bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta-analysis in Physical Therapy Education Research: Using the Pearson's Product–Moment Correlation Coefficient as a Measure of Effect Size
Authors: Wolden Mitch , Hill Brent , Farquhar Voorhees Sara
Published: December 2018

Background and Purpose.

Practicing physical therapists seek the highest levels of evidence (ie, systematic review and meta-analysis) to inform clinical decision making. Performing a meta-analysis with assimilated data from a systematic review is important for comprehensive decision making in clinical and educational practice. In educational practice, the Pearson's product–moment correlation coefficient (r) is often used as the measure of effect size to examine causal relationships between variables. Our purpose was to present the best model for conducting a meta-analysis using r.

Model Description and Evaluation.

A meta-analysis is prescribed through five steps: (1) calculation of the effect sizes, (2) selecting the appropriate effects model and computational method, (3) applying the computational method, (4) performing heterogeneity analysis, and (5) assessing for publication bias.

Outcomes.

Key statistical outcomes include: (1) total sample size, (2) number of correlations, (3) mean true score correlation, (4) variance of true score correlations, (5) 80% credibility interval, and (6) 95% confidence interval. To help with the interpretation of these results, figures (ie, forest plots and funnel plots) are used.

Discussion and Conclusion.

Central to achieving evidence-based practice is the selection and application of high-quality research. A systematic review with random-effects meta-analysis using high-quality cohort studies can provide high-quality evidence to physical therapy educators to answer their pertinent education questions.
Inflammatory Effects of Blood–Air Interface in a Porcine Cardiopulmonary Bypass Model
Authors: Carr Benjamin D. , Johnson Thomas J. , Gomez-Rexrode Amalia , Mohammed Azmath , Coughlin Megan , Toomasian John M. , Rojas-Pena Alvaro , Bartlett Robert H. , Haft Jonathan W.
Published: December 2018

Cardiopulmonary bypass (CPB) causes a systemic inflammatory response syndrome (SIRS) associated with multiorgan injury. A model was developed to test whether a blood–air interface (BAI) in the CPB circuit causes blood element activation and inflammation. Ten healthy swine were placed on partial CPB for 2 hours via the cervical vessels and monitored for 96 hours postoperatively. Five pigs (control group) had minimal air exposure in the circuit, while five were exposed to a BAI simulating cardiotomy suction. There were no significant differences in bypass flow or hemodynamics between the groups. In the BAI group, there was an increase in hemolysis after bypass (plasma-free hemoglobin 5.27 ± 1.2 vs. 0.94 ± 0.8 mg/dl; p = 0.01), more aggressive platelet consumption (28% vs. 83% of baseline; p = 0.009), leukocyte consumption (71% vs. 107% of baseline; p = 0.02), and increased granulocyte CD11b expression (409% vs. 106% of baseline; p = 0.009). These data suggest the inflammatory pattern responsible for the CPB-SIRS phenomenon may be driven by blood–air interaction. Future efforts should focus on BAI-associated mechanisms for minimizing blood trauma and inflammation during CPB.
Advances in hematopoietic cell transplant for the treatment of hematologic malignancies
Authors: Taraseviciute Agne , Pulsipher Michael A.
Published: December 2018

Purpose of review

Incorporation of minimal residual disease (MRD) testing in acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) has transformed the landscape of hematopoietic cell transplantation (HCT). Pre-HCT MRD has allowed prognostication of HCT outcomes for high-risk leukemia patients, whereas the detection of post-HCT MRD has allowed for interventions to decrease relapse.

Recent findings

In this review, we emphasize studies from the past two decades that highlight the critical role of MRD in HCT in pediatric ALL and AML. Advances in MRD detection methodology, using next-generation sequencing, have improved the sensitivity of MRD testing allowing for more accurate predictions of HCT outcomes for patients with relapsed and refractory ALL and AML. In addition, novel pre-HCT therapies, especially immunotherapy in ALL, have dramatically increased the number of patients who achieve MRD-negative remissions pre-HCT, resulting in improved HCT outcomes. Post-HCT MRD remains a challenge and new therapeutic interventions are needed to reduce post-HCT relapse.

As immunotherapy increases pre-HCT MRD-negative remissions, and next-generation sequencing-MRD is incorporated to improve the sensitivity of MRD detection, future clinical studies will investigate less toxic HCT approaches to reduce long-term sequelae and to identify which patients may benefit most from early post-HCT intervention to reduce relapse.
Augmenting Atrial Fibrillation Care After an Emergency Department Visit
Authors: Hart Danielle , Hopman Wilma M. , Hammond Sharlene , Redfearn Damian P.
Published: December 2018

Background:

Between 2010 and 2012, the Heart Rhythm team in a tertiary care hospital completed a retrospective study that found that atrial fibrillation (AF) care can be episodic and heavily reliant on hospital resources, particularly the emergency department (ED).

Problem:

Patients who attend the ED with AF are at high risk of hospital admission.

Approach:

A nurse practitioner (NP) was added to the Heart Rhythm team to create a program to improve AF care after an ED visit. Telephone practice was one of the many processes created.

Outcomes:

Findings revealed that 37 of 90 patients presented to the ED with AF prior to telephone contact and 7 of 90 patients did so post–telephone contact (P < .001).

Conclusion:

Telephone practice led by an NP provides an opportunity to improve assessment and management of patient with AF and offers a promising cost-effective method to reduce ED visits in the AF patient population.
Interleukin-17A and Chronic Stress in Pregnant Women at 24–28 Weeks Gestation
Authors: Moore Tiffany A. , Case Adam J. , Mathews Therese L. , Epstein Crystal Modde , Kaiser Katherine Laux , Zimmerman Matthew C.
Published: December 2018

Background

Allostatic load (AL) is a biopsychosocial model that suggests chronic psychosocial stress leads to physiological dysregulation and poor outcomes. The purpose of this study was to examine AL in pregnant women operationalized using proinflammatory cytokines and psychosocial indicators and perinatal outcomes.

Objectives

The aim of the study was to identify relationships between circulating cytokines/chemokines and the Prenatal Distress Questionnaire, the Maternal Antenatal Attachment Scale, the Emotional Quotient Inventory, the Life Experiences Scale, and demographics in pregnant women.

Methods

A cross-sectional design was used to recruit pregnant women between 24 and 28 weeks of gestation. Blood and stress/emotional indicators were obtained after informed consent. Plasma was abstracted to simultaneously measure 29 cytokines/chemokines using a multiplex array. Cytokine/chemokine levels were compared with continuous variables using Spearman’s rho and with categorical variables using Mann–Whitney U.

Results

Twenty-five women with medically high-risk (n = 16) and low-risk (n = 9) pregnancies consented. Most women were White (68%) with a mean age of 29 years (SD = 5.9). Although several cytokines and chemokines showed significant correlations with the stress/emotional indicators, only interleukin-17A (IL-17A) was significantly associated with all of the indicators (Prenatal Distress Questionnaire: r
s = .528, p = .012; Maternal Antenatal Attachment Scale: r
s = −.439, p = .036; Emotional Quotient Inventory total: r
s = −.545, p = .007), Life Experiences Scale (r
s = .458, p = .032), birth weight (r
s = −.499, p = .013), and race (p = .01).

Discussion

Increased levels of IL-17A, a known cytokine associated with chronic stress and with poor perinatal outcomes, were associated with high prenatal distress, low maternal attachment, and lower emotional intelligence in pregnant women. Increased levels of IL-17A also were associated with lower birth weight and non-White race. Results support the model of AL in pregnant women and highlight IL-17A as a potential biomarker of AL during pregnancy.
Genomics of Reproductive Traits and Cardiometabolic Disease Risk in African American Women
Authors: Hardy Theresa M. , de Mendoza Veronica Barcelona , Sun Yan V. , Taylor Jacquelyn Y.
Published: December 2018

Background

Age at menarche and age at natural menopause occur significantly earlier in African American women than in other ethnic groups. African American women also have twice the prevalence of cardiometabolic disorders related to the timing of these reproductive traits.

Objectives

The objectives of this integrative review were to (a) summarize the genome-wide association studies of reproductive traits in African American women, (b) identify genes that overlap with reproductive traits and cardiometabolic risk factors in African American women, and (c) propose biological mechanisms explaining the link between reproductive traits and cardiometabolic risk factors.

Methods

PubMed was searched for genome-wide association studies of genes associated with reproductive traits in African American women. After extracting and summarizing the primary genes, we examined whether any of the associations with reproductive traits had also been identified with cardiometabolic risk factors in African American women.

Results

Seven studies met the inclusion criteria. Associations with both reproductive and cardiometabolic traits were reported in or near the following genes: FTO, SEC16B, TMEM18, APOE, PHACTR1, KCNQ1, LDLR, PIK3R1, and RORA. Biological pathways implicated include body weight regulation, vascular homeostasis, and lipid metabolism.

Discussion

A better understanding of the genetic basis of reproductive traits in African American women may provide insight into the biological mechanisms linking variation in these traits with increased risk for cardiometabolic disorders in this population.
Global Transcriptomic Profile of Dorsal Root Ganglion and Physiological Correlates of Cisplatin-Induced Peripheral Neuropathy
Authors: Lessans Sherrie , Lassiter Cameron B. , Carozzi Valentina , Heindel Patrick , Semperboni Sara , Oggioni Norberto , Chiorazzi Alessia , Thompson Carleveva , Wagner Monica , Holden Janean , Rahn Elizabeth , Sweatt J. David , Cavaletti Guido , Renn Cynthia L. , Dorsey Susan G.
Published: December 2018

Background

Multiple cell signaling pathways are implicated in the development, progression, and persistence of cisplatin-induced peripheral neuropathy. Although advances have been made in terms of understanding specific neurotoxic mechanisms, there are few predictive factors identified that can help inform the clinician approach to symptom prevention or management.

Objective

We investigate the differential sensitivity to cisplatin-induced peripheral neuropathy and examine the contribution of dorsal root ganglion (DRG) transcriptional profiles across two inbred strains of mice.

Methods

Cisplatin (4 mg/kg intraperitoneal or vehicle control) was administered twice a week for 4 weeks to adult female C57BL/6J and A/J mice—the C57BL/6J strain of mice characterized by a robust mechanical allodynia and the A/J with a mild largely resistant allodynia phenotype. Peripheral nerve conduction velocities (NCVs), electrophysiological evaluation of wide dynamic range (WDR) neurons, morphological examination of DRG neurons, and microarray analysis of spinal cord tissues were compared across the 4 weeks.

Results

The A/J strain presents with an early, mild nocifensive response to cisplatin with reduced neuronal activity in WDR neurons and small changes in cross-sectional nucleus size in DRG neurons at 4 weeks. The more nocifensive-sensitive C57BL/6J strain presents with no early changes in WDR neuron responsiveness; however, there were significant changes in DRG size. Both strains demonstrate a drop in NCV after 4 weeks of treatment, with the greatest reduction present in the A/J strain. Transcriptome data implicate neuroimmune modulation in the differential response to cisplatin in the DRGs of A/J and C57BL/6J mice.

Discussion

Nocifensive responses in both strains implicate involvement of small myelinated and unmyelinated fibers in neurotoxic cisplatin response, whereas reductions in NCV reflect involvement of the largest myelinated fibers in the peripheral nerves. Microarray data analysis identifies neuropathy-relevant gene sets with differential activation of pathways, suggesting a role for antigen presentation in the differential neurotoxic response to cisplatin across strains. Further research is indicated to determine the relative contributions of each of these potential pathological mechanisms to both the neurotoxic response to cisplatin and to the potential for targeted therapy.
The Effect of a Primary Care Provider Incentive Program on Pediatric Emergency Medicine Visits
Authors: Li Joyce , Patel Binita , Giardino Angelo P. , Camp Elizabeth A. , Macias Charles G.
Published: December 2018

Objective

The aim of the study was to analyze the effect of a financial incentive program targeting primary care providers (PCPs) with the goal of decreasing emergency department (ED) utilization.

Methods

We performed a retrospective cohort analysis in a single health maintenance organization comparing ED visit/1000 member-months before and after the physician incentive program in 2009. We compared the median ED visit rate between physicians who did (PIP) and did not participate (non-PIP) from 2009 to 2012. We used 2008 data as a baseline study period to compare the ED visit rate between PIP and non-PIP providers to detect any inherent difference between the 2 groups.

Results

A total of 1376 PCPs were enrolled. A total of US $18,290,817 was spent in total on incentives. Overall, the median ED visit rate for all providers was statistically significantly lower during the study period (baseline period, study period: 56.36 ED visits/1000 member-months vs 45.82, respectively, P < 0.001). During the baseline period in our fully adjusted linear regression for degree, specialty, education, and board status, PIP versus non-PIP visits were not statistically significantly different (P = 0.17). During the study period in our fully adjusted model, we found that PIP had statistically significant fewer ED visits compared with non-PIP (P = 0.02). In a subgroup analysis of providers who did and did not receive an incentive payment, in the fully adjusted linear regression, providers who received any payment had statistically significant fewer ED visits/1000 member-months (P < 0.001). In addition, we found in the fully adjusted analysis that those providers who received at least 1 incentive payment for meeting after-hours criteria had statistically significantly fewer ED visits/1000 member-months (P < 0.001).

Conclusions

A financial incentive program to provide PCPs with specific targets and goals to decrease pediatric ED utilization can decrease ED visits.
Is a Fundamental Change in the Interpretation of Rheumatoid Arthritis Disease Activity Necessary?
Authors: Wilke William S.
Published: December 2018

Disease Activity Score (DAS) composite models are moderately precise and robust measures of disease severity when they are used in rheumatoid arthritis (RA) cohorts. They are less so when used for individual patients. This is because subjective components, patient global assessment of well-being and tender joint count, modified by factors other than RA biological disease activity, often obfuscate interpretation of disease activity. Comorbidities, especially distress, can disproportionately inflate these components. Fibromyalgia, essentially synonymous with distress, pain augmentation, and depression, is a common comorbidity. Its presence and severity can be determined by the Polysymptomatic Distress Scale (PSD). The differential effects of distress and fibromyalgia syndrome on the DAS can be demonstrated by manipulating information already there: the arithmetic differences or ratios of the tender joint count and swollen joint count and comparison of the modified disease activity score with 28 joints to the disease activity score with 28 joints-patient (DAS28-derived indices that measure the contribution of the relatively objective or relatively subjective components, respectively). The potentially more objective multibiomarker disease activity might also be used to test the severity of biological RA disease activity. These tools may be used to elucidate disproportionate values for subjective DAS model components, which then should facilitate identification of the underlying process factors, including depression, for potential treatment.
Depression Symptoms Among Older Adults With and Without Subacute Low Back Pain
Authors: Lobo César Calvo , Vilar-Fernández Juan Manuel , Losa-Iglesias Marta Elena , López-López Daniel , Rodríguez-Sanz David , Palomo-López Patricia , Becerro-de Bengoa-Vallejo Ricardo
Published: December 2018

Purpose

Lumbago, or low back pain (LBP), is a common musculoskeletal complaint among older adults that may also be associated with depression. The study objective was to investigate differences in Beck Depression Inventory depression symptoms scores among older adult patients with and without LBP.

Design

This was a case–control study.

Methods

A total of 152 older adult patients, recruited at an outpatient healthcare clinic (47 men, 105 women; 74.81 ± 6.9 years), were classified as having subacute LBP (n = 76) or non-LBP (n = 76) according to clinic records.

Findings

Beck Depression Inventory scores (mean ± SD) among LBP patients (10.93 ± 6.18) were significantly higher compared to the non-LBP group (7.62 ± 5.70; p = .000085), whose scores indicated no depression symptoms.

Conclusion

Subacute LBP may represent a potential risk for increased depression among older adults.

Clinical Relevance

Early detection of depression will assist rehabilitation nurses in prescribing the beneficial physical rehabilitation and exercise programs or provide the information and treatment recommendations to older adults with subacute LBP and their families. Also, it should be part of a nursing staff prevention strategy for patients who suffer this common musculoskeletal disorder.
Replicating the complexity of natural surfaces: technique validation and applications for biomimetics, ecology and evolution
Authors: Kumar Charchit , Palacios Alejandro , Surapaneni Venkata A. , Bold Georg , Thielen Marc , Licht Erik , Higham Timothy E. , Speck Thomas , Le Houérou Vincent
Published: December 2018

The surfaces of animals, plants and abiotic structures are not only important for organismal survival, but they have also inspired countless biomimetic and industrial applications. Additionally, the surfaces of animals and plants exhibit an unprecedented level of diversity, and animals often move on the surface of plants. Replicating these surfaces offers a number of advantages, such as preserving a surface that is likely to degrade over time, controlling for non-structural aspects of surfaces, such as compliance and chemistry, and being able to produce large areas of a small surface. In this paper, we compare three replication techniques among a number of species of plants, a technical surface and a rock. We then use two model parameters (cross-covariance function ratio and relative topography difference) to develop a unique method for quantitatively evaluating the quality of the replication. Finally, we outline future directions that can employ highly accurate surface replications, including ecological and evolutionary studies, biomechanical experiments, industrial applications and improving haptic properties of bioinspired surfaces. The recent advances associated with surface replication and imaging technology have formed a foundation on which to incorporate surface information into biological sciences and to improve industrial and biomimetic applications.

This article is part of the theme issue ‘Bioinspired materials and surfaces for green science and technology’.
Design of surfaces for controlling hard and soft fouling
Authors: Halvey Alex Kate , Macdonald Brian , Dhyani Abhishek , Tuteja Anish
Published: December 2018

In this review, we present a framework to guide the design of surfaces which are resistant to solid fouling, based on the modulus and length scale of the fouling material. Solid fouling is defined as the undesired attachment of solid contaminants including ice, clathrates, waxes, inorganic scale, polymers, proteins, dust and biological materials. We first provide an overview of the surface design approaches typically applied across the scope of solid fouling and explain how these disparate research efforts can be united to an extent under a single framework. We discuss how the elastic modulus and the operating length scale of a foulant determine its ability or inability to elastically deform surfaces. When surface deformation occurs, minimization of the substrate elastic modulus is critical for the facile de-bonding of a solid contaminant. Foulants with low modulus or small deposition sizes cannot deform an elastic bulk material and instead de-bond more readily from surfaces with chemistries that minimize their interfacial free energy or induce a particular repellant interaction with the foulant. Overall, we review reported surface design strategies for the reduction in solid fouling, and provide perspective regarding how our framework, together with the modulus and length scale of a foulant, can guide future antifouling surface designs.

This article is part of the theme issue ‘Bioinspired materials and surfaces for green science and technology’.
Transparency in the eye region of an ostracod carapace (Macrocypridina castanea, Myodocopida)
Authors: Parker A. R. , Palka B. P. , Purslow C. , Holden S. , Lewis P. N. , Meek K. M.
Published: December 2018

Many myodocopid ostracods are unusual in that they have well-developed compound eyes yet must view their environment through a shell. The cypridinidMacrocypridina castaneais relatively large among ostracods (about 5–10 mm) and is a pelagic predator. This species possess highly pigmented shells with a transparent region lying just above the eye. Here we examine the ultrastructure and transparency of this window using electron microscopy, serial-block face scanning electron microscopy and X-ray diffraction analysis and optical modelling. An internal, laminar stack was identified within the window region of the shell that formed a more regular half-wave reflector than in non-window regions, and where the distance between molecules in the chitin–protein fibrils decreases as compared to the non-window area. This results in excellent transmission properties—at around 99% transmission—for wavelengths between 350 and 630 nm due to its half-wave reflector organization. Therefore, blue light, common in the mid and deep sea, where this species inhabits, would be near-optimally transmitted as a consequence of the sub-micrometre structuring of the shell, thus optimizing the ostracod's vision. Further, pore canals were identified in the shell that may secrete substances to prevent microbial growth, and subsequently maintain transparency, on the shell surface.

This article is part of the theme issue ‘Bioinspired materials and surfaces for green science and technology’.
Re-designing materials for biomedical applications: from biomimicry to nature-inspired chemical engineering
Authors: Perera Ayomi S. , Coppens Marc-Olivier
Published: December 2018

Gathering inspiration from nature for the design of new materials, products and processes is a topic gaining rapid interest among scientists and engineers. In this review, we introduce the concept of nature-inspired chemical engineering (NICE). We critically examine how this approach offers advantages over straightforward biomimicry and distinguishes itself from bio-integrated design, as a systematic methodology to present innovative solutions to challenging problems. The scope of application of the nature-inspired approach is demonstrated via examples from the field of biomedicine, where much of the inspiration is still more narrowly focused on imitation or bio-integration. We conclude with an outlook on prospective future applications, offered by the more systematic and mechanistically based NICE approach, complemented by rapid progress in manufacturing, computation and robotics.

This article is part of the theme issue ‘Bioinspired materials and surfaces for green science and technology’.
Designing bioinspired surfaces for water collection from fog
Authors: Gurera Dev , Bhushan Bharat
Published: December 2018

A systematic study is presented on various water collectors, bioinspired by desert beetles, desert grass and cacti. Three water collecting mechanisms including heterogeneous wettability, grooved surfaces, and Laplace pressure gradient, were investigated on flat, cylindrical, conical surfaces, and conical array. It is found that higher water repellency in flat surfaces results in higher water collection rate and inclination angle (with respect to the vertical axis) has little effect. Surfaces with heterogeneous wettability have higher water collection rate than surfaces with homogeneous wettability. Both cylindrical and conical surfaces resulted in comparable water collection rate. However, only the cone transported the water droplets to its base. Heterogeneity, higher inclination and grooves increased the water collection rate. A cone has a higher collection rate per unit area than a flat surface with the same wettability. An array of cones has higher collection rate per unit area than a single cone, because droplets in a conical array coalesce, leading to higher frequency of droplets falling. Adding heterogeneity further increases the difference. Based on the findings, scaled-up designs of beetle-, grass- and cactus-inspired surfaces and nets are presented.

This article is part of the theme issue ‘Bioinspired materials and surfaces for green science and technology’.
Facile approach to develop anti-corrosive superhydrophobic aluminium with high mechanical, chemical and thermal durability
Authors: Tudu Balraj Krishnan , Kumar Aditya , Bhushan Bharat
Published: December 2018

Durable, superhydrophobic and self-cleaning aluminium surfaces with high corrosion resistance are desirable in many industrial applications. In this study, a facile approach is used to produce aluminium surfaces with superhydrophobicity with a low tilt angle by creating desired roughness structure by immersing in NaOH solution followed by lowering the surface energy by immersing in hexadecyltrimethoxysilane solution. The coated samples show water contact angle of 164 ± 7° and tilt angle of 5 ± 1°. Droplet dynamics of the coated surfaces was investigated. Surfaces exhibited self-cleaning properties. In addition, mechanical, chemical and thermal stability tests were performed. Electrochemical tests of coated surfaces demonstrated anti-corrosion properties with low corrosion current density and high corrosion potential.

This article is part of the theme issue ‘Bioinspired materials and surfaces for green science and technology’.
Fabrication of bioinspired, self-cleaning, anti-icing, superliquiphilic/phobic titanium using different pathways
Authors: Gurera Dev , Bhushan Bharat
Published: December 2018

Titanium is an important material having a high tensile strength-to-density ratio and high corrosion resistance. It has found applications in the aerospace, marine, automotive and biomedical industries. In some of the applications, it is important to have it as a highly liquid repellent, anti-icing and self-cleaning. There have been several attempts to make titanium superliquiphobic. The common pathways include chemical etching and anodizing. However, important characteristics such as self-cleaning, anti-icing and durability have not been investigated. If any durability data were reported, it was poor. In the current study, various superliquiphilic/phobic surfaces were fabricated using three pathways which include chemical etching, anodizing and nanoparticle-binder coating. Each surface was characterized for wettability, self-cleaning, anti-icing, self-cleaning properties and durability.

This article is part of the theme issue ‘Bioinspired materials and surfaces for green science and technology’.
Target Binding and Sequence Prediction With LSTMs
Authors: Teti Michael , StClair Rachel , Pavlovic Mirjana , Barenholtz Elan , Hahn William
Published: December 2018

Deep recurrent neural networks (DRNNs) have recently demonstrated strong performance in sequential data analysis, such as natural language processing. These capabilities make them a promising tool for inferential analysis of sequentially structured bioinformatics data as well. Here, we assessed the ability of Long Short-Term Memory (LSTM) networks, a class of DRNNs, to predict properties of proteins based on their primary structures. The proposed architecture is trained and tested on two different datasets to predict whether a given sequence falls into a certain class or not. The first dataset, directly imported from Uniprot, was used to train the network on whether a given protein contained or did not contain a conserved sequence (homeodomain), and the second dataset, derived by literature mining, was used to train a network on whether a given protein binds or doesn't bind to Artemisinin, a drug typically used to treat malaria. In each case, the model was able to differentiate between the two different classes of sequences it was given with high accuracy, illustrating successful learning and generalization. Upon completion of training, an ROC curve was created using the homeodomain and artemisinin validation datasets. The AUC of these datasets was 0.80 and 0.87 respectively, further indicating the models' effectiveness. Furthermore, using these trained models, it was possible to derive a protocol for sequence detection of homeodomain and binding motif, which are well-documented in literature, and a known Artemisinin binding site, respectively [1-3]. Along with these contributions, we developed a python API to directly connect to Uniprot data sourcing, train deep neural networks on this primary sequence data using TensorFlow, and uniquely visualize the results of this analysis. Such an approach has the potential to drastically increase accuracy and reduce computational time and, current major limitations in informatics, from inquiry to discovery in protein function research
Real-Time Point Process Filter for Multidimensional Decoding Problems Using Mixture Models
Authors: Yousefi Ali , Rezaei Mohamad Reza , Arai Kensuke , Frank Loren M. , Eden Uri T.
Published: December 2018

There is an increasing demand for a computationally efficient and accurate point process filter solution for real-time decoding of population spiking activity in multidimensional spaces. Real-time tools for neural data analysis, specifically real-time neural decoding solutions open doors for developing experiments in a closed-loop setting and more versatile brain-machine interfaces. Over the past decade, the point process filter has been successfully applied in the decoding of behavioral and biological signals using spiking activity of an ensemble of cells; however, the filter solution is computationally expensive in multi-dimensional filtering problems. Here, we propose an approximate filter solution for a general point-process filter problem when the conditional intensity of a cell's spiking activity is characterized using a Mixture of Gaussians. We propose the filter solution for a broader class of point process observation called marked point-process, which encompasses both clustered —mainly, called sorted— and clusterless —generally called unsorted or raw— spiking activity. We assume that the posterior distribution on each filtering time-step can be approximated using a Gaussian Mixture Model and propose a computationally efficient algorithm to estimate the optimal number of mixture components and their corresponding weights, mean, and covariance estimates. This algorithm provides a real-time solution for multi-dimensional point-process filter problem and attains accuracy comparable to the exact solution. Our solution takes advantage of mixture dropping and merging algorithms, which collectively control the growth of mixture components on each filtering time-step. We apply this methodology in decoding a rat's position in both 1-D and 2-D spaces using clusterless spiking data of an ensemble of rat hippocampus place cells. The approximate solution in 1-D and 2-D decoding is more than 20 and 4,000 times faster than the exact solution, while their accuracy in decoding a rat position only drops by less than 9% and 4% in RMSE and 95% HPD coverage performance metrics. Though the marked-point filter solution is better suited for real-time decoding problems, we discuss how the filter solution can be applied to sorted spike data to better reflect the proposed methodology versatility.
Optical imaging of single protein size, charge, mobility, binding and conformational change
Authors: Ma Guanzhong , Zhu Hao , Wan Zijian , Yang Yunze , Wang Shaopeng , Tao Nongjian
Published: December 2018

Protein analysis has relied on electrophoresis, mass spectroscopy and immunoassay, which separate, detect and identify proteins based on the size, charge, mobility and binding to antibodies. However, measuring these quantities at the single molecule level has not been possible. We tether a protein to a surface with a flexible polymer, drive the protein into mechanical oscillation with an alternating electric field, and image the protein oscillation with a near field imaging method, from which we determine the size, charge, mobility of the protein. We also measure binding of antibodies to single proteins and ligand binding-induced conformational changes in single proteins. This work provides new capabilities for protein analysis and disease biomarker detection at the single molecule level.
Revealing Hi-C subcompartments by imputing high-resolution inter-chromosomal chromatin interactions
Authors: Xiong Kyle , Ma Jian
Published: December 2018

The higher-order genome organization and its variation in different cellular conditions remains poorly understood. Recent high-resolution genome-wide mapping of chromatin interactions using Hi-C has revealed that chromosomes in the human genome are spatially segregated into distinct subcompartments. However, due to the requirement on sequencing coverage of the Hi-C data to define subcompartments, to date subcompartment annotation is only available in the GM12878 cell line, making it impractical to compare Hi-C subcompartment patterns across multiple cell types. Here we develop a new computational approach, named Sniper, based on an autoencoder and multilayer perceptron classifier to infer subcompartments using typical Hi-C datasets with moderate coverage. We demonstrated that Sniper can accurately reveal subcompartments based on Hi-C datasets with moderate coverage and can significantly outperform an existing method that uses numerous epigenomic datasets as input features in GM12878. We applied Sniper to eight additional cell lines to identify the variation of Hi-C subcompartments across different cell types. Sniper revealed that chromosomal regions with conserved and more dynamic subcompartment annotations across cell types have different patterns of functional genomic features. This work demonstrates that Sniper is effective in identifying subcompartments without the need of high-coverage Hi-C data and has the potential to provide new insights into the spatial genome organization variation across different cell types.
Honey bee parasitic mite contains the sensory organ expressing ionotropic receptors with conserved functions
Authors: Lei Jing , Liu Qiushi , Kadowaki Tatsuhiko
Published: December 2018

Honey bee parasitic mites (Tropilaelaps mercedesaeandVarroa destructor) detect temperature, humidity, and odor but the underlying sensory mechanisms are poorly understood. To uncover howT. mercedesaeresponds to environmental stimuli inside a hive, we identified the sensilla-rich sensory organ on the foreleg tarsus. The organ contained four types of sensilla, which may respond to different stimuli based on their morphology. We found the forelegs were enriched with mRNAs encoding sensory proteins such as ionotropic receptors (IRs) and gustatory receptors (GRs), as well as proteins involved in ciliary transport. We also found thatT. mercedesaeandDrosophila melanogasterIR25a and IR93a are functionally equivalent. These results demonstrate that the structures and physiological functions of ancient IRs have been conserved during arthropod evolution. Our study provides insight into the sensory mechanisms of honey bee parasitic mites, as well as potential targets for methods to control the most serious honey bee pest.
Identifying Context-specific Network Features for CRISPR-Cas9 Targeting Efficiency Using Accurate and Interpretable Deep Neural Network
Authors: Liu Qiao , He Di , Xie Lei
Published: December 2018

CRISPR-Cas9 is a powerful genome editing tool, whose efficiency and safety depends on the selection of single-guide RNA (sgRNA). Machine learning has been applied to optimize sgRNA selection, but several challenges remain. The performance of predictive model is limited by the amount of available data in many cell lines, ignorance of gene network function and its variable effect on phenotype, and elusive biological interpretation of computational models. We develop an accurate and interpretable deep learning model SeqCrispr to address these problems. In benchmark studies, SeqCrispr outperforms state-of-the-art algorithms and improves the prediction accuracy when applied to small sample size cell lines. Furthermore, we find that gene context-specific network properties are critical for the prediction accuracy in addition to the last three nucleotides in sgRNA 3’end. Our findings will bolster developing more accurate predictive models of CRISPR-Cas9 across wide spectrum of biological conditions as well as efficient and safe gene therapy.
A 3.8 Å Resolution Cryo-EM Structure of a Small Protein Bound to a Modular Imaging Scaffold
Authors: Liu Yuxi , Huynh Duc , Yeates Todd O
Published: December 2018

Proteins smaller than about 50 kDa are currently too small to be imaged by cryo-electron microscopy (cryo-EM), leaving most protein molecules in the cell beyond the reach of this powerful structural technique. Here we use a designed protein scaffold to bind and symmetrically display 12 copies of a small 26 kDa protein. We show that the bound cargo protein is held rigidly enough to visualize it at a resolution of 3.8 Å by cryo-EM, where basic structural features of the protein are visible. The designed scaffold is modular and can be modified through modest changes in its amino acid sequence to bind and display diverse proteins for imaging, thus providing a general method to break through the lower size limitation in cryo-EM.
Population extinctions driven by climate change, population size, and time since observation may make rare species databases inaccurate
Authors: Kaye Thomas , Bahm Matt A , Thorpe Andrea S , Gray Erin C , Pfingsten Ian , Waddell Chelsea
Published: December 2018

Loss of biological diversity through population extinctions is a global phenomenon that threatens many ecosystems. Managers often rely on databases of rare species locations to plan land use actions and conserve at-risk taxa, so it is crucial that the information they contain is accurate and dependable. However, climate change, small population sizes, and long gaps between surveys may be leading to undetected extinctions of many populations. We used repeated survey records for a rare but widespread orchid, Cypripedium fasciculatum (clustered lady's slipper), to model population extinction risk based on elevation, population size, and time between observations. Population size was negatively associated with extinction, while elevation and time between observations interacted such that low elevation populations were most vulnerable to extinction, but only over larger time spans. We interpret population losses at low elevations as a potential signal of climate change impacts. We used this model to estimate the probability of persistence of populations across California and Oregon, and found that 31%-56% of the 2415 populations reported in databases from this region are likely extinct. Managers should be aware that the number of populations of rare species in their databases is potentially an overestimate, and consider resurveying these populations to document their presence and condition, with priority given to older reports of small populations, especially those at low elevations or in other areas with high climate vulnerability.
A jumping crystal predicted with molecular dynamics and analysed with TLS refinement against powder diffraction data
Authors: van de Streek Jacco , Alig Edith , Parsons Simon , Vella-Zarb Liana
Published: December 2018

By running a temperature series of molecular dynamics (MD) simulations starting from the known low-temperature phase, the experimentally observed phase transition in a `jumping crystal' was captured, thereby providing a prediction of the unknown crystal structure of the high-temperature phase and clarifying the phase-transition mechanism. The phase transition is accompanied by a discontinuity in two of the unit-cell parameters. The structure of the high-temperature phase is very similar to that of the low-temperature phase. The anisotropic displacement parameters calculated from the MD simulations readily identified libration as the driving force behind the phase transition. Both the predicted crystal structure and the phase-transition mechanism were verified experimentally using TLS (translation, libration, screw) refinement against X-ray powder diffraction data.
Hypervalent organoselenium compounds stabilized by intramolecular coordination: synthesis and crystal structures
Authors: Venkateshwaran Krishnan , Deka Rajesh , Raju Saravanan , Singh Harkesh B. , Butcher Ray J.
Published: December 2018

Two novel hypervalent selenium(IV) compounds stabilized by intramolecular interactions, namely 6-phenyl-6,7-dihydro-5H-2,3-dioxa-2aλ4-selenacyclopenta[hi]indene, C14H12O2Se, 14, and 5-phenyl-5,6-dihydro-4H-benzo[c][1,2]oxaselenole-7-carbaldehyde, C14H12OSe2, 15, have been synthesized by the reaction of 2-chloro-1-formyl-3-(hydroxymethylene)cyclohexene with in-situ-generated disodium diselenide (Na2Se2). The title compounds were characterized by FT–IR spectroscopy, ESI–MS, and single-crystal X-ray diffraction studies. For 14, there is whole-molecule disorder, with occupancies of 0.605 (10) and 0.395 (10), a double bond between C and Se, and the five-membered selenopentalene rings are coplanar. The packing is stabilized by π–π stacking interactions involving one of the five-membered Se/C/C/C/O rings [centroid–centroid (Cg...Cg) distance = 3.6472 (18) Å and slippage = 1.361 Å], as well as C—H...π interactions involving a C—H group and the phenyl ring. In addition, there are bifurcated C—H...Se,O interactions which link the molecules into ribbons in the c direction. For 15, the C—Se bond lengths are longer than those of 14. The two five-membered rings are coplanar. There are no π–π or C—H...π interactions; however, molecules are linked by C—H...O interactions into centrosymmetric dimers, with graph-set notation R
2
2(16).
Contrasting patterns of plant and microbial diversity during long‐term ecosystem development
Authors: Turner Benjamin L. , Zemunik Graham , Laliberté Etienne , Drake Jeremy J. , Jones F. Andrew , Saltonstall Kristin
Published: December 2018

Long‐term ecosystem development involves changes in plant community composition and diversity associated with pedogenesis and nutrient availability, but comparable changes in soil microbial communities remain poorly understood. In particular, it is unclear whether the diversity of plants and microbes respond to similar abiotic drivers, or become decoupled as resources change over long time‐scales.

We characterized communities of archaea, bacteria and fungi in soils along a 2‐million‐year chronosequence of coastal dunes in a biodiversity hot spot in Western Australia. The chronosequence involves marked changes in soil pH and nutrient availability that drive major shifts in plant community composition and diversity as soils age.

Patterns of α‐diversity for microbial groups differed along the chronosequence. Bacterial α‐diversity was greatest in intermediate‐aged soils; archaeal diversity was greater in young alkaline or intermediate‐aged soils, while fungal α‐diversity—like plant diversity—was greatest in old, strongly weathered soils where phosphorus is the limiting nutrient.

Changes in microbial community composition along the chronosequence were explained primarily by the long‐term decline in soil pH, with a smaller influence of the relative abundance of plant nutrient‐acquisition strategies. However, changes between the prokaryote and fungal communities, and between fungal and plant communities, became increasingly decoupled along the chronosequence, demonstrating that the coordination of change in biological communities by abiotic drivers becomes weaker during long‐term ecosystem development.

Several bacterial taxa, including DA101 (Verrucomicrobia), “Candidatus Solibacter” (Acidobacteria) and Gaiella (Actinobacteria), were particularly abundant on the oldest dunes, indicating that they are adapted to acquire phosphorus from extremely infertile soils. However, we cannot disentangle the influence of phosphorus from the long‐term decline in soil pH along the chronosequence.

Synthesis. These results provide evidence for contrasting patterns of plant and microbial community composition and α‐diversity in response to acidification and nutrient depletion during long‐term pedogenesis.
Urea Fluctuations in Stream Baseflow across Land Cover Gradients and Seasons in a Coastal Plain River System
Authors: Tzilkowski Sarah S. , Buda Anthony R. , Boyer Elizabeth W. , Bryant Ray B. , Kleinman Peter J.A. , Kennedy Casey D. , Allen Arthur L. , Folmar Gordon J. , May Eric B.
Published: December 2018

Urea‐N is a component of bioavailable dissolved organic nitrogen (DON) that contributes to coastal eutrophication. In this study, we assessed urea‐N in baseflow across land cover gradients and seasons in the Manokin River Basin on the Delmarva Peninsula. From March 2010 to June 2011, we conducted monthly sampling of 11 streams (4 tidal and 7 nontidal), 2 wastewater treatment plants, an agricultural drainage ditch, and groundwater underlying a cropped field. At each site, we measured urea‐N, DON, dissolved organic carbon (DOC), total dissolved nitrogen (TDN), NO3−‐N, and NH4+‐N. In general, urea‐N comprised between 1% and 6% of TDN, with the highest urea‐N levels in drainage ditches (0.054 mg N/L) and wetland‐dominated streams (0.035–0.045 mg N/L). While urea‐N did not vary seasonally in tidal rivers, nontidal streams saw distinct urea‐N peaks in summer (0.038 mg N/L) that occurred several months after cropland fertilization in spring. Notably, the proportion of wetlands explained 78% of the variance in baseflow urea‐N levels across the Manokin watershed. In wetland‐dominated basins, we found urea‐N was positively related to water temperature and negatively related to DOC:DON ratios, indicating short‐term urea‐N dynamics at baseflow were more likely influenced by instream and wetland‐driven processes than by recent agricultural urea‐N inputs. Findings demonstrate important controls of wetlands on baseflow urea‐N concentrations in mixed land‐use basins.