bluuebunny/crossref_metadata_2025 huggingface dataset:
Nurses’ Experience Removing Superficial Nonabsorbable Sutures From the Skin
Authors: Akeroyd Jennifer , Kitada Heather H. , Plauntz Leslie , Lear William
Published: December 2016

In many dermatology settings, nurses remove superficial sutures from wounds of the skin. The current practice is to remove sutures between 5 and 14 days depending on the location of the defect to prevent wound overgrowth and subsequent complications. Yet, by 10 days, wound strength is only 5% of that of intact skin, also setting the stage for potential complications, such as dehiscence. We surveyed Dermatology Nurses’ Association members to understand their experiences with removing sutures from the skin. With a response rate of 16.75%, the sample size was 355 respondents. Over 90% of the respondents encountered wound overgrowth (i.e., ingrown sutures) when removing sutures. Moreover, mattress-type closures presented more difficulty on removal than simple-type closures. When sutures were ingrown, complications included patient pain (31.5%), wound bleeding (30.1%), inability to ensure the complete removal of sutures (19.2%), wound dehiscence (7.0%), and increased procedure time by nearly 2 minutes. Our findings of nurse experiences with suture removal support the need for innovative solutions to prevent wound overgrowth.
Localized Vesicular Eruption
Authors: Perez Caroline , Jacob Sharon E.
Published: December 2016

Teledermatology is a term to describe the provision of dermatologic medical services through telecommunication technology. In this modality, there is a transfer of patient medical information electronically (including history and visual data) obtained in one location to a provider who is in another location (Roman & Jacob, 2015). The construct of the TeleDermViewPoint column is such that cases are presented in a standardized teledermatology reader format reflective of an actual teledermatology report. This is a case of a vesicular eruption on the right posterior neck, near the hairline.
Adherence to follow-up and treatment recommendations in Greek and immigrant patients with chronic hepatitis B in Greece
Authors: Voulgaris Theodoros , Vlachogiannakos John , Ioannidou Panagiota , Papageorgiou Maria-Vasiliki , Zampeli Evi , Karagiannakis Dimitrios , Georgiou Anastasia , Papazoglou Afroditi , Karamanolis George , Papatheodoridis George V.
Published: December 2016

Background/Aim

Immigrants have multiple barriers to access to health care systems. We evaluated the adherence to follow-up and treatment recommendations of chronic hepatitis B virus (HBV) Greek and immigrant patients.

Methods

In total, 1001 consecutive adult patients with chronic HBV infection who visited our clinics for the first time between 2002 and 2011 were included. All patients born outside Greece were considered immigrants. Diagnosis was considered to be complete if patients could be classified into HBeAg-positive chronic hepatitis B (CHB), inactive carriers, HBeAg-negative CHB, or decompensated cirrhosis.

Results

Of the patients, 56% were Greeks and 44% were immigrants. Greeks visited our clinics at a significantly older mean age (50 vs. 35 years, P<0.001) and more frequently with advanced liver disease (11.4 vs. 6.4%, P=0.007). During the first year, Greeks more frequently had several tests and eventually a complete diagnosis (68 vs. 55%, P<0.001). Greeks were more frequently in the phase of HBeAg-negative CHB and less frequently in the phase of inactive carrier or HBeAg-positive CHB, but age was the main determinant for these differences in multivariate analysis. Treatment was initiated more frequently by Greeks than immigrants with treatment indications (86 vs. 65%, P<0.001). Only 30–33% of treated and 4–10% of untreated patients remained under follow-up at year 5, without significant differences between Greeks and immigrants.

Conclusion

Adherence to follow-up recommendations is rather poor for all chronic HBV patients. Immigrants are lost more frequently during the first year, but only small proportions of treated and particularly untreated Greek or immigrant patients remain under long-term follow-up.
Effect of abdominal visceral fat on the development of new erosive oesophagitis: a prospective cohort study
Authors: Nam Su Youn , Kim Young-Woo , Park Bum Joon , Ryu Kum Hei , Choi Il Ju , Nam Byung-Ho , Kim Hyun Boem
Published: December 2016

Objectives

Although abdominal visceral fat has been associated with erosive oesophagitis in cross-sectional studies, there are no data that describe its longitudinal effects. We aimed to evaluate the longitudinal effects of abdominal visceral fat on the development of new erosive oesophagitis in patients who did not have erosive oesophagitis at baseline.

Materials and methods

This was a single-centre prospective study. A total of 1503 participants without erosive oesophagitis at baseline were followed up for 34 months and they underwent oesophagogastroduodenoscopy and computed tomography at both baseline and during follow-up. The longitudinal effects of abdominal visceral fat on the development of new erosive oesophagitis were evaluated using odds ratios (ORs) and 95% confidence intervals (CIs).

Results

New oesophagitis developed in 83 patients. Compared with the first quartile, the third (OR=3.96, 95% CI: 1.54–10.18) and the fourth (OR=4.67, 95% CI: 1.79–12.23) of baseline visceral fat quartiles, the third (OR=3.03, 95% CI: 1.14–8.04) and the fourth (OR=7.50, 95% CI: 2.92–19.25) follow-up visceral fat quartiles, and the fourth visceral fat change quartile (OR=2.76, 95% CI: 1.47–5.21) were associated with increased development of new erosive oesophagitis, and the P value for each trend was less than 0.001. New erosive oesophagitis was inversely related to the follow-up Helicobacter pylori status and it was associated positively with the presence of a hiatal hernia and smoking during follow-up, but it was not associated with reflux symptoms, the H. pylori status, presence of a hiatal hernia or smoking at baseline.

Conclusion

Higher level of visceral fat at baseline and follow-up visceral fat, and greater changes in the visceral level were associated linearly with the development of new erosive oesophagitis in this longitudinal study.
Clinicopathologic and Prognostic Significance of Gelatinase A in Tunisian Colorectal Cancer: A Case-Control Study
Authors: ben Néjima Dalel , ben Zarkouna Yosr , Pujol Pascal , Gammoudi Amor , Boussen Hamouda , Manai Mohamed
Published: December 2016

Matrix metalloproteinase-2 (gelatinase A) is a well-known mediator of cancer metastasis, but it is also thought to be involved in several aspects of cancer development, including cell growth and inflammation. In the present study, we investigate whether MMP-2 SNP, MMP-2 mRNAs, and MMP-2 protein are associated with the susceptibility to colorectal cancer in the Tunisian population. The TaqMan allele discrimination assay and DNA sequencing techniques were used for genotyping; MMP-2 expression of each genotype was analyzed by semiquantitative RT-PCR, and MMP-2 protein expression was analyzed by immunohistochemistry staining. Our result showed that the levels of MMP-2 mRNA expression in patients containing the CC genotype were much higher compared with cells with the CT genotype. The frequency of the MMP-2 CC genotype was significantly higher in colorectal cancer patients when compared with controls (OR=1.94; 95% CI, 1.117-3.680). A higher intensity of staining of MMP-2 was observed in regions of invasion of the muscularis mucosa compared with superficial portions of the tumor. In addition, we found a significant progressive increase in total MMP-2 plasma levels with progression from adenomatous polyps through advancing Dukes stages (P=0.0001). Our data suggest that MMP-2 may be associated with colorectal cancer development and invasion in the Tunisian population; moreover, SNP and levels of MMP-2 could be a predictive value for colorectal cancer prevention and invasiveness.
A Perspective on Brain–Gut Communication: The American Gastroenterology Association and American Psychosomatic Society Joint Symposium on Brain–Gut Interactions and the Intestinal Microenvironment
Authors: Aroniadis Olga C. , Drossman Douglas A. , Simrén Magnus
Published: December 2016

Background

Alterations in brain–gut communication and the intestinal microenvironment have been implicated in a variety of medical and neuropsychiatric diseases. Three central areas require basic and clinical research: (1) how the intestinal microenvironment interacts with the host immune system, central nervous system, and enteric nervous system; (2) the role of the intestinal microenvironment in the pathogenesis of medical and neuropsychiatric disease; and (3) the effects of diet, prebiotics, probiotics, and fecal microbiota transplantation on the intestinal microenvironment and the treatment of disease.

Methods

This review article is based on a symposium convened by the American Gastroenterology Association and the American Psychosomatic Society to foster interest in the role of the intestinal microenvironment in brain–gut communication and pathogenesis of neuropsychiatric and biopsychosocial disorders. The aims were to define the state of the art of the current scientific knowledge base and to identify guidelines and future directions for new research in this area.

Results

This review provides a characterization of the intestinal microbial composition and function. We also provide evidence for the interactions between the intestinal microbiome, the host, and the environment. The role of the intestinal microbiome in medical and neuropsychiatric diseases is reviewed as well as the treatment effects of manipulation of the intestinal microbiome.

Conclusions

Based on this review, opportunities and challenges for conducting research in the field are described, leading to potential avenues for future research.
HIV-associated changes in the enteric microbial community: potential role in loss of homeostasis and development of systemic inflammation
Authors: Gootenberg David B. , Paer Jeffrey M. , Luevano Jesus-Mario , Kwon Douglas S.
Published: December 2016

Purpose of review

Despite HIV therapy advances, average life expectancy in HIV-infected individuals on effective treatment is significantly decreased relative to uninfected persons, largely because of increased incidence of inflammation-related diseases, such as cardiovascular disease and renal dysfunction. The enteric microbial community could potentially cause this inflammation, as HIV-driven destruction of gastrointestinal CD4+ T cells may disturb the microbiota–mucosal immune system balance, disrupting the stable gut microbiome and leading to further deleterious host outcomes.

Recent findings

Varied enteric microbiome changes have been reported during HIV infection, but unifying patterns have emerged. Community diversity is decreased, similar to pathologies such as inflammatory bowel disease, obesity, and Clostridium difficile infection. Many taxa frequently enriched in HIV-infected individuals, such as Enterobacteriaceae and Erysipelotrichaceae, have pathogenic potential, whereas depleted taxa, such as Bacteroidaceae and Ruminococcaceae, are more linked with anti-inflammatory properties and maintenance of gut homeostasis. The gut viral community in HIV has been found to contain a greater abundance of pathogenesis-associated Adenoviridae and Anelloviridae. These bacterial and viral changes correlate with increased systemic inflammatory markers, such as serum sCD14, sCD163, and IL-6.

Enteric microbial community changes may contribute to chronic HIV pathogenesis, but more investigation is necessary, especially in the developing world population with the greatest HIV burden (Video, Supplemental Digital Content 1, http://links.lww.com/COID/A15, which includes the authors’ summary of the importance of the work).
Difficulties in Performing Mesalazine Enemas and Factors Related to Discontinuation Among Patients With Ulcerative Colitis
Authors: Kawakami Aki , Tanaka Makoto , Ochiai Ryota , Naganuma Makoto , Kunisaki Reiko , Kazuma Keiko
Published: December 2016

Current first-line treatment of ulcerative colitis consists of a combination of mesalazine enemas and oral mesalazine; however, many patients may discontinue mesalazine enemas. In this single-center, cross-sectional study, 165 outpatients with ulcerative colitis completed a self-administered questionnaire regarding the frequency of mesalazine enemas, difficulties in performing these enemas, and factors possibly associated with their discontinuation, as well as patient clinical and demographic characteristics. Of 165 patients, 34 (20.6%) discontinued mesalazine enemas because of a lack of efficacy. Five of the 13 items assessing difficulties were answered affirmatively by the majority of patients. Discontinuation of enema application was associated with a perceived lack of efficacy, four or more bowel movements per day, and lower scores on measurement of the doctor–patient relationship. Application of mesalazine enemas by patients with ulcerative colitis may be improved by discussions with peers and healthcare professionals and by adjusting the frequency of application or the time of starting the enema based on worsening of ulcerative colitis.
The Psychosocial Influences of Waiting Periods on Patients Undergoing Endoscopic Submucosal Dissection
Authors: Nagao Noriko , Tsuchiya Aya , Ando Sae , Arita Mizue , Toyonaga Takashi , Miyawaki Ikuko
Published: December 2016

This study aimed to clarify psychosocial influences of waiting periods on patients undergoing endoscopic submucosal dissection for cancer at an advanced medical care facility in Japan. Subjects were consenting patients hospitalized from 2009 to 2010. Qualitative and quantitative data were gathered about patients' characteristics, disease and stage, and waiting period. Qualitative content analysis was used to analyze free statements and interview data. Subjects included 154 patients with an average wait period of 46.28 days for admission. Qualitative analysis revealed the following wait period perceptions. For calmness, results indicated (1) no anxiety, (2) relief based on doctors' positive judgment, (3) whatever happens/no choice, and (4) trust in doctor. For uneasiness, perceptions included (1) the sooner, the better/eagerly waiting, (2) anxiety and concern, and (3) emotional instability. Four waiting period coping types were identified: (1) making phone inquiries, (2) busy and forgot about the medical procedure, (3) relief from anxiety, and (4) unable to function well in daily life. Patients need to be educated about cancer progression and provided an estimated wait time. They also require more information about how to manage daily life such as monitoring factors from the nursing domain including physical condition, digestive symptoms, diet, and exercise.
Developing a Simulation-Based Training Program for the Prehospital Professionals and Students on the Management of Middle East Respiratory Syndrome
Authors: Elcin Melih , Onan Arif , Odabasi Orhan , Saylam Melahat , Ilhan Handan , Daylan Kockaya Pinar , Gurcuoglu Ilker , Uckuyu Yavuz , Cengiz Duygu , Nacar Osman Arikan
Published: December 2016

Introduction

Middle East Respiratory Syndrome (MERS) is a major global health threat. Prehospital professionals face the risk of infection as they work to save lives. They should be made aware of the disease and be prepared to handle such cases. The aims of our study are to develop a training program about the prehospital management of a MERS case using standardized patient (SP) scenarios, to evaluate the awareness and preparedness of the participants about MERS, and to evaluate the effectiveness of this training.

Methods

We developed 5 scenarios using SPs and an observation form. We included paramedic students and emergency medical service (EMS) providers in our study. They were involved in the simulations.

Results

A total of 24 paramedic students and 33 EMS providers participated in our study. Sixteen (84%) of 19 teams recognized the possibility of MERS as a measure of their awareness in the baseline evaluation. The participants lacked donning and doffing personal protective equipments, which revealed their baseline level of preparedness for MERS. Certain improvements in donning and doffing personal protective equipment were observed in the posttraining evaluation. The participants provided positive feedback on the training program.

Conclusions

The training program was appropriate for both paramedic students and EMS providers. A positive educational climate was created. Because the main concerns of this study were awareness and preparedness, which required human interaction, the SP methodology was the optimal simulation modality.
Ipsilateral Ophthalmic and Cerebral Infarctions After Cosmetic Polylactic Acid Injection Into the Forehead
Authors: Ragam Ashwinee , Agemy Steven A. , Dave Sarita B. , Khorsandi Azita S. , Banik Rudrani
Published: December 2016

A 55-year-old woman developed no light perception vision in her right eye 5 days after an injection of polylactic acid cosmetic filler into her right forehead. Diffuse corneal edema and anterior chamber inflammation prohibited any view to the posterior segment to identify the cause of her profound vision loss. MRI of the orbits with diffusion-weighted imaging showed hyperintensity of the right optic nerve with signal reduction on apparent diffusion coefficient mapping, consistent with ischemia. Our patient also was found to have acute infarctions in the distribution of the right anterior cerebral artery on MRI of the brain despite having no permanent focal neurologic deficits aside from vision loss.
Implantation of Stereoelectroencephalography Electrodes: A Systematic Review
Authors: Cardinale Francesco , Casaceli Giuseppe , Raneri Fabio , Miller Jonathan , Lo Russo Giorgio
Published: December 2016

Background:

Stereoelectroencephalography (SEEG) was developed by Talairach and Bancaud in Paris in the late 1950s. Subsequently, the Talairach methodology was adopted at a number of additional centers in Europe and Canada. Technical aspects remained essentially unchanged for the following 30 years. Only in the last two decades, because of advancements in image-guided surgery systems, robotics, and computer-aided planning, use of SEEG has become more widespread, and reports describing these new developments have been published.

Objectives:

This systematic review was designed to assess published reports of SEEG surgical techniques and safety profile.

Data sources:

An electronic search was performed of Medline, Embase, and Scopus databases. In addition, the content pages of several standard epilepsy surgery textbooks were searched. Full-text English studies describing SEEG surgical technique or pertinent epidemiological data were included. Conference abstracts, reviews, posters, editorials, comments, and letters were excluded.

Results:

Three hundred fifty-nine of 2,903 potentially eligible studies published by 32 centers were reviewed. Thirty-one of these primarily discussed the surgical technique. Thirty-five major complications (including 4 fatalities) were reported among 4,000 patients (0.8%) implanted with 33,000 electrodes.

Limitations:

The number of SEEG patients is likely to be underestimated because only a few groups have exhaustively reported their experience. Moreover, it is possible that a number of teams performing SEEG have not published studies on the topic.

Conclusions:

Rigorous SEEG, thanks to its basic principles and updated technologies, is a safe and accurate method to define the epileptogenic zone by means of stereotactically implanted intracerebral electrodes.
Stereo-EEG Implantation Strategy
Authors: Kalamangalam Giridhar P. , Tandon Nitin
Published: December 2016

Stereoelectroencephalography denotes the strategic placement of multiple depth electrodes for invasive localization of focal epilepsy in surgical patients. It differs significantly from the alternative subdural grid approach, in both conceptualization of partial epilepsy—as a 3-D distributed network, rather than as focal pathology with contiguous spread—and by the method of sampling used—which is sparse and directed rather than continuous over adjacent brain areas. The electrode implantation strategy in stereoelectroencephalography involves appreciation of these features, which are illustrated by four cases drawn from distinct electroclinical epilepsy syndromes.
Stereoelectroencephalography: Interpretation
Authors: Bulacio Juan C. , Chauvel Patrick , McGonigal Aileen
Published: December 2016

Intracranial EEG has been in use for more than 50 years in the presurgical evaluation of patients with medically intractable focal epilepsy. The stereoelectroencephalography (SEEG) method has expanded very significantly over the last 5 years, in parallel with the increase in the number of complex cases (i.e., MRI-negative) being referred with medically intractable focal epilepsy to major epilepsy surgery centers. Some centers with extensive experience in subdural electrodes are indeed changing or have changed to SEEG as the principal exploration technique, which suggests that SEEG might offer specific benefits through its approach to accurately localizing the epileptogenic zone. However, interpretation of SEEG, which is a key step to its usefulness, may vary from one center to another. This may be due to different conceptual bases and the available expertise in each center. This heterogeneity in use of SEEG should be taken into account as it could contribute to erroneous conclusions and thus unfavorable outcome of epilepsy surgery. At present, there is a lack of guidelines for optimal SEEG use, although development of these is in progress. It remains challenging to translate SEEG interpretation into a practical approach to delineating surgical strategy. Identification of clear biomarkers will help in the definition of the epileptogenic zone and subsequent cortical resection. In addition, SEEG seems to be a unique tool for the in vivo investigation of human cerebral networks distributed over several lobes or sublobar structures, allowing a better understanding of their functioning.
Electrical Stimulation for Seizure Induction and Functional Mapping in Stereoelectroencephalography
Authors: Trébuchon Agnès , Chauvel Patrick
Published: December 2016

The challenge in epilepsy surgery is to remove the epileptogenic zone without compromising postoperative function. Electrical stimulation (ES) was developed to identify with greater anatomical and physiological precision cortical structures essential to language and motor function. Because the language network is widely distributed in the left (dominant) hemisphere, and often varies among patients, brain mapping should delineate eloquent areas at the individual level. Although ES for language is commonly performed during a presurgical investigation, the procedure remains nonstandardized among centers, and differences between grids and intracerebral depth electrodes (stereoelectroencephalography) should be taken into account when comparing results from different series. Electrical simulation exerts a complex summation effect in a given volume of brain tissue; the net result may be difficult to predict because this depends on methodological and physiological factors as follows: stimulation parameters, type of electrodes used, tasks used, presence or not of an after-discharge. We discuss in the present article some methodological aspects of the stimulation procedure influencing functional mapping because it pertains in particular to language mapping. In stereoelectroencephalography, the other goal of ES is to trigger seizures. Because seizures develop in neural networks that are imperfectly sampled by intracerebral electrodes, spontaneous seizure recording is not always sufficient to properly localize the epileptogenic zone. The rationale for performing ES is based on the electrophysiological distinction between local/regional after-discharge and seizure networks. A different response to ES-induced seizures can be seen for supra- and infra-sylvian epilepsies. The procedures for triggering seizures and for functional mapping should be performed in conjunction to answer the fundamental question whether or not there is a spatio-temporal overlap between the epileptogenic and the functional network. The exploration of both networks through stimulation exemplifies the importance of anatomo-electro-clinical correlations in stereoelectroencephalography.
The Stereo-Electroencephalography: The Epileptogenic Zone
Authors: Gonzalez-Martinez Jorge A.
Published: December 2016

The stereo-electroencephalography (SEEG) methodology and technique was developed almost 60 years ago in Europe and it has proven its efficacy and safety over the last 55 years. The main advantage of the SEEG method is the possibility to study the epileptogenic neuronal network in its dynamic and tri-dimensional aspect, with an optimal time and space correlation with the clinical semiology. In this manuscript, the technical and methodological aspects of the SEEG will be discussed focusing on the planning of SEEG implantations, technical nuances, conceptualization of the epileptogenic zone, and the different methods of SEEG-guided surgical resections and ablations.
Improved Search of Large Transcriptomic Sequencing Databases Using Split Sequence Bloom Trees
Authors: Solomon Brad , Kingsford Carl
Published: December 2016

Enormous databases of short-read RNA-seq sequencing experiments such as the NIH Sequencing Read Archive (SRA) are now available. These databases could answer many questions about the condition-specific expression or population variation, and this resource is only going to grow over time. However, these collections remain difficult to use due to the inability to search for a particular expressed sequence. While some progress has been made on this problem, it is still not feasible to search collections of hundreds of terabytes of short-read sequencing experiments. We introduce an indexing scheme called Split Sequence Bloom Tree (SSBT) to support sequence-based querying of terabyte-scale collections of thousands of short-read sequencing experiments. SSBT is an improvement over the SBT [1] data structure for the same task. We apply SSBT to the problem of finding conditions under which query transcripts are expressed. Our experiments are conducted on a set of 2,652 publicly available RNA-seq experiments contained in the NIH for the breast, blood, and brain tissues. We demonstrate that this SSBT index can be queried for a 1000 nt sequence in under 4 minutes using a single thread and can be stored in just 39 GB, a five-fold improvement in search and storage costs compared to SBT. We further report that SSBT can be further optimized by pre-loading the entire index to accomplish the same search in 30 seconds.
Genetic determinants of chromatin accessibility in T cell activation across humans
Authors: Gate Rachel E. , Cheng Christine S. , Aiden Aviva P. , Siba Atsede , Tabaka Marcin , Lituiev Dmytro , Machol Ido , Gordon M. Grace , Subramaniam Meena , Shamim Muhammad , Hougen Kendrick L. , Wortman Ivo , Huang Su-Chen , Durand Neva C. , Feng Ting , De Jager Philip L. , Chang Howard Y. , Lieberman Aiden Erez , Benoist Christophe , Beer Michael A. , Ye Chun J. , Regev Aviv
Published: December 2016

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or morecis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) and RNA-seq profiles from activated CD4+T cells of up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, in patterns consistent with the 3D organization of chromosomes measured byin situHi-C in T cells. 15% of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak through disrupting binding sites for transcription factors important for T cell differentiation and activation. These ATAC quantitative trait nucleotides (ATAC-QTNs) have the largest effects on co-accessible peaks, are associated with gene expression from the same aliquot of cells, are rarely affecting core binding motifs, and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulatecis- regulatory elements, in isolation or in concert, to influence gene expression in primary immune cells that play a key role in many human diseases.
AllSome Sequence Bloom Trees
Authors: Sun Chen , Harris Robert S. , Chikhi Rayan , Medvedev Paul
Published: December 2016

The ubiquity of next generation sequencing has transformed the size and nature of many databases, pushing the boundaries of current indexing and searching methods. One particular example is a database of 2,652 human RNA-seq experiments uploaded to the Sequence Read Archive. Recently, Solomon and Kingsford proposed the Sequence Bloom Tree data structure and demonstrated how it can be used to accurately identify SRA samples that have a transcript of interest potentially expressed. In this paper, we propose an improvement called the AllSome Sequence Bloom Tree. Results show that our new data structure significantly improves performance, reducing the tree construction time by 52.7% and query time by 39 - 85%, with a price of up to 3x memory consumption during queries. Notably, it can query a batch of 198,074 queries in under 8 hours (compared to around two days previously) and a whole set ofk-mers from a sequencing experiment (about 27 milk-mers) in under 11 minutes.
How well do RNA-Seq differential gene expression tools perform in a eukaryote with a complex transcriptome?
Authors: Froussios Kimon , Schurch Nick J. , Mackinnon Katarzyna , Gierliński Marek , Duc Céline , Simpson Gordon G. , Barton Geoffrey J.
Published: December 2016

RNA-seq experiments are usually carried out in three or fewer replicates. In order to work well with so few samples, Differential Gene Expression (DGE) tools typically assume the form of the underlying distribution of gene expression. A recent highly replicated study revealed that RNA-seq gene expression measurements in yeast are best represented as being drawn from an underlying negative binomial distribution. In this paper, the statistical properties of gene expression in the higher eukaryoteArabidopsis thalianaare shown to be essentially identical to those from yeast despite the large increase in the size and complexity of the transcriptome: Gene expression measurements from this model plant species are consistent with being drawn from an underlying negative binomial or log-normal distribution and the false positive rate performance of nine widely used DGE tools is not strongly affected by the additional size and complexity of theA. thalianatranscriptome. For RNA-seq data, we therefore recommend the use of DGE tools that are based on the negative binomial distribution.
Climate-driven range shifts in fragmented ecosystems
Authors: Cristofari Robin , Liu Xiaoming , Bonadonna Francesco , Cherel Yves , Pistorius Pierre , Le Maho Yvon , Raybaud Virginie , Stenseth Nils Chr , Le Bohec Céline , Trucchi Emiliano
Published: December 2016

Range shift is the primary short-term response of species to rapid climate change but it is hampered by natural or anthropogenic habitat fragmentation. Fragmented habitats expose different critical areas of a species niche to heterogeneous environmental changes resulting in uncoupled effects. Modelling species distribution under complex real-life scenarios and incorporating such uncoupled effects has not been achieved yet. Here we identify the most vulnerable areas and the potential cold refugia of a top-predator with fragmented niche range in the Southern ocean by integrating genomic, ecological and behavioural data with atmospheric and oceanographic models. Our integrative approach constitutes an indispensable example for predicting the effect of global warming on species relying on spatially and ecologically distinct areas to complete their life-cycle (e.g., migratory animals, marine pelagic organisms, central-place foragers) and, in general, on species constrained in fragmented landscapes due to continuously-growing anthropogenic pressure.
Taming the Late Quaternary phylogeography of the Eurasiatic wild ass through ancient and modern DNA
Authors: Bennett E. Andrew , Champlot Sophie , Peters Joris , Arbuckle Benjamin S. , Guimaraes Silvia , Pruvost Mélanie , Bar-David Shirli , Davis Simon S.M. , Gautier Mathieu , Kaczensky Petra , Kuehn Ralph , Mashkour Marjan , Morales-Muñiz Arturo , Pucher Erich , Tournepiche Jean-François , Uerpmann Hans-Peter , Bălăşescu Adrian , Germonpré Mietje , Gündem Can Y. , Hemami Mahmoud-Reza , Moullé Pierre-Elie , Ötzan Aliye , Uerpmann Margarete , Walzer Chris , Grange Thierry , Geigl Eva-Maria
Published: December 2016

Taxonomic over-splitting of extinct or endangered taxa, due to an incomplete knowledge of both skeletal morphological variability and the geographical ranges of past populations, continues to confuse the link between isolated extant populations and their ancestors. This is particularly problematic with the genusEquus.To more reliably determine the evolution and phylogeographic history of the endangered Asiatic wild ass, we studied the genetic diversity and inter-relationships of both extinct and extant populations over the last 100,000 years, including samples throughout its previous range from Western Europe to Southwest and East Asia. Using 229 bp of the mitochondrial hypervariable region, an approach which allowed the inclusion of information from extremely poorly preserved ancient samples, we classify all non-African wild asses into nine clades that show a clear phylogeographic structure revealing their phylogenetic history. This study places the extinct European wild ass,E. hydruntinus, the phylogeny of which has been debated since the end of the 19thcentury, into its phylogenetic context within the Asiatic wild asses and reveals recent gene flow events between populations currently regarded as separate species. The phylogeographic organization of clades resulting from these efforts can be used not only to improve future taxonomic determination of a poorly characterized group of equids, but also to identify historic ranges, interbreeding events between various populations, and the impact of ancient climatic changes. In addition, appropriately placing extant relict populations into a broader phylogeographic and genetic context can better inform ongoing conservation strategies for this highly endangered species.
Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses
Authors: VanLeuven James T. , Ridenhour Benjamin J. , Miller Craig R. , Miura Tanya A.
Published: December 2016

The severity and outcome of respiratory viral infections is partially determined by the cellular response mounted by infected lung epithelial cells. Disease prevention and treatment is dependent on our understanding of the shared and unique responses elicited by diverse viruses, yet few studies compare host responses to different viruses while controlling other experimental parameters. We compared changes in gene expression of murine lung epithelial cells infected individually by three respiratory viruses causing mild (rhinovirus, RV1B), moderate (coronavirus, MHV-1), and severe (influenza A virus, PR8) disease in mice. RV1B infection caused numerous gene expression changes, but the differential effect peaked at 12 hours post-infection. PR8 altered an intermediate number of genes whose expression continued to change through 24 hours. MHV-1 had comparatively few effects on host gene expression. The viruses elicited highly overlapping responses in antiviral genes, though MHV-1 induced a lower type I interferon response than the other two viruses. Signature genes were identified for each virus and included host defense genes for PR8, tissue remodeling genes for RV1B, and transcription factors for MHV-1. Our comparative approach identified universal and specific transcriptional signatures of virus infection that can be used to discover mechanisms of pathogenesis in the respiratory tract.
Summary of muscle parameters for Hill-based muscle modeling in the human lower limb
Authors: Miller Ross H.
Published: December 2016

A summary is presented of five mechanical parameters from human lower limb skeletal muscles critical for Hill-based muscle modeling: the optimal fiber length, the fiber pennation angle, the physiological cross-sectional area (PCSA), the unloaded tendon length, and the fast-twitch fiber fraction. The data presented are drawn from a total of 29 publications including human cadaver studies,in vivoimaging studies of live humans, musculoskeletal modeling studies, and combinations of these methods. Where possible, parameter values were adjusted from the referenced data to present them with consistent definitions (normalization of measured fiber lengths to optimal sarcomere length, and calculation of PCSA as the ratio of fiber volume to fiber length). It is seen that within a specific muscle, optimal fiber lengths are fairly consistent between studies, pennation angles and PCSAs vary widely between studies, and data for unloaded tendon length are comparatively sparse. Few studies have reported fiber type fractions for a large number of muscles. Guidelines for implementing these parameter values in muscle modeling and musculoskeletal modeling are suggested.

Update History

December 2, 2016: original submission

December 3, 2016: discussion on maximum isometric force and specific tension added

December 6, 2016: minor edits for typos, clarity, and missing references

December 7, 2016: Tirrell et al. (2012) study added
Single-molecule sequencing of theDrosophila serratagenome
Authors: Allen Scott L. , Delaney Emily K. , Kopp Artyom , Chenoweth Stephen F.
Published: December 2016

Long read sequencing technology promises to greatly enhancede novoassembly of genomes for non-model species. While error rates have been a large stumbling block, sequencing at high coverage allows reads to be self-corrected. Here we sequence andde novoassemble the genome ofDrosophila serrata, a non-model species from themontiumsubgroup that has been well studied for clines and sexual selection. Using 11 PacBio SMRT cells, we generated 12 Gbp of raw sequence data comprising approximately 65x whole genome coverage. Read lengths averaged 8,940 bp (NRead50 12,200) with the longest read at 53 Kbp. We self-corrected reads using the PBDagCon algorithm and assembled the genome using the MHAP algorithm within the PBcR assembler. Total genome length was 198 Mbp with an N50 just under 1 Mbp. Contigs displayed a high degree of arm-level conservation withD. melanogaster. We also provide an initial annotation for this genome usingin silicogene predictions that were supported by RNA-seq data.
Long-read whole genome sequencing identifies causal structural variation in a Mendelian disease
Authors: Merker Jason D. , Wenger Aaron M. , Sneddon Tam , Grove Megan , Waggott Daryl , Utiramerur Sowmi , Hou Yanli , Lambert Christine C. , Eng Kevin S. , Hickey Luke , Korlach Jonas , Ford James , Ashley Euan A.
Published: December 2016

Current clinical genomics assays primarily utilize short-read sequencing (SRS), which offers high throughput, high base accuracy, and low cost per base. SRS has, however, limited ability to evaluate tandem repeats, regions with high [GC] or [AT] content, highly polymorphic regions, highly paralogous regions, and large-scale structural variants. Long-read sequencing (LRS) has complementary strengths and offers a means to discover overlooked genetic variation in patients undiagnosed by SRS. To evaluate LRS, we selected a patient who presented with multiple neoplasia and cardiac myxomata suggestive of Carney complex for whom targeted clinical gene testing and whole genome SRS were negative. Low coverage whole genome LRS was performed on the PacBio Sequel system and structural variants were called, yielding 6,971 deletions and 6,821 insertions > 50bp. Filtering for variants that are absent in an unrelated control and that overlap a coding exon of a disease gene identified three deletions and three insertions. One of these, a heterozygous 2,184 bp deletion, overlaps the first coding exon ofPRKAR1A, which is implicated in autosomal dominant Carney complex. This variant was confirmed by Sanger sequencing and was classified as pathogenic using standard criteria for the interpretation of sequence variants. This first successful application of whole genome LRS to identify a pathogenic variant suggests that LRS has significant potential to identify disease-causing structural variation. We recommend larger studies to evaluate the diagnostic yield of LRS, and the development of a comprehensive catalog of common human structural variation to support future studies.
High-resolution tracking of microbial colonization in Fecal Microbiota Transplantation experiments via metagenome-assembled genomes
Authors: Lee Sonny TM , Kahn Stacy A. , Delmont Tom O. , Hubert Nathaniel J. , Morrison Hilary G. , Antonopoulos Dionysios A. , Rubin David T. , Eren A. Murat
Published: December 2016

Fecal microbiota transplantation (FMT) is an effective treatment for recurrentClostridium difficileinfection and shows promise for treating other medical conditions associated with intestinal dysbioses. However, we lack a sufficient understanding of which microbial populations successfully colonize the recipient gut, and the widely used approaches to study the microbial ecology of FMT experiments fail to provide enough resolution to identify populations that are likely responsible for FMT-derived benefits. Here we used shotgun metagenomics to reconstruct 97 metagenome-assembled genomes (MAGs) from fecal samples of a single donor and followed their distribution in two FMT recipients to identify microbial populations with different colonization properties. Our analysis of the occurrence and distribution patterns post-FMT revealed that 22% of the MAGs transferred from the donor to both recipients and remained abundant in their guts for at least eight weeks. Most MAGs that successfully colonized the recipient gut belonged to the order Bacteroidales. The vast majority of those that lacked evidence of colonization belonged to the order Clostridiales and colonization success was negatively correlated with the number of genes related to sporulation. Although our dataset showed a link between taxonomy and the ability of a MAG to colonize the recipient gut, we also identified MAGs with different colonization properties that belong to the same taxon, highlighting the importance of genome-resolved approaches to explore the functional basis of colonization and to identify targets for cultivation, hypothesis generation, and testing in model systems for mechanistic insights.
The Structured Coalescent and its Approximations
Authors: Müller Nicola F. , Rasmussen David A. , Stadler Tanja
Published: December 2016

Phylogenetics can be used to elucidate the movement of genes between populations of organisms, using phylogeographic methods. This has been widely done to quantify pathogen movement between different host populations, the migration history of humans, and the geographic spread of languages or the gene flow between species using the location or state of samples alongside sequence data. Phylogenies therefore offer insights into migration processes not available from classic epidemiological or occurrence data alone. Phylogeographic methods have however several known shortcomings. In particular, one of the most widely used methods treats migration the same as mutation, and therefore does not incorporate information about population demography. This may lead to severe biases in estimated migration rates for datasets where sampling is biased across populations. The structured coalescent on the other hand allows us to coherently model the migration and coalescent process, but current implementations struggle with complex datasets due to the need to infer ancestral migration histories. Thus, approximations to the structured coalescent, which integrate over all ancestral migration histories, have been developed. However, the validity and robustness of these approximations remain unclear. We present an exact numerical solution to the structured coalescent that does not require the inference of migration histories. While this solution is computationally unfeasible for large datasets, it clarifies the assumptions of previously developed approximate methods and allows us to provide an improved approximation to the structured coalescent. We have implemented these methods in BEAST2, and we show how these methods compare under different scenarios.
A Bayesian Heteroscedastic GLM with Application to fMRI Data with Motion Spikes
Authors: Eklund Anders , Lindquist Martin A. , Villani Mattias
Published: December 2016

We propose a voxel-wise general linear model with autoregressive noise and heteroscedastic noise innovations (GLMH) for analyzing functional magnetic resonance imaging (fMRI) data. The model is analyzed from a Bayesian perspective and has the benefit of automatically down-weighting time points close to motion spikes in a data-driven manner. We develop a highly efficient Markov Chain Monte Carlo (MCMC) algorithm that allows for Bayesian variable selection among the regressors to model both the mean (i.e., the design matrix) and variance. This makes it possible to include a broad range of explanatory variables in both the mean and variance (e.g., time trends, activation stimuli, head motion parameters and their temporal derivatives), and to compute the posterior probability of inclusion from the MCMC output. Variable selection is also applied to the lags in the autoregressive noise process, making it possible to infer the lag order from the data simultaneously with all other model parameters. We use both simulated data and real fMRI data from OpenfMRI to illustrate the importance of proper modeling of heteroscedasticity in fMRI data analysis. Our results show that the GLMH tends to detect more brain activity, compared to its homoscedastic counterpart, by allowing the variance to change over time depending on the degree of head motion.
Joint inference of demography and mutation rates from polymorphism data and pedigrees
Authors: Parat Florence , Szilágyi Sándor Miklós , Wegmann Daniel , Tellier Aurélien
Published: December 2016

Inference of demography and mutation rates is of major interest but difficult because genetic data is only informative about the population mutation rate, the product of the effective population size times the mutation rate, and not about these quantities individually. Here we show that this limitation can be overcome by combining genetic data with pedigree information. To successfully use pedigree data, however, important aspects of real populations such as the presence of two sexes, unbalanced sex ratios and overlapping generations have to be taken into account. We present here an extension of the classic Wright-Fisher model accounting for these effects and show that the coalescent process under this model reduces to the classic Kingman coalescent with specific scaling parameters. We further derive the probability of a pedigree under that model and show how pedigree data can thus be used to infer demographic parameters. Finally, we present a computationally efficient inference approach combining pedigree information and genetic data summarized by the site frequency spectrum (SFS) that allows for the joint inference of the mutation rate, sex-specific population sizes and the fraction of overlapping generations. Using simulations we then show that these parameters can be accurately inferred from pedigrees spanning just a few generations, as are available for many species. We finally discuss future possible extensions of the model and inference framework necessary for applications to wild and domesticated species, namely the account for more complex demographies and the uncertainty in assigning pedigree individuals to specific generations.