bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Autologous Human Bone Marrow-Derived Mesenchymal Stem Cells in Distraction Osteogenesis for the Treatment of Bilateral Mandibular Hypoplasia
Authors: Lim Hun Jun , Lee Eui Mook , Kim Won Ki , Kim Han Jong , Kim Bong Chul , Lee Jun
Published: May 2018

Distraction osteogenesis a surgical procedure conducted to improve craniofacial deformities. Compared with conventional operations, this technique has advantages such as the ability to lengthen the soft tissue and hard tissue. Therefore, this method is used to treat severe craniofacial abnormalities.

The major disadvantage of distraction osteogenesis is the long treatment period. If the consolidation period is not sufficiently long after the distraction period, complications such as discontinuity or contraction of newly formed bone may occur. Recently, many researchers have attempted to develop methods for enhancing the ossification of newly formed bone, reducing shrinkage, and shortening the overall treatment period.

The authors injected autologous bone marrow-derived mesenchymal stem cells during the consolidation phase after distraction osteogenesis surgery in a bilateral mandibular hypoplasia patient. Here, the authors report the treatment results, which were found to be favorable.
Face Transplantation: An Update for the United States Trauma System
Authors: Farber Scott J. , Kantar Rami S. , Diaz-Siso J. Rodrigo , Rodriguez Eduardo D.
Published: May 2018

Face transplantation has evolved over the last 12 years into a safe and feasible reconstructive solution, with good aesthetic and functional outcomes for patients with severe facial defects who are not amenable to reconstruction through conventional and autologous approaches. Among patients who underwent face transplantation to date, a significant proportion did so following trauma, mostly ballistic and thermal injuries. It is therefore important for trauma surgeons who deal with these injuries regularly to be familiar with the literature on face transplantation following traumatic injuries. In this study, we provide a focused review on this topic, with an emphasis on highlighting the limitations of conventional craniomaxillofacial reconstruction, while emphasizing data available on the risks, benefits, surgical indications, contraindications, as well as aesthetic and functional outcomes of face transplantation. The authors also provide an update on all face transplants performed to date including traumatic mechanisms of injury, and extent of defects. They finally describe 2 cases performed by the senior author for patients presenting with devastating facial ballistic and thermal injuries. The authors hope that this work serves as an update for the trauma surgery community regarding the current role and limitations of face transplantation as a craniomaxillofacial reconstructive option for their patient population. This can potentially expedite the reconstructive process for patients who may benefit from face transplantation.
Facial Paralysis in Patients With Hemifacial Microsomia: Frequency, Distribution, and Association With Other OMENS Abnormalities
Authors: Li Qiang , Zhou Xu , Wang Yue , Qian Jin , Zhang Qingguo
Published: May 2018

Although facial paralysis is a fundamental feature of hemifacial microsomia, the frequency and distribution of nerve abnormalities in patients with hemifacial microsomia remain unclear. In this study, the authors classified 1125 cases with microtia (including 339 patients with hemifacial microsomia and 786 with isolated microtia) according to Orbital Distortion Mandibular Hypoplasia Ear Anomaly Nerve Involvement Soft Tissue Dependency (OMENS) scheme. Then, the authors performed an independent analysis to describe the distribution feature of nerve abnormalities and reveal the possible relationships between facial paralysis and the other 4 fundamental features in the OMENS system. Results revealed that facial paralysis is present 23.9% of patients with hemifacial microsomia. The frontal–temporal branch is the most vulnerable branch in the total 1125 cases with microtia. The occurrence of facial paralysis is positively correlated with mandibular hypoplasia and soft tissue deficiency both in the total 1125 cases and the hemifacial microsomia patients. Orbital asymmetry is related to facial paralysis only in the total microtia cases, and ear deformity is related to facial paralysis only in hemifacial microsomia patients. No significant association was found between the severity of facial paralysis and any of the other 4 OMENS anomalies. These data suggest that the occurrence of facial paralysis may be associated with other OMENS abnormalities. The presence of serious mandibular hypoplasia or soft tissue deficiency should alert the clinician to a high possibility but not a high severity of facial paralysis.
Combined Access for the Treatment of Medial Orbital Wall Fracture: Subciliary and Upper Eyelid Sulcus Incisions
Authors: de Moraes Mariana Alcantara Rodrigues , Rocha Biló João Pedro , Pereira Max Domingues
Published: May 2018

The present study presents a new surgical approach to treat medial orbital wall fractures, that is, the combined transcutaneous access through subciliary and upper eyelid sulcus incisions. The study performed the retrospective analysis of medical records belonging to 14 consecutive patients with medial orbital wall fracture, who were treated in the Plastic Surgery Division at Federal University of São Paulo, from 2005 to 2013, through the combination of subciliary and upper eyelid sulcus incisions to access the fracture foci. The mean age of the patients was 35.4 years, ranging from 8 to 66 years. Seven out of the 14 patients were women. Ten patients had fractures in the medial and inferior walls, whereas 4 patients had isolated medial wall fracture. Diplopia was found in all cases. Six patients had some type of extraocular muscle limitation. A computed tomography of the face was performed in the postoperative period to assess the orbital contour and the correct position of the grafts, whenever applicable. The patients were assessed for diplopia, enophthalmos, and scar quality. Four patients (28.6%) kept on showing diplopia at supraversion, whereas 2 patients (14.2%) evolved to enophthalmos. There was no need of reoperating the patients to reposition the grafts or the absorbable plaque. No patient evolved to ectropion or apparent scarring. The combined transcutaneous access through subciliary and upper eyelid sulcus incisions provides ample operative field, rapid exposure of the fracture foci, and adequate wall reconstruction. It can also present inconspicuous scar.
Use of Emergency Manuals During Actual Critical Events in China: A Multi-Institutional Study
Authors: Huang Jeffrey , Wu Jiayan , Dai Christina , Zhang Xianwei , Ju Hui , Chen Yiqi , Zhang Chunyuan , Ye Fan , Tan Yi , Zong Yongbo , Liu Telong
Published: May 2018

Introduction

Emergency manuals (EMs) can help healthcare providers respond to crises more efficiently. Three anesthesia EMs have been translated into Chinese. These EMs have been made publicly available as a free document downloadable in China. A year after these Chinese versions of EMs were published, we conducted a multi-institutional survey in China to assess the progress of how well EM had been adapted and used in the setting of critical events.

Methods

Our study used a multi-institutional, anonymous electronic survey. We included hospitals that had conducted group studies of EMs as well as simulation trainings. The survey consisted of the five-point Likert scale, yes or no boxes, and multiple-choice questions with five possible choices. Statistical analysis included Pearson correlation coefficient and χ2 test.

Results

Nine hospitals were included in the study. The overall response rate was 56.4%. More than 70% of all respondents reported using an EM during at least one critical event within the past 6 months in China. A total of 87.7% of all respondents self-reviewed or group studied EMs. A total of 69% participated in multidisciplinary simulation training. Emergency manual use during a critical event showed a positive correlation with multidisciplinary simulation training (R
2 = 0.896) and self-review/group study (R
2 = 0.5234). The average self-reported use of EMs during clinical critical events is twice per anesthesiologist.

Conclusions

This study demonstrated the nascent success of EM implementation in multiple Chinese institutions. Simulation training enhances the implementation and clinical usage of EM. Simulation training in an operating room was sufficient to learn how to use EM.
A Method for Functional Task Alignment Analysis of an Arthrocentesis Simulator
Authors: Adams Reid A. , Gilbert Gregory E. , Buckley Lisa A. , Nino Fong Rodolfo , Fuentealba I. Carmen , Little Erika L.
Published: May 2018

Introduction

During simulation-based education, simulators are subjected to procedures composed of a variety of tasks and processes. Simulators should functionally represent a patient in response to the physical action of these tasks. The aim of this work was to describe a method for determining whether a simulator does or does not have sufficient functional task alignment (FTA) to be used in a simulation.

Methods

Potential performance checklist items were gathered from published arthrocentesis guidelines and aggregated into a performance checklist using Lawshe's method. An expert panel used this performance checklist and an FTA analysis questionnaire to evaluate a simulator's ability to respond to the physical actions required by the performance checklist.

Results

Thirteen items, from a pool of 39, were included on the performance checklist. Experts had mixed reviews of the simulator's FTA and its suitability for use in simulation. Unexpectedly, some positive FTA was found for several tasks where the simulator lacked functionality.

Conclusions

By developing a detailed list of specific tasks required to complete a clinical procedure, and surveying experts on the simulator's response to those actions, educators can gain insight into the simulator's clinical accuracy and suitability. Unexpected of positive FTA ratings of function deficits suggest that further revision of the survey method is required.
High-Value, Cost-Conscious Communication Skills in Undergraduate Medical Education
Authors: Natt Neena , Starr Stephanie R. , Reed Darcy A. , Park Yoon Soo , Dyrbye Liselotte N. , Leep Hunderfund Andrea N.
Published: May 2018

Introduction

Training in high-value, cost-conscious care (HVCCC) is increasingly being incorporated into medical school curricula, but students may have limited opportunities to engage patients in HVCCC conversations. The aim of this study was to develop two standardized patient scenarios with associated checklists, hypothesizing that resulting scores would allow for valid formative assessments of HVCCC communication skills.

Methods

Scenarios were designed to generate a less-is-more conversation (in response to a patient requesting an unnecessary test) and a shared decision-making conversation (in response to a patient choosing between multiple effective treatment options). Checklists were developed by experts and informed by the existing literature. Validity evidence was collected from content, response process, internal structure, relations to other variables, and consequences of testing.

Results

Ninety-three third-year medical students participated during 2014–2015. Mean checklist scores were 79% (SD = 18, Cronbach α = 0.72) and 72% (SD = 13, Cronbach α = 0.62) for the less-is-more and shared decision-making scenarios, respectively. Checklist scores correlated with global ratings of performance (r = 0.65 and 0.54, respectively, both P < 0.001), and overall interrater reliability was good (r = 0.66). Checklist scores discriminated between higher and lower performers (discrimination indices of 0.84 and 0.65, respectively, both P < 0.001). Most students (83/90, 92%) agreed that the session improved their HVCCC communication skills.

Conclusions

This study provides validity evidence supporting the use of scores derived from two standardized patient scenarios for formative assessment of HVCCC communication skills among third-year medical students. These scenarios can help equip students with practical, patient-centered strategies for promoting value in clinical encounters.
Comparing Short-term and Oncologic Outcomes of Minimally Invasive Versus Open Pancreaticoduodenectomy Across Low and High Volume Centers
Authors: Torphy Robert J. , Friedman Chloe , Halpern Alison , Chapman Brandon C. , Ahrendt Steven S. , McCarter Martin M. , Edil Barish H. , Schulick Richard D. , Gleisner Ana
Published: May 2018

Objective:

To compare short-term and oncologic outcomes of patients with cancer who underwent open pancreaticoduodenectomy (OPD) versus minimally invasive pancreaticoduodenectomy (MIPD) using the National Cancer Database.

Summary Background Data:

MIPD, including laparoscopic and robotic approaches, has continued to gain acceptance despite prior reports of increased short-term mortality when compared with OPD.

Methods:

Patients with pancreatic cancer diagnosed from 2010 to 2015 undergoing curative intent resection were selected from the National Cancer Database. Patients submitted to OPD were compared with those submitted to MIPD. Laparoscopic and robotic approaches were included in the MIPD cohort. The primary outcome was 90-day mortality; secondary outcomes included 30-day mortality, hospital length of stay, unplanned 30-day readmission, surgical margins, number of lymph nodes harvested, and receipt of adjuvant chemotherapy. Propensity score-weighted random effects logistic regression models were used to examine the adjusted association between surgical approach and the specified outcomes.

Results:

Between 2010 and 2015, 22,013 patients underwent OPD or MIPD for pancreatic cancer and 3754 (17.1%) were performed minimally invasively. On multivariable analysis, there was no difference in 90-day mortality between MIPD and OPD (OR, 0.92; 95% CI, 0.75–1.14). Patients undergoing MIPD were less likely to stay in the hospital for a prolonged time (OR, 0.75; 95% CI, 0.68–0.82). 30-day mortality, unplanned readmissions, margins, lymph nodes harvested, and receipt of adjuvant chemotherapy were equivalent between groups. Regardless of surgical approach, patients operated on at high volume centers had reduced 90-day mortality.

Conclusion:

Patients selected to receive MIPD for cancer have equivalent short-term and oncologic outcomes, when compared with patients who undergo OPD.
Memantine ER Maintains Patient Response in Moderate to Severe Alzheimer’s Disease
Authors: Grossberg George T. , Alva Gustavo , Hendrix Suzanne , Ellison Noel , Kane Mary C. , Edwards John
Published: May 2018

Memantine extended release (ER) significantly outperformed placebo on co-primary endpoints of Clinician’s Interview-based Impression of Change Plus Caregiver Input (CIBIC-Plus) and baseline to endpoint changes on the Severe Impairment Battery (SIB) in a 24-week, randomized trial (NCT00322153) in patients with moderate to severe Alzheimer’s disease taking a cholinesterase inhibitor (ChEI). A post hoc analysis compared patients receiving memantine ER/ChEI to placebo/ChEI for time to onset of response and if the response was maintained (achieving improvement at weeks 8, 12, or 18 and maintaining through endpoint/week 24) on the SIB, the Neuropsychiatric Inventory (NPI), CIBIC-Plus, and Activities of Daily Living (ADL) using Fisher exact test. A second post hoc analysis compared percentages of patients for all possible combinations of 2 to 4 assessments with either no decline or clinically notable response using Wald χ2. Significantly greater percentages of memantine ER/ChEI patients achieved an early response that was maintained on SIB, NPI, and CIBIC-Plus (P<0.05) versus placebo/ChEI. Significantly greater percentages of memantine ER/ChEI-treated patients achieved and maintained a clinically notable response on ADL/NPI, SIB/ADL/NPI, and SIB/ADL/CIBIC-Plus, compared with placebo/ChEI (P<0.05). Memantine ER results in early, maintained improvement in patients with moderate to severe Alzheimer’s disease concurrently taking ChEIs, compared with cholinesterase treatment alone.
A case of NDM-carbapenemase-producing hypervirulent Klebsiella pneumoniae sequence type 23 from the UK
Authors: Roulston Kerry J. , Bharucha Tehmina , Turton Jane F. , Hopkins Katie L. , Mack Damien J. F.
Published: May 2018

Introduction. Hypervirulent capsular type K1 Klebsiella pneumoniae strains of clonal complex 23 (CC23) are associated with severe community-acquired pyogenic liver abscesses, often complicated by metastatic infections and significant mortality. The majority of hypervirulent strains reported are susceptible to most antibiotics except ampicillin. To the best of our knowledge, this is the first case of New Delhi metallo-β-lactamase (bla
NDM)-producing hypervirulent K. pneumoniae from the UK.

Case presentation. We present a case of pyogenic liver abscess in a 63-year-old female of Bangladeshi origin, with a recent diagnosis of pancreatic cancer. The patient was treated with piperacillin/tazobactam and blood cultures grew a fully susceptible Escherichia coli. Despite antimicrobial therapy and drainage of the abscess, the patient continued to deteriorate and died on day seven of admission. The fluid drained from the liver abscess grew a fully susceptible E. coli and a multi-drug-resistant K. pneumoniae. Two weeks prior to admission, a rectal screening swab grew a metallo-β-lactamase-producing K. pneumoniae. Molecular characterization revealed that both the K. pneumoniae isolates belonged to the hypervirulent K1 cluster of CC23, sequence type 23. The isolate from the rectal screen was positive for the bla
NDM metallo-β-lactamase gene.

Conclusion. The emergence of carbapenemase-producing hypervirulent K. pneumoniae strains presents a new and significant threat to global public health. Management of these infections will be extremely challenging due to the limited treatment options available and they are likely to be associated with an even greater mortality.
Repression of divergent noncoding transcription by a sequence-specific transcription factor
Authors: Wu Andrew CK , Patel Harshil , Chia Minghao , Moretto Fabien , Frith David , Snijders Ambrosius P. , van Werven Folkert
Published: May 2018

Many active eukaryotic gene promoters exhibit divergent noncoding transcription, but the mechanisms restricting expression of these transcripts are not well understood. Here we demonstrate how a sequence-specific transcription factor represses divergent noncoding transcription at highly expressed genes in yeast. We find that depletion of the transcription factor Rap1 induces noncoding transcription in a large fraction of Rap1 regulated gene promoters. Specifically, Rap1 prevents transcription initiation at cryptic promoters near its binding sites, which is uncoupled from transcription regulation in the protein-coding direction. We further provide evidence that Rap1 acts independently of chromatin-based mechanisms to repress cryptic or divergent transcription. Finally, we show that divergent transcription in the absence of Rap1 is elicited by the RSC chromatin remodeller. We propose that a sequence-specific transcription factor limits access of basal transcription machinery to regulatory elements and adjacent sequences that act as divergent cryptic promoters, thereby providing directionality towards productive transcription.
Simultaneous in vivo time-lapse stiffness mapping and fluorescence imaging of developing tissue
Authors: Thompson Amelia J. , Pillai Iva K. , Dimov Ivan B. , Holt Christine E. , Franze Kristian
Published: May 2018

Tissue mechanics is important for development; however, the spatio-temporal dynamics of in vivo tissue stiffness is still poorly understood. We here developed tiv-AFM, combining time-lapse in vivo atomic force microscopy with upright fluorescence imaging of embryonic tissue, to show that in the developing Xenopus brain, a stiffness gradient evolves over time because of differential cell proliferation. Subsequently, axons turn to follow this gradient, underpinning the importance of time-resolved mechanics measurements.
Re-assembly, quality evaluation, and annotation of 678 microbial eukaryotic reference transcriptomes
Authors: Johnson Lisa K. , Alexander Harriet , Brown C. Titus
Published: May 2018

Background

De novo transcriptome assemblies are required prior to analyzing RNAseq data from a species without an existing reference genome or transcriptome. Despite the prevalence of transcriptomic studies, the effects of using different workflows, or “pipelines”, on the resulting assemblies are poorly understood. Here, a pipeline was programmatically automated and used to assemble and annotate raw transcriptomic short read data collected by the Marine Microbial Eukaryotic Transcriptome Sequencing Project (MMETSP). The resulting transcriptome assemblies were evaluated and compared against assemblies that were previously generated with a different pipeline developed by the National Center for Genome Research (NCGR).

Results

New transcriptome assemblies contained the majority of previous contigs as well as new content. On average, 7.8% of the annotated contigs in the new assemblies were novel gene names not found in the previous assemblies. Taxonomic trends were observed in the assembly metrics, with assemblies from the Dinoflagellata and Ciliophora phyla showing a higher percentage of open reading frames and number of contigs than transcriptomes from other phyla.

Conclusions

Given current bioinformatics approaches, there is no single ‘best’ reference transcriptome for a particular set of raw data. As the optimum transcriptome is a moving target, improving (or not) with new tools and approaches, automated and programmable pipelines are invaluable for managing the computationally-intensive tasks required for re-processing large sets of samples with revised pipelines and ensuring a common evaluation workflow is applied to all samples. Thus, re-assembling existing data with new tools using automated and programmable pipelines may yield more accurate identification of taxon-specific trends across samples in addition to novel and useful products for the community.

Key Points

Re-assembly with new tools can yield new results

Automated and programmable pipelines can be used to process arbitrarily many samples.

Analyzing many samples using a common pipeline identifies taxon-specific trends.
Convolutional Neural Network-Based Instance Segmentation Algorithm to Acquire Quantitative Criteria of Early Mouse Development
Authors: Tokuoka Yuta , Yamada Takahiro G , Hiroi Noriko F , Kobayashi Tetsuya J , Yamagata Kazuo , Funahashi Akira
Published: May 2018

In embryology, image processing methods such as segmentation are applied to acquiring quantitative criteria from time-series three-dimensional microscopic images. When used to segment cells or intracellular organelles, several current deep learning techniques outperform traditional image processing algorithms. However, segmentation algorithms still have unsolved problems, especially in bioimage processing. The most critical issue is that the existing deep learning-based algorithms for bioimages can perform only semantic segmentation, which distinguishes whether a pixel is within an object (for example, nucleus) or not. In this study, we implemented a novel segmentation algorithm, based on deep learning, which segments each nucleus and adds different labels to the detected objects. This segmentation algorithm is called instance segmentation. Our instance segmentation algorithm, implemented as a neural network, which we named QCA Net, substantially outperformed 3D U-Net, which is the best semantic segmentation algorithm that uses deep learning. Using QCA Net, we quantified the nuclear number, volume, surface area, and center of gravity coordinates during the development of mouse embryos. In particular, QCA Net distinguished nuclei of embryonic cells from those of polar bodies formed in meiosis. We consider that QCA Net can greatly contribute to bioimage segmentation in embryology by generating quantitative criteria from segmented images.
Microscopy quantification of microbial birth and death dynamics
Authors: Hart Samuel F. M. , Skelding David , Waite Adam J. , Burton Justin , Xie Li , Shou Wenying
Published: May 2018

Microbes live in dynamic environments where nutrient concentrations fluctuate. Quantifying fitness (birth and death) in a wide range of environments is critical for understanding microbial evolution as well as ecological interactions where one species alters the fitness of another. Here, using high-throughput time-lapse microscopy, we have quantified howSaccharomyces cerevisiaemutants incapable of synthesizing an essential metabolite grow or die in various concentrations of the required metabolite. We establish that cells normally expressing fluorescent proteins lose fluorescence upon death and that the total fluorescence in an imaging frame is proportional to the number of live cells even when cells form multiple layers. We validate our microscopy approach of measuring birth and death rates using flow cytometry, cell counting, and chemostat culturing. For lysine-requiring cells, very low concentrations of lysine are not detectably consumed and do not support cell birth, but delay the onset of death phase and reduce the death rate. In contrast, in low hypoxanthine, hypoxanthine-requiring cells can produce new cells, yet also die faster than in the absence of hypoxanthine. For both strains, birth rates under various metabolite concentrations are better described by the sigmoidal-shaped Moser model than the well-known Monod model, while death rates depend on the metabolite concentration and can vary with time. Our work reveals how time-lapse microscopy can be used to discover non-intuitive microbial dynamics and to quantify growth rates in many environments.
Cellular Crowding Influences Extrusion and Proliferation to Facilitate Epithelial Tissue Repair
Authors: Franco Jovany , Atieh Youmna , Bryan Chase D. , Kwan Kristen M. , Eisenhoffer George T.
Published: May 2018

Epithelial wound healing requires a complex orchestration of cellular rearrangements and movements to restore tissue architecture and function after injury. While it is well-known that mechanical forces can affect tissue morphogenesis and patterning, how the biophysical cues generated after injury influence cellular behaviors during tissue repair is not well understood. Using time-lapsed confocal imaging of epithelial tissues in living zebrafish larvae, we provide evidence that localized increases in cellular crowding during wound closure promote the extrusion of non-apoptotic cells via mechanically regulated stretch-activated ion channels (SACs). Directed cell migration toward the injury site promoted the rapid changes in cell number and generated shifts in tension at cellular interfaces over long spatial distances. Perturbation of SAC activity resulted in failed extrusion and increased proliferation in crowded areas of the tissue. Together, we conclude that localized cell number plays a key role in dictating cellular behaviors that facilitate wound closure and tissue repair.
Archaeal, bacterial, and eukaryal microbial community structure of sediment and seawater in a coastal region near Puerto Nuevo, Baja California
Authors: Ul-Hasan Sabah , Bowers Robert M. , Figueroa-Montiel Andrea , Licea-Navarro Alexei F. , Beman J. Michael , Woyke Tanja , Nobile Clarissa J.
Published: May 2018

Microbial communities control numerous biogeochemical processes critical for ecosystem function and health, particularly in coastal ecosystems. However, comparatively little is known about microbial community structure in coastal regions, such that basic patterns of microbial biodiversity, such as species richness and community composition, are generally understudied. To better understand the global patterns of microbial biodiversity in coastal ecosystems, we characterized sediment and seawater microbial communities for three sites near Puerto Nuevo (Baja California, Mexico) using 16S and 18S rRNA gene amplicon sequencing methods. We found that sediment bacteria, archaea, and eukaryote microbial communities contained approximately 5 × 10^2 fold greater operational taxonomic units (OTUs) than their seawater-based counterparts (p < 0.001). Further, distinct bacterial, archaeal and eukaryal phyla were found in sediment and seawater samples. The phyla Acidobacteria, Chlorobi, and Chloroflexi were found to be abundant and unique to the sediment and Cyanobacteria, Spirochaetae, and Woesearchaeota to the seawater environment. Apicomplexa and Arthropoda were abundant eukaryal phyla found uniquely in the sediment whereas the Cryptomonadales and Protalveolata were detected only in the seawater. Furthermore, bacterial and archaeal communities were statistically different by site (p < 0.05) in both seawater and sediment samples for the Major Outlet site, the site closest to a residential area. In contrast, eukaryal microbial communities were only different among sites in the seawater samples. Overall, these results suggest that our understanding of coastal microbial biodiversity patterns require spatially robust sampling. This study contributes to a growing body of foundational microbial biodiversity and ecology knowledge, providing context to the global change that is induced by urban development.
Consistent and reproducible long-termin vitrogrowth of health and disease-associated oral subgingival biofilms
Authors: Velsko Irina M. , Shaddox Luciana M.
Published: May 2018

Background: Severalin vitrooral biofilm growth systems can reliably construct oral microbiome communities in culture, yet their stability and reproducibility through time has not been well characterized. Long-termin vitrogrowth of natural biofilms would enable use of these biofilms in bothin vitroandin vivostudies that require complex microbial communities with minimal variation over a period of time. Understanding biofilm community dynamics in continuous culture, and whether they maintain distinct signatures of health and disease, is necessary to determine the reliability and applicability of such models to broader studies. To this end, we performed next-generation sequencing on biofilms grown from healthy and disease-site subgingival plaque for 80 days to assess stability and reliability of continuous oral biofilm growth.

Results: Biofilms were grown from subgingival plaque collected from periodontitis-affected sites and healthy individuals for ten eight-day long generations, using hydroxyapatite disks. The bacterial community in each generation was determined using Human Oral Microbe Identification by Next-Generation Sequencing (HOMINGS) technology, and analyzed in QIIME. Profiles were steady through the ten generations, as determined by species abundance and prevalence, Spearman’s correlation coefficient, and Faith’s phylogenetic distance, with slight variation predominantly in low abundance species. Community profiles were distinct between healthy and disease site-derived biofilms as demonstrated by weighted UniFrac distance throughout the ten generations. Differentially abundant species between healthy and disease site-derived biofilms were consistent throughout the generations.

Conclusions: Healthy and disease site-derived biofilms can reliably maintain consistent communities through ten generations ofin vitrogrowth. These communities maintain signatures of health and disease and of individual donors despite culture in identical environments. This subgingival oral biofilm growth and perpetuation model may prove useful to studies involving oral infection or cell stimulation, or those measuring microbial interactions, which require the same biofilms over a period of time.
Full Bayesian Comparative Phylogeography from Genomic Data
Authors: Oaks Jamie R.
Published: May 2018

A challenge to understanding biological diversification is accounting for community-scale processes that cause multiple, co-distributed lineages to co-speciate. Such processes predict non-independent, temporally clustered divergences across taxa. Approximate-likelihood Bayesian computation (ABC) approaches to inferring such patterns from comparative genetic data are very sensitive to prior assumptions and often biased toward estimating shared divergences. We introduce a full-likelihood Bayesian approach,ecoevolity, which takes full advantage of information in genomic data. By analytically integrating over gene trees, we are able to directly calculate the likelihood of the population history from genomic data, and efficiently sample the model-averaged posterior via Markov chain Monte Carlo algorithms. Using simulations, we find that the new method is much more accurate and precise at estimating the number and timing of divergence events across pairs of populations than existing approximate-likelihood methods. Our full Bayesian approach also requires several orders of magnitude less computational time than existing ABC approaches. We find that despite assuming unlinked characters (e.g., unlinked single-nucleotide polymorphisms), the new method performs better if this assumption is violated in order to retain the constant characters of whole linked loci. In fact, retaining constant characters allows the new method to robustly estimate the correct number of divergence events with high posterior probability in the face of character-acquisition biases, which commonly plague loci assembled from reduced-representation genomic libraries. We apply our method to genomic data from four pairs of insular populations ofGekkolizards from the Philippines that arenotexpected to have co-diverged. Despite all four pairs diverging very recently, our method strongly supports that they diverged independently, and these results are robust to very disparate prior assumptions.
Common Neural Code for Reward and Information Value
Authors: Kobayashi Kenji , Hsu Ming
Published: May 2018

Adaptive acquisition of information is critical for goal-directed behavior. Popular theories posit that information acquisition is driven by intrinsic motives (curiosity or exploration bonus) and mediated by valuation system. However, they are insufficient when agents need to evaluate instrumental benefit of new information in a forward-looking manner. We tested whether human brain computes value of information (VOI) on a scale common with more basic rewards to acquire information. In an fMRI task, subjects purchased information for choices on monetary lotteries. Behaviorally, subjective VOI was largely driven by instrumental benefit, as normatively predicted, but additionally affected by non-instrumental motive, particularly the utility of anticipation. Neurally, VOI was represented in striatum, ventromedial prefrontal cortex, and dorsolateral prefrontal cortex. Cross-categorical decoding revealed that these regions use a common scale for VOI and another type of value, expected utility of the lotteries. These provide new insight on neurocognitive mechanism of forward-looking, value-based information acquisition.
Exceptional Solvent Tolerance inYarrowia lipolyticaIs Enhanced by Sterols
Authors: Walker Caleb , Ryu Seunghyun , Trinh Cong T.
Published: May 2018

Microbial biocatalysis in organic solvents such as ionic liquids (ILs) is attractive for making fuels and chemicals from complex substrates including lignocellulosic biomass. However, low IL concentrations of 0.5-1.0 % (v/v) can drastically inhibit microbial activity. In this study, we engineered an exceptionally robust oleaginous yeastYarrowia lipolytica, YlCW001, by adaptive laboratory evolution (ALE). The mutant YlWC001 shows robust growth in up to 18% (v/v) 1-ethyl-3-methylimidazolium acetate ([EMIM][OAc]), which makes it the most IL-tolerant microorganism published to our knowledge. Remarkably, YlCW001 exhibits broad tolerance in most commonly used hydrophilic ILs beyond [EMIM][OAc]. Scanning electron microscopy revealed that ILs significantly damage cell wall and/or membrane of wildtypeY. lipolyticawith observed cavities, dents, and wrinkles while YlCW001 maintains healthy morphology even in high concentrations of ILs up to 18% (v/v). By performing comprehensive metabolomics, lipidomics, and transcriptomics to elucidate this unique phenotype, we discovered that both wildtypeY. lipolyticaand YlCW001 reconfigured membrane composition (e.g., glycerophospholipids and sterols) and cell wall structure (e.g., chitin) under IL-stressful environments. By probing the steroid pathway at transcriptomic, enzymatic, and metabolic levels, we validated that sterols (i.e., ergosterol) are a key component of the cell membrane that enablesY. lipolyticato resist IL-responsive membrane damage and hence tolerate high IL concentrations. This study provides a better understanding of exceptional robustness ofY. lipolyticathat can be potentially harnessed as a microbial manufacturing platform for production of fuels and chemicals in organic solvents.
Multi-scale coordination of planar cell polarity in planarians
Authors: Vu Hanh Thi-Kim , Mansour Sarah , Kücken Michael , Blasse Corinna , Basquin Cyril , Azimzadeh Juliette , Myers Eugene Wimberly , Brusch Lutz , Rink Jochen Christian
Published: May 2018

Polarity is a universal design principle of biological systems that manifests at all organizational scales. Although well understood at the cellular level, the mechanisms that coordinate polarity at the tissue or organismal scale remain poorly understood. Here, we make use of the extreme body plan plasticity of planarian flatworms to probe the multi-scale coordination of polarity. Quantitative analysis of ciliary rootlet orientation in the epidermis reveals a global polarization field with head and tail as independent mediators of anteroposterior (A/P) polarization and the body margin influencing mediolateral (M/L) polarization. Mathematical modeling demonstrates that superposition of separate A/P- and M/L-fields can explain the global polarity field and we identify the core planar cell polarity (PCP) and Ft/Ds pathways as their specific mediators. Overall, our study establishes a mechanistic framework for the multi-scale coordination of planar polarity in planarians and establishes the core PCP and Ft/Ds pathways as evolutionarily conserved 2D-polarization module.
Reliable and automatic epilepsy classification with affordable, consumer-grade electroencephalography in rural sub-Saharan Africa
Authors: van Hees Vincent T. , van Diessen Eric , Sinke Michel R.T. , Buitenhuis Jan W. , van der Maas Frank , Ridder Lars , Otte Willem M.
Published: May 2018

Epilepsy is largely under-diagnosed in low-income and middle-income countries, due to lack of medical specialists and expensive electroencephalography (EEG) hardware. In this study we investigate if low-cost consumer-grade EEG in combination with machine learning techniques can offer a reliable screening tool to improve diagnosis rates.

We acquired brain signals in people with epilepsy (N=163) and healthy controls (N=138) in two difficult-to-reach areas in rural Guinea-Bissau and Nigeria. Five minutes of fourteen channel resting-state EEG data were acquired with a portable, low-cost consumer-grade EEG recording headset. EEG channel time-series were divided in four-second artifact-free epochs and transformed into delta, theta, alpha, beta and gamma wavelet frequencies. Summary measures such as the mean, standard deviation, minimal value and maximal value of the epoch signal fluctuations were used to train a random forest classifier. Epilepsy diagnosis based on at least three months seizure calendar data was used as the gold standard diagnosis. To prevent too optimistic classification the trained model was evaluated with EEG data from subjects not used in the training. In addition, we tested a classification model trained on Nigeria data against data from people in Guinea-Bissau and vice versa. The most contributing data features in the EEG were found in the beta and theta frequencies in Guinea-Bissau and Nigeria, respectively. Within-country model performance was good with area under the receiver-operating curves of 0.85 and 0.78 (± 0.02 standard errors) in unseen data in Guinea-Bissau and Nigeria, respectively. Across-country performance was moderate (0.62 and 0.64 ± 0.02).

Our data suggests that a combination of low cost electroencephalography and machine learning techniques may facilitate diagnostic screening for epilepsy in the most remote areas of the world.
Microbial life under ice: metagenome diversity and in situ activity of Verrucomicrobia in seasonally ice-covered lakes
Authors: Tran Patricia , Ramachandran Arthi , Khawasik Ola , Beisner Beatrix E. , Rautio Milla , Huot Yannick , Walsh David A.
Published: May 2018

Northern lakes are ice-covered for a large part of the year, yet our understanding of microbial diversity and activity during winter lags behind that of the ice-free period. In this study, we investigated under-ice diversity and metabolism of Verrucomicrobia in seasonally ice-covered lakes in temperate and boreal regions of Quebec, Canada using 16S rRNA sequencing, metagenomics and metatranscriptomics. Verrucomicrobia, particularly the V1, V3 and V4 subdivisions, were abundant during ice-covered periods. A diversity of Verrucomicrobia genomes were reconstructed from Quebec lake metagenomes. Several genomes were associated with the ice-covered period and were represented in winter metatranscriptomes, supporting the notion that Verrucomicrobia are metabolically active under ice. Verrucomicrobia transcriptome analysis revealed a range of metabolisms potentially occurring under ice, including carbohydrate degradation, glycolate utilization, scavenging of chlorophyll degradation products, and urea use. Genes for aerobic sulfur and hydrogen oxidation were expressed, suggesting chemolithotrophy may be an adaptation to conditions where labile carbon may be limited. The expression of genes for flagella biosynthesis and chemotaxis was detected, suggesting Verrucomicrobia may be actively sensing and responding to winter nutrient pulses, such as phytoplankton blooms. These results increase our understanding on the diversity and metabolic processes occurring under ice in northern lakes ecosystems.
Genomic evidence for the degradation of terrestrial organic matter by pelagic Arctic Ocean Chloroflexi bacteria
Authors: Colatriano David , Tran Patricia , Guéguen Celine , William Williams J. , Lovejoy Connie , Walsh David A.
Published: May 2018

The Arctic Ocean currently receives a large supply of global river discharge and terrestrial dissolved organic matter. Moreover, an increase in freshwater runoff and riverine transport of organic matter to the Arctic Ocean is a predicted consequence of thawing permafrost and increased precipitation. The fate of the terrestrial humic-rich organic material and its impact on the marine carbon cycle are largely unknown. Here, the first metagenomic survey of the Canada Basin in the Western Arctic Ocean showed that pelagic Chloroflexi from the Arctic Ocean are replete with aromatic compound degradation genes, acquired in part by lateral transfer from terrestrial bacteria. Our results imply marine Chloroflexi have the capacity to use terrestrial organic matter and that their role in the carbon cycle may increase with the changing hydrological cycle.
Construction, validation and application of nocturnal pollen transport networks in an agro-ecosystem: a comparison using microscopy and DNA metabarcoding
Authors: Macgregor Callum J. , Kitson James J.N. , Fox Richard , Hahn Christoph , Lunt David H. , Pocock Michael J.O. , Evans Darren M.
Published: May 2018

Moths are globally relevant as pollinators but nocturnal pollination remains poorly understood. Plant-pollinator interaction networks are traditionally constructed using either flower-visitor observations or pollen-transport detection using microscopy. Recent studies have shown the potential of DNA metabarcoding for detecting and identifying pollen-transport interactions. However, no study has directly compared the realised observations of pollen-transport networks between DNA metabarcoding and conventional light microscopy.

Using matched samples of nocturnal moths, we construct pollen-transport networks using two methods: light microscopy and DNA metabarcoding. Focussing on the feeding mouthparts of moths, we develop and provide reproducible methods for merging DNA metabarcoding and ecological network analysis to better understand species-interactions.

DNA metabarcoding detected pollen on more individual moths, and detected multiple pollen types on more individuals than microscopy, but the average number of pollen types per individual was unchanged. However, after aggregating individuals of each species, metabarcoding detected more interactions per moth species. Pollen-transport network metrics differed between methods, because of variation in the ability of each to detect multiple pollen types per moth and to separate morphologically-similar or related pollen. We detected unexpected but plausible moth-plant interactions with metabarcoding, revealing new detail about nocturnal pollination systems.

The nocturnal pollination networks observed using metabarcoding and microscopy were similar, yet distinct, with implications for network ecologists. Comparisons between networks constructed using metabarcoding and traditional methods should therefore be treated with caution. Nevertheless, the potential applications of metabarcoding for studying plant-pollinator interaction networks are encouraging, especially when investigating understudied pollinators such as moths.
S-MiRAGE: A quantitative, secreted RNA-based reporter of gene expression and cell persistence
Authors: Mitra Kinshuk , Feist William N. , Anfossi Simone , Fuentes-Mattei Enrique , Almeida Maria Ines , Kim Jean J. , Calin George A. , Warmflash Aryeh
Published: May 2018

Non-destructive measurements of cell persistence and gene expression are crucial for longitudinal research studies and for prognostic assessment of cell therapies. Here we describe S-MiRAGE, a platform that utilizes small secreted RNA molecules as sensitive and quantitatively accurate reporters of cellular processes. We demonstrate the utility of S-MiRAGE by monitoring the differentiation status of human embryonic stem cells in vitro, and tumor growth in a mouse model in vivo.