bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship between Age and Facial Asymmetry
Authors: Linden Olivia E. , He Jun Kit , Morrison Clinton S. , Sullivan Stephen R. , Taylor Helena O. B.
Published: October 2018

Background:

Facial symmetry is a fundamental goal of plastic surgery, yet some asymmetry is inherent in any face. Three-dimensional photogrammetry allows for rapid, reproducible, and quantitative facial measurements. With this tool, the authors investigated the relationship between age and facial symmetry.

Methods:

The authors imaged normal subjects using three-dimensional photogrammetry. Facial symmetry was calculated by identifying the plane of maximum symmetry and the root-mean-square deviation. Regression analysis was used to assess the relationship between age and symmetry. Subgroup analyses were performed among facial thirds.

Results:

The authors imaged 191 volunteers with an average age of 26.7 ± 22.2 years (range, 0.3 to 88 years). Root-mean-square deviation of facial symmetry clustered between 0.4 and 1.3 mm (mean, 0.8 ± 0.2 mm). The authors found a significant positive correlation between increasing age and asymmetry (p < 0.001; r = 0.66). The upper, middle, and lower facial third’s average root-mean-square deviations were 0.5 ± 0.2 mm (range, 0.2 to 1.2 mm), 0.6 ± 0.2 mm (range, 0.2 to 1.4 mm), and 0.6 ± 0.2 mm (range, 0.2 to 1.2 mm), respectively. Asymmetry also increased with age across all facial thirds (p < 0.001).

Conclusions:

Facial asymmetry increases with age in each facial third, with a greater asymmetry and increase in asymmetry in the lower two-thirds. Contributing factors may include asymmetric skeletal remodeling along with differential deflation and descent of the soft tissues. The observed correlation between increasing facial asymmetry and age may be a useful guide in plastic surgery to produce age-matched features.
Gender Disparities in Preoperative Resource Use for Wrist Arthroscopy
Authors: Billig Jessica I. , Sterbenz Jennifer M. , Zhong Lin , Chung Kevin C.
Published: October 2018

Background:

Although national efforts to minimize gender biases exist, gender differences in surgery persist. This study aims to investigate gender differences in preoperative resource use of patients undergoing wrist arthroscopy for nontraumatic wrist pain.

Methods:

Patients who underwent a wrist arthroscopy for nontraumatic pain from 2009 to 2015 were selected from the Truven MarketScan databases. Demographic and preoperative resource use data were recorded. Multivariable regression models were performed to examine the relationship between gender and preoperative resource use and to investigate the cost of these services.

Results:

A total of 8792 patients, 3805 men and 4987 women, met our inclusion criteria. Women were less likely to use imaging modalities preoperatively (OR, 0.08; 95 percent CI, 0.07 to 1.00; p = 0.02). However, women used more occupational therapy (OR, 1.2; 95 percent CI, 1.1 to 1.3; p = 0.002), nonnarcotic analgesia (OR, 1.2; 95 percent CI, 1.1 to 1.3; p = 0.001), and narcotic analgesia (OR, 1.6; 95 percent CI, 1.5 to 1.8; p < 0.001). Preoperative costs during the 12 months before surgery were similar between genders ($1308 versus $1367, respectively; p = 0.07). However, women accrued more costs from occupational therapy ($130 versus $93; p = 0.003), and nonnarcotic ($65 versus $46; p < 0.001) and narcotic medications ($568 versus $197; p < 0.001).

Conclusions:

Significant gender differences exist in the preoperative care for patients undergoing wrist arthroscopy. Men use more imaging, implying more intense preoperative investigation for wrist pain, whereas women use more conservative measures, highlighting possible implicit provider biases in preoperative management and potential gender differences in disease presentation.
CRISPR Craft: DNA Editing the Reconstructive Ladder
Authors: Roh Danny S. , Li Edward B.-H. , Liao Eric C.
Published: October 2018

The clustered regularly interspaced short palindromic repeats (CRISPR) system of genome editing represents a major technological advance spanning all areas of genetics and downstream applications. CRISPR’s potential impact on treating human disease encompasses all clinical specialties, including areas important to the plastic surgeon such as oncology, wound healing, immunology, and craniofacial malformations. Plastic surgeons should gain familiarity with this gene editing technology, and become active contributors and leaders in applying CRISPR to their respective areas of expertise. This review describes the history and basic mechanism of CRISPR genome editing, highlights current and future applications, and discusses limitations. The authors will consider CRISPR’s potential impact and use in plastic and reconstructive surgery.
Regional Variation and Trends in the Timing of Lower Extremity Reconstruction: A 10-Year Review of the Nationwide Inpatient Sample
Authors: Sheckter Clifford C. , Pridgen Brian , Li Alexander , Curtin Catherine , Momeni Arash
Published: October 2018

Background:

The ideal timing of soft-tissue coverage for open lower extremity fractures remains controversial. Using U.S. national data, this study aims to characterize secular trends and regional variation in the timing of soft-tissue coverage.

Methods:

Using discharge data from the Nationwide Inpatient Sample (2002 to 2011), the authors identified 888 encounters admitted from the emergency department with isolated open lower extremity fractures treated with pedicled or free tissue transfer. Soft-tissue coverage timing was assessed by patient factors, hospital characteristics, and fracture patterns. Statistical significance and secular trends were analyzed with generalized linear models.

Results:

The mean day of soft-tissue reconstruction was at 6.64 days. Over the 10-year period, the day of reconstruction increased significantly (from 6.12 days in 2002 to 12.50 days in 2011; coefficient, 0.09; 95 percent CI, 0.05 to 0.12; p < 0.001). Demographic and facility factors did not significantly impact timing. Elixhauser comorbidity scores greater than 2 were associated with later coverage (10.13 days versus 6.29 days; p = 0.001) along with multisite fractures (8.35 days; p = 0.022) and external fixators (8.78 days; p < 0.001). The U.S. Census division showed significant variation in timing ranging from 0.94 days (East North Central) to 9.84 days (Pacific).

Conclusions:

A progressive delay in the timing of soft-tissue reconstruction was noted and may be attributed to negative-pressure wound therapy. The timing of soft-tissue coverage varied by region after adjusting for patient and hospital factors. Additional studies are needed to understand the impact of delayed soft-tissue coverage on patient outcomes and health services utilization.
Amputation-Site Soft-Tissue Restoration Using Adipose Stem Cell Therapy
Authors: Bourne Debra A. , Thomas R. Dallin , Bliley Jacqueline , Haas Gretchen , Wyse Aaron , Donnenberg Albert , Donnenberg Vera S. , Chow Ian , Cooper Rory , Coleman Sydney , Marra Kacey , Pasquina Paul F. , Rubin J. Peter
Published: October 2018

Soft-tissue deficits in amputation stumps can lead to significant pain and disability. An emerging treatment option is stem cell–enriched fat grafting. This is the first study assessing the potential for this treatment modality in lower extremity amputation sites. In this prospective cohort study, five injured military personnel suffering from pain and limited function at amputation sites were recruited. Fat grafting enriched with stromal vascular fraction was performed at amputation sites to provide additional subcutaneous tissue padding over bony structures. Outcomes measures included complications, demographic data, physical examination, cellular subpopulations, cell viability, graft volume retention, pain, Lower Extremity Functional Scale, Functional Mobility Assessment, 36-Item Short-Form Health Survey, and rates of depression. Follow-up was 2 years. There were no significant complications. Volume retention was 61.5 ± 24.0 percent. Overall cell viability of the stromal vascular fraction was significantly correlated with volume retention (p = 0.016). There was no significant correlation between percentage of adipose-derived stem cells or number of cells in the stromal vascular fraction and volume retention. There was a nonsignificant trend toward improvement in pain scores (3.0 ± 2.5 to 1.2 ± 1.6; p = 0.180 at 2 years). There were no significant changes in disability indexes. Results from this pilot study demonstrate that stromal vascular fraction–enriched fat grafting is a safe, novel modality for the treatment of symptomatic soft-tissue defects in traumatic lower extremity amputations. Volume retention can be anticipated at slightly over 60 percent. Further studies are needed to assess efficacy.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Management of Fat Necrosis after Autologous Fat Transplantation for Breast Augmentation
Authors: Lin Jeng-Yee , Song Ping , Pu Lee L. Q.
Published: October 2018

Background:

Palpable lumps as sequelae of fat necrosis after fat grafting to the breast may not only cause physical or psychological symptoms to patients but also potentially complicate breast cancer screening. In this article, the authors present their experience in management of fat necrosis following fat grafting for breast augmentation.

Methods:

Over a 5-year period, a total of 685 Asian women (age range, 20 to 58 years) underwent autologous fat transplantation to the breasts. The average volume of fat graft to each breast was 205 ± 45 cc. The preoperative and postoperative photographs and the breast volume were recorded. Detection of fat necrosis was based on clinical examinations and imaging studies. The mean follow-up was 208 ± 36 days.

Results:

The mean volume increase was 135 ± 20 cc in a single breast, with a mean graft retention rate of 65 percent. Sixty-six patients (9.6 percent) were found to have fat necrosis in the form of solitary or multiple cysts, sclerotic nodules, or calcifications in either one or both breasts postoperatively. The average time before first detection of the breast lump was 108 ± 45 days. Management of fat necrosis included aspiration or excision based on the authors’ treatment algorithm. The symptoms related to fat necrosis such as discomfort on palpation, pain, or possible skin reaction were significantly improved in 54 of 57 patients (94.7 percent).

Conclusions:

Fat necrosis following autologous fat grafting for breast augmentation can be managed successfully and its related symptoms can be relieved in 94.7 percent of patients. It can be approached safely based on a sound algorithm developed by the authors.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
A New Paradigm in Cleft Lip Procedural Excellence: Creation and Preliminary Digital Validation of a Lifelike Simulator
Authors: Rogers-Vizena Carolyn R. , Saldanha Francesca Y. L. , Hosmer Andrew L. , Weinstock Peter H.
Published: October 2018

Simulation is becoming an increasingly important tool for hands-on surgical education in a no-risk environment. Cleft lip repair is a common procedure where precise technique is needed to achieve optimal outcome, making it an ideal candidate for simulation. A digital simulated patient with a typical unilateral complete cleft lip and alveolus was constructed using existing three-dimensional imaging studies. Key surface and internal anatomical elements were characterized in detail. A prototype high-fidelity simulator was constructed with silicone and synthetic polymers over a supportive scaffold, piloted by three surgeons using multiple techniques, and digitally compared to real patients. All surgeons completed key steps of a cleft lip repair on the simulator and found it approximated the haptics and anatomy of a cleft lip. Surface change and anthropometric movements accomplished on the simulator were similar for all three surgeons. In digital comparison to analogous real patient data, the simulator anthropometric movements and topographic change were similar to real nasolabial movement. A high-fidelity cleft lip simulator provides “on-demand” opportunity to realistically practice all steps of a cleft lip repair, with implications for overcoming volume-outcome relationship challenges of diminishing operative experience for resident surgeons.
Altered Hypothalamus-Pituitary-Adrenal Axis Function: A Potential Underlying Biological Pathway for Multiple Concurrent Symptoms in Patients With Advanced Lung Cancer
Authors: Oh In-Jae , Kim Kyu-Sik , Kim Young-Chul , Park Jai-Young , Yoo Keun-Young , Do Sang-Hwan , Ahn Ryun-Sup
Published: October 2018

Objective

Patients with advanced cancer commonly experience multiple symptoms that present as groups or clusters. The present study aimed to examine whether hypothalamus-pituitary-adrenal (HPA) axis dysfunction underlies the concurrent multiple symptoms in patients with advanced cancer.

Methods

Patients' cortisol levels were determined in saliva samples collected after awakening (0, 30, and 60 minutes after awakening) and at nighttime (21:00–22:00 PM) from 46 patients with lung cancer (15.2% women), with a mean (standard deviation) age of 64.3 (9.2) years and 47 healthy participants (53.2% women; age = 62.0 [4.6] years). Cancer-related symptoms were measured using the M.D. Anderson Symptom Inventory (MDASI).

Results

Compared with healthy participants, patients showed a significantly reduced cortisol awakening response (F(1,364) = 46.2, p < .001) and had flatter diurnal slope of cortisol (larger β values) (mean [standard error of the mean] = −0.64 [0.06] versus −0.18 [0.05], p < .001). Altered HPA axis function was significantly and adversely associated with performance status and burden of symptoms (all p values < .01). However, each MDASI item varied widely in the degree of association with the HPA axis function. Hierarchical clustering analysis based on Spearman's rank correlation with complete linkage identified that nausea was clustered with vomiting, numbness, and dry mouth, whereas the other nine MDASI core symptoms associated with altered HPA axis function were clustered together.

Conclusions

Altered HPA axis function may be a possible biological pathway that can explain the concurrence of core symptoms in patients with advanced lung cancer.
Incidence of Infectious Adverse Events in Patients With Rheumatoid Arthritis and Spondyloarthritis on Biologic Drugs—Data From the Brazilian Registry for Biologics Monitoring
Authors: Cecconi Mariana , Ranza Roberto , Titton David C. , Moraes Júlio C. B. , Bertolo Manoel , Bianchi Washington , Brenol Claiton , Carvalho Hellen M. , de Castro Glaucio R. W. , Costa Izaias P. , Cunha Maria F. L. , Duarte Ângela , Fernandes Vander , Freire Marlene , Louzada-Junior Paulo , Macieira José C. , Miranda José R. S. , Pereira Ivanio A. , Pinheiro Geraldo R. C. , Stadler Barbara , Toledo Roberto A. , Valim Valeria , Descalzo Miguel A. , Pinto Rogerio M. C. , Laurindo Ieda
Published: October 2018

Background

The safety profile of biologic drugs might present substantial regional differences. Since 2009, the Brazilian Society of Rheumatology has maintained BIOBADABRASIL (Brazilian Registry for Biologic Drugs), a registry for monitoring of biologic therapies in rheumatic diseases.

Objectives

The aim of this study was to verify the incidence rate (IR) of serious infections in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients on biologic drugs.

Methods

BIOBADABRASIL prospectively included patients with rheumatic diseases who started the first biologic drug or a synthetic disease-modifying antirheumatic drug as a parallel control group. This study focuses on serious infectious adverse events (SIAEs) in RA and SpA patients on biologic drugs compared with controls, from January 2009 to June 2015. Time of exposure was set from initiation of the drug to the date of last administration or censorship. Serious infectious adverse events IR was calculated per 1000 patient/years with 95% confidence interval (CI).

Results

A total of 1698 patients (RA, 1121; SpA, 577) were included, 7119 patient/years. Serious infectious adverse events were more common among patients on tumor necrosis factor inhibitors (TNFi's) than controls (adjusted IR ratio, 2.96 [95% CI, 2.01–4.36]; p < 0.001). Subsequent TNFi was associated with a higher SIAEs incidence when compared with first TNFI (adjusted IR ratio, 1.55 [95% CI, 1.15–2.08]; p = 0.004). Serious infectious adverse events were associated with age and corticosteroids intake. Serious infectious adverse events were more frequent in the respiratory tract in all subgroups.

Conclusions

In BIOBADABRASIL, biologic drugs, especially the subsequent TNFi, were associated with a higher risk of serious infections compared with synthetic DMARDs. Corticosteroid intake and age represented risk factors for SIAEs. Constant monitoring is required to follow the safety profile of drugs in the clinical setting of rheumatic conditions in Brazil.
Treatment of Life-Threatening ACE-Inhibitor–Induced Angioedema
Authors: Hirschy RaeAnn , Shah Tanvi , Davis Tamara , Rech Megan A.
Published: October 2018

Incidence of angioedema associated with angiotensin-converting enzyme inhibitors (ACE-I) has been estimated at 0.1%–2.2% of patients receiving treatment. Despite the potential severity of this disease state, standardized treatment is lacking. Traditional pharmacotherapy options include medications that target inflammatory mediators and the angiotensin pathway. However, because ACE-I-induced angioedema is caused by accumulation of bradykinin, these medications fail to target the underlying pathophysiology. Recently, novel therapies that target the kallikrein–bradykinin pathway have been studied. These include icatibant, ecallantide, C1 esterase inhibitors, and fresh-frozen plasma. Recent randomized controlled trials exhibit contradictory results with the use of icatibant. This is a focused review on traditional and novel treatment strategies for ACE-I-induced angioedema.
Nonstandard Advance Health Care Directives in Emergency Departments
Authors: Gilbert Julia , Boag Jane
Published: October 2018

People have tattooed themselves for thousands of years, and it remains popular with various groups across mainstream society. Although many people choose tattoos that express their life philosophy, epic events in their life, or their personal mantra, the use of tattooing in medicine such as a “do not resuscitate” tattoo is increasingly becoming more common (Drew, 2017
;
Islam et al., 2016). As these tattoos do not meet the legal requirements for an advance health directive, they are at best a guide to the person's wishes and at worst a useless, painful exercise. New technology such as “talking tattoos” or implantable microchips could conceivably be used to record either an audible advance health directive or directions for emergency responders to access an individual's advance health directive. This article discusses the ethical and legal implications of nonstandard advance health directive tattoos in emergency treatment situations.
Translating surveillance data into incidence estimates
Authors: Bourhis Yoann , Gottwald Timothy R. , van den Bosch Frank
Published: October 2018

Monitoring a population for a disease requires the hosts to be sampled and tested for the pathogen. This results in sampling series from which to estimate the disease incidence,i.e. the proportion of hosts infected. Existing estimation methods assume that disease incidence is not changing between monitoring rounds, resulting in underestimation of the disease incidence. In this paper we develop an incidence estimation model accounting for epidemic growth with monitoring rounds sampling varying incidence. We also show how to accommodate the asymptomatic period characteristic to most diseases. For practical use, we produce an approximation of the model, which is subsequently shown accurate for relevant epidemic and sampling parameters. Both the approximation and the full model are applied to stochastic spatial simulations of epidemics. The results prove their consistency for a very wide range of situations.
Epigenome-wide Analysis Identifies Genes and Pathways Linked to Neurobehavioral Variation in Preterm Infants
Authors: Everson Todd M. , Marsit Carmen J. , O’Shea T. Michael , Burt Amber , Hermetz Karen , Pastyrnak Steven L , Neal Charles R , Carter Brian S , Helderman Jennifer , McGowan Elisabeth C. , Smith Lynne M , Soliman Antoine , Hofheimer Julie A , DellaGrotta Sheri A , Dansereau Lynne M , Padbury James F , Lester Barry M
Published: October 2018

Background & Objectives

Neonatal neurobehavioral performance measures, such as the NICU Network Neurobehavioral Scale (NNNS), have been developed to assess the neurobehavioral characteristics of infants and provide insights into future developmental trajectories. The identification of molecular biomarkers of very early life neurobehavioral experiences could lead to better predictions of the long-term developmental outcomes of high-risk infants including preterm infants. To this end, we aimed to examine whether variability in DNA methylation (DNAm) or epigenetic age from surrogate tissues are associated with NNNS profiles in a cohort of infants born less than 30 weeks postmenstrual age (PMA).

Methods

This study was performed within the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study and included those infants with complete NNNS assessment data and DNAm measured from buccal cells, collected at near term-equivalent age using the Illumina EPIC array (N=536). We tested whether epigenetic age and age acceleration differed between infants based on their NNNS profile classifications. Then we performed an epigenome-wide association study, to test whether DNAm at individual epigenetic loci varied between these NNNS profile groupings. Models were adjusted for recruitment site, infant sex, postmenstrual age, and estimated tissue heterogeneity.

Results

We found that infants with an optimal NNNS profile had slightly older epigenetic age than other NOVI infants (β1 = 0.201, p-value = 0.026), and that infants with an atypical NNNS profile had differential methylation at 29 CpG sites (FDR < 10%). The genes annotated to these differentially methylated CpGs included PLA2G4E, TRIM9, GRIK3, and MACROD2, which have previously been associated with neurological structure and function, or with neurobehavioral disorders.

Conclusions

Greater epigenetic age is associated with optimal NNNS responses while altered DNAm of multiple genes are associated with an atypical neurobehavioral profile at near-term equivalent age. These findings build upon the existing evidence that epigenetic variations in buccal cells may serve as markers of neonatal neurobehavior and might facilitate early identification of children at risk for abnormal developmental outcome.
Spatial and Temporal Analysis of the Stomach and Small Intestinal Microbiota in Fasted Healthy Humans
Authors: Seekatz Anna M. , Schnizlein Matthew K. , Koenigsknecht Mark J. , Baker Jason R. , Hasler William L. , Bleske Barry E. , Young Vincent B. , Sun Duxin
Published: October 2018

Although the microbiota in the proximal gastrointestinal (GI) tract has been implicated in health and disease, much of these microbes remains understudied compared to the distal GI tract. This study characterized the microbiota across multiple proximal GI sites over time in healthy individuals.

As part of a study of the pharmacokinetics of oral mesalamine administration, healthy, fasted volunteers (N=8; 10 observation periods total) were orally intubated with a four-lumen catheter with multiple aspiration ports. Samples were taken from stomach, duodenal, and multiple jejunal sites, sampling hourly (≤7 hours) to measure mesalamine (administered at t=0), pH, and 16S rRNA gene-based composition.

We observed a predominance of Firmicutes across proximal GI sites, with significant variation compared to stool. The microbiota was more similar within individuals over time than between subjects, with the fecal microbiota being unique from that of the small intestine. The stomach and duodenal microbiota displayed highest intra-individual variability compared to jejunal sites, which were more stable across time. We observed significant correlations in the duodenal microbial composition with changes in pH; linear mixed models identified positive correlations with multipleStreptococcusoperational taxonomic units (OTU) and negative correlations with multiplePrevotella and PasteurellaceaeOTUs. Few OTUs correlated with mesalamine concentration.

The stomach and duodenal microbiota exhibited greater compositional dynamics compared to the jejunum. Short-term fluctuations in the duodenal microbiota was correlated with pH. Given the unique characteristics and dynamics of the proximal GI tract microbiota, it is important to consider these local environments in health and disease states.
Reliability and Generalizability of Similarity-Based Fusion of MEG and fMRI Data in Human Ventral and Dorsal Visual Streams
Authors: Mohsenzadeh Yalda , Mullin Caitlin , Lahner Benjamin , Cichy Radoslaw , Oliva Aude
Published: October 2018

To build a representation of what we see, the human brain recruits regions throughout the visual cortex in cascading sequence. Recently, an approach was proposed to evaluate the dynamics of visual perception in high spatiotemporal resolution at the scale of the whole brain. This method combined functional magnetic resonance imaging (fMRI) data with magnetoencephalography (MEG) data using representational similarity analysis and revealed a hierarchical progression from primary visual cortex through the dorsal and ventral streams. To assess the replicability of this method, here we present results of a visual recognition neuro-imaging fusion experiment, and compare them within and across experimental settings. We evaluated the reliability of this method by assessing the consistency of the results under similar test conditions, showing high agreement within participants. We then generalized these results to a separate group of individuals and visual input by comparing them to the fMRI-MEG fusion data of Cichy et al (2016), revealing a highly similar temporal progression recruiting both the dorsal and ventral streams. Together these results are a testament to the reproducibility of the fMRI-MEG fusion approach and allows for the interpretation of these spatiotemporal dynamic in a broader context.
Insomnia and problematic gaming: a study in 9 low-and middle-incomes countries
Authors: Sosso FAE , Kuss Daria J.
Published: October 2018

Withdrawal Statements: The authors have withdrawn their manuscript as they have discovered some potential inconsistencies in the analysis of the data. Therefore, the authors do not wish this work to be cited as reference for the project.

The second author has data integrity concerns and wishes to distance herself unequivocally from the lead author.
Challenges and recommendations to improve installability and archival stability of omics computational tools
Authors: Mangul Serghei , Mosqueiro Thiago , Abdill Richard J. , Duong Dat , Mitchell Keith , Sarwal Varuni , Hill Brian , Brito Jaqueline , Littman Russell Jared , Statz Benjamin , Lam Angela Ka-Mei , Dayama Gargi , Grieneisen Laura , Martin Lana S. , Flint Jonathan , Eskin Eleazar , Blekhman Ran
Published: October 2018

Developing new software tools for analysis of large-scale biological data is a key component of advancing modern biomedical research. Scientific reproduction of published findings requires running computational tools on data generated by such studies, yet little attention is presently allocated to the installability and archival stability of computational software tools. Scientific journals require data and code sharing, but none currently require authors to guarantee the continuing functionality of newly published tools. We have estimated the archival stability of computational biology software tools by performing an empirical analysis of the internet presence for 36,702 omics software resources published from 2005 to 2017. We found that almost 28% of all resources are currently not accessible through URLs published in the paper they first appeared in. Among the 98 software tools selected for our installability test, 51% were deemed “easy to install,” and 28% of the tools failed to be installed at all due to problems in the implementation. Moreover, for papers introducing new software, we found that the number of citations significantly increased when authors provided an easy installation process. We propose for incorporation into journal policy several practical solutions for increasing the widespread installability and archival stability of published bioinformatics software.
Exploratory analysis of multiple traits co-adaptations in the population history
Authors: Nakamichi Reiichiro , Kitada Shuichi , Kishino Hirohisa
Published: October 2018

During the history of range expansion, the populations encounter with variety of environments. They respond to the local environments by modifying the mutually interacting traits. Therefore, to understand the whole life history of the populations, it is ideal to capture the history of their range expansion with reference to the series of surrounding environments and to infer the coadaptation of the multiple traits. Toward this end, we provide an exploratory analysis based on the features of populations: site frequency spectra of populations, population-specific FST, association between genes and environments, positive selections on traits mapped on the admixture graph, and GWAS results. Correspondence analysis of genes, environments, and traits provides a bird’s-eye view of the history of population differentiation and range expansion and various types of environmental selections at the times. Principal component analysis of the estimated trait-specific polygenic adaptations mapped on the admixture graph enables to understand the coadaptation of multiple traits. The potential usefulness was confirmed by analyzing a public dataset of wild poplar in northwestern America. In response to the northern cold temperature and longer daylength, the populations increased the photosynthetic activity and nutrient use efficiency at the expense of the risk of pathogen invasion, and in response to warm temperature, they increased the growth. At higher altitude, they shifted the maximum activity to earlier period in spring to reduce the activity in dry summer. The R codes for our representation method and simulations of population colonization used in this study are available as supplementary script.
Stimulus domain transfer in recurrent models for large scale cortical population prediction on video
Authors: Sinz Fabian H. , Ecker Alexander S. , Fahey Paul G. , Walker Edgar Y. , Cobos Erick , Froudarakis Emmanouil , Yatsenko Dimitri , Pitkow Xaq , Reimer Jacob , Tolias Andreas S.
Published: October 2018

To better understand the representations in visual cortex, we need to generate better predictions of neural activity in awake animals presented with their ecological input: natural video. Despite recent advances in models for static images, models for predicting responses to natural video are scarce and standard linear-nonlinear models perform poorly. We developed a new deep recurrent network architecture that predicts inferred spiking activity of thousands of mouse V1 neurons simulta-neously recorded with two-photon microscopy, while accounting for confounding factors such as the animal’s gaze position and brain state changes related to running state and pupil dilation. Powerful system identification models provide an opportunity to gain insight into cortical functions through in silico experiments that can subsequently be tested in the brain. However, in many cases this approach requires that the model is able to generalize to stimulus statistics that it was not trained on, such as band-limited noise and other parameterized stimuli. We investigated these domain transfer properties in our model and find that our model trained on natural images is able to correctly predict the orientation tuning of neurons in responses to artificial noise stimuli. Finally, we show that we can fully generalize from movies to noise and maintain high predictive performance on both stimulus domains by fine-tuning only the final layer’s weights on a network otherwise trained on natural movies. The converse, however, is not true.
Dopamine modulation of prefrontal cortex activity is manifold and operates at multiple temporal and spatial scales
Authors: Lohani Sweyta , Martig Adria K. , Deisseroth Karl , Witten Ilana B. , Moghaddam Bita
Published: October 2018

While the function of dopamine in subcortical structures is largely limited to reward and movement, dopamine neurotransmission in the prefrontal cortex (PFC) is critical to a multitude of temporally and functionally diverse processes such as attention, working memory, behavioral flexibility, action selection, and stress adaptation. How does dopamine influence PFC computation of multiple temporally diverse functions? Here we find causation between sustained and burst patterns of phasic dopamine neuron activation and contemporaneous modulation of PFC neuronal activity at multiple spatio-temporal scales. These include a multidirectional and weak impact on individual PFC neuron rate activity and a robust influence on coordinated ensemble activity, gamma oscillations, and gamma-theta coupling that persisted for minutes. In addition, PFC network responses to burst pattern of dopamine firing were selectively strengthened in behaviorally active states. Thus, dopamine modulation of PFC is spatiotemporally diverse and is dictated by the pattern of dopamine neuron activation and behavioral state. These findings provide insight on the multiplex pattern of modulation by dopamine that may influence PFC computation of temporally diverse functions.
Orbitofrontal neuron ensembles contribute to inhibitory control
Authors: Priyadharsini Balasubramani Pragathi , Hayden Benjamin Y.
Published: October 2018

Stopping, or inhibition, is a form of self-control that is a core part of adaptive behavior. We hypothesize that inhibition commands originate, in part, from the orbitofrontal cortex (OFC). We recorded activity of OFC neurons in macaques performing a stop signal task. Decoding analyses revealed a clear difference in ensemble responses that distinguish successful from failed inhibition that begins after the stop signal and before the stop signal reaction time. We also found a different and unrelated ensemble pattern that distinguishes successful from failed stopping before the beginning of the trial. These signals were distinct from, and orthogonal to, value encoding, which was also observed in these neurons. The timing of the early and late signals was, respectively, consistent with the idea that OFC contributes both proactively and reactively to inhibition. These results support the view, inspired by anatomy, that OFC gathers diverse sensory inputs to compute early-stage executive signals.
Asymmetric dispersal is a critical element of concordance between biophysical dispersal models and spatial genetic structure in Great Barrier Reef corals
Authors: Riginos C , Hock K , Matias AM , Mumby PJ , van Oppen MJH , Lukoschek V.
Published: October 2018

Aim

Widespread coral bleaching, crown-of-thorns seastar outbreaks, and tropical storms all threaten foundational coral species of the Great Barrier Reef, with impacts differing over time and space. Yet, dispersal via larval propagules could aid reef recovery by supplying new settlers and enabling the spread of adaptive variation among regions. Documenting and predicting spatial connections arising from planktonic larval dispersal in marine species, however, remains a formidable challenge.

Location

The Great Barrier Reef, Australia

Methods

Contemporary biophysical larval dispersal models were used to predict longdistance multigenerational connections for two common and foundational coral species (Acropora tenuisandAcropora millepora). Spatially extensive genetic surveys allowed us to infer signatures of asymmetric dispersal for these species and evaluate concordance against expectations from biophysical models using coalescent genetic simulations, directions of inferred gene flow, and spatial eigenvector modelling.

Results

At long distances, biophysical models predicted a preponderance of north to south connections and genetic results matched these expectations: coalescent genetic simulations rejected an alternative scenario of historical isolation; the strongest signals of inferred gene flow were from north to south; and asymmetric eigenvectors derived from north to south connections in the biophysical models were significantly better predictors of spatial genetic patterns than eigenvectors derived from symmetric null spatial models.

Main conclusions

Results are consistent with biophysical dispersal models yielding approximate summaries of past multigenerational gene flow conditioned upon directionality of connections. ForA. tenuisandA. millepora, northern and central reefs have been important sources to downstream southern reefs over the recent evolutionary past and should continue to provide southward gene flow. Endemic genetic diversity of southern reefs suggests substantial local recruitment and lack of long distance gene flow from south to north.
Bayesian learning ecosystem dynamics with delayed dependencies from incomplete multiple source data : an application to plant epidemiology
Authors: Dupas Stéphane
Published: October 2018

Ecosystem dynamics forecasting is central to major problems in ecology, society, and economy. The existing models serve as decision tools but their parameters valitity are usually not confronted to real data in a formalized approach. Dynamics bayesian network inference is promissing but limited when dealing with incomplete multiple source time series with delayed time dependencies. We propose here a temporal bayesian network with time delay and aproximate inference algorithm, to learn altogether cryptic ecosystem variables, missing data, and model parameters. The novelty in the approach is that it combines simulation-based and likelihood-based aproximate bayesian inference. The advantage of simulation based is that it allows to sample hidden processes. The advantage of likelihood based is that it provides a summary statistics that is really representing the model we are interested in. The ecosystem variables and the missing data are simulated from indicator variables using the probabilistic indicator-ecosystem model. The likelihood is estimated by averaging the probability of observed-simulated data over simulations, the parameter space is sampled with Metropolis Hasting algorithm. Another innovative proposition is to parametrize the network structure in order to learn model structure within a space provided by prior distribution. We apply to plant epidemiology.
A new method for enamel amino acid racemization dating: a closed system approach
Authors: Dickinson Marc R. , Lister Adrian M. , Penkman Kirsty E. H.
Published: October 2018

Analysis of the predictable breakdown of proteins and amino acids in ancient biominerals enables age estimation over the Quaternary. We postulate that enamel is a suitable biomineral for the long-term survival of endogenous amino acids. Analysis of multiple amino acids for geochronological studies is typically achieved using a RP-HPLC method. However, the low concentrations of amino acids coupled with high concentrations of inorganic species make accurate determination of amino concentrations challenging. We have developed a method for the routine preparation of multiple enamel samples using biphasic separation. Furthermore, we have shown that amino acids that exhibit effectively closed system behaviour can be isolated from enamel through an exposure time of 72 h to bleach. Elevated temperature experiments investigating the processes of intra-crystalline protein degradation (IcPD) do not appear to match the patterns from fossil samples, reinforcing the need for a comprehensive understanding of the underlying mechanisms of protein degradation. This novel preparative method isolates intra-crystalline amino acids suitable for the development of mammalian geochronologies based on enamel protein degradation. The lower rates of racemisation in enamel (cf.Bithyniaopercula) suggest that the enamel AAR may be able to be used as a relative dating technique over time scales > 2.8 Ma. Enamel AAR has the potential to estimate the age of mammalian remains past the limit of all other current direct dating methods, providing an invaluable tool for geochronological studies.
Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank
Authors: Tachmazidou Ioanna , Hatzikotoulas Konstantinos , Southam Lorraine , Esparza-Gordillo Jorge , Haberland Valeriia , Zheng Jie , Johnson Toby , Koprulu Mine , Zengini Eleni , Steinberg Julia , Wilkinson Jeremy M , Bhatnagar Sahir , Hoffman Joshua , Buchan Natalie , Süveges Dániel , Consortium arcOGEN , Yerges Armstrong Laura , Davey Smith George , Gaunt Tom R , Scott Robert A , McCarthy Linda C , Zeggini Eleftheria
Published: October 2018

Osteoarthritis is the most common musculoskeletal disease and the leading cause of disability globally. Here, we perform the largest genome-wide association study for osteoarthritis to date (77,052 cases and 378,169 controls), analysing 4 phenotypes: knee osteoarthritis, hip osteoarthritis, knee and/or hip osteoarthritis, and any osteoarthritis. We discover 64 signals, 52 of them novel, more than doubling the number of established disease loci. Six signals fine map to a single variant. We identify putative effector genes by integrating eQTL colocalization, fine-mapping, human rare disease, animal model, and osteoarthritis tissue expression data. We find enrichment for genes underlying monogenic forms of bone development diseases, and for the collagen formation and extracellular matrix organisation biological pathways. Ten of the likely effector genes, includingTGFB1,FGF18,CTSKandIL11have therapeutics approved or in clinical trials, with mechanisms of action supportive of evaluation for efficacy in osteoarthritis.
ETDB-Caltech: a blockchain-based distributed public database for electron tomography
Authors: Ortega Davi R. , Oikonomou Catherine M. , Ding H. Jane , Rees-Lee Prudence , Alexandria  , Jensen Grant J.
Published: October 2018

Three-dimensional electron microscopy techniques like electron tomography provide valuable insights into cellular structures, and present significant challenges for data storage and dissemination. Here we explored a novel method to publicly release more than 11,000 such datasets, more than 30 TB in total, collected by our group. Our method, based on a peer-to-peer file sharing network built around a blockchain ledger, offers a distributed solution to data storage. In addition, we offer a user-friendly browser-based interface, https://etdb.caltech.edu, for anyone interested to explore and download our data. We discuss the relative advantages and disadvantages of this system and provide tools for other groups to mine our data and/or use the same approach to share their own imaging datasets.
Integrating molecular markers and environmental covariates to interpret genotype by environment interaction in rice (Oryza sativa L.) grown in temperate areas
Authors: Monteverde Eliana , Gutierrez Lucía , Blanco Pedro , de Vida Fernando Pérez , Rosas Juan E. , Bonnecarrère Victoria , Quero Gastón , McCouch Susan
Published: October 2018

Understanding the genetic and environmental basis of genotype × environment interaction (G×E) is of fundamental importance in plant breeding. If we consider G×E in the context of genotype × year interactions (G×Y), predicting which lines will have stable and superior performance across years is an important challenge for breeders. A better understanding of the factors that contribute to the overall grain yield and quality of rice (Oryza sativa L.) will lay the foundation for developing new breeding and selection strategies for combining high quality, with high yield. In this study, we used molecular marker data and environmental covariates (EC) simultaneously to predict rice yield, milling quality traits and plant height in untested environments (years), using both reaction norm models and partial least squares (PLS), in two rice breeding populations (indica and tropical japonica). We also sought to explain G×E by differential quantitative trait loci (QTL) expression in relation to EC. Our results showed that PLS models trained with both molecular markers and EC gave better prediction accuracies than reaction norm models when predicting future years. We also detected several milling quality QTL that showed a differential expression conditional on humidity and solar radiation, providing insight for the main environmental factors affecting milling quality in temperate rice growing areas.
Access schedules mediate the impact of high fat diet on ethanol intake and insulin and glucose function in mice
Authors: Coker Caitlin R. , Aguilar Elizabeth A. , Snyder Angela E. , Bingaman Sarah S. , Graziane Nicholas M. , Browning Kirsteen N. , Arnold Amy C. , Silberman Yuval
Published: October 2018

Alcoholism and high fat diet (HFD)-induced obesity individually promote insulin resistance and glucose intolerance in clinical populations, increasing risk for metabolic diseases. Conversely, animal studies, typically utilizing forced/continuous alcohol (EtOH) access, tend to show that EtOH intake mitigates HFD-induced effects on insulin and glucose function, while HFD decreases voluntary EtOH intake in continuous access models. However, the impact of HFD on intermittent EtOH intake and resultant changes to metabolic function are not well characterized. The present studies sought to determine if HFD alters EtOH intake in male C57Bl/6J mice given differing two-bottle choice EtOH access schedules, and to assess resultant impact on insulin sensitivity and glucose tolerance. In the first experiment, mice had Unlimited Access EtOH (UAE)+HFD (n=15; HFD=60% calories from fat, 10% EtOH v/v, ad libitum) or UAE+Chow (n=15; control diet=16% calories from fat, ad libitum) for 6 weeks. UAE+HFD mice had lower EtOH preference, consumed significantly less EtOH, and were insulin resistant and hyperglycemic compared with UAE+Chow mice. In the second experiment, mice had Limited Access EtOH (LAE, 4 hrs/d; 3 d/wk)+HFD (n=15) or LAE+Chow (n=15) with increasing EtOH concentrations (10%, 15%, 20%). LAE+HFD mice had no difference in total EtOH consumption compared to LAE+Chow mice, but exhibited hyperglycemia, insulin resistance, and glucose intolerance. In the third experiment, mice had intermittent HFD access (single 24 hr session/week) with limited access to EtOH (iHFD-E, 4hrs/d; 4 d/wk) (n=10). iHFD-E mice displayed binge eating behaviors and consumed significantly more EtOH than mice given ad libitum chow or HFD, suggesting transfer of binge eating to binge drinking behaviors. Although iHFD-E mice did not have significantly altered body composition, they developed insulin insensitivity and glucose intolerance. These results suggest that access schedules determine the impact of HFD on EtOH consumption and resultant metabolic dysfunction.