bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient Prediction of Vitamin B Deficiencies via Machine-learning Using Routine Blood Test Results in Patients With Intense Psychiatric Episode
Authors: Tamune Hidetaka , Ukita Jumpei , Hamamoto Yu , Tanaka Hiroko , Narushima Kenji , Yamamoto Naoki
Published: August 2019

Background

Vitamin B deficiency is common worldwide and may lead to psychiatric symptoms; however, vitamin B deficiency epidemiology in patients with intense psychiatric episode has rarely been examined. Moreover, vitamin deficiency testing is costly and time-consuming, which has hampered effectively ruling out vitamin deficiency-induced intense psychiatric symptoms. In this study, we aimed to clarify the epidemiology of these deficiencies and efficiently predict them using machine-learning models from patient characteristics and routine blood test results that can be obtained within one hour.

Methods

We reviewed 497 consecutive patients deemed to be at imminent risk of seriously harming themselves or others over 2 years in a single psychiatric tertiary-care center. Machine-learning models (k-nearest neighbors, logistic regression, support vector machine, and random forest) were trained to predict each deficiency from age, sex, and 29 routine blood test results gathered in the period from September 2015 to December 2016. The models were validated using a dataset collected from January 2017 through August 2017.

Results

We found that 112 (22.5%), 80 (16.1%), and 72 (14.5%) patients had vitamin B1, vitamin B12, and folate (vitamin B9) deficiency, respectively. Further, the machine-learning models were well generalized to predict deficiency in the future unseen data, especially using random forest; areas under the receiver operating characteristic curves for the validation dataset (i.e. the dataset not used for training the models) were 0.716, 0.599, and 0.796, respectively. The Gini importance of these vitamins provided further evidence of a relationship between these vitamins and the complete blood count, while also indicating a hitherto rarely considered, potential association between these vitamins and alkaline phosphatase (ALP) or thyroid stimulating hormone (TSH).

Discussion

This study demonstrates that machine-learning can efficiently predict some vitamin deficiencies in patients with active psychiatric symptoms, based on the largest cohort to date with intense psychiatric episode. The prediction method may expedite risk stratification and clinical decision-making regarding whether replacement therapy should be prescribed. Further research includes validating its external generalizability in other clinical situations and clarify whether interventions based on this method could improve patient care and cost-effectiveness.
Enhancement of alcohol aversion by the nicotinic acetylcholine receptor drug sazetidine-A
Authors: Touchette Jillienne C. , Moen Janna K. , Robinson Jenna M. , Lee Anna M.
Published: August 2019

The prevalence of alcohol use disorders (AUDs) has steadily increased in the United States over the last 30 years. Alcohol acts on multiple receptor systems including the nicotinic acetylcholine receptors (nAChRs), which are known to mediate alcohol consumption and reward. We previously reported that the preclinical drug sazetidine-A, a nAChR agonist, reduces alcohol consumption without affecting nicotine consumption in C57BL/6J mice. Here, we found that sazetidine-A enhances the expression of alcohol aversion without affecting the expression or acquisition of conditioned alcohol reward in C57BL/6J mice. Microinjection of sazetidine-A into the ventral midbrain targeting the ventral tegmental area (VTA) reduced binge alcohol consumption, implicating the neurocircuitries in this region in mediating the effects of sazetidine-A. Furthermore, sazetidine-A-induced reduction in alcohol consumption was mediated by non-α4 containing nAChRs, as sazetidine-A reduced binge alcohol consumption in both α4 knock-out and wild-type mice. Finally, we found that in mice pre-treated with sazetidine-A, alcohol induced Fos transcript within Th-expressing but not Gad2-expressing neurons in the VTA as measured by increased Fos transcript expression. In summary, we find that sazetidine-A acts on non-α4 nAChRs to enhance the expression of alcohol aversion, which may underlie the reduction in alcohol consumption induced by sazetidine-A. Elucidating the identity of non-α4 nAChRs in alcohol aversion mechanisms will provide a better understanding the complex role of nAChRs in alcohol addiction and potentially reveal novel drug targets to treat AUDs.
Placental neurosteroids shape cerebellar development and social behaviour
Authors: Vacher Claire-Marie , O’Reilly Jiaqi J. , Salzbank Jacquelyn , Lacaille Helene , Bakalar Dana , Sebaoui-Illoul Sonia , Liere Philippe , Clarkson-Paredes Cheryl , Sasaki Toru , Sathyanesan Aaron , Kawasawa Yuka Imamura , Popratiloff Anastas , Hashimoto-Torii Kazue , Gallo Vittorio , Schumacher Michael , Penn Anna A.
Published: August 2019

Compromised placental function or premature loss has been linked to diverse neurodevelopmental disorders 1,2. The placenta is the first functional foetal endocrine organ, but the direct impact of placental hormone loss on foetal brain in late gestation has not been empirically tested. Allopregnanolone (ALLO) is a non-glucocorticoid, progesterone derivative that acts as a positive modulator of GABA-A receptor activity3 with the potential to alter critical GABA-mediated developmental processes 4,5. To directly test the role of placental ALLO, we generated a novel mouse model in which the gene encoding the synthetic enzyme for ALLO (Akr1c14) is specifically deleted in trophoblasts using a tissue-specific Cre-Lox strategy. ALLO concentrations are significantly decreased in late gestation in placenta and brain when placental Akr1c14 is removed, indicating placenta as the primary gestational ALLO source. We now demonstrate that targeted placental ALLO loss leads to permanent changes in brain development in a sex- and regionally-specific manner. Placental ALLO insufficiency led to male-specific cerebellar white matter (WM) abnormalities characterized by excess myelination with increased myelin protein expression, similar to changes reported in boys with autism spectrum disorders (ASD)6,7. Behavioural testing of these mice revealed increased repetitive behaviour and sociability deficits, two hallmarks of ASD, only in male offspring with placental ALLO insufficiency. Notably, a strong positive correlation was seen between the cerebellar contents of myelin basic protein (MBP) and the severity of ASD-like behaviours. A single injection of ALLO during gestation was sufficient to rescue both cerebellar MBP levels and aberrant behaviours. This study reveals a new role for a placental hormone in shaping specific brain structures and behaviours, and suggests that identifying placental hormone insufficiency or preterm loss may offer novel therapeutic opportunities to prevent later neurobehavioural disorders.
DUX4 regulates oocyte to embryo transition in human
Authors: Vuoristo Sanna , Hydén-Granskog Christel , Yoshihara Masahito , Bhagat Shruti , Gawriyski Lisa , Jouhilahti Eeva-Mari , Damdimopoulos Anastassius , Ranga Vipin , Tamirat Mahlet , Huhtala Mikko , Hashimoto Kosuke , Krjutskov Kaarel , Recher Gaëlle , Ezer Sini , Paluoja Priit , Paloviita Pauliina , Takegami Yujiro , Kanemaru Ai , Lundin Karolina , Airenne Tomi , Otonkoski Timo , Tapanainen Juha S , Kawaji Hideya , Murakawa Yasuhiro , Bürglin Thomas R , Varjosalo Markku , Johnson Mark S , Tuuri Timo , Katayama Shintaro , Kere Juha
Published: August 2019

In oocyte to embryo transition, the fertilized oocyte undergoes final maturation and the embryo genome is gradually activated during the first three cell divisions. How this transition is coordinated and which factors drive the processes in humans is largely unknown. Here we studied the role of the double homeodomain transcription factor DUX4 in regulating the human oocyte to embryo transition. DUX4 knockdown zygotes show delayed transcriptome reprogramming during the first three days after fertilization. Our combined experimental approaches allowed integrated analysis on the transcriptome, chromatin, and proteome data in human embryos or a DUX4 expressing human embryonic stem cell model. We conclude that DUX4 is a pioneering factor that regulates human oocyte to embryo transition through regulating oocyte mRNA degradation, as well as direct binding and activation of minor genome activation genes, and genomic repeat elements.
A mathematical model of mitochondrial calcium-phosphate dissolution as a mechanism for persistent post-CSD vasoconstriction
Authors: Xu Shixin , Chang Joshua C. , Chow Carson C. , Huang Huaxiong
Published: August 2019

Cortical spreading depolarization (CSD) is the propagation of a relatively slow wave in cortical brain tissue that is linked to a number of pathological conditions such as stroke and migraine. Most of the existing literature investigates the dynamics of short term phenomena such as the depolarization and repolarization of membrane potentials or large ion shifts. Here, we focus on the clinically-relevant hour-long state of neurovascular malfunction in the wake of CSDs. This dysfunctional state involves widespread vasoconstriction and a general disruption of neurovascular coupling. We demonstrate, using a mathematical model, that dissolution of calcium that has aggregated within the mitochondria of vascular smooth muscle cells can drive an hour-long disruption. We determine the rate of calcium clearance as well as the dynamical implications on overall blood flow. Based on reaction stoichiometry, we quantify a possible impact of calcium phosphate dissolution on the maintenance of F0F1-ATP synthase activity.
Comparing transcriptional dynamics of the epithelial-mesenchymal transition
Authors: Cook David P. , Vanderhyden Barbara C.
Published: August 2019

Epithelial-mesenchymal (E/M) heterogeneity is ubiquitous within all epithelial tissues and the reversible transition between these two states provides cells with plasticity that contributes to organogenesis in the developing embryo, tissue homeostasis in adults, and tumour progression1. While the epithelial-mesenchymal transition (EMT) has been extensively studied, no common, EMT-defining gene expression program has been identified2. Here, we leverage highly multiplexed single-cell RNA sequencing (scRNA-seq) to compare the transcriptional program associated with the EMT across a variety of contexts, assessing 103,999 cells from 960 samples, comprising 12 EMT time course experiments and 16 independent kinase inhibitor screens. We demonstrate that the EMT is not simply a linear transition between E/M states, and transcriptional dynamics are widely variable across contexts, regardless of the cell type and cytokine used to induce the transition. While many canonical EMT genes were poor markers of the transition in our models, we identified 86 conserved mesenchymal-associated genes also coexpressed in a variety of mouse and human epithelial and carcinoma tissues. Despite the heterogeneous transcriptional responses, we identified a core set of largely conserved transcription factors coordinating these dynamics, including RELB and SOX4. Finally, we found that the EMT is associated with a broad increase in expression of secreted factors. Kinase inhibitor screens revealed multiple paracrine dependencies of the EMT, including a novel association between TGFB1 and the TNF-associated kinase RIPK1. Together, these results comprehensively highlight the complexity and diversity of the EMT, but also reveal dynamics conserved across contexts. This work will provide the foundation for understanding the nature of E/M heterogeneity and its functional consequences, which could elucidate various physiological processes and be leveraged for cancer treatments.
Cell-substrate adhesion drives Scar/WAVE activation and phosphorylation, which controls pseudopod lifetime
Authors: Singh Shashi Prakash , Thomason Peter A. , Lilla Sergio , Schaks Matthias , Tang Qing , Goode Bruce L. , Machesky Laura M. , Rottner Klemens , Insall Robert H.
Published: August 2019

The Scar/WAVE complex is the principal catalyst of pseudopod and lamellipod formation. Here we show that Scar/WAVE’s proline-rich domain is polyphosphorylated after the complex is activated. Treatments that stop activation block phosphorylation in bothDictyosteliumand mammalian cells. This implies that phosphorylation modulates pseudopods after they have been formed, rather than controlling whether a protrusion is initiated. Unexpectedly, activation-dependent phosphorylation is not promoted by chemotactic signalling, or by signal-dependent kinases such as ERKs, but is greatly stimulated by cell:substrate adhesion. Scar/WAVE that has been mutated to be either unphosphorylatable or phosphomimetic is activated normally, and rescues the phenotype ofscar−cells, demonstrating that phosphorylation is dispensible for activation and actin regulation. However, pseudopods and patches of Scar/WAVE complex recruitment last substantially longer in unphosphorylatable mutants, altering cell polarisation and the efficiency of migration. We conclude that pseudopod engagement with substratum is more important than extracellular signals at regulating Scar/WAVE’s activity, and that phosphorylation acts as a timer, restricting pseudopod lifetime by promoting Scar/WAVE turnover.
Essential dynamic interdependence of FtsZ and SepF for Z-ring and septum formation inCorynebacterium glutamicum
Authors: Sogues Adrià , Martinez Mariano , Gaday Quentin , Ben-Assaya Mathilde , Graña Martin , Voegele Alexis , VanNieuwenhze Michael , England Patrick , Haouz Ahmed , Chenal Alexandre , Trépout Sylvain , Duran Rosario , Wehenkel Anne Marie , Alzari Pedro
Published: August 2019

The mechanisms of Z-ring assembly and regulation in bacteria are poorly understood, particularly in non-model organisms.Actinobacteria, one of the largest bacterial phyla that includes the deadly human pathogenMycobacterium tuberculosis, lack the canonical FtsZ-membrane anchors as well as all positive and negative Z-ring regulators described forE. coli. Here we investigate the physiological function ofCorynebacterium glutamicumSepF, the only cell division-associated protein fromActinobacteriaknown to directly interact with the conserved C-terminal tail of FtsZ but whose actual mode of action in cytokinesis is yet to be elucidated. We used a mechanistic cell biology approach to unveil the essential interdependence of FtsZ and SepF required for the formation of a functional Z-ring in the actinobacterial model organismC. glutamicum. The crystal structure of the SepF-FtsZ complex reveals a hydrophobic FtsZ-binding pocket, which defines the SepF homodimer as the functional unit, and a reversible oligomerization interface regulatedviaan alpha helical switch. FtsZ filaments and lipid membranes have opposing effects on SepF polymerization, leading to a complex dynamic role of the protein at the division site, involving FtsZ bundling, Z-ring tethering and membrane reshaping activities that are needed for proper Z-ring assembly and function.
Development and application of eDNA-based tools for the conservation of white-clawed crayfish
Authors: Troth Christopher R. , Burian Alfred , Mauvisseau Quentin , Bulling Mark , Nightingale Jen , Mauvisseau Christophe , Sweet Michael J.
Published: August 2019

eDNA-based methods represent non-invasive and cost-effective approaches for species monitoring and their application as a conservation tool has rapidly increased within the last decade. Currently, they are primarily used to determine the presence/absence of invasive, endangered or commercially important species, but they also hold potential to contribute to an improved understanding of the ecological interactions that drive species distribution. However, this next step of eDNA-based applications requires a thorough method development.

We developed an eDNA assay for the white-clawed crayfish (Austropotamobius pallipes), a flagship species of conservation in the UK. Multiple subsequent in-situ and ex-situ validation tests aimed at improving method performance allowed us to apply eDNA-based surveys to evaluate interactions between white-clawed crayfish, crayfish plague and invasive signal crayfish.

The assay performed well in terms of specificity (no detection of non-target DNA) and sensitivity, which was higher than more established traditional species survey methods. Quantification of species biomass was, however, less reliable.

Comparison of eDNA sampling methods (precipitation vs. various filtration approaches) revealed that optimal sampling method differed across environments and might depend on inhibitor concentrations.

Finally, we applied our methodology together with established assays for crayfish plague and the invasive signal crayfish and demonstrated their significant interactions in a UK river system.

Our analysis highlights the importance of thorough methodological development of eDNA-based assays. Only a critical evaluation of methodological strengths and weaknesses will allow us to capitalise on the full potential of eDNA-based methods and use them as decision support tools in environmental monitoring and conservation practices.
Discovery of aPseudomonas aeruginosaType VI secretion system toxin targeting bacterial protein synthesis using a global genomics approach
Authors: Nolan Laura M. , Cain Amy K. , Manoli Eleni , Sainz-Polo Maria A. , Dougan Gordon , Mavridou Despoina A.I. , Albesa-Jové David , Parkhill Julian , Filloux Alain
Published: August 2019

The Type VI secretion system (T6SS) is a bacterial weapon which delivers toxic effectors to kill competitors or subvert some of their key functions. Here we usetransposondirected insertion-sitesequencing (TraDIS) to identify T6SS toxins associated with the H1-T6SS, one of the three T6SS machines found inPseudomonas aeruginosa. This approach identified several putative toxin-immunity pairs, including Tse8-Tsi8. Full characterization of this protein pair demonstrated that Tse8 is delivered by the VgrG1a spike complex into prey cells where it targets the transamidosome, a multiprotein complex involved in protein synthesis in bacteria lacking either one or both of the asparagine or glutamine tRNA synthases. Our data suggests that Tse8 combines as a non-cognate component of the transamidosome complex, reducing fitness by limiting the ability of the cell to synthesize proteins. This is the first demonstration of a T6SS toxin affecting protein synthesis, expanding the range of cellular components targeted by this bacterial weapon. The success of the current study validates the use of our TraDIS approach as a tool to drastically expand the repertoire of T6SS toxins in any T6SS-encoding bacterium.
Cytosolic Adaptation to Mitochondrial Precursor Overaccumulation Stress Induces Progressive Muscle Wasting
Authors: Wang Xiaowen , Middleton Frank A. , Tawil Rabi , Chen Xin Jie
Published: August 2019

Mitochondrial dysfunction causes muscle wasting (or atrophy) in many diseases and probably also during aging. The underlying mechanism is unclear. Accumulating evidence suggests that substantial levels of bioenergetic deficiency and oxidative stress are insufficient by themselves to intrinsically cause muscle wasting, raising the possibility that non-bioenergetic factors may contribute to mitochondria-induced muscle wasting. In this report, we show that chronic adaptation to mitochondria-induced proteostatic stress in the cytosol induces muscle wasting. We generated transgenic mice with unbalanced mitochondrial protein loading and import, by a two-fold increase in the expression of the nuclear-encoded mitochondrial carrier protein, Ant1. We found that the ANT1-transgenic mice progressively lose muscle mass. Skeletal muscle is severely atrophic in older mice without affecting the overall lifespan. Mechanistically, Ant1 overloading induces aggresome-like structures and the expression of small heat shock proteins in the cytosol. The data support mitochondrial Precursor Overaccumulation Stress (mPOS), a recently discovered cellular stress mechanism caused by the toxic accumulation of unimported mitochondrial precursors/preproteins. Importantly, the ANT1-transgenic muscles have a drastically remodeled transcriptome that appears to be trying to counteract mPOS, by repressing protein synthesis, and by stimulating proteasomal function, autophagy and lysosomal amplification. These anti-mPOS responses collectively reduce protein content, which is known to decrease myofiber size and muscle mass. Our work therefore revealed that a subtle imbalance between mitochondrial protein load and import is sufficient to induce mPOS in vivo, and that anti-mPOS adaptation is a robust mechanism of muscle wasting. This finding may help improve the understanding of how mitochondria contribute to muscle wasting. It could have direct implications for several human diseases associated with ANT1 overexpression, including Facioscapulohumeral Dystrophy (FSHD).

One Sentence Summary

Proteostatic adaptations to proteostatic stress in the cytosol caused by unbalanced mitochondrial protein loading and import lead to progressive muscle wasting.
quasitools: A Collection of Tools for Viral Quasispecies Analysis
Authors: Marinier Eric , Enns Eric , Tran Camy , Fogel Matthew , Peters Cole , Kidwai Ahmed , Ji Hezhao , Van Domselaar Gary
Published: August 2019

quasitools is a collection of newly-developed, open-source tools for analyzing viral quasispcies data. The application suite includes tools with the ability to create consensus sequences, call nucleotide, codon, and amino acid variants, calculate the complexity of a quasispecies, and measure the genetic distance between two similar quasispecies. These tools may be run independently or in user-created workflows.

Availability

The quasitools suite is a freely available application licensed under the Apache License, Version 2.0. The source code, documentation, and file specifications are available at: https://phac-nml.github.io/quasitools/

Contact

gary.vandomselaar@canada.ca
Signaling gradients in surface dynamics as basis for planarian regeneration
Authors: Scheel Arnd , Stevens Angela , Tenbrock Christoph
Published: August 2019

We introduce and analyze a mathematical model for the regeneration of planarian flatworms. This system of differential equations incorporates dynamics of head and tail cells which express positional control genes that in turn translate into localized signals that guide stem cell differentiation. Orientation and positional information is encoded in the dynamics of a long rangewnt-related signaling gradient. We motivate our model in relation to experimental data and demonstrate how it correctly reproduces cut and graft experiments. In particular, our system improves on previous models by preserving polarity in regeneration, over orders of magnitude in body size during cutting experiments and growth phases. Our model relies on tristability in cell density dynamics, between head, trunk, and tail. In addition, key to polarity preservation in regeneration, our system includes sensitivity of cell differentiation to gradients ofwnt-related signals relative to the tissue surface. This process is particularly relevant in a small tissue layer close to wounds during their healing, and modeled here in a robust fashion through dynamic boundary conditions.
Is Vagus Nerve Stimulation Brain Washing?
Authors: Cheng Kevin P. , Brodnick Sarah K. , Blanz Stephan L. , Zeng Weifeng , Kegel Jack , Pisaniello Jane A. , Ness Jared P. , Ross Erika , Nicolai Evan N. , Settell Megan L. , Trevathan James K. , Poore Samuel O. , Suminski Aaron J. , Williams Justin C. , Ludwig Kip A.
Published: August 2019

Vagal nerve stimulation (VNS) is an FDA approved treatment method for intractable epilepsy, treatment resistant depression, cluster headaches and migraine with over 100,000 patients having received vagal nerve implants to date. Moreover, evidence in the literature has led to a growing list of possible clinical indications, with several small clinical trials applying VNS to treat conditions ranging from neurodegenerative diseases to arthritis, anxiety disorders, and obesity. Despite the growing list of therapeutic applications, the fundamental mechanisms by which VNS achieves its beneficial effects are poorly understood and an area of active research. In parallel, the glymphatic and meningeal lymphatic systems have recently been proposed and experimentally validated to explain how the brain maintains a healthy homeostasis without a traditionally defined lymphatic system. In particular, the glymphatic system relates to the interchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF) whose net effect is to wash through the brain parenchyma removing metabolic waste products and misfolded proteins from the interstitium. Of note, clearance is sensitive to adrenergic signaling, and a primary driver of CSF influx into the parenchyma appears to be cerebral arterial pulsations and respiration. As VNS has well-documented effects on cardiovascular and respiratory physiology as well as brain adrenergic signaling, we hypothesized that VNS delivered at clinically derived parameters would increase CSF influx in the brain. To test this hypothesis, we injected a low molecular weight (3 kD) lysine-fixable fluorescent tracer (TxRed) into the CSF system of mice with a cervical vagus nerve cuff implant and measured the amount of CSF penetrance following VNS. We found that the clinical VNS group showed a significant increase in CSF dye penetrance as compared to the naïve control and sham groups. This study demonstrates that VNS therapeutic strategies already being applied in the clinic today may induce intended effects and/or unwanted side effects by altering CSF/ISF exchange in the brain. This may have broad ranging implications in the treatment of various CNS pathologies.

One Sentence Summary

Cervical vagus nerve stimulation using clinically derived parameters enhances movement of cerebrospinal fluid into the brain parenchyma presenting a previously unreported effect of vagus nerve stimulation with potential clinical utility.
Profiling of presynaptic mRNAs reveals a role for axonal PUMILIOs in associative memory formation
Authors: Arey Rachel , Kaletsky Rachel , Murphy Coleen T.
Published: August 2019

Presynaptic protein synthesis is important in the adult central nervous system; however, the set of mRNAs localized to presynaptic areas has yet to be identified in any organism. We differentially labeled somatic and synaptic compartments nervous system-wide in adult C. elegans and isolated synaptic regions for deep sequencing. Analysis of the synaptic transcriptome reveals that synaptic transcripts are predicted to have specialized functions in neurons. Differential expression analysis identified 543 genes enriched in synaptic regions relative to somatic regions, with synaptic functions conserved in higher organisms. We find that mRNAs for pumilio RNA-binding proteins are abundant in synaptic regions, which we confirmed through high-sensitivity in situ hybridization. We identified a new role for the PUM2 orthologs puf-7/8 as repressors of memory formation through regulation of the mitochondrial dynamics regulator, mff-1. Identification of presynaptic mRNAs provides insight into mechanisms that regulate synaptic function and behavior.
MCF2 is linked to a complex perisylvian syndrome and affects cortical lamination
Authors: Molinard-Chenu Aude , Fluss Joël , Laurent Sacha , Guipponi Michel , Dayer Alexandre G
Published: August 2019

The combination of congenital bilateral perisylvian syndrome (CBPS) with lower motor neuron dysfunction is unusual and suggests a potential common genetic insult affecting basic neurodevelopmental processes. Here we identify a putatively pathogenic missense mutation in the MCF2 gene in a boy with CBPS. Using in utero electroporation to genetically manipulate cortical neurons during corticogenesis, we demonstrate that the mouse Mcf2 gene controls the embryonic migration of cortical projection neurons. Strikingly, we find that the CBPS-associated MCF2 mutation impairs cortical laminar positioning, supporting the hypothesis that alterations in the process of embryonic neuronal migration can lead to rare cases of CBPS.
An integrative approach uncovers genes with perturbed interactions in cancers
Authors: Kobren Shilpa Nadimpalli , Chazelle Bernard , Singh Mona
Published: August 2019

A major challenge in cancer genomics is to identify genes with functional roles in cancer and uncover their mechanisms of action. Here, we introduce a unified analytical framework that enables rapid integration of multiple sources of information in order to identify cancer-relevant genes by pinpointing those whose interaction or other functional sites are enriched in somatic mutations across tumors. Our accompanying method PertInInt combines knowledge about sites participating in interactions with DNA, RNA, peptides, ions or small molecules with domain, evolutionary conservation and gene-level mutation data. When applied to 10,037 tumor samples across 33 cancer types, PertInInt uncovers both known and newly predicted cancer genes, while simultaneously revealing whether interaction potential or other functionalities are disrupted. PertInInt’s analysis demonstrates that somatic mutations are frequently enriched in binding residues and domains in oncogenes and tumor suppressors, and implicates interaction perturbation as a pervasive cancer driving event.

(Software at http://github.com/Singh-Lab/PertInInt.)
SHYBRID: A graphical tool for generating hybrid ground-truth spiking data for evaluating spike sorting performance
Authors: Wouters Jasper , Kloosterman Fabian , Bertrand Alexander
Published: August 2019

Spike sorting is the process of retrieving the spike times of individual neurons that are present in an extracellular neural recording. Over the last decades, many spike sorting algorithms have been published. In an effort to guide a user towards a specific spike sorting algorithm, given a specific recording setting (i.e., brain region and recording device), we provide an open-source graphical tool for the generation of hybrid ground-truth data in Python. Hybrid ground-truth data is a data-driven modelling paradigm in which spikes from a single unit are moved to a different location on the recording probe, thereby generating a virtual unit of which the spike times are known. The tool enables a user to efficiently generate hybrid ground-truth datasets and make informed decisions between spike sorting algorithms, fine-tune the algorithm parameters towards the used recording setting, or get a deeper understanding of those algorithms.
Crystal structure and Hirshfeld surface analysis of bis(benzoato-κ2
O,O′)[bis(pyridin-2-yl-κN)amine]nickel(II)
Authors: Phiokliang Phichitra , Promwit Phakamat , Chainok Kittipong , Wannarit Nanthawat
Published: August 2019

A new mononuclear NiII complex with bis(pyridin-2-yl)amine (dpyam) and benzoate (benz), [Ni(C7H5O2)2(C10H9N3)], crystallizes in the monoclinic space group P21/c. The NiII ion adopts a cis-distorted octahedral geometry with an [NiN2O4] chromophore. In the crystal, the complex molecules are linked together into a one-dimensional chain by symmetry-related π–π stacking interactions [centroid-to-centroid distance = 3.7257 (17) Å], along with N—H...O and C—H...O hydrogen bonds. The crystal packing is further stabilized by C—H...π interactions, which were investigated by Hirshfeld surface analysis.
Contingent worker and innovation performance in electronics manufacturing service industry
Authors: Chen Chun-Hsi Vivian , Yeh Pi-Wen , Madsen Jean
Published: August 2019

Purpose

This study aims to explore the influences of contingent workers on organizations’ innovation performance and develop a framework examining how innovation performance benefits from the utilization of contingent workers. Built up on a strategic human resource (HR) flexibility model, the importance of coordination flexibility of contingent worker skills and behaviors is highlighted.

Design/methodology/approach

Structural equation modeling is used to test the proposed hypotheses by using data collected from 163 paired surveys in Taiwan. The results provide support on the hypotheses.

Findings

The findings in this study highlight the coordination flexibility of contingent worker skills and behaviors, adaptive capability and knowledge integration on innovation performance in highly competitive industries. This study provides evidence linking coordination flexibility of contingent worker skills and behaviors and organizational innovation performance, and can contribute to the strategic HR management literature.

Originality/value

Coordination flexibility of contingent worker skills and behaviors contributes positively to innovation performance. According to the findings, managers should pay more attention on the contingent workers’ coordination practices to enhance organizational innovation performance in the manufacturing firms. In addition to the managerial implications, research limitations and future research directions are also discussed.
Multi-level approach for important component identification and reliability evaluation for complex system by survival signature
Authors: Ge Liling , Zhang Yingjie
Published: August 2019

Purpose

The purpose of this paper is to identify the critical components of a complex system by using survival signature. First, a complex system is abstracted with varying scales and generates a multi-levels model. Then reliability evaluations can be conducted by survival signature from rough to fine for tracing and identifying them. Finally, the feasibility of the proposed approach is demonstrated by an actual production system.

Design/methodology/approach

The paper mainly applies a multi-level evaluating strategy for the reliability analysis of complex systems with components of multiple types. In addition, a multi-levels model of a complex system is constructed and survival signature also used for evaluation.

Findings

The proposed approach was demonstrated to be the feasibility by an actual production system that is used in the case study.

Research limitations/implications

The case study was performed on a system with simple network structure, but the proposed approach could be applied to systems with complex ones. However, the approach to generate the digraphs of abstraction levels for complex system has to be developed.

Practical implications

So far the approach has been used for the reliability analysis of a machining system. The approach that is proposed for the identification of critical components also can be applied to make maintenance decision.

Originality/value

The multi-level evaluating strategy that was proposed for reliability analysis and the identification of critical components of complex systems was a novel method, and it also can be applied as index to make maintenance planning.
Study on the research evolution of Nobel laureates 2018 based on self-citation network
Authors: Wen Fangfang
Published: August 2019

Purpose

Science is a continuum of experiences consisting of authors and their publications, and the authors’ experience is an integral part of their work that gets reflected through self-citations. Thus, self-citations can be employed in measuring the relevance between publications and tracking the evolution of research. The paper aims to discuss this issue.

Design/methodology/approach

Based on the bibliographic data obtained from Scopus, this study constructs and visualizes the self-citation networks of ten Nobel laureates 2018, in the fields of Physiology or Medicine, Physics, Chemistry and Economic Science, to demonstrate the evolving process of each laureate’s research across his or her scholarly career.

Findings

Statistics indicate that prominent scientists, such as Nobel laureates, have also frequently cited their own publications. However, their self-cited rates are quite low. Self-citations constitute an indispensable part of the citation system but contribute little to authors’ scientific impact, regardless of artificial self-citations. Self-citation networks present a trajectory that shows the evolving process of research across a scientist’s long-term scholarly career. There are obvious differences in self-citation patterns and network structures of different laureates without a disciplinary difference observed. The structures of self-citation networks are significantly influenced by laureates’ productivity. In addition, it is laureates’ own research patterns and citation habits that lead to the diversified patterns and structures of self-citation networks.

Research limitations/implications

Only scientific achievements presented in the form of publications are investigated and other kinds of scientific output, such as patents, are not included. Moreover, this approach is fit for scientists who have had a longer career and higher productivity.

Originality/value

This study proves the feasibility and effectiveness of self-citation analysis as a new way to examine research evolution.
A conceptual model for enterprise risk management
Authors: Almeida Rafael , Teixeira José Miguel , Mira da Silva Miguel , Faroleiro Paulo
Published: August 2019

Purpose

The purpose of this paper is to ease the ISO 31000 standard understanding and provide mechanisms that allow organizations to adopt and adapt this standard to their reality.

Design/methodology/approach

The research methodology adopted in this research was the design science research methodology.

Findings

Key finding is that enterprise architecture (EA) models and EA tools can help reduce the complexity of the ISO 31000 standard and improve the communication between stakeholders.

Practical implications

The research proposal serves the purpose of supporting the evidence collection for an enterprise risk management (ERM) initiative in an as-was, as-is, or to-be perspective.

Originality/value

Traditional ERM efforts operate on silos, limiting the sharing of risk information and the achievement of an organization-wide view of risks. EA can provide a common way to model complex business systems, from the strategic level to implementation details. This paper proposes the use of an EA model and an EA tool (Atlas) to represent ISO 31000, allowing a better understanding on the value of assets that can be affected from the manifestation of some risks over time.
Utilising stakeholder theory for social marketing process evaluation in a food waste context
Authors: Hodgkins Samuel , Rundle-Thiele Sharyn , Knox Kathy , Kim Jeawon
Published: August 2019

Purpose

Calls for theoretically informed interventions and a more reflexive stance are apparent in social marketing. Moving from a “prove” to “improve” mentality requires evaluations that learn from experience gained to identify improvements to inform future programme success. This paper considers the value of inclusion of stakeholders in process evaluation.

Design/methodology/approach

Two participant groups (n = 90, n = 182) and one key stakeholder group (n = 22) were surveyed in person, over the phone and online. Open-ended qualitative responses were analysed for recurring themes.

Findings

Key stakeholders contribute unique and valuable insight into programme implementation and engagement, expanding evaluation beyond participant feedback. Most notably, the process evaluation illuminated the engagement insight of programme volunteers, mid-level expansion opportunities offered by participating chefs and the perceived value of involvement across all stakeholder groups.

Research limitations/implications

The study is limited by a lack of systematic stakeholder identification and to a single context, namely food waste.

Practical implications

This paper affirms the importance of process evaluation and application of stakeholder theory to social marketing. These contributions suggest a widened focus for the widely accepted NSMC benchmark criteria which centre attention on the end users targeted for change. Stakeholders should be included in process evaluations given they contribute important and unique partnership insights.

Originality/value

This paper extends stakeholder theory use in social marketing providing showcasing potential for this approach to deliver a more reflexive stance.
Advertising cooperation of dual-channel low-carbon supply chain based on cost-sharing
Authors: Yu Chao , Wang Chuanxu , Zhang Suyong
Published: August 2019

Purpose

This paper aims to analyze the impact of the cost coefficient of product emission reduction, coefficient of low-carbon product advertising effort cost, and sharing ratio of low-carbon product advertising effort cost on the profit of a dual-channel supply chain. After determining the best model and relevant influencing factors, the paper puts forward corresponding management inspirations and suggestions.

Design/methodology/approach

The paper opts for an exploratory study using Stackelberg game theory to construct a centralized decision-making (MC mode), a low carbon product advertising effort cost free sharing decentralized decision-making (SD model) and a low carbon product advertising effort cost sharing decentralized decision-making (JD model) game model. Through using optimization methods to get the equilibrium solution, the relevant management suggestions are obtained by comparison analysis.

Findings

The paper shows that the JD model is better than the SD model in terms of the profits of the manufacturer, retailer and supply chain, and the improvement of Pareto is realized. The proportion of cost sharing of low carbon product advertising effort is positively related to the wholesale price and direct influence coefficient of low carbon product advertising effort on channel, while negatively related to the retail price and the cross influence coefficient of low carbon product advertising effort on alternative channels. Under the JD model, the manufacturer can reduce advertising costs through improving the efficiency and pertinence of direct channel advertising and urging the retailer to do a better job in sales management to improve gross margin and require the retailer to increase advertising efficiency and pertinence of retail channel to reduce advertising costs of retail channel and other ways to increase their profits. The retailer can make use of its advantages closer with consumers to improve the efficiency and pertinence of advertising in the retail channel to raise the influence coefficient of advertising and reduce the advertising cost in the retail channel.

Originality/value

The innovations of this paper are listed as follows: First, it has considered advertising investment from both the manufacturer and the retailer simultaneously. Second, it has considered a low-carbon background to investigate cooperative advertising decision for low-carbon products. Third, it has considered the decision on the level of product emission reduction and the level of low-carbon product advertising effort investment simultaneously.
Overcoming imposter syndrome: the adventures of two new instruction librarians
Authors: Martinez Jessica , Forrey Meredith
Published: August 2019

Purpose

New librarians rarely feel fully prepared for academic library instruction. This could be attributed to many factors in both Master of Library and Information Science programs and work environments. Imposter syndrome or imposter phenomenon is a common way this insecurity manifests. Imposter phenomenon, first defined in 1978, is an individual’s feeling that they will be exposed as a fraud, regardless of how qualified or knowledgeable they actually are. Throughout the first year as new instruction librarians, the authors tracked their experiences with instruction and the imposter phenomenon. This paper aims to illuminate how imposter phenomenon impacts library instruction, provide suggestions for individual librarians and identify what academic libraries can do institutionally to mitigate feelings of fraudulence among their employees.

Design/methodology/approach

This paper outlines the history and symptoms of imposter phenomenon, focusing on its presence in libraries. The authors draw on existing literature in psychology and library science, their own experience and a survey of 172 librarians. Suggestions for best practices for easing imposter phenomenon are then discussed based on the experiences of the authors and survey respondents.

Findings

This paper suggests several ways to ease the feelings of imposter phenomenon among those employed in academic libraries.

Research limitations/implications

This paper is based on the authors’ experiences, as well as a survey of 172 librarians. The survey was self-selecting, so the results may be skewed, but the themes apparent throughout the responses indicate that imposter phenomenon in libraries is pervasive and warrants further research.

Practical implications

The recommendations presented in this paper will provide new librarians and library administrators with concrete ways to identify and ameliorate imposter phenomenon among new instruction librarians.

Originality/value

Though imposter phenomenon has gained popular attention in wider society, extant research has not sufficiently addressed its role in the realm of academic library instruction. Given that most MLIS programs focus on theory rather than practice, finding ways to give new instruction librarians confidence in their positions is an area of research that warrants more exploration.
Self-help groups in India: challenges and a roadmap for sustainability
Authors: Nayak Akhaya Kumar , Panigrahi Prabin Kumar , Swain Biswanath
Published: August 2019

Purpose

Self-help groups (SHGs) have widely been accepted by developing nations for their contribution to inclusive development. Despite its importance and the recognition of the same, SHGs and their members face several challenges. The purpose of this paper is to comprehensively investigate the inhibiting factors affecting the effectiveness of women SHGs. The paper also proposes a roadmap for all the self-help promoting institutions, such as banks, state and central government, and non-government organizations to address the challenges.

Design/methodology/approach

The study adopts an exploratory research design to undertake this applied research. It uses phenomenographic and interpretative approaches. Qualitative data have been collected from 24 members belonging to eight SHGs from the eastern Indian state of Odisha with the help of a semi-structured interview schedule. The result has been analyzed by using content analysis.

Findings

The study finds that SHG members in Odisha face several challenges in the form of financial bottlenecks, entrepreneurial obstacles, capacity-building impediments, mentor-ship challenges, socio-structural challenges and group dynamics.

Research limitations/implications

The study finds many unique and contextual inhibiting factors, which are valuable additions to the existing literature. At the same time, the result may not be applicable to other kinds of SHGs, such as Alcoholic Anonymous, as their nature, composition and deliverables are quite different from the SHG that the current study has taken into consideration.

Practical implications

The proposed roadmap would be useful to policymakers, non-government organizations and other agencies involved in the promotion and capacity building of SHGs operating in Odisha in particular and India in general.

Originality/value

The literature is mainly concerned with the impact evaluation of SHG programs. This study investigates the challenges faced by SHGs in a systematic way and provides a roadmap to address the same in a comprehensive way.