bluuebunny/crossref_metadata_2025 huggingface dataset:
Subvaluationism and classical recapture
Authors: Teijeiro Paula
Published: October 2018

Adopting a non-classical logic may not imply resigning the classical theories that have proven their worth. Nevertheless, the project of classical recapture poses some challenges, some of them specific to paraconsistent approaches. In this article, we analyse the consequences of introducing a recovery operator to subvaluationist logic. We argue that the classical recovery can indeed be carried out in a subvaluationist setting, but that doing so amounts to committing to a hierarchy of recaptures.
Posaconazole Administration in Hospitalized Children in the United States
Authors: Lavigne Sondra , Fisher Brian T , Ellis Darcy , Zaoutis Theoklis E , Downes Kevin J
Published: October 2018

In this study, we evaluated posaconazole use among hospitalized children between October 2006 and September 2015 using data from the Pediatric Health Information System. A total of 878 children (in 1949 admissions) received posaconazole, and administration increased 22% per year overall and 27% per year in children aged <13 years for whom the drug was not approved.
Interpreting results
Authors: Raine Tim , Collins George , Hall Catriona , Hjelde Nina , Dawson James , Sanders Stephan , Eccles Simon
Published: October 2018

This chapter explores interpreting results, including blood tests, full blood count (FBC), clotting, cardiac markers, inflammatory response, urea and electrolytes (U+E), liver function tests (LFT) and amylase, calcium and phosphate, endocrine tests, cardiology, electrocardiogram (ECG), respiratory, chest X-ray (CXR), arterial blood gases (ABGs), respiratory function tests, gastrointestinal, abdomen X-ray (AXR), urine tests, neurological, CSF, musculoskeletal, autoantibodies and associated diseases, cervical spine radiographs, and skeletal radiographs.
AKARI mission program: Excavating Mass Loss History in extended dust shells of Evolved Stars (MLHES). I. Far-IR photometry
Authors: Ueta Toshiya , Torres Andrew J , Izumiura Hideyuki , Yamamura Issei , Takita Satoshi , Tomasino Rachael L
Published: October 2018

We performed a far-IR imaging survey of the circumstellar dust shells of 144 evolved stars as a mission program of the AKARI infrared astronomical satellite using the Far-Infrared Surveyor (FIS) instrument. With this survey, we deliver far-IR surface brightness distributions of roughly 10′ × 40′ or 10′ × 20′ areas of the sky around the target evolved stars in the four FIS bands at 65, 90, 140, and 160 μm. Our objectives are to characterize the far-IR surface brightness distributions of the cold dust component in the circumstellar dust shells, from which we derive the amount of cold dust grains as low as 20 K and empirically establish the early mass loss history. In this first installment of the series, we introduce the project and its aims, describe the observations, data reduction, and surface brightness correction process, and present the entire data set along with the results of integrated photometry measurements (i.e., the central source and circumstellar dust shell together). We find that: (1) far-IR emission is detected from all but one object at the spatial resolution about 30′–50′ in the corresponding bands; (2) roughly 60%–70% of the target sources show some extension; (3) previously unresolved nearby objects in the far IR are now resolved around 28 target sources; (4) the results of photometry measurements are reasonable with respect to the entries in the AKARI/FIS Bright Source Catalogue, despite the fact that the targets were assumed to be point sources when catalogue flux densities were computed; and (5) an IR two-color diagram would place the target sources in a roughly linear distribution that may correlate with the age of the circumstellar dust shell and can potentially be used to identify which targets are more extended than others.
Incentivizing Medical Teachers: Exploring the Role of Incentives in Influencing Motivations
Authors: Wisener Katherine M. , Eva Kevin W.
Published: October 2018

Purpose

Medical education is dependent on clinicians and other faculty who volunteer time and expertise to teaching. Unfortunately, the literature reports increasing levels of dissatisfaction, burnout, and attrition. Incentivization provides an obvious intervention, but rewards must be implemented judiciously or risk unintended consequences. With little known about the effects of incentives in medical education, the authors investigate key insights across three disciplines to explain how, why, and when incentives can be used effectively.

Method

In this critical synthesis, a purposeful and iterative literature search was conducted by exploring a variety of databases to identify seminal articles, key concepts, and generative search terms. Particularly fruitful disciplines were then explored more deliberately.

Results

Psychologists argue that the impact of an incentive depends on an individual’s motivational drives. Organizational behaviorists draw attention to environmental incentives and disincentives that build or detract from motivation. Behavioral economists posit that size, type, and way in which an incentive is provided affect motivation differently.

Conclusions

The influence of an incentive depends on how it interacts with underlying mechanisms deemed important for motivation. These mechanisms change across tasks, individuals, and contexts. Recommendations derived from the effort include being deliberate about (1) determining what is driving the individual to act, (2) considering the unique interactions between incentives and motivation types, and (3) considering barriers that may interfere with incentive effectiveness. In examining each of these, the authors argue that the field needs greater clarity regarding how, when, and why incentives operate within the many contexts in which medical educators work.
Unilateral Eyelid Swelling as a Sign of Antimelanoma Differentiation–Associated Gene 5 (Anti-MDA5)-Antibody–Positive Dermatomyositis
Authors: Lam Stacey C. , Yuen Hunter K. L.
Published: October 2018

The authors describe a 40-year-old woman who presented with unilateral eyelid swelling, and later on developed heliotrope rash, extensive oral and cutaneous ulcers, and muscle weakness. She was diagnosed with dermatomyositis associated with antimelanoma differentiation–associated gene 5 antibody. Even after combination of immunosupressants including a corticosteroid, tacrolimus, and rituximab, her eyelid swelling and oral ulcers progressively worsened. Administration of loading and then monthly intravenous immunoglobulin resulted in clinical remission, suggesting that intravenous immunoglobulin could be a useful remedy in cases refractory to conventional immunosuppressive agents, especially those with antimelanoma differentiation–associated gene 5 antibody-dermatomyositis.
Enduring Effects of One-Day Training in Good Psychiatric Management on Clinician Attitudes About Borderline Personality Disorder
Authors: Masland Sara Rose , Price Daniel , MacDonald Jacob , Finch Ellen , Gunderson John , Choi-Kain Lois
Published: October 2018

Time-limited interventions may attenuate stigma and negative beliefs about borderline personality disorder (BPD) among mental health clinicians. This study examined whether a 1-day training in good psychiatric management (GPM) changed clinician attitudes and beliefs and whether those changes persisted over time. Fifty-two mental health clinicians attended a 1-day GPM training and completed a 13-item assessment of attitudes about BPD before and after the training and again 6 months later. One-way repeated-measures analysis of variances and dependent sample t-tests demonstrated significant changes for all items, 11 of which were in the direction of more positive attitudes about BPD. For six items, attitudes did not change immediately after training, but 6 months later had changed significantly. Findings indicate that brief training can foster enduring improvements in clinician attitudes and beliefs about BPD.
The Emotional Cost of Caring for Others
Authors: Walden Marlene , Adams Greg , Annesley-Dewinter Elissa , Bai Shasha , Belknap Nici , Eichenlaub Amy , Green Angela , Huett Amy , Lea Katie , Lovenstein Austin , Ramick Amy , Salassi-Scotter Mary , Webb Tammy , Wessel Valerie
Published: October 2018

OBJECTIVE

This study examined the prevalence of compassion fatigue and life stress of pediatric nurses.

BACKGROUND

Distressing patient situations over time may affect nurses' professional quality of life and result in compassion fatigue. If not addressed, compassion fatigue may have personal and organizational consequences.

METHODS

Using a descriptive, correlational design, a convenience sample of 268 nurses completed a web-based survey.

RESULTS

High compassion satisfaction and moderate to low burnout and secondary traumatic stress were described by 49% of participants. Education was statistically associated with burnout and secondary traumatic stress. Life stress scores were significantly associated with age, experience, organizational tenure, and professional engagement. Narrative commentary yielded 5 themes: staffing, recognition, boundaries, expectations, and hopelessness. Organizational initiatives to prevent or mitigate compassion fatigue focused on awareness, balance, and connections.

CONCLUSIONS

Nurses are negatively impacted by the emotional cost of caring. Future studies need to identify interventions to minimize compassion fatigue.
Quantitative Dual-Energy Computed Tomography Predicts Regional Perfusion Heterogeneity in a Model of Acute Lung Injury
Authors: Kay Fernando Uliana , Beraldo Marcelo A. , Nakamura Maria A. M. , De Santis Santiago Roberta , Torsani Vinicius , Gomes Susimeire , Roldan Rollin , Tucci Mauro R. , Abbara Suhny , Amato Marcelo B. P. , Amaro Edson
Published: October 2018

Objective

The aims of this study were to investigate the ability of contrast-enhanced dual-energy computed tomography (DECT) for assessing regional perfusion in a model of acute lung injury, using dynamic first-pass perfusion CT (DynCT) as the criterion standard and to evaluate if changes in lung perfusion caused by prone ventilation are similarly demonstrated by DECT and DynCT.

Methods

This was an institutional review board–approved study, compliant with guidelines for humane care of laboratory animals. A ventilator-induced lung injury protocol was applied to 6 landrace pigs. Perfused blood volume (PBV) and pulmonary blood flow (PBF) were respectively quantified by DECT and DynCT, in supine and prone positions. The lungs were segmented in equally sized regions of interest, namely, dorsal, middle, and ventral. Perfused blood volume and PBF values were normalized by lung density. Regional air fraction (AF) was assessed by triple-material decomposition DECT. Per-animal correlation between PBV and PBF was assessed with Pearson R. Regional differences in PBV, PBF, and AF were evaluated with 1-way analysis of variance and post hoc linear trend analysis (α = 5%).

Results

Mean correlation coefficient between PBV and PBF was 0.70 (range, 0.55–0.98). Higher PBV and PBF values were observed in dorsal versus ventral regions. Dorsal-to-ventral linear trend slopes were −10.24 mL/100 g per zone for PBV (P < 0.001) and −223.0 mL/100 g per minute per zone for PBF (P < 0.001). Prone ventilation also revealed higher PBV and PBF in dorsal versus ventral regions. Dorsal-to-ventral linear trend slopes were −16.16 mL/100 g per zone for PBV (P < 0.001) and −108.2 mL/100 g per minute per zone for PBF (P < 0.001). By contrast, AF was lower in dorsal versus ventral regions in supine position, with dorsal-to-ventral linear trend slope of +5.77%/zone (P < 0.05). Prone ventilation was associated with homogenization of AF distribution among different regions (P = 0.74).

Conclusions

Dual-energy computed tomography PBV is correlated with DynCT-PBF in a model of acute lung injury, and able to demonstrate regional differences in pulmonary perfusion. Perfusion was higher in the dorsal regions, irrespectively to decubitus, with more homogeneous lung aeration in prone position.
FDG PET for Evaluation of Bone Marrow Status in T-Cell Lymphoma
Authors: Koh Youngil , Lee Jung Min , Woo Go-Un , Paeng Jin Chul , Youk Jeonghwan , Yoon Sung-Soo , Kim Inho , Kang Keon Wook
Published: October 2018

Purpose

In T-cell lymphoma, the role of FDG PET for bone marrow (BM) evaluation is not established yet. We investigated diagnostic performance and prognostic implication of FDG PET for BM evaluation in peripheral T-cell lymphoma (PTCL) and extranodal NK/T-cell lymphoma (NKTCL).

Patients and Methods

Patients with PTCL or NKTCL, who underwent initial staging with FDG PET and BM biopsy, were retrospectively enrolled and analyzed. PET BM finding was evaluated using visual analysis and a quantitative index (marrow-to-liver ratio [MLR]). Diagnostic performance of PET for BM involvement was assessed with biopsy as the gold standard. Prognostic value of PET findings was also assessed regarding progression-free survival (PFS) and overall survival (OS).

Results

A total of 109 (63 PTCL and 46 NKTCL) patients were analyzed. Biopsy revealed BM involvement in 35.8% of cases. Sensitivity and specificity of PET for diagnosing positive BM biopsy were 61.5% and 75.7% by visual analysis and 64.1% and 72.9% by MLR. Diagnostic performance of PET was not different across lymphoma types. Survival analysis revealed that MLR and BM biopsy result is significant for both PFS and OS. In multivariate analysis, MLR was an independent prognostic factor for both PFS and OS. Marrow-to-liver ratio was also a significant prognostic factor in BM biopsy-negative patients.

Conclusions

Despite fair correlation with BM biopsy result, PET may not replace BM biopsy in PTCL and NKTCL. However, the BM finding on PET is an independent prognostic factor, suggesting additional biological implication of PET findings.
Occult Cerebral Abscess Revealed by FDG PET/CT in a Case of Unresponsive Wakefulness Syndrome
Authors: Bund Caroline , Coca Hugo Andres , Kremer Stéphane , Pottecher Julien , Namer Izzie-Jacques
Published: October 2018

A 51-year-old woman developed profound coma complicating subarachnoid hemorrhage after aneurysmal rupture. An external ventricular drain was inserted. FDG PET/CT was performed for prognostication purposes and showed global cortical hypometabolism. This was consistent with the clinical findings of an unresponsive wakefulness syndrome. During the follow-up, ventriculitis was diagnosed. Because of no clinical improvement under focused, high-dose antimicrobial treatment, a second FDG PET/CT was performed. It showed an improved diffuse cortical fixation and an intense intraventricular hyperfixation, suggestive of intraventricular abscess. A third functional imaging, performed to monitor treatment, showed progressive metabolic recovery with especially uptake in frontoparietal areas over time.
99mTc-MAG3 Renography of Intrathoracic Renal Ectopia
Authors: ten Broek Marc R.J. , te Beek Erik T. , Stuurman-Wieringa Roos E.
Published: October 2018

We report a case of a 49-year-old woman with a rare anomaly, intrathoracic renal ectopia. Her medical history includes a surgically corrected congenital diaphragmatic hernia, which can cause late presentations of diaphragmatic hernia in adult life. The99mTc-MAG3 renogram demonstrated slower emptying of the dilated pelvis of the ectopic kidney than the normal kidney. The curve confirmed a delayed Tmax, followed by a distinct decline. These features are not indicative of a complete obstruction, but can result from partial obstruction, renal dysfunction with poor response to diuresis, pelvic dilatation (such as in our patient), or a combination.
American Urogynecologic Society Best-Practice Statement on Evaluation of Obstructed Defecation
Authors: Ridgeway Beri M. , Weinstein Milena M. , Tunitsky-Bitton Elena
Published: October 2018

The symptoms of constipation and obstructed defecation are common in women with pelvic floor disorders. Female pelvic medicine and reconstructive surgery specialists evaluate and treat women with these symptoms, with the initial consultation often occurring when a woman has the symptom or sign of posterior compartment pelvic organ prolapse (including rectocele or enterocele) or if a rectocele or enterocele is identified in pelvic imaging. This best-practice statement will review techniques used to evaluate constipation and obstructed defecation, with a special focus on the relationship between obstructed defecation, constipation, and pelvic organ prolapse.
Evaluation of the Effect of 16 Weeks of Multifactorial Exercises on the Functional Fitness and Postural Stability of a Low-Income Elderly Population
Authors: Ćwirlej-Sozańska Agnieszka , Wiśniowska-Szurlej Agnieszka , Wilmowska-Pietruszyńska Anna , Drużbicki Mariusz , Sozański Bernard , Wołoszyn Natalia , Guzik Agnieszka
Published: October 2018

A multifactorial exercise programs for older people should be introduced to low-income communities. Of the 138 people who volunteered for the trial, 50 were enrolled and randomly assigned to either the study group (multifactorial exercises and health education; MEE) or the control group (health education; E). Results shown that the MEE group had significantly improved tandem test results and mobility. Improvement in all items of the Senior Fitness Test was also observed. No statistically significant changes were observed in the control group. A multifactorial exercise program combined with health education resulted in a significant improvement in the functional status of elderly people with low incomes.
Eating Behaviors, Sociodemographics, Self-Perceived Health, and Weight Status Among Jordanian University Students
Authors: Amr Rula A. , Hammouh Fadwa G. , Al-Smadi Ahmed M. , Albandak Ghada S. , Dababneh Basem F. , Qatatsheh Alaa A.
Published: October 2018

Fast-food consumption has increased in the past few decades. The main objective of this study was to examine the prevalence and characteristics of fast-food consumption among Jordanian university students. A cross-sectional survey recruited 900 students. The results indicate that the majority of students had 2 or more fast-food meals per week. Those who were male, non-Jordanian, and between 20 and 22 years of age showed significant high fast-food consumption. With the presence of a high prevalence of fast-food consumption and associated factors shown in this study, there is a need to encourage healthy eating habits and to inform students about the negative aspects of fast-food consumption.
A derivation of Maxwell's equations using the Heaviside notation
Authors: Hampshire Damian P.
Published: October 2018

Maxwell's four differential equations describing electromagnetism are among the most famous equations in science. Feynman said that they provide four of the seven fundamental laws of classical physics. In this paper, we derive Maxwell's equations using a well-established approach for deriving time-dependent differential equations from static laws. The derivation uses the standard Heaviside notation. It assumes conservation of charge and that Coulomb's law of electrostatics and Ampere's law of magnetostatics are both correct as a function of time when they are limited to describing a local system. It is analogous to deriving the differential equation of motion for sound, assuming conservation of mass, Newton's second law of motion and that Hooke's static law of elasticity holds for a system in local equilibrium. This work demonstrates that it is the conservation of charge that couples time-varyingE-fields andB-fields and that Faraday's Law can be derived without any relativistic assumptions about Lorentz invariance. It also widens the choice of axioms, or starting points, for understanding electromagnetism.

This article is part of the theme issue ‘Celebrating 125 years of Oliver Heaviside's ‘Electromagnetic Theory’’.
The antiviral piRNA response in mosquitoes?
Authors: Varjak Margus , Leggewie Mayke , Schnettler Esther
Published: October 2018

There are several RNA interference (RNAi) pathways in insects. The small interfering RNA pathway is considered to be the main antiviral mechanism of the innate immune system; however, virus-specific P-element-induced Wimpy testis gene (PIWI)-interacting RNAs (vpiRNAs) have also been described, especially in mosquitoes. Understanding the antiviral potential of the RNAi pathways is important, given that many human and animal pathogens are transmitted by mosquitoes, such as Zika virus, dengue virus and chikungunya virus. In recent years, significant progress has been made to characterize the piRNA pathway in mosquitoes (including the possible antiviral activity) and to determine the differences between mosquitoes and the model organism Drosophila melanogaster. The new findings, especially regarding vpiRNA in mosquitoes, as well as important questions that need to be tackled in the future, are discussed in this review.
CellTool: an open source software combining bio-image analysis and mathematical modeling
Authors: Danovski Georgi , Dyankova Teodora , Stoynov Stoyno
Published: October 2018

We present CellTool, a stand-alone open source software with a Graphical User Interface for image analysis, optimized for measurement of time-lapse microscopy images. It combines data management, image processing, mathematical modeling and graphical presentation of data in a single package. Multiple image filters, segmentation and particle tracking algorithms, combined with direct visualization of the obtained results make CellTool an ideal application for rapid execution of complex tasks. In addition, the software allows for the fitting of the obtained results to predefined or custom mathematical models. Importantly, CellTool provides a platform for easy implementation of custom image analysis packages written on a variety of programing languages.

Availability and Implementation

CellTool is a free software available for MS Windows OS under the terms of the GNU General Public License. Executables and source files, supplementary information and sample data sets are freely available for download at URL: https://dnarepair.bas.bg/software/CellTool/

Contact

danovski@bio21.bas.bg; stoynov@bio21.bas.bg;

Supplementary information

Supplementary data are available at URL: https://dnarepair.bas.bg/software/CellTool/Program/CellTool_UserGuide.pdf
Reporter assays for Ebola virus nucleoprotein oligomerization, virion-like particle budding, and minigenome activity reveal the importance of nucleoprotein amino acid position 111
Authors: Lin Aaron E. , Diehl William E. , Cai Yingyun , Finch Courtney L. , Akusobi Chidiebere , Kirchdoerfer Robert N. , Bollinger Laura , Schaffner Stephen F. , Brown Elizabeth A. , Saphire Erica Ollmann , Andersen Kristian G. , Kuhn Jens H. , Luban Jeremy , Sabeti Pardis C.
Published: October 2018

For highly pathogenic viruses, reporter assays that can be rapidly performed are critically needed to identify potentially functional mutations for further study under maximal containment (e.g., biosafety level 4 [BSL-4]). The Ebola virus nucleoprotein (NP) plays multiple essential roles during the viral life cycle, yet few tools exist to study the protein under BSL-2 or equivalent containment. Therefore, we adapted reporter assays to measure NP oligomerization and virion-like particle (VLP) production in live cells and further measure transcription and replication using established minigenome assays. As a proof-of-concept, we examined the NP-R111C substitution, which emerged during the 2013–2016 Western African Ebola virus disease epidemic and rose to high frequency. NP-R111C slightly increased NP oligomerization and VLP budding but slightly decreased transcription and replication. By contrast, a synthetic charge-reversal mutant, NP-R111E, greatly increased oligomerization but abrogated transcription and replication. These results are intriguing in light of recent structures of NP oligomers, which reveal that the neighboring residue, K110, forms a salt bridge with E349 on adjacent NP molecules. By developing and utilizing multiple reporter assays, we find that the NP-111 position mediates a complex interplay between NP’s roles in protein structure, virion budding, and transcription and replication.
Ultra-sensitive measurement of brain penetration with microscale probes for brain machine interface considerations
Authors: Obaid Abdulmalik , Wu Yu-Wei , Hanna Mina , Nix William , Ding Jun , Melosh Nicholas
Published: October 2018

Microscale electrodes are rapidly becoming critical tools for neuroscience and brain-machine interfaces (BMIs) for their high spatial and temporal resolution. However, the mechanics of how devices on this scale insert into brain tissue is unknown, making it difficult to balance between larger probes with higher stiffness, or smaller probes with lower damage. Measurements have been experimentally challenging due to the large deformations, rapid events, and small forces involved. Here we modified a nanoindentation force measurement system to provide the first ultra-high resolution force, distance, and temporal recordings of brain penetration as a function of microwire diameter (7.5 µm to 100 µm) and tip geometry (flat, angled, and electrosharpened). Surprisingly, both penetration force and tissue compression scaled linearly with wire diameter, rather than cross-sectional area. Linear brain compression with wire diameter strongly suggest smaller probes will cause less tissue damage upon insertion, though unexpectedly no statistical difference was observed between angled and flat tipped probes. These first of their kind measurements provide a mechanical framework for designing effective microprobe geometries while limiting mechanical damage.
Identifying priority conservation areas for recovering large carnivores using citizen science data
Authors: Bonnet-Lebrun A-S. , Karamanlidis A.A. , de Gabriel Hernando M. , Renner I. , Gimenez O.
Published: October 2018

Understanding the processes related to wildlife recoveries is not only essential in solving human – wildlife conflicts, but also for identifying priority conservation areas and in turn, for effective conservation planning. We used data from a large citizen science program to study the spatial processes related to the demographic and genetic recovery of brown bears in Greece and to identify new areas for their conservation. This was achieved by visually comparing our data with an estimation of the past distribution of brown bears in Greece and by using a Point Process Model to model habitat suitability, and then comparing our results with the current distribution of brown bear records and with that of protected areas. Our results indicate that in the last 15 years bears may have increased their range by as much as 100%, by occupying mainly anthropogenic landscapes and areas with suitable habitat that are currently not legally protected, thus creating a new conservation reality for the species in Greece. This development dictates the re-evaluation of the national management and conservation priorities for brown bears in Greece by focusing in establishing new protected areas that will safeguard their recovery. Our conservation approach is a swift and cheap way of identifying priority conservation areas, while gaining important insights on the spatial processes associated with population recoveries. It will help prioritize conservation actions for brown bears in Greece and may serve as a model conservation approach to countries facing financial and logistic constraints in the monitoring of local biodiversity or facing challenges in managing rapid population recoveries. Our conservation approach appeared also to be better suited to identifying priority areas for conservation in areas with recovering wildlife populations and may therefore be used as an “early-warning” conservation system.
SNAPPY: Single Nucleotide Assignment of Phylogenetic Parameters on the Y chromosome
Authors: Severson Alissa L. , Shortt Jonathan A. , Mendez Fernando L. , Wojcik Genevieve L. , Bustamante Carlos D. , Gignoux Christopher R.
Published: October 2018

The assignment of Y chromosome data to related clusters, or haplogroups, is a common application in human population genetics. To enable this at scale, we developed SNAPPY. SNAPPY is a software program used to assign Y-chromosome phylogeny-informed haplotypes using dense genotype data. The program efficiently tests all haplotypes in a provided Y-chromosome database to find the haplogroup that is best supported by the input genotypes. Importantly, the method considers both the amount of support for the specific haplogroup, as well as its ancestral haplogroups via parsimony. This accounts for the underlying genealogy the haplotypes represent, strengthening the accuracy of the assignments. SNAPPY is fast, scalable, and uses standard file formats, making it easy to integrate into analytical pipelines.

Availability and Implementation

The program is implemented in python. The program, a user manual, haplotype databases, and test datasets are available for download at github.com/chrisgene/snappy.

Contact

Jonathan.shortt@ucdenver.edu, Chris.gignoux@ucdenver.edu
Salicylate increases fitness cost associated with MarA-mediated antibiotic resistance
Authors: Wang T. , Kunze C. , Dunlop M. J.
Published: October 2018

Antibiotic resistance is generally associated with a fitness deficit resulting from the burden of producing and maintaining resistance machinery. This additional cost suggests that resistant bacteria will be outcompeted by susceptible bacteria in conditions without antibiotics. However, in practice this process is slow due in part to regulation that minimizes expression of these genes in the absence of antibiotics. This suggests that if it were possible to turn on their expression, the cost would increase, thereby accelerating removal of resistant strains. Experimental and theoretical studies have shown that environmental chemicals can change the fitness cost associated with resistance and therefore have a significant impact on population dynamics. MarA (multiple antibiotic resistance activator) is a clinically important regulator in Escherichia coli which activates downstream genes to increase resistance against multiple classes of antibiotics. Salicylate is an inducer of MarA which can be found in the environment and de-represses marA’s expression. In this study, we sought to unravel the interplay between salicylate and the fitness cost of MarA-mediated antibiotic resistance. Using salicylate as a natural inducer of MarA, we found that a wide spectrum of concentrations can increase burden in resistant strains compared to susceptible strains. Induction resulted in rapid exclusion of resistant bacteria from mixed populations of antibiotic resistant and susceptible cells. A mathematical model captures the process and predicts its effect in various environmental conditions. Our work provides a quantitative understanding of salicylate exposure on the fitness of different MarA variants, and suggests that salicylate can lead to selection against MarA-mediated resistant strains. More generally, our findings show that natural inducers may serve to bias population membership and could impact antibiotic resistance and other important phenotypes.
Molecular inflection points in the aging human brain
Authors: Deng Eden
Published: October 2018

The onset of neurodegenerative diseases has been associated with age-dependent changes of gene expression in the brain. Research on age-dependent genes commonly assumes gradual linear relationships between gene expression and aging, failing to identify sudden changes in gene expression that may provide insight into the aging process and its role in neurodegenerative diseases. Here, a piecewise linear regression model is proposed to identify critical inflection points at which aging mechanisms may accelerate. Age-related gene expression data from tissue of four regions of the human brain (frontal cortex, hippocampus, putamen, substantia nigra) and human microglia were analyzed for inflection points. The best piecewise model represented stable expression during younger ages followed by an increase or decrease with age after the inflection point. In brain tissue, genes showing inflection points in expression pattern were enriched for gene ontology terms involved in neurodegenerative diseases. The hippocampus showed the highest proportion of genes with inflection points and the lowest variability in inflection points. These findings suggest that inflection points in gene expression may be used to characterize the aging process in the human brain and may help identify markers for the onset of neurodegenerative diseases.
Use of a visible reporter marker- myb-related gene in crop plants to minimize herbicide usage against weeds
Authors: Aly Radi , Lati Ran , Bari Vinay K. , Abu-Nassar Jackline , Eizenberg Hanan
Published: October 2018

Weeds, a main threat to agricultural productivity worldwide, are mostly controlled by herbicides. To minimize herbicide usage by targeting it to weedy areas, we developed a new image-based methodology for robust weed detection that relies on manipulating the crop plant’s leaf hue, without affecting crop fitness. We generated transgenic tobacco (Nicotiana tabacum Xanthi) lines overexpressing anthocyanin pigment as a traceable marker that differentiates transgenes from the surrounding weeds at an early stage. Transformation with the anthocyanin VlmybA1-2 gene produced purple-colored leaves. Subsequent gene silencing with vector pTRV2:VlmybA1-2 significantly reduced anthocyanin pigments in tobacco leaves 40 days after agroinfiltration, with a concomitant reduction in VlmybA1-2 transcript levels. Purple hue faded gradually, and there were no fitness costs in terms of plant height or leaf number in the silenced vs. non-silenced tobacco transgenes. These results could lead to a new sustainable weed-control method that will alleviate weed-related ecological, agricultural and economic issues.
Stepwise activation mechanism of the scramblase nhTMEM16 revealed by cryo-EM
Authors: Kalienkova Valeria , Mosina Vanessa Clerico , Bryner Laura , Oostergetel Gert T. , Dutzler Raimund , Paulino Cristina
Published: October 2018

Scramblases catalyze the movement of lipids between both leaflets of a bilayer. Whereas the X-ray structure of the protein nhTMEM16 has previously revealed the architecture of a Ca2+-dependent lipid scramblase, its regulation mechanism has remained elusive. Here, we have used cryo-electron microscopy and functional assays to address this question. Ca2+-bound and Ca2+-free conformations of nhTMEM16 in detergent and lipid nanodiscs illustrate the interactions with its environment and they reveal the conformational changes underlying its activation. In this process, Ca2+-binding induces a stepwise transition of the catalytic subunit cavity, converting a closed cavity that is shielded from the membrane in the absence of ligand, into a polar furrow that becomes accessible to lipid headgroups in the Ca2+-bound state. Additionally, our structures demonstrate how nhTMEM16 distorts the membrane at both entrances of the subunit cavity, thereby decreasing the energy barrier for lipid movement.

Impact statement

cryo-EM reveals the properties of distinct conformations occupied during activation of the lipid scramblase nhTMEM16 and provides new insights into its interactions with the lipid environment.
RadiationGeneSigDB: A database of oxic and hypoxic radiation response gene signatures and their utility in identification of hypoxia-regulated MicroRNA
Authors: Manem Venkata SK. , Dhawan Andrew
Published: October 2018

Radiation therapy is among the most effective and widely used modalities of cancer therapy in current clinical practice. With the advent of new high throughput genomic technologies and the continuous inflow of transcriptomic data, there has been a paradigm shift in the landscape of radiation oncology. In this era of personalized radiation medicine, genomic datasets hold great promise to investigate novel biomarkers predictive of radiation response. In this regard, the number of available gene expression based signatures built under oxic and hypoxic conditions is getting larger. This poses two main questions in the field, namely, i) how reliable are these signatures when applied across a compendium of datasets in different model systems; and ii) is there redundancy of gene signatures. To address these fundamental radiobiologic questions, we curated a database of gene expression signatures predictive of radiation response under oxic and hypoxic conditions. RadiationGeneSigDB has a collection of 11 oxic and 24 hypoxic signatures with the standardized gene list as a gene symbol, Entrez gene ID, and its function. We present the utility of this database through three case studies: i) comparing breast cancer oxic signatures in cell line data vs. patient data; ii) comparing the similarity of head and neck cancer hypoxia signatures in clinical tumor data; and iii) gaining an understanding of hypoxia-associated miRNA. This valuable, curated repertoire of published gene expression signatures provides a motivating example for how to search for similarities in radiation response for tumors arising from different tissues across model systems under oxic and hypoxic conditions, and how a well-curated set of gene signatures can be used to generate novel hypotheses about the functions of non-coding RNA.

Availability and implementation

RadiationGeneSigDB is implemented in R. The source code of this package and signatures can be downloaded from the GitHub: https://github.com/vmsatya/RadiationGeneSigDB
Membrane Lipid-KIR2.x Channel Interactions Enable Hemodynamic Sensing in Cerebral Arteries
Authors: Sancho Maria , Fabris Sergio , Hald Bjorn O. , Sandow Shaun L. , Poepping Tamie L. , Welsh Donald G.
Published: October 2018

Inward rectifying (KIR) K+channels are present in cerebral arterial smooth muscle and endothelial cells, a tandem arrangement suggestive of a dynamic yet undiscovered role for this channel. We explored whether vascular KIRchannels were uniquely modulated by membrane lipids and hemodynamic stimuli. A KIRcurrent was isolated in smooth muscle and endothelial cells of rat cerebral arteries and molecular analyses confirmed KIR2.1/KIR2.2 mRNA and protein expression. Electrophysiology next revealed that endothelial KIRwas sensitive to phosphatidylinositol 4,5- bisphosphate (PIP2), with depletion impairing flow-induced activation of the channel. In contrast, smooth muscle KIRwas sensitive to membrane cholesterol, with sequestration blocking pressure’s ability to inhibit this channel. Membrane lipids helped confer KIRmechanosensitivity to intact arteries; virtual models then reconceptualised KIRas a dynamic regulator of basal tone development. We conclude that specific membrane lipid-KIRinteractions enable unique channel populations to sense hemodynamic stimuli and set brain perfusion.
Autoencoder and Optimal Transport to Infer Single-Cell Trajectories of Biological Processes
Authors: Yang Karren Dai , Damodaran Karthik , Venkatchalapathy Saradha , Soylemezoglu Ali C. , Shivashankar G.V. , Uhler Caroline
Published: October 2018

Although we can increasingly image and measure biological processes at single-cell resolution, most assays can only take snapshots from a population of cells in time. Here we describe ImageAEOT, which combines an AutoEncoder, to map single-cell Images from different cell populations to a common latent space, with the framework of Optimal Transport to infer cellular trajectories. As a proof-of-concept, we apply ImageAEOT to nuclear and chromatin images during the activation of fibroblasts by tumor cells in engineered 3D tissues. We further validate ImageAEOT on chromatin images of various breast cancer cell lines and human tissue samples, thereby linking alterations in chromatin condensation patterns to different stages of tumor progression. Importantly, ImageAEOT can infer the trajectory of a particular cell from one snapshot in time and identify the changing features to provide early biomarkers for developmental and disease progression.
Neural Dynamics of Executive Function in Cognitively-able Kindergarteners with Autism Spectrum Disorders (ASD) as Predictors of Concurrent Academic Achievement
Authors: Kim So Hyun , Buzzell George , Faja Susan , Choi Yeo Bi , Thomas Hannah , Brito Natalie Hiromi , Shuffrey Lauren C. , Fifer William P. , Morrison Frederick D. , Lord Catherine , Fox Nathan
Published: October 2018

Although electrophysiological (EEG) measures of executive functions (EF) (e.g. error monitoring) have been used to predict academic achievement in typically developing (TD) children, work investigating a link between error monitoring, and academic skills in children with autism spectrum disorder (ASD) is limited. In the current study, we employed traditional electrophysiological and advanced time-frequency methods, combined with principal components analyses, to extract neural activity related to error monitoring, and tested their relations to academic achievement in cognitively-able kindergarteners with ASD. Thirty-five cognitively-able kindergarteners with ASD completed academic assessments and the child-friendly “Zoo Game” Go/No-go task at school entry. The Go/No-go task successfully elicited an error-related negativity (ERN) and error positivity (Pe) in children with ASD as young as 5 years at medio-frontal and posterior electrode sites, respectively. We also observed increased response-related theta power during errors relative to correct trials at medio-frontal sites. Both larger Pe and theta power significantly predicted concurrent academic achievement after controlling for behavioral performance on the Zoo Game and IQ. These results suggest that the use of time frequency EEG analyses, combined with traditional ERP measures, may provide new opportunities to investigate neurobiological mechanisms of EF and academic achievement in young children with ASD.
Frequency- and area-specific entrainment of intrinsic cortical oscillations by repetitive transcranial magnetic stimulation
Authors: Okazaki Yuka O. , Nakagawa Yumi , Mizuno Yuji , Hanakawa Takashi , Kitajo Keiichi
Published: October 2018

Neural oscillations are ubiquitous throughout the cortex, but the frequency of oscillations differs from area to area. To elucidate the mechanistic architectures establishing various rhythmic activities, we tested whether spontaneous neural oscillations in different cortical modules can be entrained by direct perturbation with distinct frequencies of transcranial magnetic stimulation (TMS). While recording the electroencephalogram (EEG), we applied single-pulse TMS (sTMS) and repetitive TMS (rTMS) at 5, 11, and 23 Hz to motor or visual cortex. To assess entrainment, defined as phase locking of intrinsic oscillations to periodic external force , we examined local and global modulation of the phase-locking factor (PLF). sTMS triggered transient phase locking in a wide frequency band with distinct PLF peaks at 21 Hz in the motor cortex and 8 Hz in the visual cortex. With TMS pulse trains of 11 Hz over visual cortex and 23 Hz over motor cortex, phase locking was progressively enhanced at the stimulation frequency and lasted for a few cycles after the stimulation terminated. Moreover, such local entrainment propagated to other cortical regions, suggesting that rTMS entrained intrinsic neural oscillations locally and globally via network nodes. Because the entrainment was frequency-specific for each target site, these frequencies may correspond to the natural frequency of each cortical module and of the global networks. rTMS enables direct manipulation of the brain and is thus useful for investigating the causal roles of synchronous neural oscillations and synchrony in brain functions, and for the treatment of clinical symptoms associated with impaired oscillations and synchrony.

Significance Statement

We provide the first evidence for area- and frequency-specific entrainment by frequency-tuned repetitive transcranial magnetic stimulation (rTMS), and the propagation of this entrainment to other areas. Our results indicate that rTMS at the natural frequency of each cortical system is particularly effective for entraining oscillatory phase. Moreover, local entrainment led to global entrainment in functionally coupled areas. The ability to control brain rhythms in the intact human brain is highly beneficial for studying the causal roles of rhythmic activity in brain function. Moreover, this modulatory technique has the potential to treat patients with impaired rhythmic networks in disorders such as schizophrenia and stroke.
Aurora B switches relative strength between kinetochore–microtubule attachment modes to promote error correction
Authors: Doodhi Harinath , Kasciukovic Taciana , Clayton Lesley , Tanaka Tomoyuki U.
Published: October 2018

For proper chromosome segregation, sister kinetochores must interact with microtubules from opposite spindle poles; this is called bi-orientation. To establish bi-orientation prior to chromosome segregation, any aberrant kinetochore–microtubule interaction must be resolved (error correction) by Aurora B kinase that phosphorylates outer kinetochore components. Aurora B differentially regulates kinetochore attachment to the microtubule plus end and its lateral side (end-on and lateral attachment, respectively). However, it is still not fully understood how kinetochore–microtubule interactions are exchanged during error correction. Here we reconstituted the kinetochore–microtubule interface of budding yeast in vitro by attaching the Ndc80 complexes (Ndc80C) to nanobeads. These Ndc80C–nanobeads recapitulated in vitro the lateral and end-on attachments of authentic kinetochores, on dynamic microtubules loaded with the Dam1 complex. This in vitro assay enabled the direct comparison of lateral and end-on attachment strength and showed that Dam1 phosphorylation by Aurora B makes the end-on attachment weaker than the lateral attachment. We suggest that the Dam1 phosphorylation weakens interaction with the Ndc80 complex, disrupts the end-on attachment and promotes the exchange to a new lateral attachment, leading to error correction. Our study reveals a fundamental mechanism of error correction for establishment of bi-orientation.
How cancer patients perceive clinical trials (CTs) in the era of CTs: Current perceptional status and differences between common and rare cancers
Authors: Park Ji Hyun , Lee Ji Sung , Koo HaYeong , Kim Jeong Eun , Ahn Jin-Hee , Ryu Min-Hee , Park Sook-ryun , Yoon Shin-kyo , Lee Jae Cheol , Hong Yong-Sang , Kim Sun Young , Kim Kyo-Pyo , Yoo Chang-Hoon , Hong Jung Yong , Lee Jae Lyun , Jung Kyung Hae , Rhyoo Baek-Yeol , Kim Tae Won
Published: October 2018

Background

As perception have been recently highlighted as critical determinants of clinical trials (CTs) in cancer patients, we evaluated current perceptional status of CTs in cancer patients, focusing on differences between common and rare cancers.

Materials & Methods

From November 2015 to May 2017, we prospectively surveyed patients who have received anti-cancer treatment at Asan Medical Center using the PARTAKE questionnaires.

Results

Among 333 respondents, 70.9% and 29.1% had common and rare cancers, respectively. While 87.7% and 75.3% of patients answered that they heard of and knew about CTs, willingness to participate in CTs was expressed only in approximately 56% of patients although willingness was significantly correlated with awareness and perception. Surprisingly, patients with rare cancers showed significantly lower levels of awareness and perception (64.2% vs 79.9%, p=0.003 and 77.3% vs 91.9%, p<0.001), and consequently less willingness (47.4% vs 58.9%, p=0.06) compared to patients with common cancers. In addition, cancer patients still harbored fear with concerns about safety and reward, and substantial ignorance and mistrust about voluntariness of CTs, which was more predominant in patients with rare cancers.

Conclusions

Present study identified relatively less willingness of CTs in cancer patients compared with generally favorable perception, and highlighted relative perceptional poverty in patients with rare cancers than those with common cancers. Further education and encouragement by research and public entities seem essential to raise motivation of CTs in cancer patients beyond good perception, especially for the patients with rare cancers.