bluuebunny/crossref_metadata_2025 huggingface dataset:
Creatine transporter (Slc6a8) knockout mice show an inattentive-like phenotype in the 5-choice serial reaction time test
Authors: Skelton Matthew R. , Liou Rosalyn , Perna Marla K.
Published: June 2022

Disorders of creatine (Cr) synthesis and transport cause moderate to severe intellectual disability, epilepsy, and a lack of speech development. Mutations of the X-linked Cr transporter (CrT; SLC6A8) gene are the most frequent cause of Cr deficiency and one of the leading causes of X-linked intellectual disability. There are no treatments for CrT deficiency (CTD) and there are many unanswered questions related to this disorder. Rodent models of CTD have deficits in spatial learning and memory, object recognition memory, fear conditioning, and working memory, making them high-fidelity models of CTD. While these cognitive deficits provide important information related to CTD, they lack some translational relevance and do not address important aspects of executive function like attention and impulsivity. To address this gap in knowledge, we tested brain specific Slc6a8 knockout (bKO) mice in the 5-choice serial reaction time test (5CSRTT), a correlate of the continuous performance task in humans. Following 5CSRTT training, mice were then tested for 3 sessions using trials with a variable stimulus duration followed by 3 sessions using a fixed stimulus duration and variable intertrial interval. During both the testing phases the bKO mice had reduced accuracy along with increased omissions and correct latencies compared with controls. There were no increases in premature responses during the vITI, suggesting that these mice do not have an impulsive phenotype. The results of this study expand the known phenotype of Slc6a8 deficient mice and add a translationally relevant behavioral output to test potential therapies.

Synopsis

This study shows that a mouse model of human creatine transporter deficiency, a devastating human condition, has an attention-deficit disorder-like phenotype without an increase in impulsivity.
Diversity-generating retroelements in prokaryotic immunity
Authors: Belalov Ilya S , Sokolov Arseniy A , Letarov Andrey V
Published: June 2022

Adaptive immunity systems found in different organisms fall into two major types. Prokaryotes possess CRISPR-Cas systems, recognizing former invaders using the memorized (captured) pieces of their DNA as the pathogen signatures. Mammals possess a vast repertory of antibodies and T-cell receptors variants generated in advance. In this second type of adaptive immunity, a pathogen presentation to the immune system specifically activates the cells expressing matching antibodies or receptors. These cells proliferate to fight the infection and to form the immune memory. The principle of preemptive production of diverse defense proteins for future use can hypothetically take place in microbes too. In this study we test the hypothesis that prokaryotes employ diversity-generating retroelements to prepare defense proteins against yet-unknown invaders. We identified several candidate defense systems and characterised them.
Meningeal lymphatic drainage promotes T cell responses againstToxoplasma gondiibut is dispensable for parasite control in the brain
Authors: Kovacs Michael A. , Cowan Maureen N. , Babcock Isaac W. , Sibley Lydia A. , Still Katherine , Batista Samantha J. , Labuzan Sydney A. , Sethi Ish , Harris Tajie H.
Published: June 2022

The discovery of meningeal lymphatic vessels that drain the central nervous system (CNS) has prompted new insights into how neuroinflammation develops. In this study, we examined how T cell responses against CNS-derived antigen develop in the context of infection. We found that meningeal lymphatic drainage promotes CD4+and CD8+T cell responses against the neurotropic parasiteToxoplasma gondii, and we discovered changes in the antigen-presenting cell compartment of the dural meninges that potentially support this process. Indeed, compared to uninfected controls, mice chronically infected withT. gondiidisplayed a ten-fold increase in the total number of dendritic cells in the dural meninges. These cells upregulated MHC class II, CD80, and CD86 expression, sampled cerebrospinal fluid-derived protein, and were detected within meningeal lymphatic vessels in greater numbers during infection. Disrupting meningeal lymphatic drainage via ligation surgery resulted in reduced dendritic cell number and maturation in the deep cervical lymph nodes and impaired CD4+and CD8+T cell activation, proliferation, and IFN-γ production at this site. Surprisingly, parasite-specific T cell responses in the brain remained intact following ligation, which may be due to activation of T cells at alternative sites during chronic infection, including lymph nodes that drain non-CNS tissue. Collectively, our work reveals that CNS lymphatic drainage supports the development of peripheral T cell responses againstT. gondiibut is nonetheless dispensable for host protection of the brain.
Fund style drift and stock price crash risk – analysis of the mediating effect based on corporate financial risk
Authors: Sun Yanlin , Liu Siyu , Chen Shoudong
Published: June 2022

Purpose

This paper aims to identify the direct impact of fund style drift on the risk of stock price collapse and the intermediary mechanism of financial risk, so as to better protect the interests of minority investors.

Design/methodology/approach

This paper takes all the non-financial companies on the Chinese Growth Enterprise Market from 2011 to 2020 as study object and selects securities investment funds of their top ten circulation stocks to study the relationship between fund style drift and stock price crash risk.

Findings

Fund style drift is likely to add stock price crash risk. Financial risk is positively correlated with stock price crash risk. Fund style drift affects stock price crash risk via the mediating effect of financial risk, and fund style drift and financial risk have a marked impact on the stock price crash risk of non-state enterprises, yet a non-significant impact on that of state-owned enterprises.

Originality/value

This paper links fund style drift with stock price crash risk in an exploratory manner and enriches the study perspectives of relationship between institutional investors’ behaviors and stock price crash risk, thus enjoying certain academic value. On the one hand, it furnishes a new approach to the academic frontier issue concerning financial risk and stock price crash risk, and proves that financial risk is positively correlated with stock price crash risk. On the other hand, it regards financial risk as a mediating variable of fund style drift for stock price crash risk and further explores different influencing mechanism of institutional investors’ behaviors.
What makes talents stay? Perceived organizational support and future time perspective
Authors: Wei Yu-Chen
Published: June 2022

Purpose

This study aims to integrate self-determination and social exchange theories to assess how the three-way interaction between human capital, perceived organizational support (POS) and future time perspective (FTP) affects turnover intention.

Design/methodology/approach

The study uses a sample of 586 engineers and their immediate supervisors working in Taiwanese high-technology companies to examine the hypothesized relationships.

Findings

The results indicate that human capital with a high POS has a lower turnover intention than that with a low POS. Moreover, a three-way interaction is observed between human capital, POS and FTP, indicating that human capital predicts lower turnover intention when both POS and FTP are high.

Practical implications

The findings suggest that managers should hire employees who have high human capital and who are predisposed to FTP and provide strong organizational support to retain outstanding manpower.

Originality/value

This study is one of the first to examine the interaction effects of POS and FTP on the relationship between human capital and turnover intention.
Corporate learning and technology – opportunity and risk for the learning professional
Authors: Hector Tania
Published: June 2022

Purpose

The article aims to clarify the risks and opportunities available to corporate learning professionals with the advent of a tsunami of EdTech (educational technology) that promises to be the silver bullet of lifelong learning. It acknowledges that the urgency of up/reskilling adults provides learning professionals with a unique moment to make a difference by ensuring the right skills are available as needed. However, learning professionals are simultaneously under threat of irrelevance should we fail to use the avalanche of advances in technology combined with tried and tested pedagogical principles and a multi-channel approach.

Design/methodology/approach

The paper offers the author’s opinion on the future opportunities for learning professionals, using a summarized analysis of available technology and Educational Technology. In addition, it offers opportunities for further exploration by the reader.

Findings

The Future of Work has arrived and potentially signals the beginning of a golden age for learning professionals – or the beginning of the end, ultimately to be replaced by technology. The need is clear. What is not clear is whether the learning community – en masse – have the technological savvy to step up and maximize the use of technology, and specifically AI related services, to meet this need.

Practical implications

Learning professionals have a limited moment in time to pivot their existing skill set to a better understanding and use of technology. The paper offers some suggestions for action in this regard.

Social implications

Should the learning professional fail to utilize this unique moment in time to optimize the learning experiences of adults, the world faces a skills gap that will harm innovation, employment and social stability.

Originality/value

This paper fulfills an identified need for learning professionals to adjust their approach, skill set, and deliverables and offers guidelines for focus and action in a world saturated with information.
How do consumers engage with proactive service robots? The roles of interaction orientation and corporate reputation
Authors: Li Dongmei , Liu Canmian , Xie Lishan
Published: June 2022

Purpose

This study aims to apply the elaboration likelihood model to explore when, how and why robotic services increase customer engagement.

Design/methodology/approach

A field survey and two experiments were conducted to examine the proposed theoretical framework.

Findings

The robots’ proactive behavior encouraged customers to trust and engage with them. The influence of this behavior on customer engagement increased for highly interaction-oriented customers or when the reputations of companies were poor.

Practical implications

The findings can inform the efficient management of customer–robot interactions and thus support firms’ relationship marketing objectives.

Originality/value

The literature on robotic services has recognized that robots should be proactive to ensure positive customer experiences, but few studies have explored the relational outcomes of proactive robotic services. The authors’ in-depth empirical examination thus extends research into the role these services can play in fostering customer engagement.
‘It’s not a big deal’: customer misbehaviour and social washing in hospitality
Authors: Booyens Irma , Hadjisolomou Anastasios , Nickson Dennis , Cunningham Tayler , Baum Tom
Published: June 2022

Purpose

This study aims to examine customer misbehaviour in the hospitality sector during the COVID-19 pandemic.

Design/methodology/approach

The study draws on a cross-sectional survey of employees in the Scottish hospitality sector highlighting customer misbehaviour as a key concern during the pandemic. Prevalent types of abuse and harassment experienced are outlined along with employee and management responses to incidents of misbehaviour.

Findings

Verbal abuse and sexual harassment from customers are the most prevalent types of misbehaviour either experienced or witnessed by respondents. Customer misbehaviour is commonly thought of as “part of the job” and therefore “not a big deal”. Managers, largely, expect workers to tolerate abusive behaviours from customers and do not take reports of incidents seriously.

Practical implications

Transformational managers need to foster workplace well-being with a focus on physical and psychological safety. Recognition of the issue and greater support for victims are furthermore required at an industry level and on the policy front.

Social implications

The research points to an uncomfortable reality in the service economy that needs to be confronted by society. It has, therefore, important implications for key stakeholders in ensuring fair, dignified and safe hospitality workplaces.

Originality/value

Customer misbehaviour is reportedly worsening in times of COVID-19 as demonstrated by this study. Despite rhetoric that abuse and harassment are not tolerated, dismissive attitudes from managers – who expect workers to tolerate abusive behaviour – and employee silence about incidents lead the authors to argue that the failure to acknowledge and address this issue constitutes a form of “social washing” in hospitality.
Impacts of advisory perception and cultural distance on travel intention: evidence from China
Authors: Peng Jiyuan , Yang Feng , She Yi
Published: June 2022

Purpose

This study aims to investigate the impact of travel advisory perception and cultural distance on travel intention based on the push and pull theory, the stimulus–organism–response model and protection motivation theory.

Design/methodology/approach

The paper conducts an empirical test with a questionnaire survey. The authors asked respondents to answer questions on a five-point Likert-type scale, which included threat severity, threat susceptibility, advisory perception, perceived cultural distance, travel motivation and travel intention.

Findings

In this paper, through a questionnaire of 424 respondents, the authors found that threat severity has a positive impact on advisory perception and perceived cultural distance, and that advisory perception indirectly affect travel intention through travel motivation.

Originality/value

Previous literature has discussed the influencing factors of travel intention but rarely does it consider the intrinsic relationship and interaction between advisory perception and cultural distance. The results of this study help fill some gaps in the research on advisory perception and perceived cultural distance, guide governments on how to better formulate travel advisories and provide a new perspective for tourism industry practitioners to improve their travel products after the COVID-19 pandemic especially.
Responding to pandemic challenges: leadership lessons from multinational enterprises (MNEs) in India
Authors: Hong Paul C. , Singh Nitya P. , Elangovan N. , Yeon Guydeuk
Published: June 2022

Purpose

The business sector plays a major role in achieving comprehensive economic development goals in emerging economies. Consequently, the effects of business responses to the COVID-19 pandemic are receiving increasing research attention from an organizational management development perspective. This article aims to examine the role of leadership in charting the course in an extraordinary crisis context.

Design/methodology/approach

Using institutional leadership theory, leadership contingency theory and dynamic leadership capability theory, the authors present a research framework that defines macrochallenges and organizational level responses and outcomes. The article adopts a case study approach, which includes the identification of four target companies and conducting in-depth interviews with senior management professionals within those companies at different time periods.

Findings

Based on the interviews, the steps that Indian companies adopted to respond to the COVID-19 challenge are identified. Expanding the insight from the case study, the findings suggest that although feeling overwhelmed at first, organizational leaders combine prudent (i.e. timely and speedy actions for survival first) and bold (i.e. future envisioning for expansion and growth) actions enabling these firms to weather two waves of the COVID-19 pandemic in India.

Originality/value

These multiple case studies are unique in exploring MNEs from different industries. This study also highlights the dynamic relationships between leadership practices, risk management strategies and performance outcomes based on a sound theoretical model and rigorous study methods.
Realizing the economic and circular potential of sharing business models by engaging consumers
Authors: De Bruyne Marie-Julie , Verleye Katrien
Published: June 2022

Purpose

Today's sharing economy covers a variety of business models. This research aims to (1) identify dimensions along which sharing businesses may vary and (2) investigate how these dimensions influence consumer engagement while considering consumers' sustainability orientation.

Design/methodology/approach

This research relies upon a systematic literature review (n = 67 articles) to identify five sharing business dimensions: (1) ownership transfer, (2) professional involvement, (3) compensation, (4) digitalization and (5) community scope. A discrete choice conjoint experiment in the fashion industry is employed to investigate how these dimensions affect consumer engagement with sharing businesses (n = 383 participants).

Findings

The results suggest that ownership of tangible resources elicits more engagement than access to tangible resources for both consumers with a low sustainability orientation and consumers with a high sustainability orientation. Community scope also affects consumer engagement as reflected in more engagement towards sharing businesses with a local rather than a global scope. The presence of professional service providers, monetary compensation and a digital platform only induces engagement among consumers with a low sustainability orientation.

Originality/value

This research generates a better understanding of how sharing businesses can draw on business dimensions to engage consumers with different levels of sustainability orientation and, in turn, how sharing businesses can realize their economic and/or circular potential.
The impact of anchoring bias on investment decision-making: evidence from Ghana
Authors: Owusu Sally Peaches , Laryea Esther
Published: June 2022

Purpose

The objective of this paper is to explore how anchoring affects the dynamics of investor decision-making with regard to mutual funds and how this bias differs amongst gender and level of financial knowledge.

Design/methodology/approach

An experimental research design was adopted to uncover the relationship between the variables under study; this involved the use of a questionnaire with an embedded experiment. Data obtained from the study were analysed using Pearson's chi-square test and two-way analysis of variance.

Findings

The findings show that, overall, investors were prone to be significantly influenced by the anchoring bias. The study finds a strong, albeit not significant, association between participants' susceptibility to anchor and both gender and the level of financial knowledge of participants. Females were observed to be more likely to anchor than their male counterparts. Also, a higher level of financial knowledge did not help to reduce the possibility of anchoring; it rather increased it.

Research limitations/implications

The findings of the study cannot be interpreted as suggesting causality as the study only tests for association between variables and not causality. Additionally, external validity cannot be fully established as a result of the quasi-experiment approach used.

Practical implications

The study adds to the body of knowledge on the influences of behavioural biases in the sub-region to make investors aware of their biases in order to minimise the influence of these biases on their investment decisions.

Originality/value

This study differs from earlier studies in that it analyses the presence of anchoring as influenced by a completely different set of variables (expertise and gender) and also does it within the context of an African country where there remains a paucity of research on behavioural finance.
Multiple recycling of nickel alloy powder for selective laser melting process: influence on properties of the powder and printed material
Authors: I. Sukhov Dmitry , Bogachev Igor A. , Hodyrev Nikita A. , Filonova Elena V.
Published: June 2022

Purpose

The purpose of this study is the 16-fold recycling process effect of VZH159 nickel alloy powder on its features and characteristics of the printed material obtained by selective laser melting (SLM). Chemical composition, content of gas impurities, powder grading, pore volume fraction and surface morphology of powder particles, structure and properties of SLM material, surface roughness and deviations from specified geometry of the test samples were investigated.

Design/methodology/approach

The experiment’s method procedure presumes the use of only recycled powder without adding any virgin powder at each build cycle. To avoid powder sloughing because of incomplete filling of the build space, a print area delimiter was used. For all manufactured samples, hot isostatic pressing was carried out in an ASEA Quintus-16 facility. Heat treatment was carried out in air furnaces. Structure investigations were carried out on a Leica DMIRM metallographic complex. Microstructure studies were carried out on a Verios 460 scanning electron microscope with X-ray microanalysis.

Findings

With the number of recycling stages, an increase in oxygen content is observed in the powder, which leads to an increment for oxides in the printed material. The 16-fold recycling does not have a significant effect on the features of the powder itself and the printed material if the build space is filled with manufacturing parts by no more than 20%.

Originality/value

The creep rupture strength of the SLM material, which appears to be a sensitive characteristic to the quality of the applied powder, does not change in the printed material after all stages of powder recycling as well.
Determinants of social entrepreneurial intention: empirical evidence from the Saudi context
Authors: Aloulou Wassim J. , Algarni Eidah A.
Published: June 2022

Purpose

Little previous research has investigated the determinants of social entrepreneurial intention (SEI) in the context of Saudi Arabia. The purpose of this study is to advance a research model that examines the direct and indirect effects of prior experience with social problems via empathy, moral obligation, social self-efficacy and perceived social support on SEI.

Design/methodology/approach

This study is based on data collected from a survey using questionnaires completed by 278 Saudis. To analyze data and test the developed hypotheses, an exploratory and a confirmatory factor analyses were conducted to investigate the factorial structural of the constructs, their reliability and validity. Then, goodness-of-fit statistics showed model fits of different alternative models. A hierarchical regression modeling was used to test the direct and indirect effects of main variables on SEI.

Findings

Results show positive relationships between prior experience with social problems and SEI antecedents, on one hand, and between prior experience with social problems and SEI on the other hand. Notably, no significant relationships exist between moral obligation and SEI and social support and SEI. Additionally, only empathy and social self-efficacy mediated the relationship of prior experience with social problems to SEI.

Research limitations/implications

This study contributes to the literature by showing how most of the SEI’s antecedents can play a mediating role between prior experience with social problems and SEI. The main limitation of this study is that it was not possible to generalize the findings. Future research perspectives were proposed to address this limitation and add new insights to the field considering the context of an emerging country.

Originality/value

This study is one of the first to conduct such an investigation in the Saudi context. It validates the scales of previous empirical models on SEI and partially replicates their results.
More than a phone call away: sustaining positive work behaviour
Authors: Yeo Roland K. , Li Jessica
Published: June 2022

Purpose

This paper aims to introduce an innovative approach to employee engagement through personalized calls targeted at work-from-home (WFH) employees. It explores the effects of these calls on employee motivation and work behaviour.

Design/methodology/approach

The research is based on a case study of a multinational company over a one-year period (2020–2021). In-depth interviewing in the form of engagement calls was used as the primary method of data collection. Seventy-two frontline supervisors were directly involved in calling 1,318 employees totaling 2,671 calls. Content analysis was used to identify key patterns from the data.

Findings

The employees experienced varying degrees of WFH transition based on their response to isolation and work-life boundaries. The calls made a difference to their psychological and emotional wellbeing, reaffirming their confidence in the company’s WFH arrangements and reinforcing their self-worth. This led to the employees engaging more proactively through work process improvisation and working around technological challenges. The calls also uncovered unlearning and relearning as a way of helping them make deeper sense of who they are and how they can contribute more valuably to the company.

Originality/value

This longitudinal research offers fresh insights into the transitions of employees at different phases of their WFH experience based on the first-hand accounts of frontline supervisors. Theoretically, the study contributes to a different perspective of employee engagement and work behaviour from the remote working literature in the context of Covid-19.
The nexus between corporate social responsibility and firm value: the moderating role of life-cycle stages
Authors: Khuong Nguyen Vinh , Anh Le Huu Tuan
Published: June 2022

Purpose

This study aims to examine the relationship between corporate social responsibility (CSR) and firm value (FV) with the moderating role of the organizational life cycle (OLC).

Design/methodology/approach

To fill the missing link of the CSR–FV relationship in the life cycle of the firms, this study divided the firm life cycle into five stages and tested the impact of FV on CSR in each phase. This study uses the ordinary least squares, generalized method of moments method with the dynamic panel data model of 225 Vietnamese listed companies for the period from 2014 to 2018.

Findings

This study’s findings confirm the positive effect of CSR on FV. Besides, in most of the stages of the firm life cycle, FV positively affects CSR practices, and this effect is highest in the growth stage. In the decline phase, the relationship between FV and CSR is complex depending on the resources and ability of companies. This study’s results are trusted through many robustness tests.

Research limitations/implications

This research does not include all financial, insurance and investment firms to measure the CSR–FV relationship with OLC as moderating role. Further research might conduct in the larger sample or using data in cross countries enhance the evidence for the given relationship.

Originality/value

This research contributes empirical evidence to the scientific literature on CSR, FV and OLC, which would be tremendously helpful for policymakers and business owners to enhance company efficiency.
Oldest Basement (ca. 462 Ma) in Indonesian Borneo and its Implication for Early Paleozoic Tectonic Evolution of SE Asia
Authors: ZHU Junbin , LI Shan , MURTADHA Sayed
Published: June 2022

The lack of preserved basement results in uncertain placements of many terranes in Southeast Asia. Here, we flag the first evidence of the oldest basement in Indonesian Borneo, which can help locate terranes in Borneo on the northern margin of Gondwana in the early Paleozoic and explain the regional tectonic setting of the island. Two schist samples from the Embuoi Complex in the Semitau Block, Northwest Kalimantan yielded zircon U‐Pb dates of 453.3 ± 1.9 Ma and 462.4 ± 2.6 Ma, respectively, representing the formation time of the protolith. Petrographic, internal structural and high Th/U ratios of zircons indicate that the protolith of schists is of magmatic origin. The zircons have εHf(t) values of –4.1 to +1.1 and Hf model ages of 1.37–1.69 Ga, indicating they were derived from a mixed source of juvenile crust with old components. By comparison of zircon age distribution, two‐stage Hf model ages and εHf(t) variations of the early Paleozoic igneous rocks from Semitau with those of South China, Tengchong–Baoshan, and Indochina, the Semitau Block was most likely a part of or placed next to the Indochina Block of northern Gondwana during the early Paleozoic. Such a similar tectono‐magmatic pattern on northern Gondwana formed a prolonged early Paleozoic arc‐related belt associated with subduction of the Proto‐Tethyan Ocean.
Origin of Halite in the Lanping–Simao Basin, Southeastern Tibetan Plateau, China: Evidence from Sr and Cl Isotopes
Authors: DU Shaorong , ZHENG Mianping , LÜ Yuanyuan , ZHANG Yongsheng , ZHANG Xuefei , MIAO Zhongying , LI Mingming
Published: June 2022

The Lanping–Simao Basin is located on the southeastern Tibetan Plateau, China, and contains massive evaporites. The origin of evaporites in the basin has been hotly debated because of the strong transformation by tectonic movement. Forty halite samples from borehole MK‐3 in the Mengyejing area of the basin were collected and analyzed using XRD, Cl‐Sr isotopes and chemical compositions to trace the origin of the evaporites in the basin. The Br × 103/Cl ratios of the halite samples are between 0 and 0.55, most of which are synchronized with the law of seawater evaporation and at the stage of halite precipitation from seawater, indicating that the evaporites are mainly of marine origin. The 87Sr/86Sr ratios range from 0.707489 to 0.711279; after correction, the 87Sr/86Sr 145 Ma ratios range from 0.704721 to 0.707611, equivalent with the 87Sr/86Sr ratios of seawater at 145 Ma, indicating a marine origin. The decay of 87Rb in the evaporite during deposition, change of the depositional environment and the unsealed environment at a later period resulted in the present 87Sr/86Sr ratios of some samples being high. The δ37Cl value compositions range from –0.38‰ to 0.83‰, which is consistent with the δ37Cl value composition of the world marine halite (–0.6‰ to 0.4‰), further confirming that seawater is the main origin. In addition, the high δ37Cl value of some samples at the boundary of the upper and lower evaporite layers might be related to the influence of δ37Cl‐rich brine and the incomplete dissolution of the halite.
A rare natural lipid induces neuroglobin expression to prevent amyloid oligomers toxicity and retinal neurodegeneration
Authors: Oamen Henry Patrick , Romero Romero Nathaly , Knuckles Philip , Saarikangas Juha , Radman‐Livaja Marta , Dong Yuhong , Caudron Fabrice
Published: June 2022

Most neurodegenerative diseases such as Alzheimer's disease are proteinopathies linked to the toxicity of amyloid oligomers. Treatments to delay or cure these diseases are lacking. Using budding yeast, we report that the natural lipid tripentadecanoin induces expression of the nitric oxide oxidoreductase Yhb1 to prevent the formation of protein aggregates during aging and extends replicative lifespan. In mammals, tripentadecanoin induces expression of the Yhb1 orthologue, neuroglobin, to protect neurons against amyloid toxicity. Tripentadecanoin also rescues photoreceptors in a mouse model of retinal degeneration and retinal ganglion cells in a Rhesus monkey model of optic atrophy. Together, we propose that tripentadecanoin affects p‐bodies to induce neuroglobin expression and offers a potential treatment for proteinopathies and retinal neurodegeneration.
Recombinant multimeric dog allergen prevents airway hyperresponsiveness in a model of asthma marked by vigorous TH2 and TH17 cell responses
Authors: Stark Julian M. , Liu Jielu , Tibbitt Christopher A. , Christian Murray , Ma Junjie , Wintersand Anna , Dunst Josefine , Kreslavsky Taras , Murrell Ben , Adner Mikael , Grönlund Hans , Gafvelin Guro , Coquet Jonathan M.
Published: June 2022

Background

Allergy to dogs affects around 10% of the population in developed countries. Immune therapy of allergic patients with dog allergen extracts has shown limited therapeutic benefit.

Methods

We established a mouse model of dog allergy by repeatedly administering dog dander and epithelium extracts via the intranasal route. We also assessed the efficacy of a recombinant multimeric protein containing Can f 1, f 2, f 4 and f 6 in preventing inflammatory responses to dog extracts.

Results

Repeated inhalation of dog extracts induced infiltration of the airways by TH2 cells, eosinophils and goblet cells, reminiscent of the house dust mite (HDM) model of asthma. Dog extracts also induced robust airway hyperresponsiveness and promoted TH17 cell responses, which was associated with a high neutrophilic infiltration of the airways. scRNA‐Seq analysis of T helper cells in the airways pinpointed a unique gene signature for TH17 cells. Analysis of T‐cell receptors depicted a high frequency of clones that were shared between TH17, TH2 and suppressive Treg cells, indicative of a common differentiation trajectory for these subsets. Importantly, sublingual administration of multimeric Can f 1‐2‐4‐6 protein prior to sensitization reduced airway hyperresponsiveness and type 2‐mediated inflammation in this model.

Conclusion

Dog allergen extracts induce robust TH2 and TH17 cell‐mediated responses in mice. Recombinant Can f 1‐2‐4‐6 can induce tolerance to complex dog allergen extracts.
Early bisphosphonate therapy post proximal femoral fracture fixation does not impact fracture healing: a systematic review and meta‐analysis
Authors: Tong Yui Yee Felice , Holmes Samuel , Sefton Andrew
Published: June 2022

Background

There is conjecture on the optimal timing to administer bisphosphonate therapy following operative fixation of low‐trauma hip fractures. Factors include recommendations for early opportunistic commencement of osteoporosis treatment, and clinician concern regarding the effect of bisphosphonates on fracture healing. We performed a systematic review and meta‐analysis to determine if early administration of bisphosphonate therapy within the first month post‐operatively following proximal femur fracture fixation is associated with delay in fracture healing or rates of delayed or non‐union.

Methods

We included randomized controlled trials examining fracture healing and union rates in adults with proximal femoral fractures undergoing osteosynthesis fixation methods and administered bisphosphonates within 1 month of operation with a control group. Data were pooled in meta‐analyses where possible. The Cochrane Risk of Bias Tool and the GRADE approach were used to assess validity.

Results

For the outcome of time to fracture union, meta‐analysis of three studies (n = 233) found evidence for earlier average time to union for patients receiving early bisphosphonate intervention (MD = −1.06 weeks, 95% CI −2.01–−0.12, I2 = 8%). There was no evidence from two included studies comprising 718 patients of any difference in rates of delayed union (RR 0.61, 95% CI 0.25–1.46). Meta‐analyses did not demonstrate a difference in outcomes of mortality, function or pain.

Conclusions

We provide low‐level evidence that there is no reduction in time to healing or delay in bony union for patients receiving bisphosphonates within 1 month of proximal femur fixation.
A phase I study of the safety and efficacy of talimogene laherparepvec in Japanese patients with advanced melanoma
Authors: Yamazaki Naoya , Isei Taiki , Kiyohara Yoshio , Koga Hiroshi , Kojima Takashi , Takenouchi Tatsuya , Yokota Kenji , Namikawa Kenjiro , Yi Min , Keegan Alissa , Fukushima Satoshi
Published: June 2022

Talimogene laherparepvec (T‐VEC) is approved for the treatment of unresectable melanoma in the USA, Europe, and Australia. This phase I, multicenter, open‐label, dose de‐escalation study evaluated the safety and efficacy of T‐VEC in Japanese patients with unresectable stage IIIB–IV melanoma. Eligible adult patients had histologically confirmed stage IIIB–IVM1c cutaneous melanoma, may have received prior systemic anticancer therapy, must have had ≥1 injectable lesion, serum lactate dehydrogenase ≤1.5x upper limit of normal, ECOG performance status of 0 or 1, and adequate hematologic, hepatic, and renal function. T‐VEC was injected intralesionally (first dose, ≤4.0 ml of 106 PFU/ml; after 3 weeks and then every 2 weeks thereafter, ≤4.0 ml of 108 PFU/ml). Primary endpoints were dose‐limiting toxicities (DLTs) and durable response rate (DRR). Of 18 enrolled patients (72.2% female), 16 had received ≥1 prior line of therapy. Ten patients discontinued T‐VEC due to disease progression. Median (range) follow‐up was 20.0 (4–37) months. No DLTs were observed; 17 (94.4%) patients had treatment‐emergent adverse events (AEs). Fourteen (77.8%) patients had treatment‐related AEs; the most frequent were pyrexia (44.4%), malaise (16.7%), chills, decreased appetite, pruritus, and skin ulcer (11.1% each). The primary efficacy endpoint was met: 2 (11.1%) patients had a durable partial response ≥6 months. The DRR was consistent with that observed in a phase III trial of T‐VEC in non‐Asian patients. The safety profile was consistent with the patients' underlying disease and the known safety profile of T‐VEC.
Does gender influence children's and young people's caring? A qualitative, systematic review and meta‐ethnography
Authors: Boyle Geraldine , Constantinou Georgina , Garcia Rebecca
Published: June 2022

This qualitative, systematic review explored the influence of gender on children's and young people's caring roles. However, there was very limited research in this area. Eight studies were included and the synthesis yielded seven global themes. The meta‐ethnography produced a higher‐order concept—the gendered reproduction of children's and young people's caring. The review shows that children and young people are relied on as a caring resource in the global North and South. We emphasise that gender equality in caring, particularly among adults, is necessary to enhance the lifechances of girls and young women.
Images of laser and light‐emitting diode colonoscopy for comparing large colorectal lesion visibility with linked color imaging and white‐light imaging
Authors: Yoshida Naohisa , Hayashi Yoshikazu , Kashida Hiroshi , Tomita Yuri , Dohi Osamu , Inoue Ken , Hirose Ryohei , Itoh Yoshito , Okada Masahiro , Yoshimoto Shiori , Fujinuma Toshihiro , Sakamoto Hirotsugu , Sunada Keijiro , Komeda Yoriaki , Sekai Ikue , Okai Natsuki , Yamamoto Hironori
Published: June 2022

Objectives

In light‐emitting diode (LED) and laser colonoscopy, linked color imaging (LCI) superiority to white‐light imaging (WLI) for polyp detection is shown separately. We analyzed the noninferiority of LCI between LED and laser colonoscopy and that of WLI (LECOL study).

Methods

We prospectively collected nonpolypoid lesions with WLI and LCI using LED and laser colonoscopy from January 2021 to August 2021. All images were evaluated randomly by 12 endoscopists (six nonexperts and six experts in three institutions) using the polyp visibility score: 4, excellent; 3, good; 2, fair; and 1, poor. The comparison score (LED better/similar/laser better) for redness and brightness was evaluated for WLI and LCI pictures of each lesion.

Results

Finally, 63 nonpolypoid lesions were evaluated, and the mean polyp size was 24.5 ± 13.4 mm. Histopathology revealed 13 serrated lesions and 50 adenomatous/cancerous lesions. The mean polyp visibility scores of LCI pictures were significantly higher than those of WLI in the LED (3.35 ± 0.85 vs. 3.08 ± 0.91,P < 0.001) and the laser (3.40 ± 1.71 vs. 3.05 ± 0.97,P < 0.001) group, and the noninferiority of LCI pictures between LED and laser was significant (P < 0.001). The comparison scores revealed that the evaluation of redness and brightness (LED better/similar/laser better) were 26.8%/40.1%/33.1% and 43.5%/43.5%/13.0% for LCI pictures (P < 0.001) and 20.6%/44.3%/35.1% and 60.3%/31.7%/8.0% for WLI pictures (P < 0.001), respectively.

Conclusion

The noninferiority of polyp visibility with WLI and LCI in LED and laser colonoscopy was shown. WLI and LCI of LED tended to be brighter and less reddish than those of laser.
MicroRNA inhibition using antimiRs in acute human brain tissue sections
Authors: Morris Gareth , Langa Elena , Fearon Conor , Conboy Karen , Lau E‐How Kelvin , Sanz‐Rodriguez Amaya , O'Brien Donncha F. , Sweeney Kieron , Lacey Austin , Delanty Norman , Beausang Alan , Brett Francesca M. , Cryan Jane B. , Cunningham Mark O. , Henshall David C.
Published: June 2022

Antisense inhibition of microRNAs is an emerging preclinical approach to pharmacoresistant epilepsy. A leading candidate is an "antimiR" targeting microRNA‐134 (ant‐134), but testing to date has used rodent models. Here, we develop an antimiR testing platform in human brain tissue sections. Brain specimens were obtained from patients undergoing resective surgery to treat pharmacoresistant epilepsy. Neocortical specimens were submerged in modified artificial cerebrospinal fluid (ACSF) and dissected for clinical neuropathological examination, and unused material was transferred for sectioning. Individual sections were incubated in oxygenated ACSF, containing either ant‐134 or a nontargeting control antimiR, for 24 h at room temperature. RNA integrity was assessed using BioAnalyzer processing, and individual miRNA levels were measured using quantitative reverse transcriptase polymerase chain reaction. Specimens transported in ACSF could be used for neuropathological diagnosis and had good RNA integrity. Ant‐134 mediated a dose‐dependent knockdown of miR‐134, with approximately 75% reduction of miR‐134 at 1 μmol L−1 and 90% reduction at 3 μmol L−1. These doses did not have off‐target effects on expression of a selection of three other miRNAs. This is the first demonstration of ant‐134 effects in live human brain tissues. The findings lend further support to the preclinical development of a therapy that targets miR‐134 and offer a flexible platform for the preclinical testing of antimiRs, and other antisense oligonucleotide therapeutics, in human brain.
An essential role for PTIP in mediating Hox gene regulation along PcG and trxG pathways
Authors: Cheng Qian , Xie Hao , Zhang Xiao‐Yan , Wang Ming‐Ying , Bi Cai‐Li , Wang Qiang , Wang Rui , Fang Ming
Published: June 2022

During Drosophila development, Polycomb‐group and Trithorax group proteins function to ensure correct maintenance of transcription patterns by epigenetically repressing or activating target gene expression. To get a deep insight into the PcG and trxG pathways, we investigated a BRCT domain‐containing protein called PTIP, which was generally identified as a transcriptional coactivator and belongs to the TRR complex. At the genome scale, we sorted given PTIP‐binding peaks into two groups: PTIP/TRR‐cobound and PTIP/PC‐cobound peaks. In particular, we found that PTIP mediates the molecular switch between H3K4me3/H3K27ac and H3K27me3 histone modifications at TRR or PC occupied regions. Thus, we suggest that PTIP is a mediator rather than a dedicated co‐activator along PcG and trxG pathways. Our hypothesis is further supported by the genetic assay: PTIP interacts genetically with either PcG or TrxG in a dosage‐dependent manner, suggesting that PTIP functions as a co‐factor of PcG/TrxG proteins. In addition, in accordance with the analysis of ChIP‐seq, these genetic interactions correlate with modified ectopic HOX protein levels in imaginal discs, which reveals an essential role for PTIP in PcG‐mediated Hox gene repression. Hence, we reveal a novel role for PTIP in the epigenetic regulation of gene expression along PcG and trxG pathways.
Saturated water‐weakening effects on the compressive behavior of thermally damaged granite
Authors: Zhao Ziyuan , Li Weiguo , Ma Jianzuo , Yang Mengqing , Kou Haibo , He Yi , Zheng Shifeng , Dong Pan
Published: June 2022

A detailed understanding of the compressive behavior of granite under environments of high temperature and water is critical for deep resource exploitation. In this study, uniaxial compressive strength tests were conducted on dry and water‐saturated granite with thermal damage at room temperature. A new phenomenon was discovered: With the increase of thermal damage degree of granite at different heat‐treatment temperatures, the saturated water‐induced weakening effects on the stress thresholds representing each crack development stage of granite present an obvious non‐monotonic trend. Of the saturated water‐induced weakening effects, 500°C is the key point, where the abrupt change occurs and the attenuation of compressive strength (peak stress) attains the maximum, reaching 41.77%. Further, the corresponding phenomenon was attributed to the form transformation of microcracks near 500°C based on the microstructural analysis. This study enriches the understanding of rock behavior deep underground and can provide a guide for more efficient hydraulic fracturing in deep resource exploitation, as well as the long‐term safe and stable use of nuclear waste disposal projects within the granite.
Ichthyoplankton assemblages and physical characteristics of two submarine canyons in the south central Tyrrhenian Sea
Authors: Ciannelli Lorenzo , Cannavacciuolo Antonio , Konstandinidis Peter , Mirasole Alice , Wong‐Ala Jennifer A. T. K. , Guerra Maria Teresa , D'Ambra Isabella , Riginella Emilio , Cianelli Daniela
Published: June 2022

Ichthyoplankton assemblages in the south central Tyrrhenian Sea are not known in spite of this being an intensely fished area. There are two large canyons in this region: Dohrn, in the Gulf of Naples, and Cuma, at the south end of the Gulf of Gaeta. In this study, we provide the first description of summer ichthyoplankton assemblages in the vicinity of the two canyons and present the physical features and Lagrangian particle tracking analyses at the time of the sampling. We identified fish larvae of 19 families and fish eggs of 8 families. The most abundant species was Engraulis encrasicolus, which was found at densities comparable to other known spawning grounds of the western Mediterranean. Mesopelagic species, such as Gonostomatidae and Myctophidae, were also abundant, especially at the Cuma Canyon. The notochord and standard length of the E. encrasicolus larvae ranged from 2.06 to 10.47 mm and was significantly smaller at the Cuma stations than at the Dohrn stations, suggesting the presence of sub‐populations with different spawning phenologies. The passive particle tracking analyses and the examination of currents confirmed distinct circulation features between the two sampled regions and in relation to depth and proximity to the canyon heads. These results uncover previously unknown rich assemblages of fish eggs and larvae and have conservation and management implications given the proximity of these canyons to a marine protected area and to an intensely fished continental shelf.