bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumorigenicity Assessment of Human Cancer Cell Lines Xenografted on Immunodeficient Mice as Positive Controls of Tumorigenicity Testing
Authors: Oh Seunghee , Gu Eun-Young , Han Ji-Seok , Lee Byoung-Seok , Moon Kyoung-Sik , Kim Yong-Bum , Han Kang-Hyun
Published: September 2022

Recent advances in human pluripotent stem cell (hPSC)-derived cell therapies and genome editing technologies such as CRISPR/Cas9 make regenerative medicines promising for curing diseases previously thought to be incurable. However, the possibility of off-target effects during genome editing and the nature of hPSCs, which can differentiate into any cell type and infinitely proliferate, inevitably raises concerns about tumorigenicity. Tumorigenicity acts as a major obstacle to the application of hPSC-derived and gene therapy products in clinical practice. Thus, regulatory authorities demand mandatory tumorigenicity testing as a key pre-clinical safety step for the products. In the tumorigenicity testing, regulatory guidelines request to include human cancer cell line injected positive control group (PC) animals, which must form tumors. As the validity of the whole test is determined by the tumor-forming rates (typically above 90%) of PC animals, establishing the stable tumorigenic condition of PC animals is critical for successful testing. We conducted several studies to establish the proper positive control conditions, including dose, administration routes, and the selection of cell lines, in compliance with Good Laboratory Practice (GLP) regulations and/or guidelines, which are essential for pre-clinical safety tests of therapeutic materials. We expect that our findings provide insights and practical information to create a successful tumorigenicity test and its guidelines.
‘Like the Oceans We Rise’: News Frames on Youth for Climate
Authors: Poot Freija , Bauwens Joke
Published: September 2022

In early 2019, following the example of the Swedish climate activist Greta Thunberg, youth-led climate movements around the world demonstrated massively and persistently for a more ambitious climate policy. News media gave extensive coverage to the climate activists; given that the demonstrations were mostly on school days, public debates on young people’s rights, obligations and political agency were tense and polarized. In this article we take Belgium as a case study and discuss how the Youth for Climate movement was framed in four Dutch-speaking newspapers. Based on an inductive and deductive frame analysis of 126 newspaper articles, we found six frames. Most of the frames tend to challenge persistent views of young people’s political agency, whereas remarkably few support the idea that young people are unfit for politics.
Building democracy after war? Post-rebel electoral parties and the construction of stable party systems
Authors: Tuncel Ozlem , Manning Carrie
Published: September 2022

Since 1990, multilateral organizations have invested in the idea that multiparty political systems are an essential part of building durable peace, and that former insurgents must be converted to political actors. To what extent does this foster longer term democracy and stability? In this paper, we focus on the role of electoral inclusion for post-rebel parties in the creation of stable party systems as one feature that supports both democratization and durable peace. We find that political integration of former insurgents in electoral politics not only serves the short-term purpose of bringing such groups “inside the tent” and smoothing the transition from war to peace. It also lays a foundation for the creation of stable party systems. We test our propositions with an original dataset and offer explanatory analysis of small set of parties.
Gaming addiction and screen time in a context of increase of internalizing symptoms: Moderation evaluation
Authors: Sousa Tavares Hunayara Lorena , Souza Costa Daniellede , Soares Antônio Alvim , Kestelman Iane , da Silva Antônio Geraldo , Malloy-Diniz Leandro Fernandes , de Paula Jonas Jardim , de Miranda Débora Marques
Published: September 2022

Children and adolescents were largely affected by the psychosocial impact of the 2019-2022 pandemic. During this time, there was an increase in internalizing symptoms, screen and internet use, and internet addiction. However, the interaction of these variables are not fully understood in a stressful time. Here, we have a repeated cross-sectional study aiming to model internalizing symptoms’ prediction depending on screen time and game addiction during the COVID-19 pandemic. Parent-reported online data were collected at three timepoints, 6 months apart from each other, from a total of 1211 participants. We found an increase in screen time, game addiction, and internalizing symptoms. Regardless of the time spent in front of screens, higher levels of game addiction were associated with higher levels of internalizing symptoms in children and adolescents. Even if participants demonstrated low screen time, if they were virtually dependent they tended to exhibit higher levels of internalizing symptoms. The same result was found in all three samples. There is a need to investigate the nature of the relationship between internet addiction and internalizing symptoms and the long lasting effects of long hours on the screen.
Pharmacokinetic interaction between raltegravir and rifampicin in an infant with HIV exposed to active TB: a case report
Authors: van der Veer Marlotte AA , Jacobs Tom G , Bukkems Laura H , Colbers Angela PH , Burger David M , Scherpbier Henriette J , Bijleveld Yuma A
Published: September 2022

We report a case of an infant with HIV receiving raltegravir granules for oral suspension and rifampicin-based TB prophylaxis. Raltegravir trough levels remained subtherapeutic and viral load increased during concurrent rifampicin therapy despite using double-dosed raltegravir. Even after rifampicin therapy, a higher dose was needed. This highlights the importance of therapeutic drug monitoring and dose adjustments of raltegravir in infants with rifampicin as comedication.
Experimental investigation on seismic behaviors of precast concrete shear walls with sleeve grouting defects
Authors: Yang Jun , Guo Tong , Wang Wei , Zhu Ruizhao
Published: September 2022

The grouted sleeve connector is one of the most widely used connections in precast concrete shear wall structures. Due to the technology limit of the assembly workers, the sleeve grouting often has defects, which could significantly weaken their practical performance. Only considering the effect of defects on the bearing capacity of the sleeve connector cannot simulate the effect of defects in actual engineering. To this end, an experiment was carried out to investigate the seismic performance of precast concrete shear walls with sleeve grouting defects. Four full-scale precast concrete shear walls with different defect levels of insufficient grouting were designed and tested under cyclic loads. The development of concrete cracking, failure mode, hysteresis features, load-bearing capacity, stiffness degradation, structural ductility and energy-dissipation capacity are analyzed to reveal the influence of the sleeve grouting defects on precast concrete shear walls. The test results indicated that with the increase of the defect level, the opening gap between the bottom of the wall and the top of the foundation beam widened, and the failure mode changed from tensile fracture of reinforcing steel bar to anchorage failure of the tensile reinforcement on the defective side. Meanwhile, as the level of grouting defects increased, the bearing capacity decreased, and the specimen failed prematurely. The effect of the grouting defects on cracking load was minor, while they had a significant influence on the yield bearing capacity, peak bearing capacity and ultimate bearing capacity. The experimental results also indicated that the grouting defects caused the weakening of the stiffness, ductility and energy dissipation of the precast concrete shear walls. The presented work could be used for defect prevention and evaluation of precast concrete shear walls with sleeve grouting defects.
The uses of small talk in social work: Weather as a resource for informally pursuing institutional tasks
Authors: Iversen Clara , Flinkfeldt Marie , Tuncer Sylvaine , Laurier Eric
Published: September 2022

Welfare organisations across the world are becoming more streamlined with less time for building relationships with clients, rendering non-governmental organisations increasingly important for welfare provision. In this paper, we investigate an understudied area in social work: the small talk through which volunteer organisations conduct social work tasks in interaction with clients. The data consist of 108 phone calls to a helpline that offers social contact to older people, recorded in 2020 in Sweden. We use conversation analysis to investigate how callers and call-takers rely on and produce informal sociability in providing support for clients. Specifically, we show that talk about the weather, a prosaic small talk topic, is interwoven with institutional work. By allowing or preventing outdoor activities, weather is a conduit for call-takers and callers to introduce and navigate norms of remaining active as an older adult. Cultural understandings and concerns about good or bad weather allow participants to move between reproducing client/service-provider asymmetries and reaching affiliative affective stances. Thus, the supposedly banal topic of the weather, known as a resource for sociability amongst the unacquainted, is, in this setting, used in ways particular to social work practice.
Proposing a research framework for urban lighting: The alertness, arousal and anxiety triad
Authors: Jedon R , Haans A , de Kort Y
Published: September 2022

The impact of street lighting on the visual tasks of pedestrians is well known, as are studies that have explored the relationship between street lighting and pedestrians’ feelings of safety. But there are other, less investigated, possible effects of light in mesopic situations. Research on street lighting for pedestrians has traditionally focused on visual performance (e.g., obstacle detection, face recognition) and people’s appraisals of the outdoor environment after dark. But the influence of concepts such as alertness and attentiveness on pedestrians’ experience and performance is not yet well researched even though this too can play an important role in pedestrians’ attention and safety. To remedy this, we are offering first a clarification of the relevant constructs – alertness, arousal and anxiety – and proposing a new theoretical framework. Possible benefits of using this conceptual framework are illustrated with an analysis of conclusions from a study conducted by Burtt. We make a case for more research on mechanisms underlying pedestrians’ attention and safety. Implications for future research, in particular the need for validating this framework, are discussed.
The Evaluation of the District Legislators’ Performance Affects Citizens’ Satisfaction with Democracy: The Hungarian Example
Authors: Papp Zsófia
Published: September 2022

Prior research reveals a relationship between various political system outputs and the citizens’ satisfaction with democracy (SWD). The current study contributes to this line of inquiry and demonstrates that the perception of the district legislators’ overall performance positively correlates with the citizens’ democratic satisfaction. The multivariate analysis of Hungarian panel data from 2018 reveals that the effect is most salient in the case of the winners of the election, and less so for the losers. Results are robust to a variety of changes in the model. The findings indicate that the focus on individual politicians and their work has the potential to increase democratic satisfaction even if representative political institutions such as parties, governments and parliaments are not able to win the citizens’ trust.
Recruitment characteristics of randomised trials in critical care: A systematic review
Authors: Ramanan Mahesh , Kumar Aashish , Billot Laurent , Myburgh John , Venkatesh Balasubramanian
Published: September 2022

Background/Aims:

To summarise the temporal trends of recruitment and methodological characteristics of critical care randomised controlled trials with the primary outcome of mortality.

Methods:

PubMed was searched for articles meeting inclusion and exclusion criteria. Randomised controlled trials, with primary outcome of mortality, of adult and paediatric critical care patients treated in an intensive care unit, were included. Neonatal intensive care unit trials, non-English publications and conference proceedings or abstracts without full-length publications were excluded. Duplicate literature search, article selection and quality assessment were performed by two reviewers with disputes resolved through discussion. Data were extracted into a custom-designed Research Electronic Data Capture database.

Results:

The search identified 67,199 records of which 230 were included. The annual number of critical care randomised controlled trials published increased gradually over a 30-year period from 0 in 1990 to 19 in 2014 with stabilisation at 8–11 between 2015 and 2020. Twenty-seven percent of randomised controlled trials were low risk in all categories using the Cochrane Risk of Bias tool. Methodological characteristics such as registration on clinical trials registries and data safety monitoring committee presence significantly (p < 0.001) increased over time. The median recruitment was 376 patients (interquartile range 125–895) with significant increase (p = 0.002) from 62 (interquartile range: 33–486) in 1991 to 725 (interquartile range: 537–2600) in 2020. This was accompanied by an increase in recruitment times. Thus overall, recruitment rates did not increase. Early cessation occurred in 23% (54/230) of randomised controlled trials with no temporal trend.

Conclusion:

The number, size and some methodological qualities of critical randomised controlled trials with primary outcome of mortality have increased over time, but rates of recruitment and early cessation have been unchanged.
Navigating Representation: Reflections on the Futures of Kazakh Identity From a CLA Scenarios Process
Authors: Ramos Jose
Published: September 2022

This short essay reflects on the process of running a Causal Layered Analysis scenario exercise with the Institute for Professional Development at the Academy of Public Administration in Kazakhstan in collaboration with John Sweeney (from the then Qazaq Research Institute for Futures Studies). We worked with approximately 50 public administrators over a 3 day period, culminating in a Causal Layered Analysis scenario process that challenged and reviewed the national vision. The process surfaced fundamental dynamics and tensions in national identity and representation. The findings and process are detailed here.
Long-Term Survivorship of Cervical Spine Procedures; A Survivorship Meta-Analysis and Meta-Regression
Authors: Sarraj Mohamed , Hache Philip , Foroutan Farid , Oitment Colby , Marion Travis E. , Guha Daipayan , Pahuta Markian
Published: September 2022

Study Design

Systematic Review

Objectives

To conduct a meta-analysis on the survivorship of commonly performed cervical spine procedures to develop survival function curves for (i) second surgery at any cervical level, and (ii) adjacent level surgery.

Methods

A systematic review of was conducted following PRISMA guidelines. Articles with cohorts of greater than 20 patients followed for a minimum of 36 months and with available survival data were included. Procedures included were anterior cervical discectomy and fusion (ACDF), cervical disc arthroplasty (ADR), laminoplasty (LAMP), and posterior laminectomy and fusion (PDIF). Reconstructed individual patient data were pooled across studies using parametric Bayesian survival meta-regression.

Results

Of 1829 initial titles, 16 citations were included for analysis. 73 811 patients were included in the second surgery analysis and 2858 patients in the adjacent level surgery analysis. We fit a Log normal accelerated failure time model to the second surgery data and a Gompertz proportional hazards model to the adjacent level surgery data. Relative to ACDF, the risk of second surgery was higher with ADR and PDIF with acceleration factors 1.73 (95% CrI: 1.04, 2.80) and 1.35 (95% CrI: 1.25, 1.46) respectively. Relative to ACDF, the risk of second surgery was lower with LAMP with deceleration factor .06 (95% CrI: .05, .07). ADR decreased the risk of adjacent level surgery with hazard ratio .43 (95% CrI: .33, .55).

Conclusions

In cases of clinical equipoise between fusion procedures, our analysis suggests superior survivorship with anterior procedures. For all procedures, laminoplasty demonstrated superior survivorship.
Exploring Future Research Agenda for Rural Mother’s Empowerment: A Study at the Intersection of Bibliometric and Systematic Literature Review
Authors: Kumar Ashutosh , Mishra Shreya
Published: September 2022

Women’s empowerment of rural mothers is little understood. Through the sequential review approach of systematic literature review (SLR)–Bibliometric–SLR, the study explores and analyses the literature with regards to ‘women-empowerment’, ‘mother’ and ‘rural’. The aim is to identify the future research agendas in the said direction. The literature extracted through the initial SLR process of inclusion and exclusion criteria from the SCOPUS database has been analysed by VOSviewer software, resulting in eight clusters of the author keywords comprising 60 papers. Co-occurrence for the author’s keywords is used for bibliometric analysis. The eight clusters are further classified into three themes. In the next level of analysis, the author keywords with low link strength and co-occurrences are examined to establish future research agendas. Finally, SLR is used again to identify the journals with an impact factor of 3.0 or more, reducing the number of articles to 30. The process identifies journals for potential future publications. Unlike conventional bibliometric and SLR studies, a sequential combination of the two techniques has been used to explore the future scope of research. Most of the current literature focuses on maternal and children’s growth and health related to women empowerment in the rural geographies of the global south. However, various other phenomena in the context of sociocultural norms and socio-economic conditions of the diverse geographies are under-researched. We identify some under-researched areas for the research possibilities and the ‘good’ journals in which such articles may be published.
Comparing Male and Female Entrepreneurs-Is the Comparison Justified? (A Qualitative Study in Indian Perspective)
Authors: Dixit Jitendra Kumar , Agarwal Sucheta , Ramadani Veland , Agrawal Vivek
Published: September 2022

In entrepreneurial literature male and female entrepreneurs are compared frequently. Female entrepreneur’s contributions are significantly appreciated but still they are lagging behind male entrepreneurs, is concluded in numerous studies. Women entrepreneurs have diverse motives in comparison to male while engaging in business activities. This study builds on qualitative approach and responses of 22 female entrepreneurs belonging to different industries/domains of Uttar Pradesh (UP), India were collected through face to face in-depth interviews which were analyzed afterwards as per the identified themes. The outcome has concluded that undoubtedly women are made for entrepreneurship but their comparison with male entrepreneurs is completely unjustified; even if researchers are interested, a discrete and self-reliant framework incorporating all possible challenges faced especially by women entrepreneurs should be utilized for better in-depth evaluation of their performance and productivity. Further, the outcome can also be utilized by educational and training institutions, policymakers, researchers and other stakeholders to create a more conducive environment for female entrepreneurs in male-dominant entrepreneurial world.
Education in a VUCA-driven World: Salient Features of an Entrepreneurial Pedagogy
Authors: Panthalookaran Varghese
Published: September 2022

Rendering learners future-ready has always been one of the primary purposes of education. It makes a critical appreciation of the emerging societal scenarios a necessary prerequisite for defining essential features of the conduct of education at any age. VUCA is an acronym that describes some salient features of modern day, characterized by Volatility, Uncertainty, Complexity and Ambiguity. VUCA exerts its influence on every field of human activity, including education. VUCA may also be interpreted in terms of quantity and quality of information, which make turbulent transitions in a globalized and digitalized world. The current article explores different responses toward VUCA and identifies the best-fit response for a VUCA-driven world of information. It also investigates different aspects of intellectual formation of the new generation of learners, that shall equip them to conduct their lives and careers in a VUCA-driven world. The article concludes by sketching a blueprint for a pedagogy of the digital natives founded on their very intrinsic motivations for learning. An entrepreneurial pedagogy may help new generation learners develop an entrepreneurial mindset in them, making them future-ready.
ER Membrane Contact Sites: Key Platforms for Biogenesis of RNA-Containing Extracellular Vesicles
Authors: Barman Bahnisikha , Renee Dawson T. , Weaver Alissa M.
Published: September 2022

The mechanisms by which cytoplasmic cargoes such as RNAs are incorporated into extracellular vesicles (EVs) are poorly understood. In a recent article published in Developmental Cell, we describe a novel function of endoplasmic reticulum membrane contact sites (ER MCS) in regulating biogenesis of RNA-containing EVs (Barman et al., 2022). We identified the ER MCS tether protein VAP-A and the ceramide transporter CERT as key drivers of this process. VAP-A depletion and overexpression produced corresponding changes in the overall number and RNA content of secreted EVs. Further sub-fractionation of small EVs from VAP-A depleted cells revealed a distinct loss in a specific subset of dense, RNA-loaded small EVs that are critical for the transfer of miR-100 to recipient cells. Cell imaging data confirmed the loss of RNA and RNA binding proteins (RBPs) in VAP-A-knockdown multivesicular bodies. Lipid analysis of VAP-A-knockdown EVs revealed decreases in ceramides, which are known to affect EV biogenesis. Depletion of the ceramide transfer protein CERT, which interacts with its binding partner VAP-A at ER MCS, leads to similar defects in EV number and RNA content as VAP-A-knockdown. These data suggest a model for ER MCS as platforms for biogenesis of a key EV population via ceramide transfer and RNA loading.
Exploring the Effectiveness of Legislation Combating Digital Non-consensual Sexually Explicit Image Distribution
Authors: Cole Tessa , Cole Dallas
Published: September 2022

Non-consensual porn distribution is the dissemination of sexually explicit images and/or photos without the consent of the individual featured in them. The literature suggests that non-consensual porn distribution is frequent with victims who experience similar negative effects to that of intimate partner violence (IPV) victims. It was estimated in 2014 that at least 3,000 pornographic websites contained a ‘revenge’ porn category of images. Victims who did not consent to the dissemination of their digital sexually explicit images have reported similar experiences of those who have been victims of IPV. However the research suggests that the negative effects (e.g., emotional, psychological and physical experiences) on non-consensual porn distribution victims may be heightened because of the revictimization that occurs each time the victims’ images and/or information is repeatedly observed or shared online, which has been attributed to victims of child abuse who have maladaptive responses to their abuse. Research suggests current legislation has not assisted victims in combating and prosecuting the perpetrators who disseminate the victim’s digital porn without the victim’s consent. Additionally, US federal legislation, like Section 230 of the Communication Decency Act, arguably enables the digital distribution of victims’ non-consensual pornographic images and videos. Utilizing a content analysis, the current study analyses digital non-consensual porn distribution court cases in the USA, including Washington, DC, to assess the prevalence and effects of non-consensual porn distribution court cases. The review highlights the lack of diversity in the use of types of non-consensual porn distribution state statutes and the similarities between victims of IPV (e.g., rape) and non-consensual porn distribution prosecution that often leads to negative outcomes for victims.
Inflammatory macrophages interrupt osteocyte maturation and mineralization via regulating the Notch signaling pathway
Authors: Wang Shengfang , Xiao Lan , Prasadam Indira , Crawford Ross , Zhou Yinghong , Xiao Yin
Published: September 2022

Background

It is well-known that both macrophages and osteocytes are critical regulators of osteogenesis and osteoclastogenesis, yet there is limited understanding of the macrophage-osteocyte interaction, and how their crosstalk could affect bone homeostasis and mineralization. This research therefore aims to investigate the effects of macrophage polarization on osteocyte maturation and mineralization process.

Methods

A macrophage-derived conditioned medium based osteocyte culture was set up to investigate the impact of macrophages on osteocyte maturation and terminal mineralization. Surgically induced osteoarthritis (OA) rat model was used to further investigate the macrophage-osteocyte interaction in inflammatory bone remodeling, as well as the involvement of the Notch signaling pathway in the mineralization process.

Results

Our results identified that osteocytes were confined in an immature stage after the M1 macrophage stimulation, showing a more rounded morphology, higher expression of early osteocyte marker E11, and significantly lower expression of mature osteocyte marker DMP1. Immature osteocytes were also found in inflammatory bone remodeling areas, showing altered morphology and mineralized structures similar to those observed under the stimulation of M1 macrophages in vitro, suggesting that M1 macrophages negatively affect osteocyte maturation, leading to abnormal mineralization. The Notch signaling pathway was found to be down regulated in M1 macrophage-stimulated osteocytes as well as osteocytes in inflammatory bone. Overexpression of the Notch signaling pathway in osteocytes showed a significant circumvention on the negative effects from M1 macrophage.

Conclusion

Taken together, our findings provide valuable insights into the mechanisms involved in abnormal bone mineralization under inflammatory conditions.
Protective effect of α7 nicotinic acetylcholine receptor activation on experimental colitis and its mechanism
Authors: Pu Wenyuan , Su Zhenzi , Wazir Junaid , Zhao Chen , Wei Lulu , Wang Ranran , Chen Qiyi , Zheng Saifang , Zhang Shaoyi , Wang Hongwei
Published: September 2022

Background

Inflammatory bowel disease (IBD) is a common chronic remitting disease with no satisfactory treatment. The aim of this study was to investigate the protective effect of α7 nicotinic acetylcholine receptor (α7nAChR), and to determine the underlying mechanism of its activity.

Methods

The expression and distribution of α7nAChR in the intestinal tissue of patients with ulcerative colitis and Crohn’s disease were analyzed. The effects of vagal excitation on murine experimental colitis were investigated. The colitis model was induced in C57BL/6 mice by the administration of 3% dextran sulfate sodium (DSS). The therapeutic group received treatment with the α7nAChR agonist PNU-282987 by intraperitoneal injection.

Results

Our results showed that there was significantly increased expression of α7nAChR in colitis and Crohn’s disease intestinal tissue, and its expression was mainly located in macrophages and neutrophils, which were extensively infiltrated in the disease status. Treatment with an α7nAChR agonist potently ameliorated the DSS-induced illness state, including weight loss, stool consistency, bleeding, colon shortening, and colon histological injury. α7nAChR agonist exerted anti-inflammatory effects in DSS colitis mice by suppressing the secretion of multiple types of proinflammatory factors, such as IL6, TNFα, and IL1β, and it also inhibited the colonic infiltration of inflammatory cells by blocking the DSS-induced overactivation of the NF-κB and MAPK signaling pathways. Mechanistically, activation of α7nAChR decreased the number of infiltrated M1 macrophages in the colitis intestine and inhibited the phagocytosis ability of macrophages, which were activated in response to LPS stimulation.

Conclusion

Thus, an α7nAChR agonist ameliorated colonic pathology and inflammation in DSS-induced colitis mice by blocking the activation of inflammatory M1 macrophages.
Spermidine protects against acute kidney injury by modulating macrophage NLRP3 inflammasome activation and mitochondrial respiration in an eIF5A hypusination-related pathway
Authors: Li Xianzhi , Zhou Xiaojun , Liu Xigao , Li Xiaoyun , Jiang Xianzhou , Shi Benkang , Wang Shuo
Published: September 2022

Background

Acute kidney injury (AKI) is still a critical problem in clinical practice, with a heavy burden for national health system around the world. It is notable that sepsis is the predominant cause of AKI for patients in the intensive care unit and the mortality remains considerably high. The treatment for AKI relies on supportive therapies and almost no specific treatment is currently available. Spermidine is a naturally occurring polyamine with pleiotropic effects. However, the renoprotective effect of spermidine and the underlying mechanism remain elusive.

Methods

We employed mice sepsis-induced AKI model and explored the potential renoprotective effect of spermidine in vivo with different administration time and routes. Macrophage depleting was utilized to probe the role of macrophage. In vitro experiments were conducted to examine the effect of spermidine on macrophage cytokine secretion, NLRP3 inflammasome activation and mitochondrial respiration.

Results

We confirmed that spermidine improves AKI with different administration time and routes and that macrophages serves as an essential mediator in this protective effect. Meanwhile, spermidine downregulates NOD-like receptor protein 3 (NLRP3) inflammasome activation and IL-1 beta production in macrophages directly. Mechanically, spermidine enhances mitochondrial respiration capacity and maintains mitochondria function which contribute to the NLRP3 inhibition. Importantly, we showed that eukaryotic initiation factor 5A (eIF5A) hypusination plays an important role in regulating macrophage bioactivity.

Conclusions

Spermidine administration practically protects against sepsis-induced AKI in mice and macrophages serve as an essential mediator in this protective effect. Our study identifies spermidine as a promising pharmacologic approach to prevent AKI.
Novel eIF4A1 inhibitors with anti‐tumor activity in lymphoma
Authors: Kayastha Forum , Herrington Noah B. , Kapadia Bandish , Roychowdhury Anirban , Nanaji Nahid , Kellogg Glen E. , Gartenhaus Ronald B.
Published: September 2022

Background

Deregulated translation initiation is implicated extensively in cancer initiation and progression. It is actively pursued as a viable target that circumvents the dependency on oncogenic signaling, a significant factor in current strategies. Eukaryotic translation initiation factor (eIF) 4A plays an essential role in translation initiation by unwinding the secondary structure of messenger RNA (mRNA) upstream of the start codon, enabling active ribosomal recruitment on the downstream genes. Several natural product molecules with similar scaffolds, such as Rocaglamide A (RocA), targeting eIF4A have been reported in the last decade. However, their clinical utilization is still elusive due to several pharmacological limitations. In this study we identified new eIF4A1 inhibitors and their possible mechanisms.

Methods

In this report, we conducted a pharmacophore-based virtual screen of RocA complexed with eIF4A and a polypurine RNA strand for novel eIF4A inhibitors from commercially available compounds in the MolPort Database. We performed target-based screening and optimization of active pharmacophores. We assessed the effects of novel compounds on biochemical and cell-based assays for efficacy and mechanistic evaluation.

Results

We validated three new potent eIF4A inhibitors, RBF197, RBF 203, and RBF 208, which decreased diffuse large B-cell lymphoma (DLBCL) cell viability. Biochemical and cellular studies, molecular docking, and functional assays revealed that thosenovel compounds clamp eIF4A into mRNA in an ATP-independent manner. Moreover, we found that RBF197 and RBF208 significantly depressed eIF4A-dependent oncogene expression as well as the colony formation capacity of DLBCL. Interestingly, exposure of these compounds to non-malignant cells had only minimal impact on their growth and viability.

Conclusions

Identified compounds suggest a new strategy for designing novel eIF4A inhibitors.
Variational Wavelet Ensemble Empirical (VWEE) Denoising Method for Electromagnetic Ultrasonic Signal in High-Temperature Environment with Low-Voltage Excitation
Authors: Zhou Jinjie , Zhao Shuaijie , Zheng Yang , Shen Xingquan , Zhang Jitang
Published: September 2022

Low excitation voltage for an electromagnetic acoustic transducer (EMAT) is necessary for the petrochemical equipment and facilities inspection, which work at high-temperatures, to avoid potential explosion. However, low excitation voltage causes low signal-to-noise ratio (SNR) signals that are difficult to extract features, especially in a high-temperature environment, which causes high noise. In this study, a denoising method called the variational wavelet ensemble empirical (VWEE) method was proposed by combining the advantages of the variational modal decomposition (VMD), wavelet threshold (WT) denoising, and ensemble empirical mode decomposition (EEMD) methods. To validate the VWEE method, EMAT signals obtained in the temperature range of 25 to 700 °C were analyzed. The results show that, compared with VMD, WT and empirical mode decomposition denoising methods, the SNR of proposed method is improved more than two times. The VWEE method dramatically improved the SNR of a high-temperature EMAT signal and enhanced the accuracy of defect echos extraction.
Osteoporosis pathogenesis and treatment: existing and emerging avenues
Authors: Liang Bo , Burley George , Lin Shu , Shi Yan-Chuan
Published: September 2022

Osteoporotic fractures lead to increased disability and mortality in the elderly population. With the rapid increase in the aging population around the globe, more effective treatments for osteoporosis and osteoporotic fractures are urgently required. The underlying molecular mechanisms of osteoporosis are believed to be due to the increased activity of osteoclasts, decreased activity of osteoblasts, or both, which leads to an imbalance in the bone remodeling process with accelerated bone resorption and attenuated bone formation. Currently, the available clinical treatments for osteoporosis have mostly focused on factors influencing bone remodeling; however, they have their own limitations and side effects. Recently, cytokine immunotherapy, gene therapy, and stem cell therapy have become new approaches for the treatment of various diseases. This article reviews the latest research on bone remodeling mechanisms, as well as how this underpins current and potential novel treatments for osteoporosis.
The O-glycosylating enzyme GALNT2 acts as an oncogenic driver in non-small cell lung cancer
Authors: Hu Qing , Tian Tian , Leng Yahui , Tang Yuanhui , Chen Shuang , Lv Yueyao , Liang Jingyin , Liu Yanni , Liu Tianhui , Shen Li , Dong Xiaoxia
Published: September 2022

Background

N-Acetylgalactosaminyltransferases (GALNTs), the enzymes that initiate mucin-type O-glycosylation, are closely associated with tumor occurrence and progression. However, a comprehensive analysis of GALNTs in non-small cell lung cancer (NSCLC) is lacking.

Methods

The expression profiles and prognostic values of the GALNT family members in NSCLC were analyzed using publicly available databases. Gain- and loss-of-function experiments were applied to assess the biological function of GALNT2 in NSCLC. High-throughput sequencing and bioinformatics approaches were employed to uncover the regulatory mechanism of GALNT2.

Results

Among the family members of GALNTs, only GALNT2 was frequently overexpressed in NSCLC tissues and was positively correlated with poor prognosis. In vitro assays showed that GALNT2 knockdown repressed NSCLC cell proliferation, migration, and invasion, but induced apoptosis and cell cycle arrest. Correspondently, GALNT2 overexpression exerted the opposite effects. In vivo experiments demonstrated that knockdown of GALNT2 restrained tumor formation in nude mice. Mechanistic investigations revealed that GALNT2 modified the O-glycosylation of ITGA5 and affected the activation of the PI3K/Akt and MAPK/ERK pathways. Further studies showed that miR-30d was a negative regulator of GALNT2.

Conclusions

These findings suggest that GALNT2 is an oncogene in NSCLC and has the potential as a target for NSCLC therapy.
Double Narrowband Induced Perfect Absorption Photonic Sensor Based on Graphene–Dielectric–Gold Hybrid Metamaterial
Authors: Liu Zhimin , Zhuo Shanshan , Zhou Fengqi , Zhang Xiao , Qin Yipeng , Luo Xin , Ji Cheng , Yang Guangxin
Published: September 2022

Double narrowband induced perfect absorption in the terahertz region is achieved in a graphene–dielectric–gold hybrid metamaterial, whose physical mechanism is analyzed using the coupled-mode theory (CMT), which agreed well with the finite-difference time-domain (FDTD) simulation. This study found that the Fermi level of graphene can be adjusted to improve the absorptivity when the refractive index (RI) nd of the chosen dielectric cannot achieve a good absorption effect. In addition, the blue shift of absorption spectrum can be used in the design of dual-frequency electro-optical switches, of which the modulation degree of amplitude (MDA) can reach as high as 94.05% and 93.41%, indicating that this is a very promising electro-optical switch. Most significantly, the RI sensing performance is investigated, which shows an ultra-high absorption sensitivity SA = 4.4°/RIU, wavelength sensitivity Sλ = 9.8°/RIU, and phase shift sensitivity Sφ = 2691°/RIU. At last, an interesting finding is that the two peaks (R1 and R2) of plasmon-induced absorption (PIA) show different polarization characteristics (insensitive or sensitive) to the incident light angle; this polarization-sensitive is particularly important for the PIT/PIA-based optical polarizers. Undoubtedly, this paper is of great significance to the research and design of terahertz photonic devices and sensors.
Urethral duplication associated with complex chordee: a narrative review of literature and report of a case
Authors: Nnabugwu Ikenna I. , Onoh Wilson C. , Ukekwe Francis I. , Nwosu Ekeoma O. , Iwenofu Chukwunonso A. , Anakebe Ikenna N. , Nnabugwu Chinwe A. , Onuh Augustine C.
Published: September 2022

Background

Urethral duplication (UD) is reportedly rare. It is rarer in females. Knowledge on this anomaly comes from isolated report of cases. The aim of this review is to summarize information available on this anomaly thereby revealing gaps in knowledge, and to appropriately situate a recently managed case.

Methods

Publications on UD in English language from 2001 to 2021 were searched for in the literature. Of importance were age at presentation, class of UD, nature of associated penile deformity and other structural anomalies. Available information was used to synthesize opinions after descriptive analyses using SPSS® version 21 (IBM Co., Armonk, NY, USA). In addition, a recently managed case of UD was reported and appropriately situated in the discourse.

Result

In all, 115 articles met the inclusion criteria. Majority (75.7%) were individual case reports, while the rest were retrospective review of case series. These provided a total of 269 reported cases. Of this lot, 38 cases were excluded because they either had no Effmann’s class or were not described well enough for an Effmann’s class to be assigned. Ultimately, 231 cases formed the basis for this review. Male to female ratio was 12:1. Types III and IIB had more females. Types IIA 2 (26.0%), IIA 2 “Y” (26.4%) and IA (22.5%) were frequently reported. About 61.8% males and 68.4% females had no associated defects. Isolated dorsal chordee was prevalent (7.1%), especially among type IA (16.7%) UD. Reported in 10.4%, vesicoureteric reflux may not be attributable always to high pressure voiding.

A boy who presented at the age of 18 years with Effmann type IA UD and an associated complex chordee of the penile shaft was reported. The complex nature of the chordee adds to the challenge of explaining associated penile defects in UD.

Conclusion

UD is rare, but reported from all parts of the globe. There are a number of associated defects involving the external genitalia and other organs reported in UD in the male. The mechanisms of these defects are yet to be fully understood.
International single-step SNPBLUP beef cattle evaluations for Limousin weaning weight
Authors: Bonifazi Renzo , Calus Mario P. L. , ten Napel Jan , Veerkamp Roel F. , Michenet Alexis , Savoia Simone , Cromie Andrew , Vandenplas Jérémie
Published: September 2022

Background

Compared to national evaluations, international collaboration projects further improve accuracies of estimated breeding values (EBV) by building larger reference populations or performing a joint evaluation using data (or proxy of them) from different countries. Genomic selection is increasingly adopted in beef cattle, but, to date, the benefits of including genomic information in international evaluations have not been explored. Our objective was to develop an international beef cattle single-step genomic evaluation and investigate its impact on the accuracy and bias of genomic evaluations compared to current pedigree-based evaluations.

Methods

Weaning weight records were available for 331,593 animals from seven European countries. The pedigree included 519,740 animals. After imputation and quality control, 17,607 genotypes at a density of 57,899 single nucleotide polymorphisms (SNPs) from four countries were available. We implemented two international scenarios where countries were modelled as different correlated traits: an international genomic single-step SNP best linear unbiased prediction (SNPBLUP) evaluation (ssSNPBLUPINT) and an international pedigree-based BLUP evaluation (PBLUPINT). Two national scenarios were implemented for pedigree and genomic evaluations using only nationally submitted phenotypes and genotypes. Accuracies, level and dispersion bias of EBV of animals born from 2014 onwards, and increases in population accuracies were estimated using the linear regression method.

Results

On average across countries, 39 and 17% of sires and maternal-grand-sires with recorded (grand-)offspring across two countries were genotyped. ssSNPBLUPINT showed the highest accuracies of EBV and, compared to PBLUPINT, led to increases in population accuracy of 13.7% for direct EBV, and 25.8% for maternal EBV, on average across countries. Increases in population accuracies when moving from national scenarios to ssSNPBLUPINT were observed for all countries. Overall, ssSNPBLUPINT level and dispersion bias remained similar or slightly reduced compared to PBLUPINT and national scenarios.

Conclusions

International single-step SNPBLUP evaluations are feasible and lead to higher population accuracies for both large and small countries compared to current international pedigree-based evaluations and national evaluations. These results are likely related to the larger multi-country reference population and the inclusion of phenotypes from relatives recorded in other countries via single-step international evaluations. The proposed international single-step approach can be applied to other traits and breeds.
Assessment of genotyping array performance for genome-wide association studies and imputation in African cattle
Authors: Riggio Valentina , Tijjani Abdulfatai , Callaby Rebecca , Talenti Andrea , Wragg David , Obishakin Emmanuel T. , Ezeasor Chukwunonso , Jongejan Frans , Ogo Ndudim I. , Aboagye-Antwi Fred , Toure Alassane , Nzalawahej Jahashi , Diallo Boubacar , Missohou Ayao , Belem Adrien M. G. , Djikeng Appolinaire , Juleff Nick , Fourie Josephus , Labuschagne Michel , Madder Maxime , Marshall Karen , Prendergast James G. D. , Morrison Liam J.
Published: September 2022

Background

In cattle, genome-wide association studies (GWAS) have largely focused on European or Asian breeds, using genotyping arrays that were primarily designed for European cattle. Because there is growing interest in performing GWAS in African breeds, we have assessed the performance of 23 commercial bovine genotyping arrays for capturing the diversity across African breeds and performing imputation. We used 409 whole-genome sequences (WGS) spanning global cattle breeds, and a real cohort of 2481 individuals (including African breeds) that were genotyped with the Illumina high-density (HD) array and the GeneSeek bovine 50 k array.

Results

We found that commercially available arrays were not effective in capturing variants that segregate among African indicine animals. Only 6% of these variants in high linkage disequilibrium (LD) (r2 > 0.8) were on the best performing arrays, which contrasts with the 17% and 25% in African and European taurine cattle, respectively. However, imputation from available HD arrays can successfully capture most variants (accuracies up to 0.93), mainly when using a global, not continent-specific, reference panel, which partially reflects the unusually high levels of admixture on the continent. When considering functional variants, the GGPF250 array performed best for tagging WGS variants and imputation. Finally, we show that imputation from low-density arrays can perform almost as well as HD arrays, if a two-stage imputation approach is adopted, i.e. first imputing to HD and then to WGS, which can potentially reduce the costs of GWAS.

Conclusions

Our results show that the choice of an array should be based on a balance between the objective of the study and the breed/population considered, with the HD and BOS1 arrays being the best choice for both taurine and indicine breeds when performing GWAS, and the GGPF250 being preferable for fine-mapping studies. Moreover, our results suggest that there is no advantage to using the indicus-specific arrays for indicus breeds, regardless of the objective. Finally, we show that using a reference panel that better represents global bovine diversity improves imputation accuracy, particularly for non-European taurine populations.