaged in e-government processes as co-creators it leads to e-government development. Citizen participation in e-government is a recent phenomenon where government is seeking more involvement of citizens through different platforms. Whether citizens' participation through social media platforms leads to e-government development has been a debate in literature. In this research study, the authors investigate whether social media usage influences government's role in e-government development. Power distance between government and citizen also plays a role in deciding the extent of e-participation in e-government. In this study, the authors examine the relationship between social media, power distance, citizen engagement and e-government development. Using customer focus theory and agency theory, this study establishes that e-participation initiative by government acts as a mediator in the relation between social media usage by citizen as well as power distance to e-government development.
Analysis and Evaluation of a Framework for Sampling Database in Recommenders
Authors: Hamidi Hodjat , Mousavi Reza
Published: October 2017

In this paper the authors proposed a database sampling framework that aims to minimize the time necessary to produce a sample database. They argue that the performance of current relational database sampling techniques that maintain the data integrity of the sample database is low and a faster strategy needs to be devised. The sampling method targets the production environment of a system under development that generally consists of large amounts of data computationally costly to analyze. The results have been improved due to the fact that the authors have selected the users that they had more information about them and they have made the data table denser. Therefore, by increasing the data and making the rating more comprehensive for all the users they can help to produce the more and better association rules. The obtained results were not that much suitable for Jester dataset but with their proposed methods the authors have tried to improve the quantity and quality of the rules. These results indicate that the effectiveness of the system greatly depends on the input data and the applied dataset. In addition, if the user rates more number of the items the system efficiency will be more increased.
The Satisfaction of Saudi Customers Toward Mobile Banking in Saudi Arabia and the United Kingdom
Authors: Al-Otaibi Sultan , Aljohani Naif Radi , Hoque Md. Rakibul , Alotaibi Fahd S.
Published: October 2017

Rapid advancements in technology over the last two decades played a key role in increasing the utilizations of mobile banking applications. Banks are providing this service to allow their customers to access their accounts anytime anywhere. Although many studies have assessed user satisfaction of mobile banking, most of these studies have been done in developed countries and only a few have compared mobile banking in developing with developed countries. This study assessed user satisfaction of mobile banking in both the United Kingdom and Saudi Arabia. Above 100 online questionnaires were collected from individuals who have experience in using mobile banking applications in both the UK and Saudi Arabia. The results show that system quality has a significant effect on customer satisfaction in the UK, but not in Saudi Arabia. Secondly, both information quality and interface design quality have significant effects on customer satisfaction in both the UK and Saudi Arabia. However, the overall findings from this study suggest that respondents are more satisfied with mobile banking in the UK than with mobile banking in Saudi Arabia.
Understanding Intentions to Switch Toward Cloud Computing at Firms' Level
Authors: Hachicha Zouhour Smaoui , Mezghani Karim
Published: October 2017

This research aims to study intentions to switch toward cloud computing at firms' level. As a new way to deploy information technologies (IT) within firms, switching toward cloud computing remains a hard decision that depends on several contextual factors. While several studies have focused mainly on technological aspects, this research adopts a multidimensional perspective by combining the Technology-Organization-Environment (TOE) framework with a two-factor theory perspective. Doing so, the authors attempt to propose a research model that can be useful to deeply understand how firms perform when thinking about switching toward cloud-based solutions. A multiple-case study within five Tunisian firms has been conducted to contextualize the research model and give it more explanation power. The Tunisian context should be interesting, as cloud computing adoption is a new topic that is not sufficiently studied in developing countries, particularly in those characterized by an economy in transition. Data have been collected by semi-structured interviews and coded using the Nvivo software. The analysis of interviews content shows that the expected switching benefits and risks play a mediating role between TOE factors and intentions to switch toward cloud computing. Indeed, the authors found some different results within cases revealing the dual effects of technology, organization, and environment factors on intentions by generating different expected switching benefits and risks. In light of these results, some recommendations are proposed to decision makers in this area.
Association between a Prognostic Gene Signature and Functional Gene Sets
Authors: Hummel Manuela , Metzeler Klaus H. , Buske Christian , Bohlander Stefan K. , Mansmann Ulrich
Published: October 2017

Background

The development of expression-based gene signatures for predicting prognosis or class membership is a popular and challenging task. Besides their stringent validation, signatures need a functional interpretation and must be placed in a biological context. Popular tools such as Gene Set Enrichment have drawbacks because they are restricted to annotated genes and are unable to capture the information hidden in the signature's non-annotated genes.

Methodology

We propose concepts to relate a signature with functional gene sets like pathways or Gene Ontology categories. The connection between single signature genes and a specific pathway is explored by hierarchical variable selection and gene association networks. The risk score derived from an individual patient's signature is related to expression patterns of pathways and Gene Ontology categories. Global tests are useful for these tasks, and they adjust for other factors. GlobalAncova is used to explore the effect on gene expression in specific functional groups from the interaction of the score and selected mutations in the patient's genome.

Results

We apply the proposed methods to an expression data set and a corresponding gene signature for predicting survival in Acute Myeloid Leukemia (AML). The example demonstrates strong relations between the signature and cancer-related pathways. The signature-based risk score was found to be associated with development-related biological processes.

Conclusions

Many authors interpret the functional aspects of a gene signature by linking signature genes to pathways or relevant functional gene groups. The method of gene set enrichment is preferred to annotating signature genes to specific Gene Ontology categories. The strategies proposed in this paper go beyond the restriction of annotation and deepen the insights into the biological mechanisms reflected in the information given by a signature.
Identification of the RGG Box Motif in Shadoo: RNA-Binding and Signaling Roles?
Authors: Corley Susan M. , Gready Jill E.
Published: October 2017

Using comparative genomics and in-silico analyses, we previously identified a new member of the prion-protein (PrP) family, the gene SPRN, encoding the protein Shadoo (Sho), and suggested its functions might overlap with those of PrP. Extended bioinformatics and conceptual biology studies to elucidate Sho's functions now reveal Sho has a conserved RGG-box motif, a well-known RNA-binding motif characterized in proteins such as FragileX Mental Retardation Protein. We report a systematic comparative analysis of RGG-box containing proteins which highlights the motif's functional versatility and supports the suggestion that Sho plays a dual role in cell signaling and RNA binding in brain. These findings provide a further link to PrP, which has well-characterized RNA-binding properties.
HMM_RA: An Improved Method for Alpha-Helical Transmembrane Protein Topology Prediction
Authors: Hu Jing , Yan Changhui
Published: October 2017

α-helical transmembrane (TM) proteins play important and diverse functional roles in cells. The ability to predict the topology of these proteins is important for identifying functional sites and inferring function of membrane proteins. This paper presents a Hidden Markov Model (referred to as HMM_RA) that can predict the topology of α-helical transmembrane proteins with improved performance. HMM_RA adopts the same structure as the HMMTOP method, which has five modules: inside loop, inside helix tail, membrane helix, outside helix tail and outside loop. Each module consists of one or multiple states. HMM_RA allows using reduced alphabets to encode protein sequences. Thus, each state of HMM_RA is associated with n emission probabilities, where n is the size of the reduced alphabet set. Direct comparisons using two standard data sets show that HMM_RA consistently outperforms HMMTOP and TMHMM in topology prediction. Specifically, on a high-quality data set of 83 proteins, HMM_RA outperforms HMMTOP by up to 7.6% in topology accuracy and 6.4% in α-helices location accuracy. On the same data set, HMM_RA outperforms TMHMM by up to 6.4% in topology accuracy and 2.9% in location accuracy. Comparison also shows that HMM_RA achieves comparable performance as Phobius, a recently published method.
Using a Seed-Network to Query Multiple Large-Scale Gene Expression Datasets from the Developing Retina in Order to Identify and Prioritize Experimental Targets
Authors: Hecker Laura A. , Alcon Timothy C. , Honavar Vasant G. , Greenlee M. Heather West
Published: October 2017

Understanding the gene networks that orchestrate the differentiation of retinal progenitors into photoreceptors in the developing retina is important not only due to its therapeutic applications in treating retinal degeneration but also because the developing retina provides an excellent model for studying CNS development. Although several studies have profiled changes in gene expression during normal retinal development, these studies offer at best only a starting point for functional studies focused on a smaller subset of genes. The large number of genes profiled at comparatively few time points makes it extremely difficult to reliably infer gene networks from a gene expression dataset. We describe a novel approach to identify and prioritize from multiple gene expression datasets, a small subset of the genes that are likely to be good candidates for further experimental investigation. We report progress on addressing this problem using a novel approach to querying multiple large-scale expression datasets using a ‘seed network’ consisting of a small set of genes that are implicated by published studies in rod photoreceptor differentiation. We use the seed network to identify and sort a list of genes whose expression levels are highly correlated with those of multiple seed network genes in at least two of the five gene expression datasets. The fact that several of the genes in this list have been demonstrated, through experimental studies reported in the literature, to be important in rod photoreceptor function provides support for the utility of this approach in prioritizing experimental targets for further experimental investigation. Based on Gene Ontology and KEGG pathway annotations for the list of genes obtained in the context of other information available in the literature, we identified seven genes or groups of genes for possible inclusion in the gene network involved in differentiation of retinal progenitor cells into rod photoreceptors. Our approach to querying multiple gene expression datasets using a seed network constructed from known interactions between specific genes of interest provides a promising strategy for focusing hypothesis-driven experiments using large-scale ‘omics’ data.
Characterization of Non-Trivial Neighborhood Fold Constraints from Protein Sequences using Generalized Topohydrophobicity.
Authors: Fourty Guillaume , Callebaut Isabelle , Mornon Jean-Paul
Published: October 2017

Prediction of key features of protein structures, such as secondary structure, solvent accessibility and number of contacts between residues, provides useful structural constraints for comparative modeling, fold recognition, ab-initio fold prediction and detection of remote relationships. In this study, we aim at characterizing the number of non-trivial close neighbors, or long-range contacts of a residue, as a function of its “topohydrophobic” index deduced from multiple sequence alignments and of the secondary structure in which it is embedded. The “topohydrophobic” index is calculated using a two-class distribution of amino acids, based on their mean atom depths. From a large set of structural alignments processed from the FSSP database, we selected 1485 structural sub-families including at least 8 members, with accurate alignments and limited redundancy. We show that residues within helices, even when deeply buried, have few non-trivial neighbors (0–2), whereas β-strand residues clearly exhibit a multimodal behavior, dominated by the local geometry of the tetrahedron (3 non-trivial close neighbors associated with one tetrahedron; 6 with two tetrahedra). This observed behavior allows the distinction, from sequence profiles, between edge and central β-strands within β-sheets. Useful topological constraints on the immediate neighborhood of an amino acid, but also on its correlated solvent accessibility, can thus be derived using this approach, from the simple knowledge of multiple sequence alignments.
Estimating the Fraction of Non-Coding RNAs in Mammalian Transcriptomes
Authors: Xin Yurong , Quarta Giulio , Gan Hin Hark , Schlick Tamar
Published: October 2017

Recent studies of mammalian transcriptomes have identified numerous RNA transcripts that do not code for proteins; their identity, however, is largely unknown. Here we explore an approach based on sequence randomness patterns to discern different RNA classes. The relative z-score we use helps identify the known ncRNA class from the genome, intergene and intron classes. This leads us to a fractional ncRNA measure of putative ncRNA datasets which we model as a mixture of genuine ncRNAs and other transcripts derived from genomic, intergenic and intronic sequences. We use this model to analyze six representative datasets identified by the FANTOM3 project and two computational approaches based on comparative analysis (RNAz and EvoFold). Our analysis suggests fewer ncRNAs than estimated by DNA sequencing and comparative analysis, but the verity of our approach and its prediction requires more extensive experimental RNA data.
A New Test Statistic Based on Shrunken Sample Variance for Identifying Differentially Expressed Genes in Small Microarray Experiments
Authors: Hirakawa Akihiro , Sato Yasunori , Hamada Chikuma , Yoshimura Isao
Published: October 2017

Choosing an appropriate statistic and precisely evaluating the false discovery rate (FDR) are both essential for devising an effective method for identifying differentially expressed genes in microarray data. The t-type score proposed by Pan et al. (2003) succeeded in suppressing false positives by controlling the underestimation of variance but left the overestimation uncontrolled. For controlling the overestimation, we devised a new test statistic (variance stabilized t-type score) by placing shrunken sample variances of the James-Stein type in the denominator of the t-type score. Since the relative superiority of the mean and median FDRs was unclear in the widely adopted Significance Analysis of Microarrays (SAM), we conducted simulation studies to examine the performance of the variance stabilized t-type score and the characteristics of the two FDRs. The variance stabilized t-type score was generally better than or at least as good as the t-type score, irrespective of the sample size and proportion of differentially expressed genes. In terms of accuracy, the median FDR was superior to the mean FDR when the proportion of differentially expressed genes was large. The variance stabilized t-type score with the median FDR was applied to actual colorectal cancer data and yielded a reasonable result.
Unsupervised Meta-Analysis on Diverse Gene Expression Datasets Allows Insight into Gene Function and Regulation
Authors: Engelmann Julia C. , Schwarz Roland , Blenk Steffen , Friedrich Torben , Seibel Philipp N. , Dandekar Thomas , Müller Tobias
Published: October 2017

Over the past years, microarray databases have increased rapidly in size. While they offer a wealth of data, it remains challenging to integrate data arising from different studies. Here we propose an unsupervised approach of a large-scale meta-analysis on Arabidopsis thaliana whole genome expression datasets to gain additional insights into the function and regulation of genes. Applying kernel principal component analysis and hierarchical clustering, we found three major groups of experimental contrasts sharing a common biological trait. Genes associated to two of these clusters are known to play an important role in indole-3-acetic acid (IAA) mediated plant growth and development or pathogen defense. Novel functions could be assigned to genes including a cluster of serine/threonine kinases that carry two uncharacterized domains (DUF26) in their receptor part implicated in host defense. With the approach shown here, hidden interrelations between genes regulated under different conditions can be unraveled.
The Use of Artificial Neural Networks in Prediction of Congenital CMV Outcome from Sequence Data
Authors: Arav-Boger Ravit , Boger Yuval S. , Foster Charles B. , Boger Zvi
Published: October 2017

A large number of CMV strains has been reported to circulate in the human population, and the biological significance of these strains is currently an active area of research. The analysis of complex genetic information may be limited using conventional phylogenetic techniques.

We constructed artificial neural networks to determine their feasibility in predicting the outcome of congenital CMV disease (defined as presence of CMV symptoms at birth) based on two data sets: 54 sequences of CMV gene UL144 obtained from 54 amniotic fluids of women who contracted acute CMV infection during their pregnancy, and 80 sequences of 4 genes (US28, UL144, UL146 and UL147) obtained from urine, saliva or blood of 20 congenitally infected infants that displayed different outcomes at birth. When data from all four genes was used in the 20-infants’ set, the artificial neural network model accurately identified outcome in 90% of cases. While US28 and UL147 had low yield in predicting outcome, UL144 and UL146 predicted outcome in 80% and 85% respectively when used separately. The model identified specific nucleotide positions that were highly relevant to prediction of outcome. The artificial neural network classified genotypes in agreement with classic phylogenetic analysis. We suggest that artificial neural networks can accurately and efficiently analyze sequences obtained from larger cohorts to determine specific outcomes.

The ANN training and analysis code is commercially available from Optimal Neural Informatics (Pikesville, MD).
Effect of Quantitative Nuclear Image Features on Recurrence of Ductal Carcinoma In Situ (DCIS) of the Breast
Authors: Axelrod David E. , Miller Naomi A. , Lickley H. Lavina , Qian Jin , Christens-Barry William A. , Yuan Yan , Fu Yuejiao , Chapman Judith-Anne W.
Published: October 2017

Background

Nuclear grade has been associated with breast DCIS recurrence and progression to invasive carcinoma; however, our previous study of a cohort of patients with breast DCIS did not find such an association with outcome. Fifty percent of patients had heterogeneous DCIS with more than one nuclear grade. The aim of the current study was to investigate the effect of quantitative nuclear features assessed with digital image analysis on ipsilateral DCIS recurrence.

Methods

Hematoxylin and eosin stained slides for a cohort of 80 patients with primary breast DCIS were reviewed and two fields with representative grade (or grades) were identified by a Pathologist and simultaneously used for acquisition of digital images for each field. Van Nuys worst nuclear grade was assigned, as was predominant grade, and heterogeneous grading when present. Patients were grouped by heterogeneity of their nuclear grade: Group A: nuclear grade 1 only, nuclear grades 1 and 2, or nuclear grade 2 only (32 patients), Group B: nuclear grades 1, 2 and 3, or nuclear grades 2 and 3 (31 patients), Group 3: nuclear grade 3 only (17 patients). Nuclear fine structure was assessed by software which captured thirty-nine nuclear feature values describing nuclear morphometry, densitometry, and texture. Step-wise forward Cox regressions were performed with previous clinical and pathologic factors, and the new image analysis features.

Results

Duplicate measurements were similar for 89.7% to 97.4% of assessed image features. The rate of correct classification of nuclear grading with digital image analysis features was similar in the two fields, and pooled assessment across both fields. In the pooled assessment, a discriminant function with one nuclear morphometric and one texture feature was significantly (p = 0.001) associated with nuclear grading, and provided correct jackknifed classification of a patient's nuclear grade for Group A (78.1%), Group B (48.4%), and Group C (70.6%). The factors significantly associated with DCIS recurrence were those previously found, type of initial presentation (p = 0.03) and amount of parenchymal involvement (p = 0.05), along with the morphometry image feature of ellipticity (p = 0.04).

Conclusion

Analysis of nuclear features measured by image cytometry may contribute to the classification and prognosis of breast DCIS patients with more than one nuclear grade.
Comparison of Three Information Sources for Smoking Information in Electronic Health Records
Authors: Wang Liwei , Ruan Xiaoyang , Yang Ping , Liu Hongfang
Published: October 2017

Objective

The primary aim was to compare independent and joint performance of retrieving smoking status through different sources, including narrative text processed by natural language processing (NLP), patient-provided information (PPI), and diagnosis codes (ie, International Classification of Diseases, Ninth Revision [ICD-9]). We also compared the performance of retrieving smoking strength information (ie, heavy/light smoker) from narrative text and PPL

Materials and Methods

Our study leveraged an existing lung cancer cohort for smoking status, amount, and strength information, which was manually chart-reviewed. On the NLP side, smoking-related electronic medical record (EMR) data were retrieved first. A pattern-based smoking information extraction module was then implemented to extract smoking-related information. After that, heuristic rules were used to obtain smoking status-related information. Smoking information was also obtained from structured data sources based on diagnosis codes and PPI. Sensitivity, specificity, and accuracy were measured using patients with coverage (ie, the proportion of patients whose smoking status/strength can be effectively determined).

Results

NLP alone has the best overall performance for smoking status extraction (patient coverage: 0.88; sensitivity: 0.97; specificity: 0.70; accuracy: 0.88); combining PPI with NLP further improved patient coverage to 0.96. ICD-9 does not provide additional improvement to NLP and its combination with PPI. For smoking strength, combining NLP with PPI has slight improvement over NLP alone.

Conclusion

These findings suggest that narrative text could serve as a more reliable and comprehensive source for obtaining smoking-related information than structured data sources. PPI, the readily available structured data, could be used as a complementary source for more comprehensive patient coverage.