bluuebunny/crossref_metadata_2025 huggingface dataset:
G6PD deficiency sensitizes metastasizing melanoma cells to oxidative stress and glutaminolysis
Authors: Aurora Arin B. , Khivansara Vishal , Leach Ashley , Gill Jennifer G. , Martin-Sandoval Misty , Yang Chendong , Kasitinon Stacy Y. , Bezwada Divya , Tasdogan Alpaslan , Gu Wen , Mathews Thomas , Zhao Zhiyu , DeBerardinis Ralph J. , Morrison Sean J.
Published: November 2021

The pentose phosphate pathway is a major source of NADPH for oxidative stress resistance in cancer cells but there is limited insight into its role in metastasis, when some cancer cells experience high levels of oxidative stress. To test this, we mutated the substrate binding site of Glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the first step of the pentose phosphate pathway, in patient-derived melanomas. G6PD mutant melanomas had significantly decreased G6PD enzymatic activity and depletion of intermediates in the oxidative branch of the pentose phosphate pathway. Reduced G6PD function had little effect on the formation of primary subcutaneous tumors but when these tumors spontaneously metastasized the frequency of circulating melanoma cells in the blood and metastatic disease burden were significantly reduced. G6PD mutant melanomas exhibited increased levels of reactive oxygen species (ROS), decreased NADPH levels, and depleted glutathione as compared to control melanomas. G6PD mutant melanomas compensated for this increase in oxidative stress by increasing the production of NADPH through glutaminolysis. This generated a new metabolic vulnerability as G6PD mutant melanomas were more dependent upon glutamine as compared to control melanomas. The oxidative pentose phosphate pathway and compensatory glutaminolysis thus confer layered protection against oxidative stress during metastasis.

Significance

Melanoma metastasis is limited by oxidative stress. Cells that enter the blood experience high levels of ROS and usually die of ferroptosis. We found that melanoma cells become more dependent upon the oxidative branch of the pentose phosphate pathway to manage oxidative stress during metastasis. When pentose phosphate pathway function was disabled by G6PD mutation, the melanoma cells increased their utilization of malic enzyme, fueled by increased consumption of glutamine in the tricarboxylic acid cycle. Melanoma cells thus have redundant and layered protection against oxidative stress.
Whole transcriptome sequencing reveals drought resistance-related genes in upland cotton
Authors: Zheng Juyun , Zhang Zeliang , Liang Yajun , Gong Zhaolong , Sang Zhiwei , Li Xueyuan , Wang Jungduo
Published: November 2021

China, especially the Xinjiang cotton area, is facing severe agricultural water shortages, which seriously restrain the development of the cotton industry. Discovering cotton drought resistance genes and cultivating high-quality and drought-resistant cotton materials through molecular breeding methods are of great significance to the development of the cotton industry. In this study, the drought-resistant cotton material Xinluzhong NO.82 and the drought-sensitive cotton material Kexin NO.1 were used to identify a batch of drought-resistant candidate genes through whole transcriptome sequencing. The main research results obtained were as follows: the ceRNA (competing endogenous RNAs) network was constructed using full transcriptional sequencing to screen the core genes in the core pathway; two drought-related candidate genes were obtained. Gohir.A11G156000 was upregulated at 0 h vs 12 h and downregulated at 12 h vs 24 h. Gohir.A07G220600 was downregulated at 0 h vs 12 h and upregulated at 12 h vs 24 h. The results for drought-resistant materials and drought-sensitive materials were similar. Gohir.A11G156000, encoding GABA-T, which is homologous to POP2 in Arabidopsis thaliana, affects the drought resistance of plants by regulating the GABA content. Gohir.A07G220600 encodes L-aspartate oxidase, which is homologous to AO in Arabidopsis thaliana, and is involved in the early steps of NAD biosynthesis and in plant antioxidant reactions. This study confirmed that the use of gene expression regulatory networks can quickly screen reliable drought-resistance genes and can be used for subsequent gene function verification.
Age and product dependent vaccine effectiveness against SARS-CoV-2 infection and hospitalisation among adults in Norway: a national cohort study, January – September 2021
Authors: Starrfelt Jostein , Buanes Eirik Alnes , Juvet Lene Kristine , Lyngstad Trude Marie , Isaksson Rø Gunnar Øyvind , Veneti Lamprini , Meijerink Hinta
Published: November 2021

Background

SARS-CoV-2 vaccines show high effectiveness against infection and (severe) disease. However, few studies estimate population level vaccine effectiveness against multiple COVID-19 outcomes, by age and including homologous and heterologous vaccine regimens.

Methods

Using Cox proportional hazard models on data from 4 293 544 individuals (99% of Norwegian adults), we estimated overall, age-, and product-specific vaccine effectiveness against SARS-CoV-2 infection, hospitalisation, ICU admission and death in Norway, using data from national registries. Vaccine status was included as time-dependent variable and we adjusted for sex, pre-existing medical conditions, country of birth, county of residence, and crowded living conditions.

Findings

Adjusted vaccine effectiveness among fully vaccinated is 72·1% (71·2–73·0) against SARS-CoV-2 infection, 92·9% (91·2–94·2) against hospitalisation, 95·5% (92·6–97·2) against ICU admission, and 88·0% (82·5–91·8) against death. Among partially vaccinated, the effectiveness is 24·3% (22·3–26·2) against infection and 82·7% (77·7–86·6) against hospitalisation. Vaccine effectiveness against infection is 84·7% (83·1-86·1) for heterologous mRNA vaccine regimens, 78·3% (76·8-79·7) for Spikevax (Moderna; mRNA-1273), 69·7% (68·6-70·8) for Comirnaty (Pfizer/BioNTech; BNT162b2), and 60·7% (57·5-63·6) for Vaxzevria (AstraZeneca; ChAdOx nCoV-19; AZD1222) with a mRNA dose among fully vaccinated.

Interpretation

We demonstrate good protection against SARS-CoV-2 infection and severe disease in fully vaccinated, including heterologous vaccine regimens, which could facilitate rapid immunization. Partially vaccinated were less likely to get severe disease than unvaccinated, though protection against infection was not as high, which could be essential in making vaccine prioritisation policies especially when availability is limited.

Funding

Norwegian Institute of Public Health, Helse Bergen Health Trust
Mycobacterium tuberculosis senses host Interferon-γ via the membrane protein MmpL10
Authors: Ahmed Mohamed , Mackenzie Jared , Krause Robert , Truebody Barry , Tezera Liku , Garay-Baquero Diana , Vallejo Andres , Govender Katya , Adamson John , Elkington Paul , Steyn Adrie JC , Leslie Alasdair
Published: November 2021

Mycobacterium tuberculosis (Mtb) is one of the most successful human pathogens and remains a leading cause of death from infectious disease. Interferon-γ (IFN-γ) is a central regulator of the immune defense against Mtb. Several cytokines have been shown to increase virulence of other bacterial pathogens, leading us to investigate whether IFN-γ has a direct effect on Mtb. We found that both recombinant and T-cell derived IFN-γ rapidly induced a dose-dependent increase in the oxygen consumption rate (OCR) of Mtb, consistent with increased bacterial respiration. This was also observed in clinical strains, but not in the vaccine strain Bacillus Calmette–Guérin (BCG), and did not occur for other cytokines tested, including TNF-α. IFN-γ binds to the cell surface of intact Mtb, but not BCG, whilst TNF-α binds to neither. Mass spectrometry analysis identified mycobacterial membrane protein large 10 (MmpL10) as the transmembrane binding partner. Consistent with this, IFN-γ binding and the OCR response was absent in a Mtb Δmmpl10 strain and restored by complementation of the mutant strain. RNA-sequencing of IFN-γ exposed Mtb revealed a distinct transcriptional profile, including genes involved in virulence and cholesterol catabolism. Finally, exposure of Mtb cells to IFN-γ resulted in sterilization of bacilli treated with isoniazid (INH), indicating clearance of phenotypically resistant bacteria that persist in the presence of INH alone. Our data suggest a novel mechanism allowing Mtb to respond to host immune activation that may be important in the immunopathogenesis of TB and have use in novel eradication strategies.

One-Sentence Summary

IFN-γ is a critical component of effective immune defense in human tuberculosis yet its causative agent, Mycobacterium tuberculosis it able to sense this cytokine and increase virulence and respiration in response.
The rice OsERF101 transcription factor regulates the NLR Xa1-mediated perception of TAL effectors and Xa1-mediated immunity
Authors: Yoshihisa Ayaka , Yoshimura Satomi , Shimizu Motoki , Sato Sayaka , Mine Akira , Yamaguchi Koji , Kawasaki Tsutomu
Published: November 2021

Plant nucleotide-binding leucine-rich repeat receptors (NLRs) initiate immune responses and the hypersensitive response by recognizing pathogen effectors. Xa1 encodes an NLR with an N-terminal BED domain, and recognizes transcription activator-like (TAL) effectors of Xanthomonas oryzae pv. oryzae (Xoo). The molecular mechanisms controlling the recognition of TAL effectors by Xa1 and the subsequent induction of immunity remain poorly understood.

Xa1 interacts in the nucleus with two TAL effectors via the BED domain. We identified the AP2/ERF-type transcription factor OsERF101/OsRAP2.6 as an interactor with Xa1, and found that it also interacts with the TAL effectors.

Overexpression of OsERF101 exhibited an enhanced resistance to an incompatible Xoo strain only in the presence of Xa1, indicating that OsERF101 functions as a positive regulator of Xa1-mediated immunity. Unexpectedly, oserf101 mutants also showed enhanced Xa1-dependent resistance, but in a different manner from the overexpressing plants. This result revealed an additional Xa1-mediated immune pathway that is negatively regulated by OsERF101. Furthermore, OsERF101 directly interacted with the TAL effectors.

Our results show that OsERF101 regulates the recognition of TAL effectors and the Xa1-mediated activation of the immune response. These data provide new insights into the molecular mechanism of NLR-mediated immunity in plants.
Learning induces coordinated neuronal plasticity of metabolic demands and functional brain networks
Authors: Klug Sebastian , Godbersen Godber M , Rischka Lucas , Wadsak Wolfgang , Pichler Verena , Klöbl Manfred , Hacker Marcus , Lanzenberger Rupert , Hahn Andreas
Published: November 2021

The neurobiological basis of learning is reflected in adaptations of brain structure, network organization and energy metabolism. However, it is still unknown how different neuroplastic mechanisms act together and if cognitive advancements relate to general or task-specific changes. To address these questions, we tested how hierarchical network interactions contribute to improvements in the performance of a visuo-spatial processing task by employing simultaneous PET/MR neuroimaging before and after a 4-week learning period. We combined functional PET with metabolic connectivity mapping (MCM) to infer directional interactions across brain regions and subsequently performed simulations to disentangle the role of functional network dynamics and glucose metabolism. As a result, learning altered the top-down regulation of the salience network onto the occipital cortex, with increases in MCM at resting-state and decreases during task execution. Accordingly, a higher divergence between resting-state and task-specific effects was associated with better cognitive performance, indicating that these adaptations are complementary and both required for successful skill learning. Simulations further showed that changes at resting-state were dependent on glucose metabolism, whereas those during task performance were driven by functional connectivity between salience and visual networks. Referring to previous work, we suggest that learning establishes a metabolically expensive skill engram at rest, whose retrieval serves for efficient task execution by minimizing prediction errors between neuronal representations of brain regions on different hierarchical levels.
Framework for identification of performance metrics for research and development collaborations: Construction Innovation Centre
Authors: Fayek Aminah Robinson , Golabchi Alireza
Published: November 2021

Purpose

The purpose of this study is to provide a framework to identify performance metrics for evaluating research and development collaborations.

Design/methodology/approach

The framework is developed through a review of similar centres and academic studies, followed by surveys and interviews of researchers and industry practitioners for the case of the Construction Innovation Centre (CIC). The proposed framework consists of identification of existing industry research and development needs, development of a research roadmap representing top research priorities, and identification of the most important services to provide to industry partners, which form the context for defining performance evaluation metrics.

Findings

A research roadmap is presented, outlining top research areas and methods and a list of the most in-demand services including research, practical and training and outreach services. Metrics for evaluating the performance of proposed projects, completed projects and a collaborative research centre are also identified.

Originality/value

This study presents a novel approach to defining performance metrics for the evaluation of research and development collaborations. The approach and findings of this study can be adopted by other collaborative research centres and initiatives around the world to develop effective metrics for performance measurement. The proposed framework provides a platform for defining performance metrics in the context of the research roadmap and top-priority services applicable to the research and development collaboration.
Classifying healthcare warehouses according to their performance. A Cluster Analysis-based approach
Authors: Cagliano Anna Corinna , Mangano Giulio , Rafele Carlo , Grimaldi Sabrina
Published: November 2021

Purpose

The objective of this paper is to propose an approach to comparatively analyze the performance of drugs and consumable products warehouses belonging to different healthcare institutions.

Design/methodology/approach

A Cluster Analysis is completed in order to classify warehouses and identify common patterns based on similar organizational characteristics. The variables taken into account are associated with inventory levels, the number of SKUs, and incoming and outgoing flows.

Findings

The outcomes of the empirical analysis are confirmed by additional indicators reflecting the demand level and the associated logistics flows faced by the warehouses at issue. Also, the warehouses belonging to the same cluster show similar behaviors for all the indicators considered, meaning that the performed Cluster Analysis can be considered as coherent.

Research limitations/implications

The study proposes an approach aimed at grouping healthcare warehouses based on relevant logistics aspects. Thus, it can foster the application of statistical analysis in the healthcare Supply Chain Management. The present work is associated with only one regional healthcare system.

Practical implications

The approach might support healthcare agencies in comparing the performance of their warehouses more accurately. Consequently, it could facilitate comprehensive investigations of the managerial similarities and differences that could be a first step toward warehouse aggregation in homogeneous logistics units.

Originality/value

This analysis puts forward an approach based on a consolidated statistical tool, to assess the logistics performances in a set of warehouses and, in turn to deepen the related understanding as well as the factors determining them.
Managing projects as a mode of temporal ordering. Performative organising of time and temporality in projects
Authors: Kalff Yannick
Published: November 2021

Purpose

Project studies analyse either managing practices or the temporal nature of project management, which leaves open a research gap: the temporality of managing practice. The paper demonstrates that performativity theory with a temporal perspective helps us to understand how managing a project organises limited temporal resources by aligning activities, deadlines or milestones to reach a goal in a given time.

Design/methodology/approach

The article utilises empirical data and grounded theory methodology. Ten interviews with project managers from two companies support empirically guided theory building and conceptual reasoning.

Findings

The article extends John Law's “modes of ordering” to a project-specific mode of temporal ordering. This mode of temporal ordering describes the underlying rationale of project managers who assign, order and materialise time to generate the temporal structure of the project.

Research limitations/implications

The conceptual nature of the paper and its limited empirical data restrict the generalisation of the findings. The article's goal is to initiate further research and to offer a set of tools for such research.

Originality/value

The contribution links managing practice and temporality in a performativity approach. This link focusses the actual actions of the managers and contextualises them in the temporal flow of the project. Managing projects as a mode of temporal ordering describes how project managers enact temporal structures and how they themselves and their activities are temporally embedded.
Innovating how innovation works at Procter & Gamble
Authors: Day George S. , Shea Gregory P.
Published: November 2021

Purpose

The authors map out a work system that was key to Procter & Gamble transforming its innovation practices from a slow-paced, cautious incrementalism toward a leaner, more entrepreneurial model able to make bigger and riskier long-term bets.

Design/methodology/approach

Starting in 2016, P&G began “innovating how they innovated”, supported by a strong leadership commitment to working differently.

Findings

The newly envisioned future included P&G exploring many smaller scale innovations within and across business units, with quick learning, conducted in close collaboration with consumers and driven by their problems and needs.

Practical/implications

Kathy Fish began this initiative by studying what innovation practices had produced “irresistible superiority” in the past.

Originality/value

Describes how P&G, a leading, long-established company instituted a systematic program of changing the system through which the work of innovation gets done. This system has eight action levers that collectively shape a supportive and productive work environment. Taking these actions in a coherent, coordinated fashion at Procter & Gamble, changed the operating environment and the company’s innovators adapted their behavior to the new system.
Beyond the “Great Man” narrative: scandals, cumulative reforms and the trajectory of anti-corruption efforts in colonial Hong Kong before MacLehose years
Authors: Yep Ray
Published: November 2021

Purpose

This paper aims to uncover the trajectory of the anti-corruption effort of the Hong Kong colonial Government by identifying its general approach of denial in the pre-War years. It highlights the path-dependence nature, as well as the path-creation logic of the policy process of anti-corruption reform and the anxiety of the colonial administration in maintaining trust of the local population in the post-War years. These insights should enhance the general understanding of the nature of colonial governance.

Design/methodology/approach

This paper is primarily based on archival materials available at the British National Archives and Hong Kong Public Records Office.

Findings

The paper intends to go before the “Great Man narrative” in explaining the success of the anti-corruption effort in colonial Hong Kong. Whilst the colonial government was fully aware of the endemic of corruption and the substantial involvement of European officers, she was still cocooned with the misguided belief that the core of the administration was mostly “incorruptible”. The Air Raid Precaution Department scandal in 1941 was, however, a powerful wake-up that rendered the denial and self-illusion no longer defensible. The policy ideas of the 1940s did shape the Prevention of Corruption Ordinance 1948 and other related reforms, yet they were not immediately translated into fundamental changes in the institutional set-up of the anti-graft campaign. The limitations of these half-hearted measures were fully exposed in the coming decades. The cumulative effects of the piecemeal anti-graft efforts of the colonial government over the first century of rule, however, did path the way for the “revolutionary” changes in the 1970s under Murray MacLehose.

Originality/value

This is a highly original piece based on under-explored archival materials. The findings should have a major contribution to the scholarship on the nature of colonial governance and the history of anti-corruption efforts of Hong Kong.
Herpes simplex virus DNA testing by a loop‐mediated isothermal amplification method for accurate clinical diagnosis and detection of mucosal viral shedding
Authors: Miyachi Motoko , Imamura‐Ichigatani Tomomi , Ihara Honoka , Ohga Yasunori , Nishimura Miku , Sato Emi , Hoashi Shogo , Imafuku Shinichi
Published: November 2021

Herpes simplex virus (HSV) periodically forms characteristic blisters in the perioral and genital areas in a subset of people. Because of the lack of accurate tests for this common virus, various types of perioral/anogenital lesions are often misdiagnosed as herpes. Also, though asymptomatic HSV‐positive people shed virus, the precise time course of symptoms and viral shedding is unclear. The loop‐mediated isothermal amplification (LAMP) method amplifies target DNA sequences without thermal cycles, simpler and faster than polymerase chain reaction (PCR). To investigate clinico‐laboratorial correlation and whether HSV can be detected in the oral cavity during symptom occurrence, we collected 445 specimens from 211 patients who visited our clinic with suspected herpetic lesions or non‐symptomatic volunteers. DNA was extracted from swabs simultaneously taken from lesions (n = 219) and seemingly asymptomatic oral mucosa (n = 226). HSV‐1 and HSV‐2 DNA sequences were amplified by LAMP and validated by quantitative real‐time PCR. The LAMP method detected HSV DNA almost as sensitively (97%) as PCR. Positivity for HSV DNA was found in 54% (40/74) of specimens from the perioral/oral area. Review of clinical images of recurrent herpes labialis revealed that HSV DNA was detected only from lesions located on the perioral skin and/or the dry, vermillion part of the lip; no HSV DNA was found in immunocompetent patients with lesions confined to the oral mucosa except primary infection. This observation may be an important principle for clinical diagnosis of recurrent herpes. HSV was detected in the oral mucosa in 2.7% (6/226) of samples; all of these patients had either primary infection or were immunosuppressed. Virus shedding in the mucosa was apparently tightly regulated by the immune system. Patients with suppressed or no immunity (naïve cases) did shed virus in the mucosa. LAMP is a simple method to reliably distinguish recurrent/primary herpes from other conditions.
The Avian Sense for Beauty: A Posthumanist Perspective on the Bowerbird
Authors: Amstutz Nina
Published: November 2021

This essay uses the bowerbird's practice of collecting and arranging decorative objects to attract a mate as a point of departure to question the humanist commitments of art history as a discipline, and to explore what establishing a posthumanist art history might involve. I look to Charles Darwin's concept of sexual selection and the questions that it raised regarding the evolutionary origins of human creative activity. I discuss early natural history illustrations of bowerbirds along with Darwinian anthropologies of art, which bring human and avian aesthetic practices into dialogue. Finally, I draw on Richard Prum's theories on aesthetic evolution, Elizabeth Grosz's posthumanist perspective on art's origins, the emerging discipline of multispecies ethnography, and Indigenous Papuan understandings of the bowerbird, to ask how art historians might begin to restore human animals to a larger ecology of creative beings.
Seasonal diet and microbiome shifts in wild rhesus macaques are better correlated at the level of nutrient components than food items
Authors: CUI Zhenwei , HOLMES Andrew J. , ZHANG Wenjuan , HU Dalong , SHAO Qi , WANG Zhenlong , LU Jiqi , RAUBENHEIMER David
Published: November 2021

Food supply is one of the major drivers of animal behavior, and the gut microbiome is an important mediator between food supply and its effects on physiology. However, predicting the outcome of diet change on microbiome and consequences for the animal has proven extremely challenging. We propose this reflects processes occurring at different scales. Inadequate accounting for the multi‐level complexity of nutrition (nutrients, foods, diets) obscures the diet influence on microbiome and subsequently animal. Here, we present a detailed year‐round, multi‐level analysis of diet and microbiome changes in a wild population of a temperate primate, the rhesus macaque (Macaca mulatta). Total daily food and nutrient intake of 6 male and 6 female macaques was monitored in each of the 4 seasons (total 120 days observations). For each individual, we found significant variation in the microbiome between all 4 seasons. This response was more strongly correlated with changes in macronutrient intake than with food items and much of the response could be explained at the level of 6 ecological guilds—sets of taxa sharing similar responses to nutrient intake. We conclude that study of diet, microbiome, and animal performance in ecology will more effectively identify patterns if diet is recorded at the level of nutrient intake. Although microbiome response to diet does show variation in species‐level taxa in response to food items, there is greater commonality in response at the level of guilds. A goal for microbiome researchers should be to identify genes encoding microbial attributes that can define such guilds.
Preparation and physicochemical stability of tomato seed oil microemulsions
Authors: Song Qiufeng , Guan Weiliang , Liu Wenyu , Liu Lingzhen , Wei Changqing , Cai Luyun
Published: November 2021

In this study, microemulsions were fabricated using tomato seed oil, water, Tween 80 and citric acid, and then the physicochemical characteristics and the influence of environmental stress were investigated. The physicochemical properties of the microemulsions were evaluated by transmission electron microscopy (TEM), mean particle diameter, polydispersity index (PDI) and conductivity. The phase diagrams of tomato seed oil/Tween 80/citric acid/water microemulsions were constructed under different pHs and ionic strengths. Storage stability of the systems was investigated at 4, 37 and 65°C, and changes in turbidity and lipid oxidation products were monitored. Nano‐size zeta potential analyzer results demonstrated that the mean particle diameter and polydispersity index of tomato seed oil microemulsions were 14 nm and 0.014. The transition from W/O to O/W could be detected from electrical conductivity and viscosity data with the increasing of water content. The results showed that the microemulsion areas decreased with increasing pH and NaCl concentrations. What is more, the study proved that tomato seed oil microemulsions exhibited a good storage stability.

Practical Application

In this study, the preparation of tomato seed oil microemulsion can not only make full use of the nutritional value of tomato seed oil, but also ensure the effective protection of the nutrients contained in it, and improve the problem of adding difficult. By using microemulsion as delivery carrier of tomato seed oil, the application of tomato seed oil in food, cosmetics and other fields could be enhanced. Therefore, the preparation of tomato seed oil microemulsion provides a theoretical basis for production practice.
The end of hunger: fertilizers, microbes and plant productivity
Authors: Hu Hang‐Wei , Chen Qing‐Lin , He Ji‐Zheng
Published: November 2021

It is a grand challenge to ensure the food security for a predicted world population of exceeding 9.7 billion by 2050, especially in an era of global climate change, land degradation and biodiversity loss. Current agricultural productions are mainly relying on synthetic chemical fertilisers to boost plant productivity but have undesirable effects on the environment and soil biodiversity. A promising direction in sustainable agriculture is to harness naturally occurring processes of beneficial plant‐associated microbiomes to ensure sustained crop production and global food security. Despite the significant progress made in the development of beneficial microbes as inoculants to enhance plant performance, challenges remain with the translation of knowledge of plant and soil microbiomes to successful microbial products in the agricultural sector. Here, we highlight how fertilizer technology should be renovated by harnessing microbiome‐based innovations to promote plant productivity and contribute to the end of hunger.
Soluble human leukocyte antigen‐G is a potential embryo viability biomarker and a positive predictor of live‐births in humans
Authors: Vani Venkatappa , Vasan Satya S. , Adiga Satish K. , Varsha Samson Roy , Sachdeva Geetanjali , Kumar Pratap , Seshagiri Polani B.
Published: November 2021

Problem

Human infertility affects 15–20% of reproductive‐age couples and it is mitigated by assisted reproductive technology (ART) approaches. Poor biological viability of embryos contributes to implantation failure and live birth rate (LBR). This study is aimed to examine whether or not embryo‐secreted soluble human leukocyte antigen‐G (sHLA‐G) is (i) associated with developing embryos and (ii) able to predict successful pregnancy outcome.

Method of study

A retrospective, multicentric study using 539 human embryo spent medium samples (E‐SMs), analysed for sHLA‐G levels by ELISA. Correlation analysis was performed on sHLA‐G levels with developing embryonic stages, their quality scores and pregnancy outcome in terms of LBR.

Results

Of 539 E‐SMs analysed, 445 had detectable sHLA‐G (83%) with levels varying within and across clinics and, between stages of embryonic development. Levels of sHLA‐G (ng/mL) were significantly (P < .05) different in E‐SMs of cleavage‐stage embryos versus blastocysts. There was an insignificant correlation between the sHLA‐G levels and morphology scores of embryos. But, sHLA‐G levels showed a positive correlation with grades of blastocysts and importantly, its levels were significantly (P < .05) higher in live‐birth vis‐a‐vis no‐birth cases. Also, levels were higher in live‐births out of blastocysts‐ETs versus cleavage‐stage‐embryo transfers. Altered levels were observed with embryos, which resulted in miscarriages. Overall, a significant (P < .0001) association of sHLA‐G with live births was observed.

Conclusion

Embryo‐derived sHLA‐G can be a valuable embryo viability, independent, biomarker, which can predict live‐birth outcome and it could be useful as an adjunct to existing criteria for elective single embryo transfer.
A sudden change in pacing rate: Normal or malfunction?
Authors: Han Yiru , Zhang Yubin , Liu Tong , Zheng Liangrong
Published: November 2021

A woman with a dual‐chamber pacemaker was examined for recurrent chest discomfort and palpitations at our hospital. The Holter monitor test recorded recurrent episodes of a sudden increase in pacing rate from 60 to 105 bpm, which corresponded to the symptoms. Orthodromic pacemaker‐mediated arrhythmia (OPMA), caused by ventricular lead dislodgement and atrial far‐field sensing, caused the recurrent episodes of a sudden change in pacing rate. The occurrence of OPMA may represent a rare but noteworthy pacemaker problem. To our knowledge, our study reports the first case of PMA that only occurs, and is maintained, in the DDI mode.
Glucosylsphingosine evokes pruritus via activation of 5‐HT2A receptor and TRPV4 in sensory neurons
Authors: Sanjel Babina , Kim Bo‐Hyun , Song Myung‐Hyun , Carstens Earl , Shim Won‐Sik
Published: November 2021

Background and purpose

Glucosylsphingosine (GS), an endogenous sphingolipid, is highly accumulated in the epidermis of patients with atopic dermatitis (AD) due to abnormal ceramide metabolism. More importantly, GS can evoke scratching behaviours. However, the precise molecular mechanism by which GS induces pruritus has been elusive. Thus, the present study aimed to elucidate the molecular signalling pathway of GS, especially at the peripheral sensory neuronal levels.

Experimental approach

Calcium imaging was used to investigate the responses of HEK293T cells or mouse dorsal root ganglion (DRG) neurons to application of GS. Scratching behaviour tests were also performed with wild‐type and Trpv4 knockout mice.

Key results

GS activated DRG neurons in a manner involving both the 5‐HT2A receptor and TRPV4. Furthermore, GS‐induced responses were significantly suppressed by various inhibitors, including ketanserin (5‐HT2A receptor antagonist), YM254890 (Gαq/11 inhibitor), gallein (Gβγ complex inhibitor), U73122 (phospholipase C inhibitor), bisindolylmaleimide I (PKC inhibitor) and HC067047 (TRPV4 antagonist). Moreover, DRG neurons from Trpv4 knockout mice exhibited significantly reduced responses to GS. Additionally, GS‐evoked scratching behaviours were greatly decreased by pretreatment with inhibitors of either 5‐HT2A receptor or TRPV4. As expected, GS‐evoked scratching behaviour was also significantly decreased in Trpv4 knockout mice.

Conclusion and implications

Overall, the present study provides evidence for a novel molecular signalling pathway for GS‐evoked pruritus, which utilizes both 5‐HT2A receptor and TRPV4 in mouse sensory neurons. Considering the high accumulation of GS in the epidermis of patients with AD, GS could be another pruritogen in patients with AD.
A qualitative investigation of the impact that therapeutic recreational camps have on the psychological wellbeing of siblings of individuals with health conditions
Authors: Samuels Jessica , Keenan Joseph , Jolly Allan
Published: November 2021

Background

The siblings of individuals with health conditions are often overlooked, despite being at risk of experiencing psychological difficulties. There is a lack of literature investigating interventions which could promote siblings' psychological wellbeing. Therapeutic recreational (TR) camps promote self‐perception and self‐worth, yet there are currently no UK studies qualitatively investigating siblings' experiences of TR camps.

Aims

This study aims to understand siblings' lived experiences of attending TR camps, providing a greater depth of understanding of whether these camps have a positive impact on siblings' wellbeing.

Method

Due to the paucity of qualitative research regarding individuals' experiences of TR camps, semi‐structured interviews were conducted with eight individuals who had attended TR sibling camps. Verbatim transcripts were analysed using Interpretative Phenomenological Analysis (IPA).

Results

Analysis revealed three superordinate themes. The first, an environment that facilitates autonomous challenge, demonstrated the importance of siblings having a place where they felt autonomous in a fun, care‐free environment. This encouraged participants to engage in challenges, feeling determined to overcome them. The second, an inclusive and supportive environment, highlighted the importance of connectedness. Facing challenges and reflecting on this within a supportive team, encouraged a sense of belonging. The final superordinate theme, a transformational journey, revealed that siblings gained determination and a positive outlook to facing challenges in daily life. Additionally, they gained self‐acceptance and a positive self‐image, becoming more confident with, and accepting of, their identity.

Conclusions

This study presents a novel contribution to the existing literature and highlights the importance of camp providers ensuring their TR model incorporates autonomous challenge, success and reflection. These encourage positive youth development and self‐determination in young people. In addition, recommendations include implementing teams, promoting positive volunteer‐camper relationships and implementing reflective sessions. These recommendations could potentially enhance the positive impact that TR camps have on siblings' psychological wellbeing.
The immunomodulatory effect of microglia on ECM neuroinflammation via the PD‐1/PD‐L1 pathway
Authors: Shen Yan , Li Yinghui , Zhu Qinghao , Wang Jun , Huang Yuxiao , Liang Jiao , Wu Xingan , Zhao Ya
Published: November 2021

Introduction

The experimental cerebral malaria (ECM) model in C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) has revealed microglia are involved in the ECM immune microenvironment. However, the regulation of microglia in the ECM immune response is not clear, and there is no safe and efficient treatment clinically for the protection of the nerve cells.

Aims

To elucidate the negative regulation mechanism in the ECM brain mediated by microglia. Furthermore, to investigate protective effect of the appropriate enhancement of the PD‐1/PD‐L1 pathway in the brain against ECM through the intrathecal injection of the adenovirus expressing PDL1‐IgG1Fc fusion protein.

Results

The PD‐1/PD‐L1 pathway was induced in the ECM brain and showed an upregulation in the microglia. Deep single‐cell analysis of immune niches in the ECM brainstem indicated that the microglia showed obvious heterogeneity and activation characteristics. Intrathecal injection of recombinant adenovirus expressing PD‐L1 repressed the neuroinflammation and alleviated ECM symptoms. In addition, the synergistic effect of artemisinin and intracranial immunosuppression mediated by PD‐L1 was more efficacious than either treatment alone.

Conclusion

The appropriate enhancement of the PD‐1/PD‐L1 pathway in the early stage of ECM has an obvious protective effect on the maintenance of immune microenvironment homeostasis in the brain. Regulating microglia and the PD‐1/PD‐L1 pathway could be considered as a promising approach for protection against human cerebral malaria in the future.
A novel LGI1 mutation causing autosomal dominant lateral temporal lobe epilepsy confirmed by a precise knock‐in mouse model
Authors: Hu Ping , Wu Dan , Zang Yan‐Yu , Wang Yan , Zhou Ya‐Ping , Qiao Fengchang , Teng Xiao‐Yu , Chen Jiang , Li Qing‐Qing , Sun Jia‐Hui , Liu TingTing , Feng Hao‐Yang , Zhou Qi‐Gang , Shi Yun Stone , Xu Zhengfeng
Published: November 2021

Aims

This study aimed to explore the pathomechanism of a mutation on the leucine‐rich glioma inactivated 1 gene (LGI1) identified in a family having autosomal dominant lateral temporal lobe epilepsy (ADLTE), using a precise knock‐in mouse model.

Methods and Results

A novel LGI1 mutation, c.152A>G; p. Asp51Gly, was identified by whole exome sequencing in a Chinese family with ADLTE. The pathomechanism of the mutation was explored by generating Lgi1D51G knock‐in mice that precisely phenocopied the epileptic symptoms of human patients. The Lgi1D51G/D51G mice showed spontaneous recurrent generalized seizures and premature death. The Lgi1D51G/+ mice had partial epilepsy, with half of them displaying epileptiform discharges on electroencephalography. They also showed enhanced sensitivity to the convulsant agent pentylenetetrazole. Mechanistically, the secretion of Lgi1 was impaired in the brain of the D51G knock‐in mice and the protein level was drastically reduced. Moreover, the antiepileptic drugs, carbamazepine, oxcarbazepine, and sodium valproate, could prolong the survival time of Lgi1D51G/D51G mice, and oxcarbazepine appeared to be the most effective.

Conclusions

We identified a novel epilepsy‐causing mutation of LGI1 in humans. The Lgi1D51G/+ mouse model, precisely phenocopying epileptic symptoms of human patients, could be a useful tool in future studies on the pathogenesis and potential therapies for epilepsy.
Patient perspectives of the influence of severe and non‐severe asthma on their quality of life: A national survey of asthma patients in Spain
Authors: Chiner Eusebi , Hernández Carme , Blanco‐Aparicio Marina , Funenga‐Fitas Eunice , Jiménez‐Ruiz Carlos
Published: November 2021

Introduction

Little is known about adult asthma patients' perspective of their disease burden. This study aimed to obtain a comprehensive picture of patient needs, evaluate their knowledge, source of information, and perception of the severity of their asthma, and compare these variables between severe (SA) and non‐severe (NSA) asthma patients.

Methods

We conducted an online cross‐sectional survey in Spain among asthma patients aged ≥18 years. A bespoke questionnaire was used to collect sociodemographic data, asthma characteristics, treatments, disease burden, patient's perception of disease severity, and asthma information sources. Patients were classified as SA and NSA according to GINA 2020 treatment steps recommendations. To compare populations, 600 participants (200 SA and 400 NSA) were randomly selected to complete the survey.

Results

Participants were mostly women, mean age >38 years. SA patients underestimated the severity of their asthma; 52% judged it as mild, and only 2% considered their asthma severe. Overall, 50% of NSA and 96% of SA patients had experienced ≥1 exacerbation the previous year (p < 0.001). Fewer asthma exacerbations (SA) and improved quality of life (QoL) (NSA) were the most frequently expected therapy outcomes. NSA patients believe that asthma impacts their daily life (37%) and worsens QoL (34%) to a lesser degree than SA (67% and 59%, respectively; p < 0.001). Patient‐preferred sources of information were specialists (NSA:42%; SA: 38%) and primary care physicians (NSA: 41%; SA: 33%).

Conclusions

Despite the effective therapies currently available, the results of this study still show a significant emotional burden and QoL impairment in patients with severe asthma.
Correlates of deviance detection in auditory brainstem responses of bats
Authors: Wetekam Johannes , Hechavarría Julio , López‐Jury Luciana , Kössl Manfred
Published: November 2021

Identifying unexpected acoustic inputs, which allows to react appropriately to new situations, is of major importance for animals. Neural deviance detection describes a change of neural response strength to a stimulus solely caused by the stimulus' probability of occurrence. In the present study, we searched for correlates of deviance detection in auditory brainstem responses obtained in anaesthetised bats (Carollia perspicillata). In an oddball paradigm, we used two pure tone stimuli that represented the main frequencies used by the animal during echolocation (60 kHz) and communication (20 kHz). For both stimuli, we could demonstrate significant differences of response strength between deviant and standard response in slow and fast components of the auditory brainstem response. The data suggest the presence of correlates of deviance detection in brain stations below the inferior colliculus (IC), at the level of the cochlea nucleus and lateral lemniscus. Additionally, our results suggest that deviance detection is mainly driven by repetition suppression in the echolocation frequency band, while in the communication band, a deviant‐related enhancement of the response plays a more important role. This finding suggests a contextual dependence of the mechanisms underlying subcortical deviance detection. The present study demonstrates the value of auditory brainstem responses for studying deviance detection and suggests that auditory specialists, such as bats, use different frequency‐specific strategies to ensure an appropriate sensation of unexpected sounds.
Intertap interval dependence of the subdivision effect in auditory‐synchronised tapping
Authors: Ono Kentaro , Hashimoto Junya , Sasaoka Takafumi
Published: November 2021

Precise temporal synchronisation between action and perception is crucial in daily life. Interestingly, synchronised tapping for every other tone or more (1:n tapping) is more precise than that for each tone (1:1 tapping), and this phenomenon is called ‘subdivision benefit’. One hypothesis to explain this phenomenon is that there is a tendency to underestimate an empty interval, but the subdivision is used as an additional temporal reference and causes an illusionary longer intertap interval (ITI). The other hypothesis is based on strong/weak beats in a tone sequence made by subdivision. Because the strong beat improves the sensitivity of duration perception, synchronisation with strong beats should be better compared with other beats. Instead, the first hypothesis suggests that the subdivision benefit occurs irrespective of beat strength. The present study aimed to clarify this discrepancy using a 1:3 tapping task for a sequence of three‐tone patterns and a 1:1 tapping task for a sequence of a single tone repetition. A further aim was to clarify the effect of musical experience. When the ITI was 900 ms or more, the variability of tapping showed the subdivision benefit, irrespective of beat strength. This result supports the first hypothesis, and musicians obtained more benefits than non‐musicians. Instead, the timing of tap did not shorten by subdivision, except for the ITI of 900 ms. The findings implicate that the subdivision benefit is due to the additional temporal reference by the subdivided tones, and the benefit is dependent on the ITI length.
A replication study on implicit feedback recommender systems with application to the data visualization recommendation
Authors: Lak Parisa , Bozanta Aysun , Kavaklioglu Can , Cevik Mucahit , Basar Ayse , Petitclerc Martin , Wills Graham
Published: November 2021

In this study, we compare the Bayesian personalized ranking (BPR) algorithms with two recent state‐of‐the‐art algorithms, namely, noisy‐label robust Bayesian point‐wise optimization (NBPO) and Light Graph Convolution Network (LightGCN) algorithms, to validate and generalize their performance by using six publicly available datasets and one proprietary dataset containing web‐based data visualization usage records. We follow the guidelines explained in the original studies to pre‐process the input data and evaluate these algorithms using various evaluation metrics. We also perform hyperparameter tuning for the recommendation algorithms to determine the optimal configuration resulting in the best recommendation quality. We observe that the best hyperparameter configuration varies based on the algorithms and the datasets. The results of our analysis show some similarities with the results of the original studies while differing in certain respects. We observe that adaptive oversampling BPR (AOBPR) and LightGCN algorithms generate higher quality recommendations than the other algorithms. However, algorithm convergence rates vary significantly for each dataset. We note that the AOBPR approach is particularly useful for data visualization recommendation task, and can contribute to the improved recommendations in practice.