bluuebunny/crossref_metadata_2025 huggingface dataset:
3. Global patterns of higher education
Authors: Palfreyman David , Temple Paul
Published: December 2017

‘Global patterns of higher education’ looks at the different types of education system globally. Although virtually every country has its own national higher education system, and each of these national systems has its own peculiarities (and most national systems contain considerable variations within them), scholars of higher education have defined a number of system types: the Humboldtian model, which emphasizes the integration of teaching and research; the ‘Napoleonic’ model of France; the Anglo-Saxon model; the US’s Ivy League and intensive research model; and an emerging Confucian model in Asia. The relationship between the state and the university and college is also considered along with the Bologna Process of international convergence.
6. Working in universities and colleges: more than just a job?
Authors: Palfreyman David , Temple Paul
Published: December 2017

Life for university and college professors has changed considerably. ‘Working in universities and colleges: more than just a job?’ examines academics’ working life in the modern university and college along with their sense of professional identity. Many have experienced a loss of status despite retaining their special benefits of academic tenure and freedom. Are academic subjects or disciplines now giving way to interdisciplinarity as the guiding concept for academic organization and working life? Are professors now just managed professionals, their academic autonomy and power vastly reduced? Are organizational structures of the university and college changing, along with the processes of teaching and learning, and also academic identities?
Delta: a new web-based 3D genome visualization and analysis platform
Authors: Tang Bixia , Li Feifei , Li Jing , Zhao Wenming , Zhang Zhihua
Published: December 2017

Delta is an integrative visualization and analysis platform to facilitate visually annotating and exploring the 3D physical architecture of genomes. Delta takes Hi-C or ChIA-PET contact matrix as input and predicts the topologically associating domains and chromatin loops in the genome. It then generates a physical 3D model which represents the plausible consensus 3D structure of the genome. Delta features a highly interactive visualization tool which enhances the integration of genome topology/physical structure with extensive genome annotation by juxtaposing the 3D model with diverse genomic assay outputs. Finally, by visually comparing the 3D model of the β-globin gene locus and its annotation, we speculated a plausible transitory interaction pattern in the locus. Experimental evidence was found to support this speculation by literature survey. This served as an example of intuitive hypothesis testing with the help of Delta.

Availability and implementation

Delta is freely accessible from http://delta.big.ac.cn, and the source code is available at https://github.com/zhangzhwlab/delta.

Supplementary information

Supplementary data are available at Bioinformatics online.
YAAM: Yeast Amino Acid Modifications Database
Authors: Ledesma Leonardo , Sandoval Eduardo , Cruz-Martínez Uriel , Escalante Ana María , Mejía Selene , Moreno-Álvarez Paola , Ávila Emiliano , García Erik , Coello Gerardo , Torres-Quiroz Francisco
Published: December 2017

Proteins are dynamic molecules that regulate a myriad of cellular functions; these functions may be regulated by protein post-translational modifications (PTMs) that mediate the activity, localization and interaction partners of proteins. Thus, understanding the meaning of a single PTM or the combination of several of them is essential to unravel the mechanisms of protein regulation. Yeast Amino Acid Modification (YAAM) (http://yaam.ifc.unam.mx) is a comprehensive database that contains information from 121 921 residues of proteins, which are post-translationally modified in the yeast model Saccharomyces cerevisiae. All the PTMs contained in YAAM have been confirmed experimentally. YAAM database maps PTM residues in a 3D canvas for 680 proteins with a known 3D structure. The structure can be visualized and manipulated using the most common web browsers without the need for any additional plugin. The aim of our database is to retrieve and organize data about the location of modified amino acids providing information in a concise but comprehensive and user-friendly way, enabling users to find relevant information on PTMs. Given that PTMs influence almost all aspects of the biology of both healthy and diseased cells, identifying and understanding PTMs is critical in the study of molecular and cell biology. YAAM allows users to perform multiple searches, up to three modifications at the same residue, giving the possibility to explore possible regulatory mechanism for some proteins. Using YAAM search engine, we found three different PTMs of lysine residues involved in protein translation. This suggests an important regulatory mechanism for protein translation that needs to be further studied.

Database URL: http://yaam.ifc.unam.mx/
Insights into the Pathophysiology of Hypertrophic Scars and Keloids: How Do They Differ?
Authors: Ghazawi Feras M. , Zargham Ramin , Gilardino Mirko S. , Sasseville Denis , Jafarian Fatemeh
Published: December 2017

GENERAL PURPOSE:

To provide information about the clinical presentation of hypertrophic scars and keloids based on their varied structural components.

TARGET AUDIENCE:

This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care.

LEARNING OBJECTIVES/OUTCOMES:

After completing this continuing education activity, you should be able to:

Hypertrophic scars and keloids are firm, raised, erythematous plaques or nodules that manifest when the cicatrix fails to properly heal. They result from pathologic wound healing and often cause pain and decreased quality of life. The appearance of such cosmetically unappealing scars affects the confidence and self-esteem of many patients. These scars can also cause dysfunction by interfering with flexion and extension across joints. Both possess some unique and distinct histochemical and physiologic characteristics that set them apart morphologically and at the molecular level. While these entities have been the focus of research for many years, differentiating between them remains challenging for clinicians.

This article reviews the clinical presentation of aberrant scars and illustrates how they can be differentiated. It outlines their pathophysiology and emphasizes the unique molecular mechanisms underlying each disorder. It also examines how altered expression levels and the distribution of several factors may contribute to their unique clinical characteristics and presentation. Further research is needed to elucidate optimal treatments and preventive measures for these types of aberrant scarring.
Exercise in the management of knee and hip osteoarthritis
Authors: Wellsandt Elizabeth , Golightly Yvonne
Published: December 2017

Purpose of review

This review focuses on studies published during July 2001 to August 2017 of exercise as an intervention in knee and hip osteoarthritis, including its influence on an array of patient outcomes.

Recent findings

Studies continue to illustrate the efficacy of exercise in treating and managing osteoarthritis, with current literature more focused on the knee compared with the hip joint. Both traditional (e.g. strength, aerobic, flexibility) and more nontraditional (e.g. yoga, Tai Chi, aquatic) training modes improve patient outcomes related to joint symptoms, mobility, quality of life, psychological health, musculoskeletal properties, body composition, sleep, and fatigue. Exercise that is adequately dosed (e.g. frequency, intensity) and progressive in nature demonstrated the greatest improvements in patient outcomes. Supervised, partially supervised, and nonsupervised interventions can be successful in the treatment of osteoarthritis, but patient preference regarding level of supervision and mode of exercise may be key predictors in exercise adherence and degree of outcome improvement. A topic of increasing interest in osteoarthritis is the supplementary role of behavior training in exercise interventions.

Osteoarthritis is a complex, multifactorial disease that can be successfully managed and treated through exercise, with minimal risk for negative consequences. However, to have greatest impact, appropriate exercise prescription is needed. Efforts to achieve correct exercise doses and mitigate patient nonadherence are needed to lessen the lifelong burden of osteoarthritis.
Hormone receptor positive breast cancer: state of the art
Authors: Peddi Parvin F.
Published: December 2017

Purpose of review

Hormone receptor (HR) positive breast cancer represents the vast majority of breast cancer cases. Treatment for these patients has been 5 years of endocrine therapy in the localized setting and endocrine therapy alone in the metastatic setting until progression of disease and switch to chemotherapy until quite recently.

Recent findings

The current article will review recent data on role of extended endocrine therapy with tamoxifen and aromatase inhibitors and adjuvant bisphosphonates in the localized disease setting. It will then review the role of targeted agents such as cyclin dependent kinases 4/6 inhibitors, two of which were FDA approved in 2017 in the metastatic setting and are now standard of care.

Landscape of HR positive breast cancer is changing with doubling of progression-free survival with drugs approved in the last 2 years. Although antiestrogen therapy remains the backbone of therapy, we are continuing to improve outcome for patients by changes and additions to this therapy.
Indications for morcellation in gynecologic surgery
Authors: Parker William H.
Published: December 2017

Purpose of review

Minimally invasive gynecologic procedures, in particular laparoscopic hysterectomy and myomectomy, often require tissue morcellation.

Recent findings

Whether morcellated or not, myometrial cells can be found in the abdomen and pelvis after either laparoscopic or open myomectomy. Following morcellation, careful inspection for and removal of tissue fragments and copious irrigation and suctioning of fluid can remove residual tissue and cells without the use of containment bags. The dogma of not ‘cutting-through’ cancer is not correct for many surgical specialties and irrelevant with regards to leiomyosarcoma (LMS) and minimally invasive gynecologic surgery. Eliminating residual disease in the pelvis and abdomen should be the goal of myomectomy or hysterectomy.

Morcellation of excised tissue is necessary for many women with symptomatic fibroids who choose to undergo laparoscopic myomectomy or hysterectomy. LMS is an uncommon disease, with a poor prognosis due to early hematogenous metastasis to lung, bone and liver. Preoperatively, it is often difficult to differentiate from benign fibroids. LMS has a high propensity for local recurrence despite performance of total hysterectomy. Efforts to remove all tissue and cells from the pelvis and abdomen should be the goal of minimally invasive surgery with morcellation.
Frontline therapy of ovarian cancer: trials and tribulations
Authors: Volpe Jasmin , Filipi Jennifer G. , Cooper Olivia R. , Penson Richard T.
Published: December 2017

Purpose of review

The current article reviews the advances and challenges in the fight with cancer and the hope for cure, with a focus on clinical trials, at the one time with the best outcomes; first-line therapy.

Recent findings

To date there have been four great stories that bridge inception to development of new drugs in ovarian cancer: Serendipitous insight into the role of platinum, discovery of taxanes, understanding the microenvironment and angiogenesis, and following the science in the development of Poly (ADP-Ribose) Polymerase (PARP) inhibitors. There is a fundamental difference between overall survival (OS), simply living longer; and eradicating disease, cure. The scientific underpinning of both our understanding and the recent developments encourages an optimistic view of the remaining hurdles.

There has been an unprecedented explosion in the number of new drugs approved for the treatment of ovarian cancer with three new classes of agent, and five new drugs receiving food and drug administration approval in the last 3 years (Fig. 2). Getting the right drug truly transforms patients’ experience with the seminal event being the development of imatinib in CML. In 1980, an average patient would have lived only 3 years, and now they only live 3 years less than a full lifespan [Bower et al. (2016). J Clin Oncol 34:2851].
Electronic Fetal Monitoring Documentation
Authors: Cypher Rebecca L.
Published: December 2017

Contemporaneous, complete, and objective documentation is the foundation for continuity of patient care and facilitates communication between all levels of healthcare clinicians. The impact of electronic fetal monitoring on obstetric safety has become a high priority, with documentation being essential to evaluating care quality. Over several decades, electronic fetal monitoring documentation has reached a higher level of precision because paper is being replaced with health information technology that incorporates system's features such as checklists, drop-down boxes, and decision analysis. The intent of this article is to provide a synopsis of important concepts regarding electronic fetal monitoring documentation and liability-reduction strategies for perinatal nurses.
Weekend Surgical Care and Postoperative Mortality
Authors: Smith Stephen A. , Yamamoto Jennifer M. , Roberts Derek J. , Tang Karen L. , Ronksley Paul E. , Dixon Elijah , Buie W. Donald , James Matthew T.
Published: December 2017

Background:

An association between weekend health care delivery and poor outcomes has become known as the “weekend effect.” Evidence for such an association among surgery patients has not previously been synthesized.

Objective:

To systematically review associations between weekend surgical care and postoperative mortality.

Methods:

We searched PubMed, EMBASE, and references of relevant articles for studies that compared postoperative mortality either; (1) according to the day of the week of surgery for elective operations, or (2) according to weekend versus weekday admission for urgent/emergent operations. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for postoperative mortality (≤90 d or inpatient mortality) were pooled using random-effects models.

Results:

Among 4027 citations identified, 10 elective surgery studies and 19 urgent/emergent surgery studies with a total of >6,685,970 and >1,424,316 patients, respectively, met the inclusion criteria. Pooled odds of mortality following elective surgery rose in a graded manner as the day of the week of surgery approached the weekend [Monday OR=1 (reference); Tuesday OR=1.04 (95% CI=0.97–1.11); Wednesday OR=1.08 (95% CI=0.98–1.19); Thursday OR=1.12 (95% CI=1.03–1.22); Friday OR=1.24 (95% CI=1.10–1.38)]. Mortality was also higher among patients who underwent urgent/emergent surgery after admission on the weekend relative to admission on weekdays (OR=1.27; 95% CI=1.08–1.49).

Conclusions:

Postoperative mortality rises as the day of the week of elective surgery approaches the weekend, and is higher after admission for urgent/emergent surgery on the weekend compared with weekdays. Future research should focus on clarifying underlying causes of this association and potentially mitigating its impact.
Indocyanine Green Angiography Use in Breast Reconstruction: A National Analysis of Outcomes and Cost in 110,320 Patients
Authors: Chattha Anmol , Bucknor Alexandra , Chen Austin D. , Lee Bernard T. , Lin Samuel J.
Published: December 2017

Background:

Indocyanine green angiography has gained popularity in breast reconstruction for its ability to assess mastectomy skin and tissue flap viability. The authors aim to analyze trends and outcomes associated with indocyanine green angiography use in breast reconstruction.

Methods:

Using 2012 to 2014 data from the Healthcare Cost and Utilization Project National Inpatient Sample, Agency for Healthcare Research and Quality, the authors identified breast reconstructions performed with or without indocyanine green angiography use. Trends over time were assessed using the Cochran-Armitage test. Outcomes were assessed using logistic regression and generalized linear modeling.

Results:

Over the study period, 110,320 patients underwent breast reconstruction: 107,005 (97.0 percent) without and 3315 (3.0 percent) with indocyanine green angiography use. Usage increased over time: 750 patients (1.9 percent) in 2012, increasing to 1275 patients (3.7 percent) in 2013 (p < 0.001). Smokers (p = 0.018), hypertensive patients (p = 0.046), obese patients (p < 0.001), and those with a higher comorbidity index (p < 0.001) were more likely to undergo indocyanine green angiography. Autologous reconstruction was more frequently combined with its use compared with tissue expander reconstruction (4.5 percent versus 2.1 percent; p < 0.001). There was a significant increase in the odds of débridement associated with its use (OR, 1.404; p < 0.001; 95 percent CI, 1.201 to 1.640).

Conclusions:

Indocyanine green angiography use in breast reconstruction has increased in recent years and is associated with higher débridement rates. These rates may indicate changing trends for clinicians when deciding whether to débride tissue during breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Absorbable Antibiotic Beads Prophylaxis in Immediate Breast Reconstruction
Authors: Kenna Denise M. , Irojah Busayo B. , Mudge KimberLee , Eveler Kendra
Published: December 2017

Background:

Breast reconstruction with tissue expanders is the most common mode of reconstruction following mastectomy. Infection necessitating tissue expander removal is a significant complication leading to patient distress and increased health care costs.

Methods:

Over 3 years, 127 breast reconstructions with tissue expanders were performed by a single surgeon. Fifty-nine of these reconstructions were performed using a standardized protocol in which patients washed with chlorhexidine several days before surgery and received intravenous antibiotics preoperatively. Intraoperatively, the submuscular pocket was irrigated with triple-antibiotic solution and the skin was prepared again with povidone-iodine before expander placement. This group was referred to as the preintervention group. Sixty-eight of the reconstructions were performed using the standardized protocol with the addition of biodegradable antibiotic beads (Stimulan with vancomycin and gentamicin) in the submuscular pocket. This group made up the postintervention group. The primary outcome was the rate of infection necessitating tissue expander removal.

Results:

The rate of tissue expander loss caused by infection was 11.9 percent in the preintervention group and 1.5 percent in the postintervention group (p= 0.024). Higher body mass index was associated with a statistically significant increase in infections necessitating expander removal.

Conclusion:

The use of absorbable antibiotic beads in the submuscular pocket reduced the risk of periprosthetic implant infection necessitating implant removal by 8-fold.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
The role of omadacycline in skin and soft tissue infections
Authors: Montravers Philippe , Tran-Dinh Alexy , Tanaka Sebastien
Published: December 2017

Purpose of review

Skin and soft tissue infections (SSTIs) are among the most frequent infections, contributing to significant morbidity and healthcare costs. Although numerous antibiotics are available for this indication, several medical needs remain unmet, especially for treating methicillin-resistant Staphylococcus aureus (MRSA) or mixed infections. This review summarizes the results achieved in the development of omadacycline, a new aminomethylcycline, which could have useful properties for the treatment of SSTIs.

Recent findings

The antimicrobial activity of omadacycline against the micro-organisms most frequently cultured in SSTIs has been confirmed in worldwide panels of clinical isolates, including MRSA, Gram-negative aerobes and some anaerobes. Pharmacokinetic data demonstrate interesting characteristics, allowing intravenous and oral administration. The Phase 3 OASIS-1 trial assessed the clinical efficacy and safety of omadacycline versus linezolid in SSTIs and demonstrated noninferiority and a good safety profile especially with regard to gastrointestinal effects. Analyses of subgroups of patients from this trial showed similar activity to that of the comparator drug, good safety and no dosage adjustments for age, sex or hepatic or renal impairment.

Because of its microbiological activities and pharmacokinetic profile, omadacycline may be particularly suitable for the treatment of SSTIs, whether managed in hospital or on an outpatient basis.
Resveratrol Downregulates Biomarkers of Sepsis Via Inhibition of Proteasome's Proteases
Authors: Silswal Neerupma , Reddy Nidhi S. , Qureshi Asaf A. , Qureshi Nilofer
Published: December 2017

Lipopolysaccharide (LPS) is the main agonist of gram-negative bacteria and initiates inflammation. We recently reported that plasmas from sepsis patients revealed increased levels of following group of biomarkers; VCAM-1, ICAM1, CRP, resistin, and proteasome LMP subunits. Our objective here was to compare effects of resveratrol (shown to be a nonspecific proteasome inhibitor by us) and a known LMP7 inhibitor (ONX-0914, specific inhibitor) on proteasome's activities, as well as on inflammatory markers mentioned above in human blood monocytes. Using fluorescence-based assays on blood monocytes purified proteasomes, resveratrol (0–100 μM) inhibited all three protease activities, predominantly LMP7. Similarly, resveratrol inhibited all three protease activities using cell-based luminescence assay. In contrast, ONX-0914 was more selective and potent for LMP7 activity. Resveratrol and ONX-0914, both significantly inhibited expression of LPS-induced biomarkers mentioned above in CD14+ monocytes. Moreover, resveratrol itself, as well as in combination with LPS, accumulated pIκBα in CD14+ monocytes. Collectively, our data suggest that resveratrol is a less potent inhibitor of all three; CT-like (predominantly LMP7), T-like and PA protease activities and is less toxic to human monocytes than ONX-0914 (a selector inhibitor of only LMP7) as observed by an autophagy detection kit. Also, resveratrol reduces LPS-induced inflammatory cytokine expression by decreasing the translocation of NF-κB due to an increase in inhibitor pIκBα. Therefore, resveratrol can be used to curb inflammation in diseased states like sepsis and other disorders.
Occurrence of Impaired Physical Performance in Memory Clinic Patients With Cerebral Small Vessel Disease
Authors: Verwer Jurre H. , Biessels Geert-Jan , Heinen Rutger , Exalto Lieza G. , Emmelot-Vonk Marielle H. , Koek Huiberdina L.
Published: December 2017

Cerebral small vessel disease (CSVD) occurs often in memory clinic patients. Apart from cognitive deficits, these patients can express physical decline, which predicts adverse health outcomes. In this study, we investigated the cooccurrence of clinically relevant impairments in physical performance and CSVD in memory clinic patients. We included 131 patients with vascular brain injury, mild cognitive impairment or Alzheimer disease with available 3T MRI and physical performance scores. CSVD was visually rated according to 3 subtypes and as a total burden score, composed of the presence of white matter hyperintensities (WMH), lacunar infarcts (LI), and cerebral microbleeds (MB). Physical performance was assessed with the Short Physical Performance Battery (SPPB), covering gait speed, balance, and chair stand performance. CSVD markers and impaired physical performance both occurred often. High total CSVD burdens cooccurred with impaired chair stand performances [odds ratio (OR) 2.67; 95% confidence interval (CI) (1.12-6.34)]. WMH cooccurred with impaired SPPB scores (OR, 3.76; 95% CI, 1.68-8.44), impaired gait speeds (OR, 4.11; 95% CI, 1.81-9.31) and impaired chair stand performances (OR, 5.62; 95% CI, 2.29-13.80). In memory clinic patients, high burdens of CSVD, particularly WMH, often cooccur with impairments in physical performance. The presence of WMH should alert clinicians to the presence of these, clinically relevant, physical impairments.
Mitigating the risk of Zika virus contamination of raw materials and cell lines in the manufacture of biologicals
Authors: Zmurko Joanna , Vasey Douglas B. , Donald Claire L. , Armstrong Alison A. , McKee Marian L. , Kohl Alain , Clayton Reginald F.
Published: December 2017

Ensuring the virological safety of biologicals is challenging due to the risk of viral contamination of raw materials and cell banks, and exposure during in-process handling to known and/or emerging viral pathogens. Viruses may contaminate raw materials and biologicals intended for human or veterinary use and remain undetected until appropriate testing measures are employed. The outbreak and expansive spread of the mosquito-borne flavivirus Zika virus (ZIKV) poses challenges to screening human- and animal -derived products used in the manufacture of biologicals. Here, we report the results of an in vitro study where detector cell lines were challenged with African and Asian lineages of ZIKV. We demonstrate that this pathogen is robustly detectable by in vitro assay, thereby providing assurance of detection of ZIKV, and in turn underpinning the robustness of in vitro virology assays in safety testing of biologicals.
Riemannian Geometry Boosts Representational Similarity Analyses of Dense Neural Time Series
Authors: Barachant Alexandre , King Jean-Rémi
Published: December 2017

Representational similarity analysis (RSA) is a popular technique to estimate the structure of mental representations from neuroimaging data. However, RSA can be difficult to estimate for neural time series, where mental representations may be distributed in a highly dimensional space. Here, we show that RSA can be efficiently estimated from dense neural time series using Riemannian geometry. Using a public magneto-encephalography dataset, we decoded 24 classes from the brain evoked responses to 720 visual stimuli. RSA estimated from the confusion matrices of a standard regularized logistic regression achieved an average decoding accuracy of 23% (chance=4%). Our approach based on spatial filtering and Riemannian geometry nearly doubled this score with an average 42% decoding accuracy. Finally, our results revealed how RSA becomes ill-conceived when it derives from confusion matrices of highly accurate multivariate pattern classifications. Instead, we propose to directly estimate RSA from Riemannian metrics without fitting a multivariate pattern classifier. Overall, our approach, based on Riemannian geometry provides a principled and efficient basis to study the structure of mental representations from highly dimensional neural time series.
A quantitative network modeling approach to evaluate the role of cytokine combinations on CD4+ T cell differentiation, partial polarization, and plasticity
Authors: Martinez-Sanchez Mariana E. , Huerta Leonor , Alvarez-Buylla Elena R. , Villarreal Carlos
Published: December 2017

Diverse cellular polarization states with different phenotypes and functions are derived from the differentiation of activated CD4+T naïve lymphocytes in the presence of particular cytokines. In addition, conversion of polarized cells to phenotypes different from that originally induced has been documented, highlighting the capacity of the immune response for adaptation to changing circumstances. In a recent study, we proposed a minimal Boolean regulatory network of CD4+ T differentiation that incorporates transcription factors, signaling pathways, and autocrine and exogenous cytokines. The qualitative model effectively reproduced the main polarized phenotypes of CD4+T cells and several of the plasticity events reported in the literature. Yet, the amount and the expression of cytokines relative to expression of other factors influence CD4+ T cell transitions. In this paper, we have extended the Boolean network to a continuous model that allows us to assess the effect of quantitative differences in the concentrations and combinations of exogenous and endogenous cytokines, as well as diverse levels of transcription factors expression, in order to assess the role of intracellular and extracellular components in CD4+T differentiation and plasticity. Interestingly, the model predicts either abrupt or gradual differentiation patterns between observed phenotypes depending on critical concentrations of single or multiple environmental cytokines. Plastic changes induced by environmental cytokines were observed in conditions of partial phenotype polarization in the Th1/Th2 transition. On the other hand, the Th17/iTreg transition was highly dependent on cytokine concentrations in the environment. Thus, modeling shows how the concentration of exogenous factors, the degree of initial polarization, and cell heterogeneity, may determine the differentiation and plasticity capacity of CD4+T cells. The model and results presented here are useful to further understand system-level mechanisms underlying observed patterns of CD4+T differentiation and plasticity.
Robust detrending, rereferencing, outlier detection, and inpainting for multichannel data
Authors: de Cheveigné Alain , Arzounian Dorothée
Published: December 2017

Electroencephalography (EEG), magnetoencephalography (MEG) and related techniques are prone to glitches, slow drift, steps, etc., that contaminate the data and interfere with the analysis and interpretation. These artifacts are usually addressed in a preprocessing phase that attempts to remove them or minimize their impact. This paper offers a set of useful techniques for this purpose: robust detrending, robust rereferencing, outlier detection, data interpolation (inpainting), step removal, and filter ringing artifact removal. These techniques provide a less wasteful alternative to discarding corrupted trials or channels, and they are relatively immune to artifacts that disrupt alternative approaches such as filtering.Robust detrendingallows slow drifts and common mode signals to be factored out while avoiding the deleterious effects of glitches.Robust rereferencingreduces the impact of artifacts on the reference.Inpaintingallows corrupt data to be interpolated from intact parts based on the correlation structure estimated over the intact parts.Outlier detectionallows the corrupt parts to be identified.Step removalfixes the high-amplitude flux jump artifacts that are common with some MEG systems.Ringing removalallows the ringing response of the antialiasing filter to glitches (steps, pulses) to be suppressed. The performance of the methods is illustrated and evaluated using synthetic data and data from real EEG and MEG systems. These methods, which are are mainly automatic and require little tuning, can greatly improve the quality of the data.
Metagenomic signature of natural strongyle infection in susceptible and resistant horses
Authors: Clark Allison , Sallé Guillaume , Ballan Valentine , Reigner Fabrice , Meynadier Annabelle , Cortet Jacques , Koch Christine , Riou Mickaёl , Blanchard Alexandra , Mach Núria
Published: December 2017

Gastrointestinal strongyles are a major threat to horses' health and welfare. Given that strongyles inhabit the same niche as the gut microbiota, they may interact with each other. These beneficial or detrimental interactions are unknown in horses and could partly explain contrasted susceptibility to infection between individuals. To address these questions, an experimental pasture trial with 20 worm-free female Welsh ponies (10 susceptible (S) and 10 resistant (R) to parasite infection) was implemented for five months. Fecal egg counts (FEC), hematological and biochemical data, body weight and gut microbiota composition were studied in each individual after 0, 24, 43, 92 and 132 grazing days.

The predicted R ponies exhibited lower FEC after 92 and 132 grazing days, and showed higher levels of circulating monocytes and eosinophils, while S ponies developed lymphocytosis by the end of the trial. Although the overall microbiota diversity remained similar between the two groups, R and S ponies exhibited sustained differential abundances inClostridium XIVa, Ruminococcus, Acetivibrioand unclassifiedLachnospiraceaat day 0. These bacteria may hence contribute to the intrinsic pony resistance towards strongyle infection. Moreover,Paludibacter, Campylobacter, Bacillus, Pseudomonas, Clostridium III, Acetivibrio, members of the unclassifiedEubacteriaceaeandRuminococcaceaeand fungi loads were increased in infected S ponies, suggesting that strongyle and fungi may contribute to each other’s success in the ecological niche of the equine intestines. In contrast, butyrate-producing bacteria such asRuminococcus, Clostridium XIVaand members of theLachnospiraceaefamily decreased in S relative to R ponies. Additionally, these gut microbiota alterations induced changes in several immunological pathways in S ponies, including pathogen sensing, lipid metabolism, and activation of signal transduction that are critical for the regulation of immune system and energy homeostasis. These observations shed light on a putative implication of the gut microbiota in the intrinsic resistance to strongyle infection.

Overall, this longitudinal study provides a foundation to better understand the mechanisms that underpin the relationship between host susceptibility to strongyle infection, immune response and gut microbiota under natural conditions in horses and should contribute to the development of novel biomarkers of strongyle susceptibility and provide additional control options.
Hercules: a profile HMM-based hybrid error correction algorithm for long reads
Authors: Firtina Can , Bar-Joseph Ziv , Alkan Can , Cicek A. Ercument
Published: December 2017

Motivation

Choosing whether to use second or third generation sequencing platforms can lead to trade-offs between accuracy and read length. Several studies require long and accurate reads including de novo assembly, fusion and structural variation detection. In such cases researchers often combine both technologies and the more erroneous long reads are corrected using the short reads. Current approaches rely on various graph based alignment techniques and do not take the error profile of the underlying technology into account. Memory- and time-efficient machine learning algorithms that address these shortcomings have the potential to achieve better and more accurate integration of these two technologies.

Results

We designed and developed Hercules, the first machine learning-based long read error correction algorithm. The algorithm models every long read as a profile Hidden Markov Model with respect to the underlying platform’s error profile. The algorithm learns a posterior transition/emission probability distribution for each long read and uses this to correct errors in these reads. Using datasets from two DNA-seq BAC clones (CH17-157L1 and CH17-227A2), and human brain cerebellum polyA RNA-seq, we show that Hercules-corrected reads have the highest mapping rate among all competing algorithms and highest accuracy when most of the basepairs of a long read are covered with short reads.

Availability

Hercules source code is available at https://github.com/BilkentCompGen/Hercules
The impact of HIV-1 within-host evolution on transmission dynamics
Authors: Theys Kristof , Libin Pieter , Pineda-Pena Andrea-Clemencia , Nowe Ann , Vandamme Anne-Mieke , Abecasis Ana B
Published: December 2017

The adaptive potential of HIV-1 is a vital mechanism to evade host immune responses and antiviral treatment. However, high evolutionary rates during persistent infection can impair transmission efficiency and alter disease progression in the new host, resulting in a delicate trade-off between within-host virulence and between-host infectiousness. This trade-off is visible in the disparity in evolutionary rates at within-host and between-host levels, and preferential transmission of ancestral donor viruses. Understanding the impact of within-host evolution for epidemiological studies is essential for the design of preventive and therapeutic measures. Herein, we review recent theoretical and experimental work that generated new insights into the complex link between within-host evolution and between-host fitness, revealing temporal and selective processes underlying the structure and dynamics of HIV-1 transmission.
LTRs activated by Epstein-Barr virus-induced transformation of B cells alter the transcriptome
Authors: Leung Amy , Trac Candi , Kato Hiroyuki , Costello Kevin R , Natarajan Rama , Schones Dustin E
Published: December 2017

Endogenous retroviruses (ERVs) are ancient viral elements that have accumulated in the genome through retrotransposition events. Although they have lost their ability to transpose, many of the long terminal repeats (LTRs) that originally flanked full-length ERVs maintain the ability to regulate transcription. While these elements are typically repressed in somatic cells, when this repression is lost, they can function as transcriptional enhancers and promoters. The mechanisms driving LTR activation, however, are not well understood. Epstein-Barr virus (EBV), which transforms primary B cells into continuously proliferating cells, is a tumor virus associated with lymphomas. We report here that transformation of primary B cells by EBV leads to genome-wide activation of LTR enhancers and promoters. The activation of LTRs coincides with local DNA hypomethylation and binding by transcription factors such as RUNX3, EBF1, and EBNA2. The set of EBV-activated LTRs is unique to transformed B cells when compared to other cell lines known to have activated LTRs. Furthermore, we found that EBV-induced LTR activation impacts the B cell transcriptome by upregulating transcripts driven by cryptic LTR promoters. These transcripts include genes important to oncogenesis of Hodgkin lymphoma, as well as those found in other cancers such asHUWE1/HECTH9. These data suggest that the activation of LTRs by EBV may be important to the pathology of EBV-associated cancers. Altogether, our results indicate that EBV-induced transformation of B cells alters endogenous retroviral element activity, thereby impacting host gene regulatory networks and oncogenic potential.
Reanalysis of global proteomic and phosphoproteomic data identified a large number of glycopeptides
Authors: Hu Yingwei , Shah Punit , Clark David J. , Ao Minghui , Zhang Hui
Published: December 2017

Protein glycosylation plays fundamental roles in many cellular processes, and previous reports have shown dysregulation to be associated with several human diseases, including diabetes, cancer, and neurodegenerative disorders. Despite the vital role of glycosylation for proper protein function, the analysis of glycoproteins has been lagged behind to other protein modifications. In this study, we describe the re-analysis of global proteomic data from breast cancer xenograft tissues using recently developed software package GPQuest 2.0, revealing a large number of previously unidentifiedN-linked glycopeptides. More importantly, we found that using immobilized metal affinity chromatography (IMAC) technology for the enrichment of phosphopeptides had co-enriched a substantial number of sialoglycopeptides, allowing for a large-scale analysis of sialoglycopeptides in conjunction with the analysis of phosphopeptides. Collectively, combined MS/MS analyses of global proteomic and phosphoproteomic datasets resulted in the identification of 6,724 N-linked glycopeptides from 617 glycoproteins derived from two breast cancer xenograft tissues. Next, we utilized GPQuest for the re-analysis of global and phosphoproteomic data generated from 108 human breast cancer tissues that were previously analyzed by Clinical Proteomic Analysis Consortium (CPTAC). Reanalysis of the CPTAC dataset resulted in the identification of 2,683 glycopeptides from the global proteomic data set and 4,554 glycopeptides from phosphoproteomic data set, respectively. Together, 11,292 N-linked glycopeptides corresponding to 1,731 N-linked glycosites from 883 human glycoproteins were identified from the two data sets. This analysis revealed an extensive number of glycopeptides hidden in the global and enriched in IMAC-based phosphopeptide-enriched proteomic data, information which would have remained unknown from the original study otherwise. The reanalysis described herein can be readily applied to identify glycopeptides from already existing data sets, providing insight into many important facets of protein glycosylation in different biological, physiological, and pathological processes.
Genomic heritability estimates in sweet cherry reveal non-additive genetic variance is relevant for industry-prioritized traits
Authors: Piaskowski J. , Hardner Craig , Cai Lichun , Zhao Yunyang , Iezzoni Amy , Peace Cameron
Published: December 2017

Background

Sweet cherry is consumed widely across the world and provides substantial economic benefits in regions where it is grown. While cherry breeding has been conducted in the Pacific Northwest for over half a century, little is known about the genetic architecture of important traits. We used a genome-enabled mixed model to predict the genetic performance of 505 individuals for 32 phenological, disease response and fruit quality traits evaluated in the RosBREED sweet cherry crop data set. Genome-wide predictions were estimated using a repeated measures model for phenotypic data across 3 years, incorporating additive, dominance and epistatic variance components. Genomic relationship matrices were constructed with high-density SNP data and were used to estimate relatedness and account for incomplete replication across years.

Results

High broad-sense heritabilities of 0.83, 0.77, and 0.75 were observed for days to maturity, firmness, and fruit weight, respectively. Epistatic variance exceeded 40% of the total genetic variance for maturing timing, firmness and powdery mildew response. Dominance variance was the largest for fruit weight and fruit size at 34% and 27%, respectively. Omission of non-additive sources of genetic variance from the genetic mode resulted in inflation of narrow-sense heritability but minimally influenced prediction accuracy of genetic values in validation. Predicted genetic rankings of individuals from single-year models were inconsistent across years, likely due to incomplete sampling of the population genetic variance.

Conclusions

Predicted breeding values and genetic values a measure revealed many high-performing individuals for use as parents and the most promising selections to advance for cultivar release consideration, respectively. This study highlights the importance of using the appropriate genetic model for calculating breeding values to avoid inflation of expected parental contribution to genetic gain. The genomic predictions obtained will enable breeders to efficiently leverage the genetic potential of North American sweet cherry germplasm by identifying high quality individuals more rapidly than with phenotypic data alone.
Medaka population genome structure and demographic history described via genotyping-by-sequencing
Authors: Katsumura Takafumi , Oda Shoji , Hiroshi Mitani , Oota Hiroki
Published: December 2017

Medaka is a model organism in medicine, genetics, developmental biology and population genetics. Lab stocks composed of more than 100 local wild populations are available for research in these fields. Thus, medaka represents a potentially excellent bioresource for screening disease-risk- and adaptation-related genes in genome-wide association studies. Although the genetic population structure should be known before performing such an analysis, a comprehensive study on the genome-wide diversity of wild medaka populations has not been performed. Here, we performed genotyping-by-sequencing (GBS) for 81 and 12 medakas captured from a bioresource and the wild, respectively. Based on the GBS data, we evaluated the genetic population structure and estimated the demographic parameters using an approximate Bayesian computation (ABC) framework. The autosomal data confirmed that there were substantial differences between local populations and supported our previously proposed hypothesis on medaka dispersal based on mitochondrial genome (mtDNA) data. A new finding was that a local group that was thought to be a hybrid between the northern and the southern Japanese groups was actually a sister group of the northern Japanese group. Thus, this paper presents the first population-genomic study of medaka and reveals its population structure and history based on autosomal diversity.
Archaeal community structure and underlying ecological processes in swine manure slurry
Authors: Kumari Priyanka , Choi Hong L.
Published: December 2017

The ecological processes underlying the observed patterns in community composition of archaea in swine manure slurry are poorly understood. We studied the archaeal communities from six swine manure slurry storage tanks using paired-end Illumina sequencing of the v3 hypervariable region of 16S rRNA gene. Across all samples, the archaeal community was dominated by methanogens related toThermoplasmata, Methanomicrobia, andMethanobacteriaclasses. At the genus level, the archaeal community was dominated by a single uncultured lineage of archaea,vadinCA11, followed by methanogenic generaMethanobrevibacter,Methanosarcina,Methanosphaera,Methanogenium,Methanocorpusculum,Methanoculleus, andMethanomicrococcus. Significant phylogenetic signals were detected across relatively short phylogenetic distances, indicating that closely related archaeal operational taxonomic units (OTUs) tend to have similar niches. The standardized effect sizes of mean nearest taxon distance (SES.MNTD) showed that archaeal community was phylogenetically clustered, suggesting that environmental filtering deterministically influence the within-community composition of archaea. However, between-community analysis based onβ-nearest taxon index (βNTI) revealed that both deterministic selection and stochastic processes operate simultaneously to govern the assembly of archaeal communities. These findings significantly enhance our understanding of archaeal community assembly and underlying ecological processes is swine manure slurry.
The assessment of fishery status depends on the condition of fish habitats
Authors: Brown Christopher J. , Broadley Andrew , Adame Fernanda , Branch Trevor A. , Turschwell Mischa , Connolly Rod M.
Published: December 2017

At the crux of the debate over the global sustainability of fisheries is what society must do prevent overexploitation of fisheries and aid recovery of fisheries that have historically been overexploited. The focus of debates has been on controlling fishing pressure and assessments have not considered that stock production may be affected by changes in fish habitat. Fish habitats are being modified by climate change, built infrastructure, destructive fishing practices and pollution. We conceptualise how the classification of stock status can be biased by habitat change. Habitat loss can result in either overly optimistic or overly conservative assessment of stock status. The classification of stock status depends on how habitat affects fish demography and what reference points management uses to assess status. Nearly half of the 418 stocks in a global stock assessment database use seagrass, mangroves, coral reefs and macroalgae, habitats that have well documented trends. There is also considerable circumstantial evidence that habitat change has contributed to overexploitation or enhanced production of data-poor fisheries, like inland and subsistence fisheries. Globally many habitats are in decline, so the role of habitat should be considered when assessing the global status of fisheries. New methods and global databases of habitat trends, and use of habitats by fishery species are required to properly attribute the causes of decline in fisheries, and are likely to raise the profile of habitat protection as an important complementary aim for fisheries management.