bluuebunny/crossref_metadata_2025 huggingface dataset:
The Information Theory of Developmental Pruning: Optimizing Global Network Architecture Using Local Synaptic Rules
Authors: Scholl Carolin , Rule Michael E. , Hennig Matthias H.
Published: December 2020

During development, biological neural networks produce more synapses and neurons than needed. Many of these synapses and neurons are later removed in a process known as neural pruning. Why networks should initially be over-populated, and processes that determine which synapses and neurons are ultimately pruned, remains unclear. We study the mechanisms and significance of neural pruning in model neural network. In a deep Boltzmann machine model of sensory encoding, we find that (1) synaptic pruning is necessary to learn efficient network architectures that retain computationally-relevant connections, (2) pruning by synaptic weight alone does not optimize network size and (3) pruning based on a locally-available proxy for “sloppiness” based on Fisher Information allows the network to identify structurally important vs. unimportant connections and neurons. This locally-available measure of importance has a biological interpretation in terms of the correlations between presynaptic and postsynaptic neurons, and implies an efficient activity-driven pruning rule. Overall, we show how local activity-dependent synaptic pruning can solve the global problem of optimizing a network architecture. We relate these findings to biology as follows: (I) Synaptic over-production is necessary for activity-dependent connectivity optimization. (II) In networks that have more neurons than needed, cells compete for activity, and only the most important and selective neurons are retained. (III) Cells may also be pruned due to a loss of synapses on their axons. This occurs when the information they convey is not relevant to the target population.
Genomic surveillance of antimicrobial resistance shows cattle are a moderate source of multi-drug resistant non-typhoidalSalmonellain Mexico
Authors: Delgado-Suárez Enrique Jesús , Palós-Guitérrez Tania , Ruíz-López Francisco Alejandro , Pérez Cindy Fabiola Hernández , Ballesteros-Nova Nayarit Emérita , Soberanis-Ramos Orbelín , Méndez-Medina Rubén Danilo , Allard Marc W. , Rubio-Lozano María Salud
Published: December 2020

Multi-drug resistant (MDR) non-typhoidalSalmonella(NTS) is a major public health concern globally. This study reports antibiotic susceptibility testing and genotypic antimicrobial resistance (AMR) profiles of NTS isolates from bovine lymph nodes (n=48) and ground beef (n=29). Furthermore, we compared genotypic AMR data of our isolates with those of publicly available NTS genomes from Mexico (n=1637). The probability of finding MDR isolates was higher in ground beef as compared to lymph nodes: χ2=12.0, P=0.0005. The most common resistant phenotypes involved tetracycline (40.3%), carbenicillin (26.0%), amoxicillin-clavulanic acid (20.8%), chloramphenicol (19.5%) and trimethoprim-sulfamethoxazole (16.9%), while over 55% of the isolates showed decreased susceptibility to ciprofloxacin and 26% were MDR. Occurrence of MDR isolates was strongly associated with NTS serovar (χ2=24.5, P<0.0001), with Typhimurium accounting for 40% of MDR strains. Most of these (9/10), carriedSalmonellagenomic island 1, which harbors multiple AMR genes (aadA2, blaCARB-2, floR, sul1, tetG) that confer a penta-resistant phenotype. Moreover, 100% of MDR isolates had mutations in theramRgene. Among public NTS isolates from foods and clinical cases in Mexico to date, those from cattle had the highest proportion of MDR genotypes. Our results suggest attaining significant improvements in AMR meat safety may require the identification and removal (or treatment) of product harboring MDR NTS, instead of screening forSalmonellaspp. or for isolates showing resistance to individual antibiotics. In that sense, massive integration of whole genome sequencing (WGS) technologies in AMR surveillance provides the shortest path to accomplish these goals.
Reproductive Compatibility inCapsicumis not Reflected in Genetic or Phenotypic Similarity Between Species Complexes
Authors: Parry Catherine , Wang Yen-wei , Lin Shih-wen , Barchenger Derek W.
Published: December 2020

Wild relatives of domesticatedCapsicumrepresent substantial genetic diversity and thus sources of traits of potential interest. Furthermore, the hybridization compatibility between members ofCapsicumspecies complexes remains unresolved. Improving our understanding of the relationship betweenCapsicumspecies relatedness and their ability to form hybrids is a highly pertinent issue. Through the development of novel interspecific hybrids in this study, we demonstrate interspecies compatibility is not necessarily reflected in relatedness according to establishedCapsicumgenepool complexes. Based on a phylogeny constructed by genotyping using single sequence repeat (SSR) markers and with a portion of thewaxylocus, and through principal component analysis (PCA) of phenotypic data, we clarify the relationships among wild and domesticatedCapsicumspecies. Together, the phylogeny and hybridization studies provide evidence for the misidentification of a number of species from the World Vegetable Center genebank included in this study. The World Vegetable Center holds the largest collection ofCapsicumgenetic material globally, therefore this may reflect a wider issue in the misidentification ofCapsicumwild relatives. The findings presented here provide insight into an apparent disconnect between compatibility and relatedness in theCapsicumgenus, which will be valuable in identifying candidates for future breeding programs.
Plasticity impairment alters community structure but permits successful pattern separation in a hippocampal network model
Authors: Schumm Samantha N. , Gabrieli David , Meaney David F.
Published: December 2020

Patients who suffer from traumatic brain injury (TBI) often complain of learning and memory problems. Their symptoms are principally mediated by the hippocampus and the ability to adapt to stimulus, also known as neural plasticity. Therefore, one plausible injury mechanism is plasticity impairment, which currently lacks comprehensive investigation across TBI research. For these studies, we used a computational network model of the hippocampus that includes the dentate gyrus, CA3, and CA1 with neuron-scale resolution. We simulated mild injury through weakened spike-timing-dependent plasticity (STDP), which modulates synaptic weights according to causal spike timing. In preliminary work, we found functional deficits consisting of decreased firing rate and broadband power in areas CA3 and CA1 after STDP impairment. To address structural changes with these studies, we applied modularity analysis to evaluate how STDP impairment modifies community structure in the hippocampal network. We also studied the emergent function of network-based learning and found that impaired networks could acquire conditioned responses after training, but the magnitude of the response was significantly lower. Furthermore, we examined pattern separation, a prerequisite of learning, by entraining two overlapping patterns. Contrary to our initial hypothesis, impaired networks did not exhibit deficits in pattern separation with either population- or rate-based coding. Collectively, these results demonstrate how a mechanism of injury that operates at the synapse regulates circuit function.

Author summary

Traumatic brain injury causes diverse symptoms, and memory problems are common among patients. These deficits are associated with the hippocampus, a brain region involved in learning and memory. Neural plasticity supports learning and memory by enabling the circuit to adapt to external stimulus. After brain injury, plasticity can be impaired, perhaps contributing to memory deficits. Yet, this mechanism of injury remains poorly understood. We implemented plasticity impairment and learning in a network model of the hippocampus that is unique because it has a high degree of biological detail in its structure and dynamics compared to other similar computational models. First, we examined the relationship between neurons in the network and characterized how the structure changed with injury. Then we trained the network with two input patterns to test the function of pattern separation, which is the ability to distinguish similar contexts and underpins general learning. We found that the strength of the encoded response decreased after impairment, but the circuit could still distinguish the two input patterns. This work provides insight into which specific aspects of memory become dysfunctional after injury.
Activity-mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type
Authors: Contreras Susana Andrea , Schleimer Jan-Hendrik , Gulledge Allan T. , Schreiber Susanne
Published: December 2020

During normal neuronal activity, ionic concentration gradients across a neuron’s membrane are often assumed to be stable. Prolonged spiking activity, however, can reduce transmembrane gradients and affect voltage dynamics. Based on mathematical modeling, we investigated the impact of neuronal activity on ionic concentrations and, consequently, the dynamics of action potential generation. We find that intense spiking activity on the order of a second suffices to induce changes in ionic reversal potentials and to consistently induce a switch from a regular to an intermittent firing mode. This transition is caused by a qualitative alteration in the system’s voltage dynamics, mathematically corresponding to a co-dimension-two bifurcation from a saddle-node on invariant cycle (SNIC) to a homoclinic orbit bifurcation (HOM). Our electrophysiological recordings in mouse cortical pyramidal neurons confirm the changes in action potential dynamics predicted by the models: (i) activity-dependent increases in intracellular sodium concentration directly reduce action potential amplitudes, an effect typically attributed solely to sodium channel inactivation; (ii) extracellular potassium accumulation switches action potential generation from tonic firing to intermittently interrupted output. Thus, individual neurons may respond very differently to the same input stimuli, depending on their recent patterns of activity and/or the current brain-state.

Author summary

Ionic concentrations in the brain are not constant. We show that during intense neuronal activity, they can change on the order of seconds and even switch neuronal spiking patterns under identical stimulation from a regular firing mode to an intermittently interrupted one. Triggered by an accumulation of extracellular potassium, such a transition is caused by a specific, qualitative change in of the neuronal voltage dynamics – a so-called bifurcation – which affects crucial features of action-potential generation and bears consequences for how information is encoded and how neurons behave together in the network. Also, changes in intracellular sodium can induce measurable effects, like a shrinkage of spike amplitude that occurs independently of the fast amplitude-effects attributed to sodium channel inactivation. Taken together, our results demonstrate that a neuron can respond very differently to the same stimulus, depending on its previous activity or the current brain state. This finding may be particularly relevant when other regulatory mechanisms of ionic homeostasis are challenged, for example, during pathological states of glial impairment or oxygen deprivation. Finally, Categorization of cortical neurons as intrinsically bursting or regular spiking may be biased by the ionic concentrations at the time of the observation, highlighting the non-static nature of neuronal dynamics.
p38-MAPK mediated rRNA processing and translation regulation enables PrE differentiation during mouse blastocyst maturation
Authors: Bora Pablo , Gahurova Lenka , Mašek Tomáš , Hauserova Andrea , Potěšil David , Jansova Denisa , Susor Andrej , Zdráhal Zbyněk , Ajduk Anna , Pospíšek Martin , Bruce Alexander W.
Published: December 2020

Background

p38-MAPKs are stress-activated kinases necessary for placental development and nutrient and oxygen transfer during murine post-implantation development. In preimplantation development, p38-MAPK activity is required for blastocyst formation. Additionally, we have previously reported its role in regulating specification of inner cell mass (ICM) towards primitive endoderm (PrE), although a comprehensive mechanistic understanding is currently limited. Adopting live embryo imaging, proteomic and transcriptomic approaches, we report experimental data that directly address this deficit.

Results

Chemical inhibition of p38-MAPK activity during blastocyst maturation causes impaired blastocyst cavity expansion, most evident between the third and tenth hours post inhibition onset. We identify an overlapping minimal early blastocyst maturation window of p38-MAPKi inhibition (p38-MAPKi) sensitivity, that is sufficient to impair PrE cell fate by the late blastocyst (E4.5) stage. Comparative proteomic analyses reveal substantial downregulation of ribosomal proteins, the mRNA transcripts of which are also significantly upregulated. Ontological analysis of the differentially expressed transcriptome during this developmental period reveals “translation” related gene transcripts as being most significantly, yet transiently, affected by p38-MAPKi. Moreover, combined assays consistently report concomitant reductions inde novotranslation that are associated with accumulation of unprocessed rRNA precursors. Using a phosphoproteomic approach, ± p38-MAPKi, we identifiedMybpp1a,an rRNA transcription and processing regulator gene, as a potential p38-MAPK effector. We report that siRNA mediated clonal knockdown ofMybpp1ais associated with significantly diminished PrE contribution. Lastly, we show that defective PrE specification caused by p38-MAPKi (but not MEK/ERK signalling inhibition) can be partially rescued by activating the archetypal mTOR mediated translation regulatory pathway.

Conclusions

Activated p38-MAPK controls blastocyst maturation in an early and distinctly transient developmental window by regulating gene functionalities related to translation, that creates a permissive environment for appropriate specification of ICM cell fate.
Aberrant structural synaptic dynamics precede disorganization of temporal and spatial coding in the hippocampus upon repeated stress exposure
Authors: Chenani Alireza , Weston Ghabiba , Ulivi Alessandro F. , Castello-Waldow Tim P. , Chen Alon , Attardo Alessio
Published: December 2020

Stress exposure strongly contributes to the pathophysiology of psychiatric diseases such as depression, schizophrenia, anxiety, and post-traumatic stress disorder. It also affects both function and structure of hippocampal CA1, leading to episodic memory impairment. Here, we used deep-brain optical imaging to elucidate the effects of stress on CA1 pyramidal neuron structural connectivity and activity.

We tracked dynamics of dendritic spines during repeated stress and found decrease in spinogenesis followed by decrease in spine stability. In contrast to repeated stress, acute stress led to stabilization of the spines born in temporal proximity to the stressful event. To investigate the link between structural plasticity and activity patterns upon repeated stress, we studied the activity of thousands of CA1 pyramidal neurons in freely-moving. We found an increase in activity and loss of temporal organization followed by a disruption in temporal and spatial coding. Our data suggest that stress-induced sustained increase in activity leads to loss of structural connectivity and subsequent temporal and spatial coding impairments.
pH Effect on the Dynamics of SARS-CoV-2 Main Protease (Mpro)
Authors: Sharma Shilpa , Deep Shashank
Published: December 2020

The SARS-CoV-2 main protease (Mpro) is a crucial enzyme responsible for the maturation of novel coronavirus, thus it serves as an excellent target for drug discovery. SARS-CoV-2 is found to have similarity with SARS-CoV, which showed conformational changes upon varying pH. There is no study till date on how pH change affect the conformtional flexibilty of SARS-CoV-2 Mpro, therefore, we attempt to find the effect of pH variation through constant pH molecular dynamics simulation studies. Protein is found to be most stable at neutral pH and as pH turns basic protein structure becomes most destabilized. Acidic pH also tends to change the structural properties of Mpro. Our study provides evidence that the flexibility of Mprois pH dependent like SARS-CoV Mpro.
Virophages and retrotransposons colonize the genomes of a heterotrophic flagellate
Authors: Hackl Thomas , Duponchel Sarah , Barenhoff Karina , Weinmann Alexa , Fischer Matthias G.
Published: December 2020

Virophages can parasitize giant DNA viruses and may provide adaptive anti-giant-virus defense in unicellular eukaryotes. Under laboratory conditions, the virophage mavirus integrates into the nuclear genome of the marine flagellateCafeteria burkhardaeand reactivates upon superinfection with the giant virus CroV. In natural systems, however, the prevalence and diversity of host-virophage associations has not been systematically explored. Here, we report dozens of integrated virophages in four globally sampledC. burkhardaestrains that constitute up to 2% of their host genomes. Theseendogenousmavirus-likeelements (EMALEs) separated into eight types based on GC-content, nucleotide similarity, and coding potential and carried diverse promoter motifs implicating interactions with different giant viruses. Between host strains, some EMALE insertion loci were conserved indicating ancient integration events, whereas the majority of insertion sites were unique to a given host strain suggesting that EMALEs are active and mobile. Furthermore, we uncovered a unique association between EMALEs and a group of tyrosine recombinase retrotransposons, revealing yet another layer of parasitism in this nested microbial system. Our findings show that virophages are widespread and dynamic in wildCafeteriapopulations, supporting their potential role in antiviral defense in protists.
A window in time for β-cell regeneration
Authors: Weidemann Benjamin J. , Bass Joseph
Published: December 2020

In vivo regeneration of β cells provides hope for self-renewal of functional insulin-secreting cells following β-cell failure, a historically fatal condition now sustainable only by administration of exogenous insulin. Despite advances in the treatment of diabetes mellitus, the path toward endogenous renewal of β-cell populations has remained elusive. Intensive efforts have focused on elucidating pancreatic transcriptional programs that can drive the division and (trans-)differentiation of non-β cells to produce insulin. A surprise has been the identification of an essential role of the molecular circadian clock in the regulation of competent insulin-producing β cells. In this issue of Genes & Development, work by Petrenko and colleagues (pp. 1650–1665) now shows a requirement for the intrinsic clock in the regenerative capacity of insulin-producing cells following genetic ablation of β cells. These studies raise the possibility that enhancing core clock activity may provide an adjuvant in cell replacement therapies.
Confirming Antibody Specificity in Xenopus
Authors: Martin Sian A. , Page Suzannah J. , Piccinni Maya Z. , Guille Matthew J.
Published: December 2020

Verifying that a new antibody recognizes its target can be difficult. In this protocol, expression of a target protein in Xenopus embryos is either knocked down using CRISPR–Cas9 technology (for zygotic proteins) or enhanced by microinjection of a synthetic mRNA (for maternal proteins). Western blotting analysis is then performed. If the antibody recognizes the target protein, the western blot will show a relatively weak band for CRISPR-injected embryos and a relatively strong band for RNA-injected embryos. This represents a straightforward, powerful strategy for confirming antibody specificity in Xenopus.
An analysis of factors that influence the decision to export: perspective of Brazilian companies
Authors: Mataveli Mara , Ayala Juan Carlos , Gil Alfonso J.
Published: December 2020

Purpose

The objective of this work is to examine the factors that influence the decision of Brazilian companies to export.

Design/methodology/approach

A questionnaire was used to collect data from a statistically significant sample of 318 Brazilian exporting firms. Three types of study were carried out; an exploratory study that simplified the information through a principal component analysis, a descriptive study of the factors that influence the decision to export by Brazilian companies and a study of variance that allowed comparison of groups of firms.

Findings

After an analysis of the literature, 11 factors were proposed that influence the decision to export. Two unique factors resulted from the principal components analysis: “resource optimisation” and “performance and development”. The “performance and development” factor was more valued than the “resource optimisation” factor. From the analysis of variance, significant differences were only found in the variable “firm size”.

Originality/value

This paper contributes to the literature by presenting further knowledge of export factors in developing countries, the management of companies and instruments for decision making in the area of internationalisation.
Faysal Asset Management mutual funds performance evaluation
Authors: Kumar Vikesh , Bhayo Mujeeb-U-Rehman , Kumar Sundeep , Kumar Rakesh , Dakhan Sarfraz Ahmed
Published: December 2020

Learning outcomes

The learning outcomes are as follows: to teach the concept of mutual fund as whole, how mutual fund works and who are the investors; discuss how any asset management company can work and what is their investment process; discuss how mutual funds are affected by changes in economic outlook/macro-economic variables; discuss the alternative risk-adjusted measures of performance evaluation, such as the Sharpe ratio, Treynor, Jensen’s alpha and measure of risk-adjusted performance; and discuss which index to use as a benchmark and how to improve funds’ performance.

Case overview/synopsis

In April 2019, Khaldoon Bin latif, Chief Executive Officer (CEO) of Faysal Asset Management, reflected on the changes that had occurred during his two and a half years at Faysal. He was quite pleased with the recent performance of Faysal Funds and the company’s relationship-oriented approach to money management for individuals with high net worth. Yet, he wanted to ensure that both the investment-process and performance-evaluation measures that he had implemented at Faysal would continue to provide superior returns. Latif also wanted Faysal to outperform the relevant indices, not only on an absolute basis, but also on a risk-adjusted basis. He pondered which indices and models Faysal should use in the future based on their performance.

Complexity academic level

Undergraduate/graduate

Supplementary materials

Teaching Notes are available for educators only.

Subject code

CSS 1: Accounting and Finance.
Economic policy uncertainty and house prices in Germany: evidence from GSADF and wavelet coherence techniques
Authors: Kirikkaleli Dervis , Gokmenoglu Korhan , Hesami Siamand
Published: December 2020

Purpose

This study aims to answer the following questions which have not been investigated in the literature to the best knowledge: Is there any bubble in the German housing sector between 2005–2009 and 2012–2017? and Is there any linkage between economic policy uncertainty and the housing sector price index?

Design/methodology/approach

This study aims to shed some light on the German’s housing sector by investigating the housing sector bubble and the causal link between the housing sector index and economic policy uncertainty in Germany, using GSADF, Granger causality, Toda Yamamoto causality and wavelet coherence tests.

Findings

The findings reveal that there are some bubbles in the housing sector in Germany for the periods investigated, there is a positive correlation between economic policy uncertainty and housing sector price index at different frequencies and different periods and between 2008 and 2009 and between 2011 and 2013, economic policy uncertainty leads housing sector price index. The consistency of the findings from wavelet coherence is confirmed by the outcomes of Granger causality and Toda Yamamoto causality tests.

Originality/value

To the best knowledge, this is the first study that empirically investigates the relationship between the housing sector and EPU using a novel wavelet econometric method. In addition, this paper extends the research focused on the associations between the housing sector and EPU, by checking the bubbles in the market in different time horizons by using the longest available data span. Furthermore, the consistency of the findings from wavelet causality is confirmed by the outcomes of Granger causality and Toda Yamamoto causality tests. Finally, compared to the previous literature on the relationship between housing and EPU, the study uses a hedonic index for housing for the first time in the case of Germany.
Assessment of changes to Saudi Labour Law regarding unfair dismissal of employees
Authors: Alharbi Meshal Nayef
Published: December 2020

Purpose

Saudi Arabia recently amended the Labour Law provisions governing the unfair dismissal of employees in the private sector. The previous version of the legislation, which had been in force for many years, had entitled employees to demand reinstatement or make a claim for fair financial compensation equal to the damages sustained. The recent amendments eliminated the right of a dismissed employee to seek reinstatement and also revised the rules relating to monetary compensation. The purpose of this paper is to critically analyse and evaluate the new approach, which has been criticized heavily. In addition, it suggests feasible alternative ways to handle unfair employee dismissal, which can be incorporated into the current Saudi Labour Law.

Design/methodology/approach

This paper presents an analysis of the existing approach to dealing with unfair employee termination in the Saudi Labour Law. It is based mainly on information collected from various legal materials, such as books, review of judgments issued by the Commission for the Settlement of Labour Disputes in Saudi Arabia and relevant Islamic rules.

Findings

The results of this examination clearly show that there are several flaws in the current approach to dealing with the issue of unfair dismissal of employees. To correct this situation, workable approaches have been suggested for possible consideration and incorporation into the Saudi Labour Law.

Originality/value

To the author’s knowledge, this is the first academic study to analyse the current approach to handling unfair employee dismissal in the Saudi Labour Law.
Viewpoint: service research in Post-Soviet states and the former eastern bloc
Authors: Gnusowski Marek
Published: December 2020

Purpose

This paper aims to improve the service discipline’s understanding of the unique challenges and opportunities that services marketers encounter in Central, Eastern and Southeastern Europe (CESEE) and Post-Soviet states. This paper also serves as an introduction to the special section about services marketing perspectives in this region.

Design/methodology/approach

Considering the Post-Soviet reality, the paper is a viewpoint regarding the specific development potential of services marketing in the CESEE region. In addition, the three papers included in the special section use a variety of research methods, participants and service settings.

Findings

First, this paper outlines the positive and negative consequences of the radical changes in the services markets over the past 30 years. Next, all three papers included in the special section explore the distinctive customer perspective of services marketing. Finally, this paper discusses the specific relationship building environment of the Post-Soviet reality and how its unique do-it-yourself background contributes to the existing discussion on consumers’ involvement in the co-creation of value.

Research limitations/implications

The findings from this special section have valuable implications for future research on services marketing in the CESEE markets, although these may not always be generalizable beyond the unique context of the research detailed in each of these papers.

Practical implications

This research, along with the three papers, presents some useful directions for services marketing managers cooperating with the CESEE markets, such as understanding and managing the expectations of their customers or employees.

Originality/value

This paper is one of the first attempts to understand the uniqueness of the under-researched area of services marketing in the CESEE and Post-Soviet States, both from a theoretical and empirical point of view. This also provides previously under-represented authors from the region the opportunity to present their perspective to an international service community.
Untangling insurance, rebuilding, and wellbeing in bushfire recovery
Authors: Eriksen Christine , de Vet Eliza
Published: December 2020

Home and contents insurance is framed as key to Australia's national strategy for disaster resilience. Despite the perceived importance of financial indemnity, ambiguity characterises the ways in which it facilitates both short‐ and long‐term everyday household recovery when disaster strikes. Addressing such ambiguity, this article explores how insurance impacts upon households' capacities to rebuild and recover after disastrous bushfire. In‐depth interviews conducted with residents in the Blue Mountains of New South Wales four years after they were affected by the October 2013 bushfires show that insurance was fundamental to recovery. Swift claims handling and payouts allowed participants to access rental accommodation, material necessities, and sufficient finances to repair, rebuild, and refurnish their houses—essentials in restoring everyday routines and a sense of normalcy. Yet, many people were underinsured and used alternative strategies to stretch “adequate” insurance coverage, which had practical and emotional implications. Importantly, while insurance reduced post‐disaster stress and trauma, the length and depth of recovery were more closely determined by the impacts of personal and situational circumstances than by insurance. On that basis, analysis points to the conclusion that while insurance is a crucial tool for disaster resilience, greater levels of psychosocial support are needed to improve households' short‐ and longer‐term recovery.
Mini‐review: Role of the PI3K/Akt pathway and tyrosine phosphatases in Alzheimer's disease susceptibility
Authors: Curtis David , Bandyopadhyay Sreejan
Published: December 2020

A variety of findings from in vitro experiments and animal models support the hypothesis that one contribution to pathogenesis in Alzheimer's disease (AD) is enhanced phosphorylation of tau protein, which may be triggered by amyloid β (Aβ) and mediated by impaired activity of the PI3K/Akt signaling pathway. A number of tyrosine phosphatases act to reduce PI3K/Akt activity, and inhibition of tyrosine phosphatases is protective against Aβ toxicity in cell cultures and whole animals. Results from analysis of exome sequenced late onset AD cases and controls similarly show that rare coding variants predicted to damage PI3K functioning increase AD risk, whereas those which are predicted to damage genes for tyrosine phosphatase genes are protective. Taken together, these results support the proposition that tyrosine phosphatase antagonists might be trialed as therapeutic agents to protect against the development of AD.
Innovation in the Agri‐Food sector: Exploiting opportunities for Industry 4.0
Authors: Oltra‐Mestre Maria Jose , Hargaden Vincent , Coughlan Paul , Segura‐García del Río Baldomero
Published: December 2020

Agri‐Food producers have a responsibility to provide safe, secure and sustainable food in a world characterized by disruption and increasing intolerance of waste along supply chains. As such, it is critical that they adopt new technologies to ensure efficient and effective management of their responsibility. While Industry 4.0 (I4.0) technologies can underpin process innovation opportunities, there is a gap in research‐based understanding of how they influence innovation practice and outcomes in Agri‐Food. In this paper, we investigate how I4.0, as a set of enabling technologies, influences core process innovation practice and product innovation outcomes in Agri‐Food firms. We present case studies of two Spanish firms processing fresh food products, competing in two important subsectors of the industry, meat and fruit and vegetables. We used secondary material and semi‐structured interviews as data sources. The findings describe how, in the two cases, I4.0 has enabled responses to new customers requirements through process innovations resulting in enhanced functionality, aesthetics and meaning of the delivered products. Our paper contributes a framework identifying for researchers and managers how I4.0 technologies act as enablers of the core innovation processes and competitive outcomes.
The migration of neighboring and antagonist teeth three months after implant placement in healed single tooth‐missing sites
Authors: Guo Danni , Pan Shaoxia , Mühlemann Sven , Zhou Yongsheng , E. Jung Ronald
Published: December 2020

Objectives

To quantify the neighboring and antagonist teeth migration of a single posterior tooth‐missing site within 3 months using digital scanning and measuring techniques.

Materials and Methods

Intraoral scans (IOS) were made in 40 patients presenting a single posterior tooth‐missing gap and receiving implant therapy. IOS were obtained at the day of and three months after implant surgery rendering a digital baseline model (BM) and a digital follow‐up model (FM). Digital models were superimposed using the implant scan body as reference. Antagonist models were processed by the best fit alignment. Dimensional change between anatomical landmarks on neighboring teeth and that of featuring points on antagonistic teeth were measured using a three‐dimensional analysis software. The Mann–Whitney U test was applied to compare the tooth‐moving distance between the mesial and distal neighboring teeth. The Kruskal–Wallis one‐way ANOVA was used to test the difference in dimensional change in tooth‐missing site among age subgroups.

Results

The mean dimensional change in the tooth‐missing site was −37.62 ± 106.36 μm (median: −28.33 μm, Q25 −72.65/Q75 38.97) mesial‐distally and −67.91 ± 42.37 μm (median: −61.50 μm, Q25 −88.25/Q75 −36.75) occlusal‐gingivally. Eighteen out of 40 mesial neighboring teeth and 24 out of 40 distal neighboring teeth showed migration towards the implants. When patients were grouped according to age, the mesial‐distal reduction in the tooth‐missing site was significantly larger in patients younger than 30 years compared with those older than 50 years (p < .05).

Conclusions

The dimensions of posterior tooth‐missing sites decreased over an observation period of 3 months.
Conversion from calcineurin inhibitors to sirolimus in transplant‐associated thrombotic microangiopathy
Authors: Kanunnikov Mikhail M. , Rakhmanova Zhemal Z. , Levkovsky Nikita V. , Vafina Aliya I. , Goloshapov Oleg V. , Shchegoleva Tatiana S. , Vlasova Julia J. , Paina Olesya V. , Morozova Elena V. , S. Zubarovskaya Ludmilla , Kulagin Alexander D. , S. Moiseev Ivan
Published: December 2020

Transplant‐associated thrombotic microangiopathy (TA‐TMA) is a specific complication of allogeneic hematopoietic cell transplantation with a multifactorial etiology. There is little evidence published regarding the efficacy and factors influencing the outcome of substitution of calcineurin inhibitors (CNIs) with other agentsas a widely accepted practice in this disorder; however, there are limited data on the options for immunosuppression manipulation (ISM). In our study, we retrospectively analyzed outcomes of 45 patients with TA‐TMA with ISM and substitution either with steroids (steroid group) or anmTOR inhibitor sirolimus (sirolimus group). In our study, sirolimus was associated with significantly better 1‐year overall survival (HR 0.3, 95% CI 0.13‐0.7, p = .004) and faster time to normalization of LDH (HR 2.2, 95% CI 0.99‐4.99, p = .044). Replacing CNIs with sirolimus could be an effective option in patients with TA‐TMA. A multicenter confirmatory study of CNIs replacement with sirolimus is justified.
Updating concepts on atherosclerotic inflammation: From pathophysiology to treatment
Authors: Ministrini Stefano , Carbone Federico , Montecucco Fabrizio
Published: December 2020

Background

Atherosclerosis is recognized as a systemic low‐grade inflammatory disease. Furthermore, the dysregulation of the inflammatory response and its timely resolution is a pivotal process in determining the clinical manifestations of cardiac and cerebral acute ischaemia following atherothrombosis.

Methods

This narrative review is based on the material searched on PubMed up to October 2020. The search terms we used were as follows: "atherosclerosis, inflammation, acute myocardial infarction and ischemic stroke" in combination with "biomarker, inflammatory cells and molecules, treatment."

Results

The expected goal of addressing inflammation for the treatment of atherosclerosis and its acute ischaemic complications is reducing mortality and morbidity related to atherosclerotic cardiovascular disease, which are currently the first cause of death and disability worldwide. In this narrative review, we summarize the evidence about the main cellular and molecular mechanisms of inflammation in atherogenesis, atherothrombosis and acute ischaemic complications, with particular focus on the potential molecular targets for novel pharmacological treatments.

Conclusion

Although a large amount of evidence from animal models of atherothrombotic disease, and promising results of clinical trials, anti‐inflammatory treatments against atherosclerosis are not yet recommended. A deepest understanding of pathophysiological mechanisms underlying the mechanisms driving resolution of the acute inflammation will probably allow to identify the optimal molecular target.
Interest and readiness for digital mental health in coordinate specialty care for early course psychosis: A survey study of 42 programs in 30 states
Authors: Camacho Erica , Torous John
Published: December 2020

Aim

As in‐person healthcare services become suspended due to the COVID‐19 pandemic, the need for digital technologies to augment early course psychosis care has risen. Although technology offers many benefits including increasing access to care, the advantages of such tools are restricted by their implementation into the program. The goal of this study is to better understand the current usage of technology, clinical needs, and digital literacy in Coordinated Specialty Care (CSC) programs.

Methods

An online survey of CSC staff and clinicians assessed their attitudes, preparedness, and comfort with technology implementation into care.

Results

In total, 42 programs from 30 states responded to the web‐based survey. Of the six key roles of CSC, the role believed to be most capable for technology to augment was Family Education and Support by 90% (38/42) of participants. Eighty‐two per cent (34/42) of clinicians and staff felt that they would benefit from and have interest in receiving digital skills training (41% [17/42] strongly agree, 41% [17/42] agreed). Evaluation of respondent sentiments towards technology revealed that 70 per cent (29/42) (“agree”, or “strongly agree”) believe that technology can integrate into care easily.

Conclusions

Survey responses show overall positive sentiments towards technology implementation in early psychosis care. Findings also reveal that the digital tool would be better sustained if CSC staff and clinicians received digital skills education. This survey demonstrates that technology can augment early psychosis care while improving quality of care and expanding access to care.
Diagnosing cognitive disorders in older adults with epilepsy
Authors: Reyes Anny , Kaestner Erik , Edmonds Emily C. , Christina Macari Anna , Wang Zhong Irene , Drane Daniel L. , Punia Vineet , Busch Robyn M. , Hermann Bruce P. , McDonald Carrie R. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: December 2020

Objective

To characterize the nature and prevalence of cognitive disorders in older adults with temporal lobe epilepsy (TLE) and compare their cognitive profiles to patients with amnestic mild cognitive impairment (ie, aMCI).

Methods

Seventy‐one older patients with TLE, 77 aMCI, and 69 normal aging controls (NACs), all 55‐80 years of age, completed neuropsychological measures of memory, language, executive function, and processing speed. An actuarial neuropsychological method designed to diagnose MCI was applied to individual patients to identify older adults with TLE who met diagnostic criteria for MCI (TLE‐MCI). A linear classifier was performed to evaluate how well the diagnostic criteria differentiated patients with TLE‐MCI from aMCI. In TLE, the contribution of epilepsy‐related and vascular risk factors to cognitive impairment was evaluated using multiple regression.

Results

Forty‐three TLE patients (60%) met criteria for TLE‐MCI, demonstrating marked deficits in both memory and language. When patients were analyzed according to age at seizure onset, 63% of those with an early onset (<50 years) versus 56% of those with late onset (≥ 50 years) met criteria for TLE‐MCI. A classification model between TLE‐MCI and aMCI correctly classified 81.1% (90.6% specificity, 61.3% sensitivity) of the cohort based on neuropsychological scores. Whereas TLE‐MCI showed greater deficits in language relative to aMCI, patients with aMCI showed greater rapid forgetting on memory measures. Both epilepsy‐related risk factors and the presence of leukoaraiosis on MRI contributed to impairment profiles in TLE‐MCI.

Significance

Cognitive impairment is a common comorbidity in epilepsy and it presents in a substantial number of older adults with TLE. Although the underlying etiologies are unknown in many patients, the TLE‐MCI phenotype may be secondary to an accumulation of epilepsy and vascular risk factors, signal the onset of a neurodegenerative disease, or represent a combination of factors.
Helicobacter pylori adhesins: HpaA a potential antigen in experimental vaccines for H. pylori
Authors: Banga Ndzouboukou Jo‐Lewis , Lei Qing , Ullah Nadeem , Zhang Yandi , Hao Ling , Fan Xionglin
Published: December 2020

Background

Helicobacter pylori is a gram‐negative bacterium involved in many gastric pathologies such as ulcers and cancers. Although the treatment for this infection has existed for several years, the development of a vaccine is nevertheless necessary to reduce the severe forms of the disease. For more than three decades, many advances have been made particularly in the understanding of virulence factors as well as the pathogenesis of gastric diseases caused by H. pylori. Among these key virulence factors, specific antigens have been identified: Urease, Vacuolating cytotoxin A (VacA), Cytotoxin‐associated gene A (CagA), Blood group antigen‐binding adhesin (BabA), H. pylori adhesin A (HpaA), and others.

Objectives

This review will focus on H. pylori adhesins, in particular, on HpaA and on the current knowledge of H. pylori vaccines.

Methods

All of the information included in this review was retrieved from published studies on H. pylori adhesins in H. pylori infections.

Results

These proteins, used in their native or recombinant forms, induce protection against H. pylori in experimental animal models.

Conclusion

H. pylori adhesins are known to be promising candidate vaccines against H. pylori. Future research should be carried out on adhesins, in particular, on HpaA.
Knowledge, attitude and practice of residents in the prevention and control of COVID‐19: An online questionnaire survey
Authors: Yang Kaihan , Liu Hui , Ma Lihua , Wang Song , Tian Yali , Zhang Feifei , Li Zhuyue , Song Yuanyuan , Jiang Xiaolian
Published: December 2020

Aims

To explore the status quo and the influencing factors of residents’ knowledge, attitude and practice (KAP) in the prevention and control of coronavirus disease 2019 (COVID‐19), and the difficulties or challenges perceived by residents in their preventive practice.

Design

An online questionnaire survey.

Methods

The self‐designed questionnaire was distributed among residents online in February 2020. Descriptive statistics, two independent samples t‐tests, one‐way analysis of variance, Pearson's correlation analysis, multivariate linear regression and content analysis were performed.

Results

A total of 919 valid questionnaires were collected. The scoring rates of residents’ KAP were 85.2%, 92.9% and 84.4% respectively. Main factors influencing residents’ knowledge included gender and occupation; while those influencing attitude were occupation, family economic level and knowledge; and those influencing practice included place of residence, occupation, with or without chronic disease, knowledge and attitude. Mass media was the primary approach for people to learn the knowledge and information of COVID‐19. Difficulties or challenges faced were mainly lack of protective equipments, concerns about the risk of prevention and control, impact on daily life, work and study, lack of knowledge and consensus, psychological problems and information problems.

Conclusion

The attitude of residents towards COVID‐19 prevention and control is generally positive. The knowledge and practice have been popularized to a certain extent, but there are still deviations or deficiencies in residents’ understanding of certain important knowledge and the adoption of relevant preventive measures. Evidence‐based tailored public education initiatives are indicated.

Impact

Findings of this study add important knowledge about residents’ understanding, attitude, practice and the influencing factors on COVID‐19 prevention and control, which serves as a scientific foundation for optimizing the pandemic public education and decision‐making.
Laboratory evaluation of Orthocentrus brachycerus (Hymenoptera: Ichneumonidae), as a potential biological control agent in mushroom cultivation
Authors: Mukai Hiromi , Kitajima Hiroshi
Published: December 2020

Fungus gnats in the genus Neoempheria Osten Sacken (Diptera: Mycetophilidae) are serious pests of the shiitake mushroom, Lentinula edodes (Berk.) Sing. (Agaricales: Omphalotaceae), a prize edible. Recently, we found that the parasitoid wasp Orthocentrus brachycerus Humala & Lee, 2020 (Hymenoptera: Ichneumonidae) attacks larvae of Neoempheria. We have shown in previous research that O. brachycerus suppresses population growth of Neoempheria in simulated cultivation conditions, and thus shows potential for use as a biological control agent. However, the behavioural and ecological aspects of this wasp have not been studied. Here, under controlled laboratory conditions, we investigated the fecundity, longevity and host stage specificity of O. brachycerus against Neoempheria larvae. We found that O. brachycerus are prolific throughout their life cycle. On average, female O. brachycerus made over 140 attempts to parasitize pest larvae, and over 90% of Neoempheria larvae were parasitized or died before emergence. Parasitoid females kept at 20°C survived for an average of 15.4 ± 3.58 days, and some females survived >30 days. Females continued to oviposit eggs throughout their life cycle and parasitized all stages of host larvae, but not eggs. These observations indicate that O. brachycerus may be effective for control of Neoempheria larvae in shiitake cultivation facilities. These results provide a basis for establishing a protocol for using O. brachycerus in mushroom cultivation.