bluuebunny/crossref_metadata_2025 huggingface dataset:
Medial septum glutamate neurons are essential for spatial goal-directed memory
Authors: Bott Jean-Bastien , Robinson Jennifer , Manseau Frederic , Gauthier-Lafrenière Etienne , Williams Sylvain
Published: March 2022

The medial septum (MS), a brain region containing acetylcholine, GABA and glutamate neurons, is essential for learning and memory. However, whether MS glutamate neurons contribute to memory is unknown. Here, we use calcium imaging and optogenetic silencing to determine the function of MS glutamate neurons in mice performing a spatial allocentric memory navigation task. While MS glutamate neurons appeared randomly active during free exploration, two groups of glutamate neurons emerged during training in a five-arm star maze, distinguished by their peak activity. The largest group was predominantly activated before locomotion whereas the other was primarily active when mice reached the reward site. Both populations were preferentially activated for correct over incorrect trajectories. Interestingly, optogenetic silencing of MS glutamate neurons immediately before mice start navigating, induced significant spatial memory impairments. Together these results demonstrate that MS glutamate neurons heterogeneously encode navigationally relevant information and are essential for spatial learning.
Chimpanzees organize their social relationships like humans
Authors: Escribano Diego , Doldán-Martelli Victoria , Cronin Katherine A. , Haun Daniel B.M. , van Leeuwen Edwin J.C. , Cuesta José A. , Sánchez Angel
Published: March 2022

Human relationships are structured in a set of layers, ordered from higher (intimate relationships) to lower (acquaintances) emotional and cognitive intensity. This structure arises from the limits of our cognitive capacity and the different amounts of resources required by different relationships. However, it is unknown whether nonhuman primate species organize their affiliative relationships following the same pattern. We here show that the time chimpanzees devote to grooming other individuals is well described by the same model used for human relationships, supporting the existence of similar social signatures for both humans and chimpanzees. Furthermore, the relationship structure depends on group size as predicted by the model, the proportion of high intensity connections being larger for smaller groups.
Broad neutralization of SARS-CoV-2 variants by circular mRNA producing VFLIP-X spike in mice
Authors: Seephetdee Chotiwat , Bhukhai Kanit , Buasri Nattawut , Leelukkanaveera Puttipatch , Lerdwattanasombat Pat , Manopwisedjaroen Suwimon , Phueakphud Nut , Kuhaudomlarp Sakonwan , Olmedillas Eduardo , Saphire Erica Ollmann , Thitithanyanont Arunee , Hongeng Suradej , Wongtrakoongate Patompon
Published: March 2022

Next-generation COVID-19 vaccines are critical due to the ongoing evolution of SARS-CoV-2 virus and waning duration of the neutralizing antibody response against current vaccines. The mRNA vaccines mRNA-1273 and BNT162b2 were developed using linear transcripts encoding the prefusion-stabilized trimers (S-2P) of the wildtype spike, which have shown a reduced neutralizing activity against the variants of concern B.1.617.2 and B.1.1.529. Recently, a new version of spike trimer, termed VFLIP has been suggested to possess native-like glycosylation, and greater pre-fusion trimeric stability as opposed to S-2P. Here, we report that the spike protein VFLIP-X, containing six rationally substituted amino acids to reflect emerging variants (K417N, L452R, T478K, E484K, N501Y and D614G), offers a promising candidate for a next-generation SARS-CoV-2 vaccine. Mice immunized by a circular mRNA (circRNA) vaccine prototype producing VFLIP-X elicited neutralizing antibodies for up to 7 weeks post-boost against SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs). In addition, a balance in TH1 and TH2 responses was achieved by immunization with VFLIP-X. Our results indicate that the VFLIP-X delivered by circRNA confers humoral and cellular immune responses, as well as neutralizing activity against broad SARS-CoV-2 variants.
A general framework for identifying oligogenic combinations of rare variants in complex disorders
Authors: Pounraja Vijay Kumar , Girirajan Santhosh
Published: March 2022

Genetic studies of complex disorders such as autism and intellectual disability (ID) are often based on enrichment of individual rare variants or their aggregate burden in affected individuals compared to controls. However, these studies overlook the influence of combinations of rare variants that may not be deleterious on their own due to statistical challenges resulting from rarity and combinatorial explosion when enumerating variant combinations, limiting our ability to study oligogenic basis for these disorders. Here, we present RareComb, a framework that combines the Apriori algorithm and statistical inference to identify specific combinations of mutated genes associated with complex phenotypes. RareComb overcomes computational barriers and exhaustively evaluates variant combinations to identify nonadditive relationships between simultaneously mutated genes. Using RareComb, we analyzed 6189 individuals with autism and identified 718 combinations significantly associated with ID, and carriers of these combinations showed lower IQ than expected in an independent cohort of 1878 individuals. These combinations were enriched for nervous system genes such as NIN and NGF, showed complex inheritance patterns, and were depleted in unaffected siblings. We found that an affected individual can carry many oligogenic combinations, each contributing to the same phenotype or distinct phenotypes at varying effect sizes. We also used this framework to identify combinations associated with multiple comorbid phenotypes, including mutations of COL28A1 and MFSD2B for ID and schizophrenia and ABCA4, DNAH10 and MC1R for ID and anxiety/depression. Our framework identifies a key component of missing heritability and provides a novel paradigm to untangle the genetic architecture of complex disorders.
Analyzing the stock market performance of central public sector enterprises disinvested through public offering mode: Indian evidence
Authors: Mandiratta Priya , Bhalla G.S.
Published: March 2022

Purpose

The present study aims to examine the short-term effect of disinvestment oriented IPOs and FPOs on the stock market performance of Indian central public sector enterprises (CPSEs), which divested their equity between 2000 and 2017.

Design/methodology/approach

The analysis of stock price reaction is conducted for listing dates only in the case of IPOs and three different dates in the case of FPOs through the event study methodology. The three-event dates related to FPOs are public notification date (PND), issue announcement date (IAD) and price band date (PBD).

Findings

Overall empirical analysis indicates that investor sentiments are generally insignificant prior to and posts the PND (first date). The second major date of announcement that is (IAD) is new information in the market and returns are found to be significantly negative across both the periods that is before and after IAD. Thus, the analysis depicts strongly negative investor sentiments in the case of IAD. These results are further substantiated by negatively significant CAR (cumulative abnormal returns) values for both the pre and post-event windows of PBD as well.

Research limitations/implications

Empirical analysis concludes that investors do not stand a chance to gain abnormal returns through initiating positions in the stocks of CPSEs during the alternative event dates analyzed.

Originality/value

Since the year 2000, disinvestment through public offering has gathered momentum, and this mode accounts for approximately 62% of the collective disinvestment funds generated by the government of India till now. But there have been very limited research studies on the market performance of disinvested CPSEs. This analysis provides new empirical evidence for the market reactions of retail investors in response to the sale of equity by the Indian government in CPSEs.
Social network analysis of the Construction Community in the anti-epidemic emergency project: a case study of Wuhan Huoshenshan Hospital, China
Authors: Wang Xiaoming , He Nanjun , Li Xiaokang
Published: March 2022

Purpose

Anti-epidemic Emergency Projects (AEEPs) have unique characteristics such as a short construction period, high-quality requirements, complex construction environment, many construction participants and many uncertain affecting factors. The purpose of this paper was to propose the establishment method for the Construction Community (CC) of AEEPs (CC-AEEPs) by analyzing the management features of AEEPs, to establish the method of the Social Network Analysis (SNA) for CC-AEEPs, and to apply this method and the framework to Wuhan Huoshenshan Hospital for their verification.

Design/methodology/approach

According to the CC theory, this paper explored the member composition and the establishment method for CC-AEEPs. The optimal management factors of CC-AEEPs were proposed by combining the management features of AEEPs and the SNA method for CC-AEEPs was further established. Finally, the applicability of the method was verified through a case study, and some countermeasures for the CC-AEEP social networks were proposed.

Findings

The establishment of CC-AEEPs is an important guarantee to complete AEEPs with top speed and high quality. Ten types of CC-AEEP members all played different but irreplaceable roles in cooperative construction, among which the Government, the Contractor, and the Supervisor had outstanding performances. The SNA method could effectively analyze the complexity and cooperative relationship among the members in four aspects. The case study of Huoshenshan Hospital validated the important role of CC-AEEP and its social network in the AEEP research providing beneficial enlightenment for the cooperative optimization path of the AEEP construction participants.

Originality/value

The new establishment method for CC-AEEPs was proposed from the perspective of “cooperation among human, society, and engineering” according to the theories of the engineering sociology and the CC. In this paper, the SNA method was applied to the research on the AEEP construction for the first time and the SNA method for CC-AEEPs was purposed. The optimal management factors of CC-AEEPs and the expansion path of the CC-AEEP social networks were proposed according to the whole-process tracking of AEEPs in Wuhan.
A qualitative research study of the tech startup journey through entrepreneurial pivoting
Authors: Sala Pavan Kumar , Philbin Simon P. , Barikzai Safia
Published: March 2022

Purpose

As part of the entrepreneurial journey, high-tech entrepreneurs are faced with the need to develop a competitive value proposition and leverage emerging technology to strengthen the value proposition. Entrepreneurial pivoting can be adopted to address this requirement since it enables the startup to validate and refine the company’s strategy and business model. Therefore, this research study provides an empirical investigation of the pivoting concept explained in the context of the lean startup approach (LSA) and technology entrepreneurship to improve the understanding of the entrepreneurial journey for high-tech entrepreneurs.

Design/methodology/approach

A qualitative research method was conducted by interviewing 30 high-tech entrepreneurs across the United Kingdom to validate the theories behind the LSA and identify new insights on entrepreneurial pivoting.

Findings

The research study has validated the existing types of pivots and identified two new pivots (giving 16 in total). The study has validated the existing 11 factors that trigger a tech startup to change its direction and identified three new factors (giving 14 in total). The research study also determined that there can be a domino effect in pivoting and the value proposition can be created and sustained through pivoting.

Originality/value

This study provides empirical evidence on pivots and the factors associated with pivots. Furthermore, it helps in understanding the influence of the phases of technology entrepreneurship on pivoting. The study also discusses the challenges faced by tech startups while pursuing pivots, the domino effects in pivoting and has found evidence that pivoting eventually leads to achieving the desired results.
The impact of power and relationship commitment on customer integration: a replication and extension
Authors: Zhang Min , Zhao Xiande , Huo Baofeng , Flynn Barbara
Published: March 2022

Purpose

This study aims to examine the relationships between power, relationship commitment and customer integration by replicating and extending Zhao et al. (2008) in China and the USA.

Design/methodology/approach

This study collects data from 210 manufacturers in China and 202 manufacturers in the USA. In this study, structural equation modelling is used to analyse the data.

Findings

This study finds that normative relationship commitment is positively associated with customer integration and expert and referent power are positively associated with normative relationship commitment in China and the USA. Reward and coercive power are positively associated with instrumental relationship commitment in China, whereas referent power is negatively associated. Referent, legal legitimate and reward power are positively associated with instrumental relationship commitment in the USA, whereas expert and legitimate power are negatively associated.

Originality/value

This study provides empirical evidence on the distinct impacts of different bases of mediated and non-mediated power in China and the USA, contributing to the development of the power-relationship commitment theory. The findings also provide insights into where and when the theory applies. The results can provide guidelines for managers to adjust the use of power to improve relationship commitment and customer integration in China and the USA.
Addressing how small suppliers cope with large customers: using the dual dimension of a product portfolio and customer buying center
Authors: Lacoste Sylvie , Ben Abdelaziz Fouad , Youssef Meriem
Published: March 2022

Purpose

This paper is about customer relationships from the perspective of small suppliers. More precisely, this paper aims to examine the relational implications through a product portfolio model with the main participants of the buying center (buyer/business manager).

Design/methodology/approach

The study first uses an in-depth qualitative data analysis to explore how elements of small suppliers’ relationship with such large customer’s main actors are affected by the nature of the product (categorized between strategic, bottleneck and non-critical items). From the results, an empirical model is drawn of small suppliers’ relational strategies in a product-centered and buyer/business manager relationship typology. To analyze the results of the empirical model, a quantitative analysis is performed, using the fuzzy set qualitative comparative analysis approach.

Findings

This study contributes to deepen the supplier–customer relationship analysis, from a product-centered and customer dyadic perspective (buyer and customer business manager). The findings highlight three different small suppliers’ relationship strategy with a different level of involvement of the different participants of the buying center.

Originality/value

Few studies so far analyze vertical asymmetric relationships from a triadic perspective composed of the small supplier, the buyer and the business manager – hence, this study contributes to unveiling some of the relationship complexity within a triad of actors and how small suppliers can navigate through this complexity according to their product or service positioning.
Marketing #neurodiversity for well-being
Authors: Go Jefferies Josephine , Ahmed Wasim
Published: March 2022

Purpose

The purpose of this study is to develop a bottom-up segmentation of people affected by neurodiversity using Twitter data.

Design/methodology/approach

This exploratory study uses content analysis of information shared by Twitter users over a three-month period.

Findings

Cultural currents affect how the label of “neurodiversity” is perceived by individuals, marketplace actors and society. The extent to which neurodiversity provides a positive or negative alternative to stigmatizing labels for mental disorders is shaped by differentiated experiences of neurodiversity. The authors identify five neurodiversity segments according to identifiable concerns and contextual dynamics that affect mental wellbeing. Analyzing Twitter data enables a bottom-up typology of stigmatized groups toward improving market salience.

Originality/value

To the authors knowledge, this study is the first to investigate neurodiversity using Twitter data to segment stigmatized consumers into prospective customers from the bottom-up.
Utilising dentist-dental health educator skill-mix to implement oral health promotion that better supports diverse communities
Authors: Modha Bhaven
Published: March 2022

Purpose

Dentists may be seen as the most prominent figures within dentistry. Yet, a number of dental care professionals make significant contributions to the profession. The dental health educator (DHE) is one prime example. This teammate is typically a dental nurse who has achieved a post-registration qualification in oral health education (OHE). Through interactions with patients, members of the community and other pertinent stakeholders, the DHE empowers people through promoting the importance of good oral health. The purpose of this paper is to cast light on the unique and invaluable roles that DHEs can play within their organisations.

Design/methodology/approach

This paper aims to share some examples of dentist-DHE collaborations, where OHE initiatives were implemented within an ethnically diverse London Borough in England.

Findings

It was found that such interprofessional, skill-mix efforts were more productive, when the dentist and DHE worked together, rather than the latter working independently.

Originality/value

There exists great potential for DHEs to act as ambassadors for their dental establishments, network and collaborate with other organisations and build worthwhile relations with other healthcare professionals and stakeholders.
Drivers of support for corporate social responsibility: what matters most to Brazilian business leaders
Authors: Gimenes Fernanda Sousa , Souza Piao Roberta
Published: March 2022

Purpose

This study aims to examine the drivers prompting business leaders to support corporate social responsibility (CSR) practices in Brazil.

Design/methodology/approach

The research design selected is a qualitative exploratory multiple-case approach. Data were collected through 16 in-depth interviews with leaders of Brazilian companies.

Findings

Evidence is found that the main drivers prompting leaders to support CSR in Brazilian companies are linked to firm performance (economic opportunities and risk management) rather than ethical or external drivers (national policies and stakeholder pressure). In addition to this, the study identifies that for Brazilian business leaders, CSR practices have little to do with individual responsibility and personal fulfilment, but rather with a search for better overall effectiveness of the firm.

Originality/value

This study adds to a relevant and increasing body of literature on organisational behaviour from a societal perspective, offering an understanding of what catalyses organisations to engage in CSR practices.
Effect of Cu, Ni, Ag addition on creeping properties of Sn5Sb-0.5Cu-0.1Ni-0.5Ag for high temperature packaging
Authors: Han Bangyao , Sun Fenglian , Zhang Chi , Wang Xinlei
Published: March 2022

Purpose

This paper aims to investigate the effect of the Cu, Ni and Ag addition in Sn5Sb-based alloy on the mechanical properties and its mechanism.

Design/methodology/approach

The micro-indentation, creeping test of the Cu/Sn5Sb–0.5Cu–0.1Ni–0.5Ag/Cu and Cu/Sn–5Sb/Cu were conducted, and its microstructure was analysed. The scanning electron microscope and the metallographic microscope characterized the microstructure of the Sn5Sb–0.5Cu–0.1Ni–0.5Ag/Cu and Sn–5Sb/Cu joints.

Findings

The microstructure of Cu/Sn5Sb–0.5Cu–0.1Ni–0.5Ag/Cu is distributed with the fine (Cu,Ni)6Sn5 and Ag3Sn intermetallic compounds (IMCs), whereas the Cu6Sn5 and Sn3Sb2 in Cu/Sn–5Sb/Cu is larger and far more less. This investigation reveals that the addition of the Cu, Ni and Ag elements reinforced mechanical properties and provided a technical basis for the development of Sn–Sb alloy with good mechanical properties.

Originality/value

This paper reveals that the hardness and the modulus of the bulk solder Cu/Sn–5Sb/Cu solder joints were improved with the addition of Cu, Ni and Ag trace elements. Meanwhile, the creep resistance and plasticity were also improved. This study has a great value for exploring high-performance Sn–Sb based solder alloy and has proved an example.
E‐participation for combating corruption, increasing voice and accountability, and developing government effectiveness: A cross‐country data analysis
Authors: Waheduzzaman Wahed , Khandaker Sarod
Published: March 2022

The national‐level data extracted from the World Bank, Transparency International, and the United Nations databases were analysed in this study to examine the contribution of e‐participation in improving governance factors through its influence on corruption, voice and accountability, and government effectiveness. The analysis has provided a mixed outcome in improving governance through e‐participation, showing a significant relationship between e‐participation and corruption‐perception, and government effectiveness. Meanwhile, the relationships between e‐participation and voice and accountability are insignificant. This finding indicates that the present form of e‐participation in ensuring citizens’ voices for holding service providers accountable may have some limitations. The findings have implications for international organisations and government institutions to redesign their e‐participation methods and tools to warrant citizens’ voice and ensure accountability of service providers at the national level.
Diverse responses ofpqqC‐ andphoD‐harbouring bacterial communities to variation in soil properties of Moso bamboo forests
Authors: Shi Wenhui , Xing Yijing , Zhu Ying , Gao Ning , Ying Yeqing
Published: March 2022

Phosphate‐mobilizing bacteria (PMB) play a critical role in the regulation of phosphorus availability in the soil. The microbial genespqqCandphoDencode pyrroloquinoline quinone synthase and bacterial alkaline phosphatase, respectively, which regulate inorganic and organic phosphorus mobilization, and are therefore used as PMB markers. We examined the effects of soil properties in three Moso bamboo forest sites on the PMB communities that were profiled using high‐throughput sequencing. We observed differentiated responses ofpqqC‐ andphoD‐harbouring PMB communities to various soil conditions. There was significant variation among the sites in the diversity and structure of thephoD‐harbouring community, which correlated with variation in phosphorus levels and non‐capillary porosity; soil organic carbon and soil water content also affected the structure of thephoD‐harbouring community. However, no significant difference in the diversity ofpqqC‐harbouring community was observed among different sites, while the structure of thepqqC‐harbouring bacteria community was affected by soil organic carbon and soil total nitrogen, but not soil phosphorus levels. Overall, changes in soil conditions affected thephoD‐harbouring community more than thepqqC‐harbouring community. These findings provide a new insight to explore the effects of soil conditions on microbial communities that solubilize inorganic phosphate and mineralize organic phosphate.
Enhancing the capability of Klebsiella pneumoniae to produce 1, 3‐propanediol by overexpression and regulation through CRISPR‐dCas9
Authors: Wang Xin , Zhang Lin , Liang Shaoxiong , Yin Ying , Wang Pan , Li Yicao , Chin Wee Shong , Xu Jianwei , Wen Jianping
Published: March 2022

Klebsiella pneumoniae is a common strain of bacterial fermentation to produce 1, 3‐propanediol (1, 3‐PDO). In general, the production of 1, 3‐PDO by wild‐type K. pneumoniae is relatively low. Therefore, a new gene manipulation of K. pneumoniae was developed to improve the production of 1, 3‐PDO by overexpressing in the reduction pathway and attenuating the by‐products in the oxidation pathway. Firstly, dhaB and/or dhaT were overexpressed in the reduction pathway. Considering the cost of IPTG, the constitutive promoter P32 was selected to express the key gene. By comparing K.P. pET28a‐P32‐dhaT with the original strain, the production of 1, 3‐PDO was increased by 19.7%, from 12.97 to 15.53 g l−1 (in a 250 ml shaker flask). Secondly, three lldD and budC regulatory sites were selected in the by‐product pathway, respectively, using the CRISPR‐dCas9 system, and the optimal regulatory sites were selected following the 1, 3‐PDO production. As a result, the 1, 3‐PDO production by K.P. L1‐pRH2521 and K.P. B3‐pRH2521 reached up to 19.16 and 18.74 g l−1, which was increased by 47.7% and 44.5% respectively. Overexpressing dhaT and inhibiting expression of lldD and budC were combined to further enhance the ability of K. pneumoniae to produce 1, 3‐PDO. The 1, 3‐PDO production by K.P. L1‐B3‐PRH2521‐P32‐dhaT reached 57.85 g l−1 in a 7.5 l fermentation tank (with Na+ neutralizer), which is higher than that of the original strain. This is the first time that the 1, 3‐PDO production was improved in K. pneumoniae by overexpressing the key gene and attenuating by‐product synthesis in the CRISPR‐dCas9 system. This study reports an efficient approach to regulate the expression of genes in K. pneumoniae to increase the 1, 3‐PDO production, and such a strategy may be useful to modify other strains to produce valuable chemicals.
Inhibition of unfolded protein response prevents post‐anesthesia neuronal hyperactivity and synapse loss in aged mice
Authors: Chen Kai , Hu Qiuping , Gupta Riya , Stephens Jessie , Xie Zhongcong , Yang Guang
Published: March 2022

Delirium is the most common postoperative complication in older patients after prolonged anesthesia and surgery and is associated with accelerated cognitive decline and dementia. The neuronal pathogenesis of postoperative delirium is largely unknown. The unfolded protein response (UPR) is an adaptive reaction of cells to perturbations in endoplasmic reticulum function. Dysregulation of UPR has been implicated in a variety of diseases including Alzheimer's disease and related dementias. However, whether UPR plays a role in anesthesia‐induced cognitive impairment remains unexplored. By performing in vivo calcium imaging in the mouse frontal cortex, we showed that exposure of aged mice to the inhalational anesthetic sevoflurane for 2 hours resulted in a marked elevation of neuronal activity during recovery, which lasted for at least 24 hours after the end of exposure. Concomitantly, sevoflurane anesthesia caused a prolonged increase in phosphorylation of PERK and eIF2α, the markers of UPR activation. Genetic deletion or pharmacological inhibition of PERK prevented neuronal hyperactivity and memory impairment induced by sevoflurane. Moreover, we showed that PERK suppression also reversed various molecular and synaptic changes induced by sevoflurane anesthesia, including alterations of synaptic NMDA receptors, tau protein phosphorylation, and dendritic spine loss. Together, these findings suggest that sevoflurane anesthesia causes abnormal UPR in the aged brain, which contributes to neuronal hyperactivity, synapse loss and cognitive decline in aged mice.
Spatial patterns of stand structure and canopy disturbance in a fire‐maintainedPinus palustriswoodland
Authors: Phillips David L. , Goode J. Davis , Hart Justin L.
Published: March 2022

Question

Stand structural complexity is increasingly valued by forest managers to promote resilience, and quantitative spatial data from reference stands can help achieve these goals. We questioned how stand structural elements were spatially distributed across aPinus palustriswoodland. Specifically, we sought to quantify patterns of individual trees, tree clumps, openings, and canopy disturbance and examine spatial relationships betweenP. palustrissaplings andP. palustrisandQuercusspp. trees.

Location

Fall Line Hills, Alabama, USA (32°56′12′′ N, 87°25′37′′ W).

Methods

We recorded tree species, diameter, age, and location of all trees, and reconstructed canopy disturbance events across a 1‐ha site in aP. palustriswoodland. We used global point pattern analysis (g(r)function) and a local spatial classification method (individuals, clumps, and openings) to examine the distribution of stand structural elements and canopy disturbance.

Results

Trees were generally clustered by taxa and diameter.Pinus palustrissaplings exhibited no spatial relationship withP. palustristrees, but were clustered aroundQuercustrees at variable distances. Approximately half of the trees in the stand occurred in large clumps, and ca. 10% of trees occurred as individuals that did not touch crowns with neighbors. For three of the five disturbance periods, canopy disturbances were clustered in space at various distances.

Conclusions

Spatial randomness and clustering of structural elements and canopy disturbance events were evident across the reference site. The spatial patterns of stand structure quantified here, in conjunction with data from other georeferenced studies, can be used to develop silvicultural guidelines to enhance structural complexity and promote resilience.
The respiratory depressant effects of mitragynine are limited by its conversion to 7‐OH mitragynine
Authors: Hill Rob , Kruegel Andrew C. , Javitch Jonathan A. , Lane J. Robert , Canals Meritxell
Published: March 2022

Background and Purpose

Mitragynine, the major alkaloid in Mitragyna speciosa (kratom), is a partial agonist at the μ opioid receptor. CYP3A‐dependent oxidation of mitragynine yields the metabolite 7‐OH mitragynine, a more efficacious μ receptor agonist. While both mitragynine and 7‐OH mitragynine can induce anti‐nociception in mice, recent evidence suggests that 7‐OH mitragynine formed as a metabolite is sufficient to explain the anti‐nociceptive effects of mitragynine. However, the ability of 7‐OH mitragynine to induce μ receptor‐dependent respiratory depression has not yet been studied.

Experimental Approach

Respiration was measured in awake, freely moving, male CD‐1 mice, using whole body plethysmography. Anti‐nociception was measured using the hot plate assay. Morphine, mitragynine, 7‐OH mitragynine and the CYP3A inhibitor ketoconazole were administered orally.

Key Results

The respiratory depressant effects of mitragynine showed a ceiling effect, whereby doses higher than 10 mg·kg−1 produced the same level of effect. In contrast, 7‐OH mitragynine induced a dose‐dependent effect on mouse respiration. At equi‐depressant doses, both mitragynine and 7‐OH mitragynine induced prolonged anti‐nociception. Inhibition of CYP3A reduced mitragynine‐induced respiratory depression and anti‐nociception without affecting the effects of 7‐OH mitragynine.

Conclusions and Implications

Both the anti‐nociceptive effects and the respiratory depressant effects of mitragynine are partly due to its metabolic conversion to 7‐OH mitragynine. The limiting rate of conversion of mitragynine into its active metabolite results in a built‐in ceiling effect of the mitragynine‐induced respiratory depression. These data suggest that such ‘metabolic saturation’ at high doses may underlie the improved safety profile of mitragynine as an opioid analgesic.
High glucose‐mediated VPS26a down‐regulation dysregulates neuronal amyloid precursor protein processing and tau phosphorylation
Authors: Chae Chang Woo , Choi Gee Euhn , Jung Young Hyun , Lim Jae Ryong , Cho Ji Hyeon , Yoon Jee Hyeon , Han Ho Jae
Published: March 2022

Background and Purpose

The relationship between hyperglycaemia‐induced retromer dysfunction impairing intracellular trafficking and Alzheimer's disease (AD) remains unclear, although diabetes mellitus (DM) is considered a risk factor for AD. Here, we investigated the effects of high glucose on the retromer and defined the dysregulation of mechanisms of amyloid precursor protein (APP) processing and tau phosphorylation.

Experimental Approach

We used human induced‐pluripotent stem cell‐derived neuronal differentiated cells and SH‐SY5Ys exposed to high glucose to identify the underlying mechanisms. Streptozotocin‐induced diabetic mice were used to elucidate whether the retromer contributes to the AD‐like pathology.

Key Results

We found that vacuolar protein sorting‐associated protein 26a (VPS26a) was decreased in the hippocampus of diabetic mice and high glucose‐treated human neuronal cells. High glucose down‐regulated VPS26a through ROS/NF‐κB/DNA methyltransferase1‐mediated promoter hypermethylation. VPS26a recovery blocked retention of APP and cation‐independent mannose‐6‐phosphate receptor in endosomes and promoted transport to the trans‐Golgi, which decreased Aβ levels, and improved cathepsin D activity, reducing p‐tau levels, respectively. Retromer enhancement ameliorated synaptic deficits, astrocyte over‐activation, and cognitive impairment in diabetic mice.

Conclusion and Implications

In conclusion, VPS26a is a promising candidate for the inhibition of DM‐associated AD pathogenesis by modulating APP processing and tau phosphorylation.
The heterogeneous effects of COVID‐19 on Canadian household consumption, debt and savings
Authors: MacGee James , Pugh Thomas Michael , See Kurt
Published: March 2022

This paper develops an agent‐based model to quantify the impact of COVID‐19 on household debt and savings. To build a representative cross‐section of households that vary by income, debt portfolios and consumption baskets, we merge data from the Survey of Household Spending and the Survey of Financial Security. We construct paths for consumption and employment over the crisis, accounting for heterogeneous risk of unemployment across demographics, government transfers, and substitution between expenditure categories that vary in contact intensity. Our model simulations yield a heterogeneous effect of COVID‐19 across the income distribution. Low‐income households face the highest risk of unemployment, but transfers provide generous income replacement. Middle‐income job losers see the fastest rise in debt because transfers only partially replace lost income. Most unplanned savings are accumulated by high‐income households that face lower risk of unemployment and larger declines in hard‐to‐distance spending. We find the rise in savings could generate a brief jump of nearly 6% of monthly consumption.
High PD‐L1 level of advanced hepatic lymphoepithelioma‐like carcinoma response favorably to lenvatinib plus toripalimab
Authors: Zhu Yueting , Dang Zhuyi , Xu Hang , Yuan Yunlong , Chen Ye , Li Zhiping
Published: March 2022

Lymphoepithelioma‐like carcinoma (LELC) is an uncommon subtype of primary liver cancer with predominant lymphocyte infiltration and a relatively favorable outcome. However, no standard treatment for advanced hepatic LELC has been established. Here, we give a first report of a 60‐year‐old man with advanced hepatic LELC who had a high expression of PD‐L1 in tumor cells and a high level of tumor‐infiltrating leukocytes (TILs) in the tumor microenvironment (TME). After receiving six cycles of multiple receptor tyrosine kinase inhibitor (rTKI) with lenvatinib plus PD‐1 inhibitor toripalimab treatment, the patient achieved persistent partial response (PR). Our report indicates that advanced hepatic LELC with high expression of PD‐L1 may benefit from the combination of rTKI and PD‐L1/PD‐1 blockade. Therefore, this potential strategy should be considered when treating those rare liver cancers.
Protective and risk activities for emotional and behavioural well‐being of children and adolescents during the COVID‐19 lockdown
Authors: Nicolì Ilaria , Spinelli Maria , Lionetti Francesca , Logrieco Maria Grazia , Fasolo Mirco
Published: March 2022

Background

The lockdown imposed to contain the COVID‐19 pandemic brought deep changes in the daily life of Italian children and adolescents, increasing the time spent at home. This study aims to explore how activities that children and adolescents carried out at home during the lockdown were related to their emotional and behavioural well‐being.

Method

Parents completed an anonymous online survey on how much time their children and adolescents dedicated to social networks, solitary screen time, play time and to a series of parent–child dyadic activities. They also reported on their offspring's emotional difficulties and behavioural problems.

Results

The use of social networks had a negative impact on children's emotional difficulties, while it promoted well‐being in adolescents. Pertaining to solitary screen activities, these were associated with more behavioural problems in both children and adolescents. Regarding parent–child dyadic activities, get along with the parent was associated with less emotional difficulties and behavioural problems in children and with less behavioural problems in adolescents. Furthermore, for adolescents, the more they talked with the parent, the less behavioural problems they evidenced.

Conclusion

The current study may help to identify activities that could be promoted and those that should be limited to effectively menage home time, in order to ultimately safeguard the emotional and behavioural well‐being of children and adolescents.
The role of keratinized mucosa width as a risk factor for peri‐implant disease: A systematic review, meta‐analysis, and trial sequential analysis
Authors: Ravidà Andrea , Arena Claudia , Tattan Mustafa , Caponio Vito Carlo Alberto , Saleh Muhammad H. A. , Wang Hom‐Lay , Troiano Giuseppe
Published: March 2022

Background

Studies have examined the benefit of having keratinized peri‐implant mucosa width with mixed results.

Purpose

This study examines whether the lack of a prespecified (2 mm) amount of keratinized mucosa width (KMW) is a risk factor for peri‐implant diseases.

Methods

A systematic electronic and manual search of randomized or nonrandomized controlled or noncontrolled clinical trials was conducted. Qualitative review, quantitative meta‐analysis, and trial sequence analysis (TSA) of implants inserted at sites with <2 mm or ≥2 mm of KMW were analyzed to compare all the predetermined outcome variables. The level of evidence concerning the role of KMW in peri‐implant health was evaluated via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system guide.

Results

Nine studies were included in the qualitative analysis and four in the meta‐analysis and TSA. No significant inter‐group difference (p > 0.05) and a low power of evidence were found for probing depth, soft‐tissue recession, and marginal bone loss. A significant difference favoring ≥2 mm KMW had a lower mean plaque index (MD = 0.37, 95% CI: [0.16, 0.58], p = 0.002) (3 studies, 430 implants, low‐quality evidence). GRADE system showed very low and low quality of evidence for all other outcome measures.

Conclusion

Based on the available studies, the impact of amount of KMW (either <2 mm or ≥ 2 mm) as a risk factor for developing peri‐implant disease remains low. Future control studies with proper sample size and longer follow‐up are needed to further validate current findings.
Comparison of textbook versus three‐dimensional animation versus cadaveric training videos in teaching laparoscopic rectal surgery: a prospective randomized trial
Authors: Benlice Cigdem , Elcircevi Ala , Kutlu Burak , Dogan Celal Deha , Acar Halil Ibrahim , Kuzu Mehmet Ayhan
Published: March 2022

Aim

The aim of this prospective randomized study was to compare the effectiveness of various educational tools in laparoscopic rectal surgery, including surgical textbooks, animation and cadaveric videos.

Method

Initially, an electronic assessment test assessing knowledge of laparoscopic rectal surgery was created and validated. The test was sent to graduates completing a general surgery residency programme in Turkey, who were then randomized into four groups based on the type of study material. After a 4 week study period, the volunteers were asked to answer the same electronic assessment test imported into an edited live laparoscopic rectal surgery video. Pre‐ and posteducation assessment tests among the groups were compared.

Results

A total of 168 volunteers completed the pre‐education assessment test and were randomized into four groups. Pre‐education assessment test scores were similar among the groups (p > 0.05). Of 168 volunteers, 130 (77.3%) completed the posteducation assessment test. Posteducation assessment test scores were significantly higher in the three‐dimensional (3D) animation + cadaveric video group (p < 0.01), the 3D animation group (p < 0.01) and the cadaveric group (p < 0.01) compared with the textbook group. Moreover, posteducation assessment test scores were significantly higher in the 3D animation + cadaveric video group than the 3D animation group (p < 0.01). Each group’s posteducation assessment test scores were significantly higher than the pre‐education assessment test scores, with the exception of the textbook group.

Conclusion

Our study demonstrates that 3D animation + cadaveric videos, 3D animation alone and cadaveric videos are all superior to a surgical textbook when teaching laparoscopic rectal cancer surgery. Finally, our results show that 3D animation and cadaveric videos are also superior to textbooks in enabling an understanding of rectal surgery.
The Neural Correlates of Analogy Component Processes
Authors: Parsons John‐Dennis , Davies Jim
Published: March 2022

Analogical reasoning is a core facet of higher cognition in humans. Creating analogies as we navigate the environment helps us learn. Analogies involve reframing novel encounters using knowledge of familiar, relationally similar contexts stored in memory. When an analogy links a novel encounter with a familiar context, it can aid in problem solving. Reasoning by analogy is a complex process that is mediated by multiple brain regions and mechanisms. Several advanced computational architectures have been developed to simulate how these brain processes give rise to analogical reasoning, like the “learning with inferences and schema abstraction” architecture and the Companion architecture. To obtain this power to simulate human reasoning, theses architectures assume that various computational “subprocesses” comprise analogical reasoning, such as analogicalaccess, mapping, inference, andschema induction, consistent with the structure‐mapping framework proposed decades ago. However, little is known about how these subprocesses relate to actual brain processes. While some work in neuroscience has linked analogical reasoning to regions of brain prefrontal cortex, more research is needed to investigate the wide array of specific neural hypotheses generated by the computational architectures. In the current article, we review the association between historically important computational architectures of analogy and empirical studies in neuroscience. In particular, we focus on evidence for a frontoparietal brain network underlying analogical reasoning and the degree to which brain mechanisms mirror the computational subprocesses. We also offer a general vantage on the current‐ and future‐states of neuroscience research in this domain and provide some recommendations for future neuroimaging studies.
Understanding Imitation inPapio papio: The Role of Experience and the Presence of a Conspecific Demonstrator
Authors: Formaux Anthony , O'Sullivan Eoin , Fagot Joël , Claidière Nicolas
Published: March 2022

What factors affect imitation performance? Varying theories of imitation stress the role of experience, but few studies have explicitly tested its role in imitative learning in non‐human primates. We tested several predictions regarding the role of experience, conspecific presence, and action compatibility using a stimulus–response compatibility protocol. Nineteen baboons separated into two experimental groups learned to respond by targeting on a touch screen the same stimulus as their neighbor (compatible) or the opposite stimulus (incompatible). They first performed the task with a conspecific demonstrator (social phase) and then a computer demonstrator (ghost phase). After reaching a predetermined success threshold, they were then tested in an opposite compatibility condition (i.e., reversal learning conditions). Seven baboons performed at least two reversals during the social phase, and we found no significant difference between the compatible and incompatible conditions, although we noticed slightly faster response times (RTs) in the compatible condition that disappeared after the first reversal. During the ghost phase, monkeys showed difficulties in learning the incompatible condition, and the compatible condition RTs tended to be slower than during the social phase. Together, these results suggest that (a) there is no strong movement compatibility effect in our task and that (b) the presence of a demonstrator plays a role in eliciting correct responses but is not essential as has been previously shown in human studies.
The Impact of Information Structure on the Emergence of Differential Object Marking: An Experimental Study
Authors: Tal Shira , Smith Kenny , Culbertson Jennifer , Grossman Eitan , Arnon Inbal
Published: March 2022

Many languages exhibit differential object marking (DOM), where only certain types of grammatical objects are marked with morphological cases. Traditionally, it has been claimed that DOM arises as a way to prevent ambiguity by marking objects that might otherwise be mistaken for subjects (e.g., animate objects). While some recent experimental work supports this account, research on language typology suggests at least one alternative hypothesis. In particular, DOM may instead arise as a way of marking objects that are atypical from the point of view of information structure. According to this account, rather than being marked to avoid ambiguity, objects are marked when they are given (already familiar in the discourse) rather than new. Here, we experimentally investigate this hypothesis using two artificial language learning experiments. We find that information structure impacts participants’ object marking, but in an indirect way: atypical information structure leads to a change in word order, which then triggers increased object marking. Interestingly, this staged process of change is compatible with documented cases of DOM emergence. We argue that this process is driven by two cognitive tendencies. First, a tendency to place discourse given information before new information, and second, a tendency to mark noncanonical word order. Taken together, our findings provide corroborating evidence for the role of information structure in the emergence of DOM systems.