bluuebunny/crossref_metadata_2025 huggingface dataset:
Epistasis and physico-chemical constraints contribute to spatial clustering of amino acid substitutions in protein evolution
Authors: Taverner Andrew M. , Blaine Logan J. , Andolfatto Peter
Published: August 2020

The causes of rate variation among sites within proteins are as yet poorly understood. Here, we compare the spatial autocorrelation of non-synonymous substitutions among species within diverse phylogenetic groups:Saccharomyces, Drosophila, Arabidopsis, and primates. Across these taxa, we find that amino acid substitutions exhibit excess clustering that extends over a 20-30 codon length (10-20 Angstrom distance) scale. We show that these substitutions cluster more strongly and exhibit compensatory dynamics within species lineages but exhibit patterns of convergent evolution between lineages. We evaluate a simple model of thermodynamic constraints on protein folding and conclude that it is unable to recapitulate the observed spatial clustering of substitutions. While pairs of substitutions with the strongest epistasis tend to spatially cluster in these simulations, the magnitude and length scale are smaller than that observed in real data. Additionally, we show that the pattern of convergent substitution is also not expected under this model, suggesting it is likely caused by factors other than these simple thermodynamic constraints. Our results support a prevalent role for epistasis and convergent evolution in shaping protein evolution across the tree of life.
CRISPR/Cas9 technology abolishes theBCR/ABL1oncogene in chronic myeloid leukemia and restores normal hematopoiesis
Authors: Vuelta Elena , Ordoñez José Luis , Alonso-Pérez Verónica , Méndez Lucía , Hernández-Carabias Patricia , Saldaña Raquel , Sevilla Julián , Sebastian Elena , Muntión Sandra , Sánchez-Guijo Fermín , Hernadez-Rivas Jesús María , García-Tuñón Ignacio , Sánchez-Martín Manuel
Published: August 2020

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease produced by a unique oncogenic event involving the constitutively active tyrosine kinase (TK)BCR/ABL1. TK activity explains most features of CML, such as tumor development and maintenance. TK-inhibitory (TKI) drugs have changed its prognosis and natural history. Unfortunately, theABL1gene persists unaffected by TKIs, leukemic stem cells (LSCs) remains, resistant mutations arise and adverse effects may occur during treatment. To address this problem, we have designed a potential therapeutic alternative with CRISPR/Cas9 genome editing nucleases that target LSCs. The strategy was successfully developed in murine and human cell lines and finally was evaluated in primary LSCs isolated from CML transgenic mice and from CML patients. Mouse CML-LSCs edited were orthotopic transplanted in immunodeficient NSG niches where restored the normal hematopoiesis. Importantly, patient-derived xenografts with CD34+-LSCs edited, repopulated and restored the normal hematopoiesis in immunodeficient NSG niches. We show, for the first time, how CRISPR technology efficiently interrupts theBCR/ABL1oncogene in murine and human LSCs to provide a significant therapeutic benefit. We propose human CML as a potential candidate for CRISPR therapy, providing proof-of-principle for genome editing in CML patients, and open new avenues for the application of this technique in other fusion genes.

Key points

CRISPR system destroys BCR/ABL oncogene and induces a therapeutic benefit in a CML mouse model and CML patient derived xenografts.
Oak regeneration at the arid boundary of the temperate deciduous forest biome: insights from a seeding and watering experiment
Authors: Erdős László , Szitár Katalin , Öllerer Kinga , Ónodi Gábor , Kertész Miklós , Török Péter , Baráth Kornél , Tölgyesi Csaba , Bátori Zoltán , Somay László , Orbán Ildikó , Kröel-Dulay György
Published: August 2020

Temperate deciduous forests dominated by oaks cover extensive areas in European lowlands. These ecosystems have been under intense anthropogenic use for millennia, thus their natural dynamics, and their regeneration in particular, is still not well understood. Previous studies found that pedunculate oak (Quercus robur), one of the most widespread and abundant species in European deciduous forests, regenerates in open habitats and forest edges, but not in closed forest interiors. However, these observations usually come from the core areas of the biome, and much less is known about such processes at its arid boundary, where limiting factors may be different, and climate change may first exert its effects.

In a full factorial field experiment, we tested the effects of different habitats and increased growing season precipitation on the early regeneration of pedunculate oak in a forest-steppe ecosystem in Central Hungary, at the arid boundary of temperate deciduous forests. We planted acorns into three neighbouring habitats (grassland, forest edge, forest interior) and studied seedling emergence and plant performance under ambient weather and additional watering for four years.

In the grassland habitat, seedling emergence was very low, and no seedlings survived by the fourth year. In contrast, seedling emergence was high and similar at forest edges and forest interiors, and was not affected by water addition. Most seedlings survived until the fourth year, with no difference between forest edge and forest interior habitats in numbers, and only minor or transient differences in size (leaf number, height).

The lack of oak regeneration in the grassland contradicts previous reports on successful oak regeneration in open habitats, and may be related to a shift from light limitation to other limiting factors, such as moisture or microclimatic extremes, when moving away from the core of the deciduous forest biome towards its arid boundary. The similar number and performance of seedlings in forest edges and forest interiors may also be related to the decreasing importance of light limitation. The above-average precipitation in the year of seedling emergence (2016) might be a reason why watering had no effect on oak regeneration.

Overall, our results highlight that oak regeneration and thus forest dynamics may be limited by different factors at a biome boundary compared to its core areas. Indeed, this very simple mechanism (inability of oak regeneration in grassland habitats) may contribute to the opening up of the closed forest biome, and the emergence of a biome transition zone.
Auditory cortex supports verbal working memory capacity
Authors: Bidelman Gavin M. , Brown Jane A. , Bashivan Pouya
Published: August 2020

Working memory (WM) is a fundamental construct of human cognition. The neural basis of auditory WM is thought to reflect a distributed brain network consisting of canonical memory and central executive brain regions including frontal lobe, prefrontal areas, and hippocampus. Yet, the role of auditory (sensory) cortex in supporting active memory representations remains controversial. Here, we recorded neuroelectric activity via EEG as listeners actively performed an auditory version of the Sternberg memory task. Memory load was taxed by parametrically manipulating the number of auditory tokens (letter sounds) held in memory. Source analysis of scalp potentials showed that sustained neural activity maintained in auditory cortex (AC) prior to memory retrieval closely scaled with behavioral performance. Brain-behavior correlations revealed lateralized modulations in left (but not right) AC predicted individual differences in auditory WM capacity. Our findings confirm a prominent role of auditory cortex, traditionally viewed as a sensory-perceptual processor, in actively maintaining memory traces and dictating individual differences in behavioral WM limits.
A comprehensive macaque fMRI pipeline and hierarchical atlas
Authors: Jung Benjamin , Taylor Paul A. , Seidlitz Jakob , Sponheim Caleb , Perkins Pierce , Ungerleider Leslie G. , Glen Daniel , Messinger Adam
Published: August 2020

Functional neuroimaging research in the non-human primate (NHP) has been advancing at a remarkable rate. The increase in available data establishes a need for robust analysis pipelines designed for NHP neuroimaging and accompanying template spaces to standardize the localization of neuroimaging results. Our group recently developed the NIMH Macaque Template (NMT), a high-resolution population average anatomical template and associated neuroimaging resources, providing researchers with a standard space for macaque neuroimaging (Seidlitz, Sponheim et al., 2018). Here, we release NMT v2, which includes both symmetric and asymmetric templates in stereotaxic orientation, with improvements in spatial contrast, processing efficiency, and segmentation. We also introduce the Cortical Hierarchy Atlas of the Rhesus Macaque (CHARM), a hierarchical parcellation of the macaque cerebral cortex with varying degrees of detail. These tools have been integrated into the neuroimaging analysis software AFNI (Cox, 1996) to provide a comprehensive and robust pipeline for fMRI processing, visualization and analysis of NHP data. AFNI’s new @animal_warper program can be used to efficiently align anatomical scans to the NMT v2 space, and afni_proc.py integrates these results with full fMRI processing using macaque-specific parameters: from motion correction through regression modeling. Taken together, the NMT v2 and AFNI represent an all-in-one package for macaque functional neuroimaging analysis, as demonstrated with available demos for both task and resting state fMRI.

Highlights

The NMT v2, a stereotaxically aligned symmetric macaque template, is introduced.

A new atlas (CHARM), defined on NMT v2, parcellates the cortex at six spatial scales.

AFNI’s @animal_warper aligns and maps data between monkey anatomicals and templates.

AFNI’s afni_proc.py facilitates monkey fMRI analysis with automated scripting and QC.

Demos of macaque task and resting state fMRI analysis with these tools are provided.
ThermoBRET: a ligand-engagement nanoscale thermostability assay applied to GPCRs
Authors: Hoare Bradley L. , Tippett David N. , Kaur Amandeep , Cullum Sean A. , Miljuš Tamara , Koers Eline J. , Harwood Clare R. , Dijon Nicola , Holliday Nicholas D. , Sykes David A. , Veprintsev Dmitry B.
Published: August 2020

Measurements of membrane protein thermostability allows indirect detection of ligand binding. Current thermostability assays require protein purification or rely on pre-existing radiolabelled or fluorescent ligands, limiting their application to established target proteins. Alternative methods detect protein aggregation which requires sufficiently high level of protein expression.

Here, we present a ThermoBRET method to quantify the relative thermostability of G protein coupled receptors (GPCRs), using cannabinoid receptors (CB1and CB2) and the β2-adrenoceptor (β2AR) as model systems. ThermoBRET reports receptor unfolding, does not need labelled ligands and can be used with non-purified proteins. It uses Bioluminescence Resonance Energy Transfer (BRET) between Nanoluciferase (Nluc) and a thiol-reactive fluorescent dye that binds cysteines exposed by unfolding. We demonstrate that the melting point (Tm) of Nluc-fused GPCRs can be determined in non-purified detergent solubilised membrane preparations or solubilised whole cells, revealing differences in thermostability for different solubilising conditions and in the presence of stabilising ligands. We extended the range of the assay by developing the thermostable tsNLuc by incorporating mutations from the fragments of split-Nluc (Tmof 87 ⁰C vs 59 ⁰C). ThermoBRET allows determination of GPCR thermostability, which is useful for protein purification optimisation and as part of drug discovery screening strategies.
PI3K inhibition reverses migratory direction of single cells but not cell groups in electric field
Authors: Sun Y , Yue H , Copos C , Zhu K , Zhang Y , Sun Y , Gao X , Reid B , Lin F , Zhao M , Mogilner A
Published: August 2020

Motile cells migrate directionally in the electric field in a process known as galvanotaxis. Galvanotaxis is important in wound healing, development, cell division, and nerve growth. Different cell types migrate in opposite directions in electric fields, to either cathode, or anode, and the same cell can switch the directionality depending on chemical conditions. We previously reported that individual fish keratocyte cells sense electric fields and migrate to the cathode, while inhibition of PI3K reverses single cells to the anode. Many physiological processes rely on collective, not individual, cell migration, so here we report on directional migration of cohesive cell groups in electric fields. Uninhibited cell groups of any size move to the cathode, with speed decreasing and directionality increasing with the group size. Surprisingly, large groups of PI3K-inhibited cells move to the cathode, in the direction opposite to that of individual cells, which move to the anode, while such small groups are not persistently directional. In the large groups, cells’ velocities are distributed unevenly: the fastest cells are at the front of the uninhibited groups, but at the middle and rear of the PI3K-inhibited groups. Our results are most consistent with the hypothesis, supported by the computational model, that cells inside and at the edge of the groups interpret directional signals differently. Namely, cells in the group interior are directed to the cathode independently of their chemical state. Meanwhile, edge cells behave like the individual cells: they are directed to the cathode/anode in uninhibited/PI3K-inhibited groups, respectively. As a result, all cells drive uninhibited groups to the cathode, but a mechanical tug-of-war between the inner and edge cells directs large PI3K-inhibited groups with cell majority in the interior to the cathode, while rendering small groups non-directional.

Significance statement

Motile cells migrate directionally in electric fields. This behavior – galvanotaxis – is important in many physiological phenomena. Individual fish keratocytes migrate to the cathode, while inhibition of PI3K reverses single cells to the anode. Uninhibited cell groups move to the cathode. Surprisingly, large groups of PI3K-inhibited cells also move to the cathode, in the direction opposite to that of individual cells. The fastest cells are at the front of the uninhibited groups, but at the middle and rear of the PI3K-inhibited groups. We posit that inner and edge cells interpret directional signals differently, and that a tug-of-war between the edge and inner cells directs the cell groups. These results shed light on general principles of collective cell migration.
Pre-attentive processing of neutral and emotional sounds in congenital amusia
Authors: Pralus Agathe , Gomot Marie , Graves Jackson , Cholvy Fanny , Fornoni Lesly , Tillmann Barbara , Caclin Anne
Published: August 2020

Congenital amusia is a life-long deficit of musical processing. This deficit can extend to the processing of language and in particular, emotional prosody. In a previous behavioral study, we revealed that while amusic individuals had difficulties in explicitly recognizing emotions for short vowels, they rated the emotional intensity of these same vowels as did their matched control participants. This finding led to the hypothesis that congenital amusics might be impaired for explicit emotional prosody recognition, but not for its implicit processing. With the aim to investigate amusics’ automatic processing of prosody, the present study measured electroencephalography (EEG) when participants listened passively to vowels presented within an oddball paradigm. Emotionally neutral vowel served as the standard and either emotional (anger and sadness) or neutral vowels as deviants. Evoked potentials were compared between participants with congenital amusia and control participants matched in age, education, and musical training. The MMN was rather preserved for all deviants in amusia, whereas an earlier negative component was found decreased in amplitude in amusics compared to controls for the neutral and sadness deviants. For the most salient deviant (anger), the P3a was decreased in amplitude for amusics compared to controls. These results showed some preserved automatic detection of emotional deviance in amusia despite an early deficit to process subtle acoustic changes. In addition, the automatic attentional shift in response to salient deviants at later processing stages was reduced in amusics in comparison to the controls. In the three ERPs related to the deviance, between-group differences were larger over bilateral prefrontal areas, previously shown to display functional impairments in congenital amusia. Our present study thus provides further understanding of the dichotomy between implicit and explicit processing in congenital amusia, in particular for vocal stimuli with emotional content.
ALIX and ceramide differentially control polarized exosome release from epithelial cells
Authors: Matsui Takahide , Hiragi Shu , Osaki Futaba , Sakamaki Yuriko , Fukuda Mitsunori
Published: August 2020

Exosomes, new players in cell-cell communication, are extracellular vesicles of endocytic origin. Although single cells are known to release various kinds of exosomes (referred to as exosomal heterogeneity), very little is known about the mechanisms by which they are produced and released. Here, we established methods for studying exosomal heterogeneity by using polarized epithelial cells and showed that distinct types of exosomes are differentially secreted from the apical and basolateral sides. We also identified GPRC5C (G protein-coupled receptor class C group 5 member C) as an apical-exosome-specific protein. We further demonstrated that basolateral exosome release depends on ceramide, whereas ALIX, an ESCRT (endosomal sorting complexes required for transport)-related protein, not the ESCRT machinery itself, is required for apical exosome secretion. Thus, two independent machineries, the ALIX–Syntenin1– Syndecan1 machinery (apical side) and the sphingomyelinase-dependent ceramide production machinery (basolateral side), are likely to be responsible for the polarized exosome release from epithelial cells.
Characterization of soft X-ray FEL pulse duration with two-color photoelectron spectroscopy
Authors: Owada Shigeki , Fushitani Mizuho , Matsuda Akitaka , Fujise Hikaru , Sasaki Yuuma , Hikosaka Yasumasa , Hishikawa Akiyoshi , Yabashi Makina
Published: August 2020

The pulse duration of soft X-ray free-electron laser (FEL) pulses of SACLA BL1 (0.2–0.3 nC per bunch, 0.5–0.8 MeV) were characterized by photoelectron sideband measurements. The intensity of the He 1 s−1 photoelectron sidebands generated by a near-infrared femtosecond laser was measured as a function of the time delay between the two pulses using an arrival time monitor. From the width of the cross-correlation trace thus derived, the FEL pulse duration was evaluated to be 28 ± 5 fs full width at half-maximum in the photon energy range between 40 eV and 120 eV.
Performance implication of supplier relationship quality: a structural analysis
Authors: Yang Jie , Xie Hongming , Wang Jifu , Yang Yingnan
Published: August 2020

Purpose

This study aims to examine the impact of supplier relationship quality on curtailing opportunism and promoting cooperation between the exchange partners. It also investigates the contingent impact of contract specificity on the relationships and assesses performance implications of relationship quality for both buyer and its major supplier in the exchange.

Design/methodology/approach

Confirmatory factor analysis and path analysis were performed based on data collected from manufacturers in a survey. The hypotheses were tested using path analysis.

Findings

The findings of this study indicate a pivotal role of supplier relationship quality in suppressing opportunism and enhancing cooperation between exchange parties, which lead to dyadic performance. Furthermore, the effect of supplier relationship quality is strengthened by contract specificity.

Originality/value

This study adds value to the existing streams of studies in several ways. First, informed by the nexus of relational capital theory and transaction cost economics, the authors emphasize the pivotal role of relationship quality in curtailing opportunism and fostering cooperation and the moderating effect of contract specificity on the above linkages. Second, this study provides empirical evidence of the mechanism of the effect of contract specificity on opportunism and cooperation.
The potential impact of managerial entrenchment on firms’ corporate social responsibility activities and financial performance: evidence from Iran
Authors: Salehi Mahdi , Mahmoudabadi Mahbubeh , Adibian Mohammad Sadegh , Rezaei Ranjbar Hossein
Published: August 2020

Purpose

The present study aims to assess the effect of managerial entrenchment on firms’ corporate social responsibility (CSR) activities and financial performance in Iran.

Design/methodology/approach

In this paper, the variable of managerial entrenchment, which includes board independence, management duality, management tenure, the board compensation, independence and ownership percentage, is initially analyzed using the exploratory factor analysis method, and its effect on performance and CSR is evaluated using the multivariable regression test. Given that a total of 103 listed companies on the Tehran Stock Exchange are selected during 2012–2017. In this paper, return on assets (ROA) and Tobin’sQare the two variables to measure financial performance.

Findings

The results of hypotheses testing indicate that there is a positive and significant relationship between managerial entrenchment and financial performance based on the ROA and Tobin’sQindices, separately. Moreover, the results of this study indicate that there is also a positive and significant relationship between managerial entrenchment and CSR activities.

Originality/value

The current study almost is the first study, conducted in a developing country similar to Iran, and the provided results might be beneficial to other developing countries.
Sustainable operations practices and sustainable performance: relationships and moderators
Authors: Tondolo Vilmar Antonio Gonçalves , D'Agostini Marina , Camargo Maria Emília , Tondolo Rosana da Rosa Portella , Souza Josefer de Lima , Longaray André Andrade
Published: August 2020

Purpose

The purpose of this study is to analyze the relationships among four types of sustainable operations practices and sustainable performance in the environmental, economic and social dimensions and identifies significant moderators.

Design/methodology/approach

In order to achieve the proposed goal, this study was developed through a systematic review of the literature followed by a meta-analysis of the correlations and by a meta-regression. The sampling criteria were quantitative operations management articles published through 2019.

Findings

The results suggest that all 13 analyzed relationships are positive and are affected by moderators.

Research limitations/implications

In theoretical terms, this study reinforces the positive relationship between sustainable operations practices and performance and, more importantly, detects moderating effects. One of the study limitations is the composition of the sample, focusing exclusively on quantitative correlational articles published in journals.

Practical implications

In practice, the findings of this study imply that managers should be vigilant in implementing sustainable operations practices, observing the conditions in which more of these practices can be implemented into performance.

Originality/value

This study differs from others because it includes the social dimension of sustainable performance and the identification of moderators.
Research literature on leadership of knowledge workers: where are we, and where should we be heading?
Authors: Issahaka Abdallah Wumpini , Lines Rune
Published: August 2020

Purpose

With the transition into a knowledge economy, the concept of leading knowledge workers (KWs) has gained an increasing amount of attention in organisational studies and among practitioners. The emerging literature on the leadership of KW addresses an important phenomenon, but theoretical underpinnings and empirical inquiry into leadership effectiveness in a KW context do not agree on a common conceptualisation of KWs. Thus, a concerted research effort seems warranted.

Design/methodology/approach

The purpose of this study is to take stock of the existing literature on the leadership of KW. Based on a critical literature review, this paper provides a timely synthesis of the diffuse literature and identifies research gaps facing the leadership of KW field.

Findings

This paper suggests that the literature to date is deficient in terms of theory and evidence for how KWs are different from other classes of workers and argues that this deficiency stands in the way of developing ideas about how KWs could be effectively led.

Research limitations/implications

This paper extends a discussion on establishing “KW” as a clear, independent construct and how the nomological network in which KW is situated (i.e. leadership antecedents, and workplace outcomes) may be elucidated, extended and researched.

Originality/value

This paper extends beyond the identified research gaps and findings to present an agenda for future research. Specifically, we propose that insights from research in educational psychology should be used as a platform for theorising about how to lead in a KW context.
Sport nostalgia builds customer equity and future behavior
Authors: Cho Heetae , Chiu Weisheng
Published: August 2020

Purpose

The purpose of this study was to examine the relationships among nostalgia, customer equity and behavioral intentions. Specifically, consumers' intentions of purchase and word of mouth were assessed in this study.

Design/methodology/approach

A total of 272 responses were collected from football fans in Singapore. This study conducted partial least squares structural equation modeling (PLS-SEM) to test hypotheses using SmartPLS 3.0.

Findings

Results showed that the paths from nostalgia to value equity, brand equity and relationship equity were significant, whereas the direct influence of nostalgia on revisit intention and word-of-mouth intention was not found. In addition, value equity, brand equity and relationship equity positively affected intentions of revisitation and word of mouth.

Originality/value

The findings contribute to expanding the literature by introducing nostalgia and providing theoretical and practical implications, which enable marketers and managers to predict consumers' behavior and optimize their customer equity.
Personality and behavioral changes in Asian elephants (Elephas maximus) following the death of herd members
Authors: RUTHERFORD Lucy , MURRAY Lindsay E.
Published: August 2020

Elephants are highly social beings with complex individual personalities. We know that elephants have a general interest in death, investigating carcasses, not just limited to kin; however, research does not explore in depth whether individuals change their behavior or personality following traumatic events, such as the death of a conspecific. Within a captive herd of Asian elephants (Elephas maximus) housed at Chester Zoo, UK, we measured social behavior and proximity and personality using the Ten‐Item Personality Inventory, and found age‐related and relationship‐related changes in both behavior and personality following the deaths of herd members. Overall, the herd spent less time socializing and engaging in affiliative behaviors following the death of the adult female when compared to baseline data, yet spent more time engaging in these behaviors after the death of two calves. The death of the central female had a dramatic impact on her infant calf, resulting in increasingly withdrawn behavior, yet had the opposite effect on her adult daughter, who subsequently established a more integrated role within the herd. Emotional Stability fell in the motherless calf but rose in an adult female, who had lost her adult daughter, but had a new calf to care for. We suggest that the greater impact on the behavior and personality of surviving herd members following the deaths of calves, compared to an adult member, attests to the significance of the unifying role played by calves within an elephant herd.
Accurate detection of spontaneous seizures using a generalized linear model with external validation
Authors: Fumeaux Nicolas F. , Ebrahim Senan , Coughlin Brian F. , Kadambi Adesh , Azmi Aafreen , Xu Jen X. , Abou Jaoude Maurice , Nagaraj Sunil B. , Thomson Kyle E. , Newell Thomas G. , Metcalf Cameron S. , Wilcox Karen S. , Kimchi Eyal Y. , Moraes Marcio F. D. , Cash Sydney S.
Published: August 2020

Objective

Seizure detection is a major facet of electroencephalography (EEG) analysis in neurocritical care, epilepsy diagnosis and management, and the instantiation of novel therapies such as closed‐loop stimulation or optogenetic control of seizures. It is also of increased importance in high‐throughput, robust, and reproducible pre‐clinical research. However, seizure detectors are not widely relied upon in either clinical or research settings due to limited validation. In this study, we create a high‐performance seizure‐detection approach, validated in multiple data sets, with the intention that such a system could be available to users for multiple purposes.

Methods

We introduce a generalized linear model trained on 141 EEG signal features for classification of seizures in continuous EEG for two data sets. In the first (Focal Epilepsy) data set consisting of 16 rats with focal epilepsy, we collected 1012 spontaneous seizures over 3 months of 24/7 recording. We trained a generalized linear model on the 141 features representing 20 feature classes, including univariate and multivariate, linear and nonlinear, time, and frequency domains. We tested performance on multiple hold‐out test data sets. We then used the trained model in a second (Multifocal Epilepsy) data set consisting of 96 rats with 2883 spontaneous multifocal seizures.

Results

From the Focal Epilepsy data set, we built a pooled classifier with an Area Under the Receiver Operating Characteristic (AUROC) of 0.995 and leave‐one‐out classifiers with an AUROC of 0.962. We validated our method within the independently constructed Multifocal Epilepsy data set, resulting in a pooled AUROC of 0.963. We separately validated a model trained exclusively on the Focal Epilepsy data set and tested on the held‐out Multifocal Epilepsy data set with an AUROC of 0.890. Latency to detection was under 5 seconds for over 80% of seizures and under 12 seconds for over 99% of seizures.

Significance

This method achieves the highest performance published for seizure detection on multiple independent data sets. This method of seizure detection can be applied to automated EEG analysis pipelines as well as closed loop interventional approaches, and can be especially useful in the setting of research using animals in which there is an increased need for standardization and high‐throughput analysis of large number of seizures.
Characterisation and in vitro cytotoxicity of toxic and degradation compounds in bamboo shoots (Dendrocalamus Sinicus) during traditional fermentation
Authors: Yi Junjie , Li Meiqi , Yang Meilian , Cai Shengbao , Zhao Tianrui , Cao Jianxin , Cheng Guiguang
Published: August 2020

Fermentation has been historically applied to reduce bamboo shoot (BS) toxicity. However, the underlying degradation pathway of the toxic compounds remains unknown. In this work, the cytotoxicity of BS against the BRL‐3A cells was evaluated, and the changes in chemical constituents were determined to reveal the influence of fermentation on BS. The in vitro toxic evaluation revealed fermentation time was crucial in decreasing the toxicity. The main compounds in fresh and fermented were qualitatively and quantitatively determined and were further targeted isolated and identified. A mathematical model to describe the change rate as a function of fermentation time was formulated. Dynamic profiling revealed that taxiphyllin 1, p‐hydroxybenzaldehyde 2 and methyl‐p‐hydroxybenzoate 3 decreased and transformed into intermediate compounds (p‐hydroxybenzoic acid 4 and p‐hydroxybenzyl alcohol 5), finally converting into p‐hydroxytoluene 6 during fermentation. The results provided basis on the chemical components for practical fermentation and the quality control of BS products.
Nurses working in healthcare facilities during natural disasters: a qualitative enquiry
Authors: Scrymgeour G. C. , Smith L. , Maxwell H. , Paton D.
Published: August 2020

Aim

To explore the ability of nurses to be adequately ready for and to respond to a disaster caused by a natural hazard.

Background

During a disaster involving a healthcare facility, nurses are commonly the largest group of healthcare workers impacted. The range of problems facing nurses working in healthcare facilities in Australia and New Zealand at the time of disasters triggered by earthquakes and bushfires have been underexamined.

Methods

A qualitative enquiry was used to explore matters facing nurses working in residential healthcare facilities during a natural disaster. Inductive thematic analysis was used to identify the key themes from fifteen in‐depth interviews with nurses.

Findings

Participants preserved a robust sense of professional duty, personal obligation and responsibility to their family, patients and the facility, demonstrating the ability to adapt, cope and respond despite experiencing diverse personal, structural and organizational barriers.

Discussion

Support was provided for using interactive systems and socio‐ecological frameworks to better understand the contributions that individuals, teams and organizations make to facilitate the development and maintenance of adaptive capacity and resilience in a nursing workforce. An ecological model of adaptive capacity can be operationalized to guide education, training for nurses and the development of organizational systems and strategies.

Conclusion

This study identified factors that help and hinder a nursing workforce’s ability to prepared for, adapt to and learn from natural hazard disasters.

Implications for Nursing Policy

This understanding of disaster preparedness and how this may be applied to enable the growth of adaptive nurses provides an insight for a global audience which also adds to nurse education, service delivery, organizational and policy development.
A review of the systematics of small mammalian carnivores
Authors: Veron G.
Published: August 2020

Small mammalian carnivores represent over half of the species of the order Carnivora. Over the past few decades, molecular studies have improved the systematics of small carnivore families, resulting in the recognition of four additional families. Several new species of small carnivores have also been proposed recently, but some of these have not been validated by genetic data. Studies of intraspecific genetic polymorphism and structure have helped in the process of defining conservation units, which is crucial for the management of zoo populations.
Low‐energy shock wave pretreatment recruit circulating endothelial progenitor cells to attenuate renal ischaemia reperfusion injury
Authors: Liu Jingyu , Dou Quanliang , Zhou Changcheng , Zhou Liuhua , Zhao Feng , Xu Luwei , Xu Zheng , Ge Yuzheng , Wu Ran , Jia Ruipeng
Published: August 2020

Low‐energy shock wave (LESW) has been recognized as a promising non‐invasive intervention to prevent the organs or tissues against ischaemia reperfusion injury (IRI), whereas its effect on kidney injury is rarely explored. To investigate the protective role of pretreatment with LESW on renal IRI in rats, animals were randomly divided into Sham, LESW, IRI and LESW + IRI groups. At 4, 12, 24 hours and 3 and 7 days after reperfusion, serum samples and renal tissues were harvested for performing the analysis of renal function, histopathology, immunohistochemistry, flow cytometry and Western blot, as well as enzyme‐linked immunosorbent assay. Moreover, circulating endothelial progenitor cells (EPCs) were isolated, labelled with fluorescent dye and injected by tail vein. The fluorescent signals of EPCs were detected using fluorescence microscope and in vivo imaging system to track the distribution of injected circulating EPCs. Results showed that pretreatment with LESW could significantly reduce kidney injury biomarkers, tubular damage, and cell apoptosis, and promote cell proliferation and vascularization in IRI kidneys. The renoprotective role of LESW pretreatment would be attributed to the remarkably increased EPCs in the treated kidneys, part of which were recruited from circulation through SDF‐1/CXCR7 pathway. In conclusion, pretreatment with LESW could increase the recruitment of circulating EPCs to attenuate and repair renal IRI.
Selectively Compliant Annuloplasty Ring to Enable Annular Dynamics in Mitral Valve Repair Evaluated by In-Vitro Stereovision
Authors: Frishman Samuel , Kight Ali , Pirozzi Ileana , Imbrie-Moore Annabel M. , Paulsen Michael J. , Woo Joseph Y. , Cutkosky Mark R.
Published: August 2020

Mitral valve (MV) annular dynamics are critical to the long term efficacy of MV repair. Today’s annuloplasty rings, used to restore MV function, impose significant constraints on the motion profile of the MV annulus. We present a selectively compliant ring that provides sufficient stiffness to stabilize a diseased annulus while allowing physiological annular dynamics. Ring design is informed by a finite element analysis and experimentally evaluated with in-vitro stereophotogrammetry. We compare the ring dynamics to commercially available semi-rigid rings as well as values found in literature for healthy annuli. The results demonstrate that motion of the selectively compliant ring is significantly closer to that of a healthy annulus based on standard metrics that define MV annular movement. Specifically, the metrics for the new ring compare to those in literature as follows: change in orifice area 12.5 ± 3% vs.10 ± 2%; change in anterior-posterior diam. 5.4 ± 0.3% vs. 7 ± 1%; change in inter-commissural diam. 6.6 ± 1.3% vs. 5 ± 1%.
Visualizing Telemetry Metrics From Upper-Airway Stimulation to Enhance Sleep Therapy Management
Authors: Araujo Matheus , Lee Kent , Ni Quan , Srivastava Jaideep
Published: August 2020

Upper-Airway Stimulation (UAS) therapy is an innovative alternative to Continuous Positive Airway Pressure (CPAP) treatment for patients with obstructive sleep apnea (OSA) and CPAP intolerance. Patients who have implanted a UAS device are responsible for activating and managing the therapy at home before sleep. Consistent nightly use is required for a reduced OSA burden, measured by the apnea-hypopnea index. Thus, understanding patient behavior and possible challenges to nightly use are crucial to therapy success. In this work, we present two novel visualizations to monitor telemetry data recorded by the UAS sleep remote. They provide doctors and sleep clinicians with detailed information to easily classify therapy use and sleep patterns. We also present how to show daily metrics such as hours of average usage, therapy intensity, and duration of therapy pauses, to identify optimal therapy settings and measure the long-term effectiveness of interventions.
A Hydraulic Bimodal Ankle to Improve Mobility and Stability for Prosthesis Users
Authors: Koehler-McNicholas Sara , Voss Gregory , Ficanha Evandro , Looft John , Walker Nicole , Colvin James , Hansen Andrew , Wernke Matthew
Published: August 2020

A bimodal prosthetic ankle-foot system has been developed to support the demands of both walking mobility and standing balance. Using a novel hydraulic locking mechanism, this system provides a curved effective rocker shape for walking and a flat effective rocker shape for standing and swaying on non-level surfaces. To date, the hydraulic cylinder sub-assembly has been cycle tested to 1.2 million cycles. Future testing with lower-limb prosthesis users is planned, which will reveal the extent to which this new hydraulic ankle-foot design improves standing balance on both level and non-level surfaces. The capacity for an automatic switching algorithm, designed to appropriately detect and switch between modes as users transition between walking and standing tasks, will also be evaluated.
Development of a Portable Blood Potassium Monitoring Device for Dialysis Patients
Authors: Vora Parth , Inserni Miguel , Lai Alan , Lapinski Maya M. , Wang Justin , Kim Min Jae , Lee Diane , Yu Rebecca , Manbachi Amir , Atta Mohamed G.
Published: August 2020

Approximately 500,000 dialysis patients in America are at a high risk of hyperkalemia, a condition where blood potassium becomes elevated above normal levels. Hyperkalemia is extremely dangerous, as it can result in severe cardiac complications if untreated. Hyperkalemia may be silent or present vague symptoms until those complications develop, at which point patients require emergency medical care. However, if patients have the ability to measure their potassium levels at home, they could detect hyperkalemia before it reaches a dangerous stage, and seek preventative medical care to avoid severe complications.

Therefore, we have designed a novel device allowing patients to measure their blood potassium levels at home. The workflow of our solution is as follows: (1) patients obtain a blood sample from a finger prick, (2) potassium concentration is measured with an ion specific electrode (ISE), and (3) the device displays their potassium levels and a recommended course of action based on their hyperkalemic risk.

We validate our solution with three major tests. First, our portable ISE technology must accurately measure potassium concentration in blood samples. Second, appropriate lancet parameters (gauge and depth) to minimize hemolysis in capillary blood samples must be found to minimize falsely elevated readings. Third, device portability and ease of use must be evaluated using patient input, as these factors will affect patient compliance. We have validated the use of portable ISE technology to feasibly measure potassium, and we continue to collect data for our second and third tests.
Deep Learning Algorithm for Image Classification of Waveforms Obtained From Electrically Stimulated Hypoxic Skeletal Muscle Bundles
Authors: Upchurch Weston , Deakyne Alex , Ramirez David A. , Iaizzo Paul A.
Published: August 2020

Acute compartment syndrome is a serious condition that requires urgent surgical treatment. While the current emergency treatment is straightforward — relieve intra-compartmental pressure via fasciotomy — the diagnosis is often a difficult one. A deep neural network is presented here that has been trained to detect whether isolated muscle bundles were exposed to hypoxic conditions and became ischemic.
A Flow Cytometry Method for Characterizing Platelet Activation
Authors: Alzua Brian , Smith Mark , Chen Yan
Published: August 2020

Hemocompatibility testing is critical for assessing the safety of blood-contacting medical devices. Comprehensive hemocompatibility testing requires examining a wide range of possible adverse effects cause by direct or indirect blood contact, such as hemolysis, complement activation, and thrombus formation [1]. Moreover, these domains each encompass complex intercellular processes with many potential targets for analysis. For example, the current testing paradigm of platelet function may involve exposing the device to human whole blood and performing simple blood counts and/or macroscopic evaluation to determine the extent of platelet activation and clot formation as described in ASTM F2888-19. However, this approach does not capture any observations for device-mediated initiation of any steps in the platelet activation pathway prior to aggregation. We have validated a method to evaluate platelet activation by quantifying surface p-selectin expression after exposure to various materials. This method will provide an additional level of detail about potential platelet activating properties of a medical device.

Flow cytometry has been used previously to measure platelet activation for clinical and research purposes. We sought to adapt this method to test for platelet activation induced by exposure of blood to medical devices or materials. We determined that processing fresh whole blood to platelet-rich plasma (PRP) by gentle centrifugation enhanced the signal compared to fresh blood itself. In each experiment, devices were exposed to PRP according to an extraction ratio of 6 cm2/mL for 1 hour. A blank control consisting of untreated PRP, and a positive control consisting of ADP, a potent agonist, were also used. After the exposure, excess plasma was removed from the articles and combined with anti-CD61 (to stain for platelets) and anti-CD62P (to stain for activated platelets) antibodies. Flow cytometry was then performed to quantify the percentage of CD62P+ over the total CD61+ cells to measure the percentage of activated platelets. In order to optimize the method, we investigated the effect of several experimental factors, including anticoagulant usage, donor variability, and selection of reference materials to serve as controls. Our results indicate that the flow cytometry-based method is consistent and reproducible, quick and easy to perform, and is well-correlated with results from the standard platelet and leukocyte count assay. The flow cytometry-based platelet activation method is a powerful supplement to the standard regimen of medical device hemocompatibility testing.
Thrombogenicity Testing Results for Control Legally Marketed Comparator Devices (LMCD): Comparison Between Traditional Non-Anticoagulated Venous Implant (NAVI) Assay and an In Vitro Ovine Blood Loop Test
Authors: Smith Mark E. , Chen Yan
Published: August 2020

Legally marketed comparator devices (LMCD) are required by many regulatory bodies in as a control for thrombogenicity testing when evaluating new devices. It is assumed by both the medical device manufacturing industry and regulatory bodies that these LMCD’s have good clinical history and should perform with no to minimal thrombus accumulation and thereby serve as valid negative controls for the assay. APS regularly performs these assays for many medical device manufacturers, all of whom select a predicate comparator device (required by FDA to be an LMCD), for both the in vivo Non-Anticoagulated Venous Implant (NAVI) assay as well as a custom in vitro blood loop AVI. In this retrospective analysis, we have compiled thrombogenicity scores of control/predicate devices (limited to assays which used LMCD’s), both the discrete score from the classification standard scoring scheme and the continuous values obtained from the percent surface area associated with thrombus. We have compared results from 37 NAVI studies and 22 in vitro blood loop studies. These compiled results show ∼25% of LMCDs score ≥ 3 (> 50% of the surface covered in thrombus) in the NAVI model while < 5% of LMCDs score ≥ 3 (> 50% thrombus) in the Blood-Loop assay. In addition, the median score and mean % thrombus for LMCD in the blood loop assay is substantially lower than the median and mean scores for LMCD in the NAVI assay. This retrospective assessment highlights a high proportion of false-positive scores for LMCD in a large number of NAVI assays.