bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipidome profiling of human and equine neutrophil-derived extracellular vesicles and their potential contribution to the ensemble of synovial fluid-derived extracellular vesicles during joint inflammation
Authors: Varela Laura , Mol Sanne , Taanman-Kueter Esther W. , Ryan Sarah E. , Taams Leonie S. , de Jong Esther , van Weeren P. René , van de Lest Chris H.A. , Wauben Marca H.M.
Published: November 2023

The molecular signature of cell-derived extracellular vesicles (EVs) from synovial fluid (SF) offers valuable insights into the cells and molecular processes associated with joint disorders and can be exploited to define biomarkers. The signature of EVs is determined by cargo molecules and the lesser-studied lipid bilayer. We here investigated the lipidome of SF-EVs in inflamed joints derived from Rheumatoid Arthritis (RA) and Spondyloarthritis (SpA) patients, two autoimmune-driven joint diseases, and compared these signatures to the lipid profile of equine SF-EVs obtained during induced acute synovitis. Since neutrophils are primary SF-infiltrating cells during these inflammatory joint diseases, we also analyzed how inflammatory stimuli alter the lipidomic profile of human and equine neutrophil-derived EVs (nEVs)in vitroand how these signatures relate to the lipidome signatures of SF-EVs from inflamed joints. We identified neutrophil stimulation-intensity dependent changes in the lipidomic profile of nEVs with elevated presence of dihexosylceramide (lactosylceramide), phosphatidylserine, and phosphatidylethanolamine ether-linked lipid classes in human nEVs upon full neutrophil activation. In horses, levels of monohexosylceramide (glucosylceramide) increased instead of dihexosylceramide, indicating species-specific differences. The lipid profiles of RA and SpA SF-EVs were relatively similar and showed a relative resemblance with stimulated human nEVs. Similarly, the lipidome of equine synovitis-derived SF-EVs closer resembled the one of stimulated equine nEVs. Hence, lipidome profiling can provide insights into the contribution of nEVs to the heterogeneous pool of SF-EVs, deepening our understanding of inflammatory joint diseases and revealing molecular changes in joint homeostasis, which can lead to the development of more precise disease diagnosis and treatment strategies.
Deep learning and direct sequencing of labeled RNA captures transcriptome dynamics
Authors: Martinek Vlastimil , Martin Jessica , Belair Cedric , Payea Matthew J , Malla Sulochan , Alexiou Panagiotis , Maragkakis Manolis
Published: November 2023

Quantification of the dynamics of RNA metabolism is essential for understanding gene regulation in health and disease. Existing methods rely on metabolic labeling of nascent RNAs and physical separation or inference of labeling through PCR-generated mutations, followed by short-read sequencing. However, these methods are limited in their ability to identify transient decay intermediates or co-analyze RNA decay with cis-regulatory elements of RNA stability such as poly(A) tail length and modification status, at single molecule resolution. Here we use 5-ethynyl uridine (5EU) to label nascent RNA followed by direct RNA sequencing with nanopores. We developed RNAkinet, a deep convolutional and recurrent neural network that processes the electrical signal produced by nanopore sequencing to identify 5EU-labeled nascent RNA molecules. RNAkinet demonstrates generalizability to distinct cell types and organisms and reproducibly quantifies RNA kinetic parameters allowing the combined interrogation of RNA metabolism and cis-acting RNA regulatory elements.
Single-cell transcriptomic and neuropathologic analysis reveals dysregulation of the integrated stress response in progressive supranuclear palsy
Authors: Whitney Kristen , Song Won-Min , Sharma Abhijeet , Dangoor Diana K. , Farrell Kurt , Krassner Margaret M. , Ressler Hadley W. , Christie Thomas D. , Walker Ruth H. , Nirenberg Melissa J. , Zhang Bin , Frucht Steven J. , Riboldi Giulietta M , Crary John F. , Pereira Ana C.
Published: November 2023

Progressive supranuclear palsy (PSP) is a sporadic neurodegenerative tauopathy variably affecting brainstem and cortical structures and characterized by tau inclusions in neurons and glia. The precise mechanism whereby these protein aggregates lead to cell death remains unclear. To investigate the contribution of these different cellular abnormalities to PSP pathogenesis, we performed single-nucleus RNA sequencing and analyzed 45,559 high quality nuclei targeting the subthalamic nucleus and adjacent structures from human post-mortem PSP brains with varying degrees of pathology compared to controls. Cell-type specific differential expression and pathway analysis identified both common and discrete changes in numerous pathways previously implicated in PSP and other neurodegenerative disorders. This included EIF2 signaling, an adaptive pathway activated in response to diverse stressors, which was the top activated pathway in vulnerable cell types. Using immunohistochemistry, we found that activated eIF2α was positively correlated with tau pathology burden in vulnerable brain regions. Multiplex immunofluorescence localized activated eIF2α positivity to hyperphosphorylated tau (p-tau) positive neurons and ALDH1L1-positive astrocytes, supporting the increased transcriptomic EIF2 activation observed in these vulnerable cell types. In conclusion, these data provide insights into cell-type-specific pathological changes in PSP and support the hypothesis that failure of adaptive stress pathways play a mechanistic role in the pathogenesis and progression of PSP.
Early life pain alters the response to an immune challenge in adult male and female rats
Authors: Gomez Morgan G. , Macik Melani , Harder Hannah J. , Pandit Malika H. , Murphy Anne Z.
Published: November 2023

Infants born prematurely are more likely to be admitted to the Neonatal Intensive Care Unit (NICU) where they experience upwards of 10-18 painful procedures each day, often with no anesthesia or analgesia. Pre-clinical studies have shown that early exposure to pain disrupts CNS development in multiple ways that persist into adulthood, with similar findings observed clinically. The present study explores the effects of neonatal injury on the response to an immune challenge in adulthood. Male and female rats were exposed to a short-term inflammatory insult induced by intraplantar administration of 1% carrageenan (CGN) on the day of birth (P0). In adulthood (P60-P90), rats were implanted with Thermicron iButtons to monitor core body temperature; 14 days later, lipopolysaccharide (LPS) was administered to elicit an immune response. Rats were sacrificed after 24 hours or at their peak fever point and brain tissue collected for immunohistochemical analysis. LPS administration resulted in a significantly greater febrile response in males and females exposed to early life pain compared to controls. Immunohistological analysis revealed sex and treatment differences in Fos labeling in several brain regions, including the PVN. No sex or treatment differences were observed for VGat, VGlut2, or EP3R expression in the MnPO; however, all three increased significantly following LPS administration. Together, these studies are consistent with clinical studies reporting children experiencing unresolved pain during the perinatal period show an increased severity of sickness behavior and altered immune signaling following exposure to a pathogen and will provide a foundation for future studies examining the biological underpinnings.
Monocyte subpopulations exhibit distinct TNF-dependent aging signatures
Authors: Bentz Anna Woo , Gutierrez Monica , Loukov Dessi , Eckman Blair , Gadhvi Gaurav , Cuda Carla , Bowdish Dawn M. E. , Winter Deborah R.
Published: November 2023

Monocytes are a key cell type contributing to age-associated inflammation or inflammaging. Since monocytes have the potential to enter circulation and differentiate into macrophages in tissues, they are capable of having a systemic effect on health. Here, we characterize the effect of aging on the transcriptional regulation of monocyte subpopulations in the bone marrow. We find that aging classical (Ly6c high) and non-classical (Ly6c low) monocytes exhibit distinct transcriptional profiles. These were associated with changes to the epigenomic landscape driven by the activity of specific TFs that often had opposing effects in monocyte subpopulations. Next, we determined that the aging signature was diminished in TNF-KO mice indicating that monocytes are altered in a TNF-dependent manner. Finally, we found that a subset of the aging signature was triggered by TNF over-expression. Together, our results implicate key factors driving age-associated changes to the transcriptional regulation of monocyte subpopulations. This study provides a better understanding of the impact of aging on monocytes and identifies targets for future investigation aiming to improve health in aging.
Retinal neurons establish mosaic patterning by excluding homotypic somata from their dendritic territory
Authors: Kozlowski Christopher , Hadyniak Sarah E. , Kay Jeremy N.
Published: November 2023

In vertebrate retina, individual neurons of the same type are distributed regularly across the tissue in a pattern known as a mosaic. Establishment of mosaics during development requires cell-cell repulsion among homotypic neurons, but the mechanisms underlying this repulsion remain unknown. Here we show that two mouse retinal cell types, OFF and ON starburst amacrine cells, establish mosaic spacing by using their dendritic arbors to repel neighboring homotypic somata. Using newly-generated transgenic tools and single cell labeling, we identify a transient developmental period when starburst somata receive extensive contacts from neighboring starburst dendrites; these serve to exclude somata from settling within the neighbor’s dendritic territory. Dendrite-soma exclusion is mediated by MEGF10, a cell-surface molecule required for starburst mosaic patterning. Our results implicate dendrite-soma exclusion as a key mechanism underlying starburst mosaic spacing, and suggest that this could be a general mechanism for mosaic patterning across many cell types and species.
Convergent relaxation of molecular constraint in mammalian herbivores highlights the roles of liver and kidney functions in carnivory
Authors: Pollard Matthew D. , Meyer Wynn K. , Puckett Emily E.
Published: November 2023

Mammalia comprises a great diversity of diet types and associated adaptations. An understanding of the genomic mechanisms underlying these adaptations may offer insights for improving human health. Comparative genomic studies of diet that employ taxonomically restricted analyses or simplified diet classifications may suffer reduced power to detect molecular convergence associated with diet evolution. Here, we used a quantitative carnivory score—indicative of the amount of animal protein in the diet—for 80 mammalian species to detect significant correlations between the relative evolutionary rates of genes and changes in diet. We identified six genes—ACADSB,CLDN16,CPB1,PNLIP,SLC13A2, andSLC14A2—that experienced significant changes in evolutionary constraint alongside changes in carnivory score, becoming less constrained in lineages evolving more herbivorous diets. We further considered the biological functions associated with diet evolution and observed that pathways related to amino acid and lipid metabolism, biological oxidation, and small molecule transport experienced reduced purifying selection as lineages became more herbivorous. Liver and kidney functions showed similar patterns of constraint with dietary change. Our results indicate that, in highly carnivorous lineages, selection acts on the liver and kidneys to maintain sufficient metabolism and excretion of substances found in excess in carnivorous diets. These biological functions become less important with the evolution of increasing herbivory, so experience a relaxation of constraint in more herbivorous lineages.
Developing the framework of blockchain-enabled agri-food supply chain
Authors: Sharma Anandika , Bhatia Tarunpreet , Singh Rohit Kumar , Sharma Anupam
Published: November 2023

Purpose

The food supply chain has faced many challenges due to its complex and complicated nature. Blockchain technology is one of the mechanisms used to improve agri-food supply chain processes by evolving organization capabilities. A study is being conducted to scrutinize the adoption of blockchain technology in the agri-food supply chain through the lens of the operational capability approach. It further makes an attempt to identify the capabilities of blockchain to improve supply chain processes.

Design/methodology/approach

The qualitative research method with semi-structured interviews was used to gather information from experts and professionals in the food supply chain and blockchain technology. The authors have adopted a systematic approach of coding using open, axial and selective methods to depict and identify the themes that represent the blockchain-enabled agri-food supply chain. The data were collected from 32 interviews of selected participants.

Findings

The result shows five critical areas where blockchain can come up to enhance the agri-food supply chain performance by providing traceability, transparency, information security, transactions, and trust and quality. Further, the study reveals that blockchain will provide safety, lower the cost of transactions and can create trust among users to communicate within the whole supply chain without the intervention of a third party. This study demonstrated that the capabilities need to be considered when introducing technology into the practice.

Research limitations/implications

The study implies thought-provoking implications for bridging the theory-practice gap by examining the empirical data to demonstrate how the operational capabilities of blockchain technology further strengthen the agri-food supply chain. Additionally, this study provides some suggestions for utilizing the results and proposes a framework to understand more about blockchain use cases in the agri-food supply chain as well as extend the application of blockchain using an operational capability approach for future academic researchers in this area.

Practical implications

This study presented some more important managerial implications which reveal that the majority of organisations were in the initial stages of adoption process of blockchain technology. Further, the positive influence of managers and IT experts can help the information technology companies (IT) and stakeholders for developing and promoting blockchain solutions in the agri-food supply chain. The important implication of blockchain enabled agri-food supply chain is to maintain information security and incresae supply chain performance.

Originality/value

The study shows the operational capabilities of agri-food supply chain using blockchain technology. Blockchain can contribute in enhancing the agri-food supply chain to increase traceability and transparency and helps to reduce the risk of disruptions.
Why are you in disaster studies? Liberating future scholars from oppressive disaster science
Authors: Marchezini Victor
Published: November 2023

Purpose

The question of “why we are in disaster studies” can be essential to reflect on discourses and practices – as students, researchers and professors – in constituting an oppressive disaster science and finding ways to liberate from it.

Design/methodology/approach

This paper is based on autobiographical research and institutional ethnography to observe and analyze the discourses and practices about career trajectories as students, researchers and professors in disaster studies.

Findings

The paper provides some categories, concepts, theoretical approaches and lived experiences helpful for discussing ways of liberating disaster studies, such as public sociology of disaster.

Originality/value

Few papers have focused on professional trajectories in disaster studies, bringing insights from public sociology and questioning oppressive disaster science.
An analysis of space efficiency in Asian supertall towers
Authors: Ilgın Hüseyin Emre
Published: November 2023

Purpose

Supertall towers (300 m+) offer a viable solution to the increasing demand for housing and commercial space caused by rapid urban growth, migration from rural to urban areas and economic expansion in Asia. In this particular context, the efficient utilization of space becomes a crucial factor in the design process for Asian skyscrapers as they seek to address the changing socioeconomic landscape. This study will provide valuable guidance, especially to architectural and structural designers in the pursuit of sustainable development for Asian skyscrapers by analyzing space efficiency.

Design/methodology/approach

The methodology employed in this paper involved a case study approach to gather data on 75 Asian supertall towers in order to examine space efficiency.

Findings

Findings of the research can be summarized as follows: (1) the average space efficiency of these towers was 67.5%, ranging from a minimum of 55% to a maximum of 82%; (2) the average proportion of the core area to the gross floor area (GFA) was 29.5%, with values ranging from 14% to 38%; (3) the majority of Asian skyscrapers exhibited a tapered form and adopted a central core typology, which catered to mixed-use and office purposes; (4) the most frequently utilized structural system was a combination of composite and outriggered frames; (5) space efficiency tended to decrease as the height of the tower increased; and (6) there was no noteworthy difference in the impact of various load-bearing systems and building forms on space efficiency.

Originality/value

There is a noticeable lack of extensive research into space efficiency in supertall towers in Asia, which serves as a hub for skyscrapers. This study seeks to fill this substantial gap in the current scientific literature.
Educators' core competencies: a study of university-led B-schools of South Asia
Authors: Maheshkar Chandan
Published: November 2023

Purpose

The study aimed to explore the core competencies that make educators competent in delivering and achieving the purpose of business/management education effectively.

Design/methodology/approach

An exploratory-cum-descriptive approach has been used. Educators at different academic levels in university-led B-schools were the participants of this study. For data collection, a structured questionnaire was developed and implemented.

Findings

This study has explored ten core competencies that educators must possess. These competencies have been described based on their attributes and relevance in an educator's academic role.

Research limitations/implications

This study was limited to university-led B-schools of South Asia, thus further validation may more adequately generalize the findings.

Practical implications

This study is raising awareness of the current state of educators in university-led B-schools in South Asian countries and the need for educator competencies toward responsible management education. This study would help educators to develop core competencies, and university-led B-schools to make and manage a system for their educators to keep them competent and performing.

Originality/value

Business/management education is expected to offer the required competencies and opportunities to learn the intricacies of business and management, so students can readily enter into corporate life. It exhibits the significance of educators' competencies. University-led South Asian institutions have seldom tried to develop a standardized framework for the sensitization and development of their educators. It is a key challenge to identify, understand and define a diverse range of competencies and methods of competency development.
Corporate climate change disclosures and capital structure strategies: evidence from Türkiye
Authors: Gahramanova Gultakin , Kutlu Furtuna Özlem
Published: November 2023

Purpose

There has been an increase in research examining whether and how companies disclose climate change impacts and how these disclosures influence capital structure strategies in recent years. However, prior literature has generally focused on developed countries. This paper proposes to examine the impact of voluntary climate change disclosures on corporate financing decisions in an emerging economy.

Design/methodology/approach

The dataset includes 335 firm-year observations listed in the Borsa Istanbul (BIST) 100 manufacturing industry firms that participated in the Carbon Disclosure Project (CDP) questionnaire from 2016 to 2020, characterized by high public awareness of greenhouse gas emissions in Turkey. To accomplish this aim, two models have been constructed that link capital structure strategies with voluntary corporate climate change disclosures while controlling for firm-level attributes in terms of size, profitability, market value and free float ratio (FFR).

Findings

The significant and negative relationship between the voluntary disclosure of climate-related activities and long-term borrowing is consistent with the arguments that companies with high commitments are unlikely to reduce default risk in emerging markets. This paper also provides empirical evidence that the high size and the level of low profitability magnify this relationship between CDP and financial leverage.

Originality/value

The Paris Agreement seems to be a significant point where corporate lenders have become aware of the commitment of policymakers to fight climate change. The results have significant implications for both managerial strategies and environmental regulatory policy-making issues. In addition, the findings shed light on the strategic behavior of managers in the consideration of climate change risks and related transparency.
Impact of geopolitical risk on tourism demand: evidence from asymmetric NARDL approach
Authors: Parray Waseem Ahmad , Soudager Mohammed Ayub , Dada Zubair Ahmad , Yasmin Effat , Darzi Tanveer Ahmad
Published: November 2023

Purpose

Many tourism academics have investigated the linkages between tourism, power and space; few have specifically addressed the profound links between tourism and geopolitics. In view of the restrictive assumptions of the linear framework used in the earlier studies, and hidden asymmetries present in the time series data. Against this backdrop, the study tries to find out how tourists may respond differently to favourable and unfavourable shocks in geopolitical risk (GPR).

Design/methodology/approach

In order to capture this asymmetric nature of the problem, the study employs the non-linear autoregressive distributed lag (NARDL) model to evaluate data from 2001Q1 to 2019Q4.

Findings

The results show that both positive and negative shock to GPR does not produce results of equal magnitude. A positive shock to GPR has a more detrimental effect on foreign tourist arrivals (FTA) than a beneficial effect a negative shock produces. Besides this, the present study also looks at the effect of other macro-economic variables on FTA. An ascend in the real effective exchange rate (REER) i.e. appreciation of the domestic currency has an unfavourable impact on foreign visitor arrivals, while an increase in world gross domestic product amplify it. The results of the study are robust to alternative measures of the control variable.

Practical implications

The study is significant for policymakers in understanding the short and long-run implications of GPR on FTA in India. The present study can assist policymakers, and destination managers to manage the external and internal risks and minimise the consequences of geopolitical threats on the Indian tourism industry. Consequently, destination managers can utilise the study's findings in calibrating their operations and designing crisis marketing strategies within the geopolitical dynamics of the Indian state.

Originality/value

The study tries to find out how tourists may exhibit distinct reactions to positive and negative disturbances in GPR. The study provides first-hand evidence of how GPR impacts tourism demand. The paper also includes the existing body of literature related to GPR factors and their effect on tourist influx, specifically in the framework of the Indian tourism sector.
New technologies in small business models: use of electric vehicles in last-mile delivery for fast-moving consumer goods
Authors: Toraman Yavuz , Bayirli Mehmet , Ramadani Veland
Published: November 2023

Purpose

The share of fast-moving consumer goods (FMCG) in e-commerce has increased, particularly after COVID-19, alongside the growing volume of e-commerce transactions. The increased number of orders necessitates the optimization of delivery operations. This situation has made using different technologies in last-mile delivery processes necessary. Currently, used electric vehicles (EVs) play a significant role in integrating these technologies into delivery operations. Adapting to new technologies emerges as a critical need for small enterprises to survive in the face of advancing technologies. In this context, the main purpose of this paper is to examine and identify attitudes of small businesses toward EVs’ usage in last-mile delivery for FMCG.

Design/methodology/approach

The theoretical frameworks commonly used in studies investigating new technologies, namely the theory of planned behavior (TPB) and technology acceptance model (TAM) have been employed. The analysis of the study was conducted using partial least squares-structural equation modeling (PLS-SEM) and the Smart PLS software package.

Findings

When examining the results of the study, a significant and positive relationship was found between compatibility and enjoyment with perceived usefulness. Furthermore, a significant and positive relationship was identified between attitude toward use, perceived behavioral control and perceived usefulness. Ultimately, a strong relationship was found between intention, which is a precursor to active usage and attitude. Based on the obtained data, it can be concluded that EVs can be actively used in last-mile delivery in the future.

Originality/value

In FMCG processes in Türkiye, EVs are limitedly used in last-mile delivery operations. However, there are very few studies on the use of EVs in FMCG. Therefore, it is expected that the current research will contribute to the literature by providing information on the factors that influence the acceptance of EV usage and their implications. The TAM and TPB models were used in the current study.
Multi-objective optimization to specify optimal selective laser melting process parameters for SS316 L powder
Authors: Prasanth Kumar Reddy K. , Boggarapu Nageswara Rao , Narayana Murty S.V.S.
Published: November 2023

Purpose

This paper adopts a modified Taguchi approach to develop empirical relationships to the performance characteristics (output responses) in terms of process variables and demonstrated their validity through comparison of test data. The method suggests a few tests as per the orthogonal array and provides complete information for all combinations of levels and process variables. This method also provides the estimated range of output responses so that the scatter in the repeated tests can be assessed prior to the tests.

Design/methodology/approach

In order to obtain defect-free products meeting the required specifications, researchers have conducted extensive experiments using powder bed fusion (PBF) process measuring the performance indicators (namely, relative density, surface roughness and hardness) to specify a set of printing parameters (namely, laser power, scanning speed and hatch spacing). A simple and reliable multi-objective optimization method is considered in this paper for specifying a set of optimal process parameters with SS316 L powder. It was reported that test samples printed even with optimal set of input variables revealed irregular shaped, microscopic porosities and improper melt pool formation.

Findings

Finally, based on detailed analysis, it is concluded that it is impossible to express the performance indicators, explicitly in terms of equivalent energy density (E_0ˆ*), which is a combination of multiple sets of selective laser melting (SLM) process parameters, with different performance indicators. Empirical relations for the performance indicators are developed in terms of SLM process parameters. Test data are within/close to the expected range.

Practical implications

Based on extensive analysis of the SS316 L data using modified Taguchi approach, the optimized process parameters are laser power = 298 W, scanning speed = 900 mm/s and hatch distance = 0.075 mm, for which the results of surface roughness = 2.77 Ra, relative density = 99.24%, hardness = 334 Hv and equivalent energy density is 4.062. The estimated data for the same are surface roughness is 3.733 Ra, relative density is 99.926%, hardness is 213.64 Hv and equivalent energy density is 3.677.

Originality/value

Even though equivalent energy density represents the energy input to the process, the findings of this paper conclude that energy density should no longer be considered as a dependent process parameter, as it provides multiple results for the specified energy density. This aspect has been successfully demonstrated in this paper using test data.
Powering the transition: examining factors influencing the intention to adopt electric vehicles
Authors: Thakur Anand , Krishnan K Jithin , Ansari Alisha
Published: November 2023

Purpose

The purpose of the study is to examine the factors that influence people's intention to adopt electric vehicles (EVs). The study used an expanded theory of planned behaviour (TPB) along with the addition of perceived trust and consideration of future consequences (CFC).

Design/methodology/approach

The study is based on primary data collected from 282 respondents in Punjab through a questionnaire. The collected data were analysed using SPSS 26 and AMOS 24 to perform confirmatory factor analysis and structural equation modelling.

Findings

The empirical analysis indicates that attitude, subjective norms and perceived trust have a significant influence on the adoption intention (AI) of EVs.

Research limitations/implications

The implications provide policymakers and marketers with better insights into marketing EVs in the trajectory of sustainable mobility. Marketers should create focussed marketing materials that highlight the environmental ease of use, lower running costs and sophisticated technology of electric automobiles. The limitations of the study provide valuable insights for future researchers.

Originality/value

This is the first study that uses CFC with the TPB model in the context of AI of EVs specifically for the Punjab region.
Intracoronal tooth bleaching – A review and treatment guidelines
Authors: Amer M
Published: November 2023

Intracoronal bleaching is a minimally invasive procedure that was introduced into dentistry in the 19th century. The role of that procedure in enhancing the colour of teeth subjected to internal discolouration while being conservative made it extremely popular amongst dental professionals. Different materials and techniques have been utilized over the years attempting to obtain predictable long‐term results while minimizing any associated risks. Contemporarily, bleaching agents are mainly based on peroxide‐releasing compounds in different formulations and delivery systems. Different theories have been formulated on the bleaching mechanism of such agents, but the exact mechanism is yet to be proven. The effect of hydrogen peroxide‐based bleaching agents on the organic structure of enamel and dentine has been extensively investigated to address the effects of bonding of resin‐based restorative materials to hard tooth structure. Multiple case reports raised a concern about the contribution of intracoronal bleaching in developing invasive root resorption. Modification of intracoronal bleaching techniques was thus necessary to address such concerns. This review will provide a summary of the important aspects of intracoronal bleaching, focusing on how it applies to the contemporary clinical setting. © 2023 Australian Dental Association.
Real‐time OXPHOS capacity analysis in wounded skin from diabetic mice: A pilot study
Authors: Pinho Aryane Cruz Oliveira , Santos Diana , Oliveira Paulo J. , Leal Ermelindo Carreira , Carvalho Eugenia
Published: November 2023

Introduction

Diabetes mellitus (DM) impairs wound healing. The aim was to determine whether DM influences mitochondrial respiration in wounded skin (WS) and non‐wounded skin (NWS), in a pre‐clinical wound healing model of streptozotocin (STZ)‐induced diabetes.

Methods

Six weeks after diabetes induction, two wounds were created in the back of C57BL/J6 mice. Using high‐resolution respirometry (HRR), oxygen flux was measured, in WS and NWS, using two substrate‐uncoupler‐inhibitor titration protocols, at baseline (day 0), day 3 and 10 post‐wounding, in STZ‐DM and non‐diabetic (NDM) mice. Flux control ratios for the oxidative phosphorylation (OXPHOS) capacity were calculated.

Results

A significant increase in mitochondrial respiration was observed in STZ‐DM skin compared to control skin at baseline. The OXPHOS capacity was decreased in WS under diabetes at day 3 post‐wounding (inflammation phase). However, at day 10 post‐wounding (remodeling phase), the OXPHOS capacity was higher in WS from STZ‐DM compared to NDM mice, and compared to NWS from STZ‐DM mice. A significant relative contribution of pyruvate, malate and glutamate (PMG) oxidation to the OXPHOS capacity was observed in WS compared to NWS from STZ‐DM mice, at day 10, while the relative contribution of fatty acid oxidation to the OXPHOS capacity was higher in NWS. The OXPHOS capacity is altered in WS from STZ‐DM compared to NDM mice across the healing process, and so is the substrate contribution in WS and NWS from STZ‐DM mice, at each time point.

Conclusion

HRR may be a sensitive tool to evaluate the underlying mechanisms of tissue repair during wound healing.
Breaking barriers with tofersen: Enhancing therapeutic opportunities in amyotrophic lateral sclerosis
Authors: Saini Aniket , Chawla Pooja A.
Published: November 2023

Background and purpose

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily affects adults, characterized by muscle weakness resulting from the specific death of motor neurons in the spinal cord and brain. The pathogenesis of ALS is associated with the accumulation of mutant superoxide dismutase 1 (SOD1) proteins and neurofilaments in motor neurons, highlighting the critical need for disease‐modifying treatments. Current therapies, such as riluzole and edaravone, provide only symptomatic relief. Recently, tofersen gained approval from the US FDA under the brand name Qalsody as the first and only gene therapy for ALS, addressing a significant pathological aspect of the disease.

Methods

We carried out a literature survey using PubMed, Scopus, National Institutes of Health, and Biogen for articles published in the English language concerned with “amyotrophic lateral sclerosis”, pathophysiology, current treatment, treatment under clinical trial, and the newly approved drug “tofersen” and its detailed summary.

Results

A comprehensive review of the literature on the pathophysiology, available treatment, and newly approved drug for this condition revealed convincing evidence that we are now able to better monitor and treat ALS.

Conclusions

Although treatment of ALS is difficult, the newly approved drug tofersen has emerged as a potential therapy to slow down the progression of ALS by targeting SOD1 mRNA, representing a significant advancement in the treatment of ALS.
Efficacy and safety of the implantable, magnetic resonance imaging‐compatible StimRouter neuromodulation system in the treatment of refractory lower urinary tract symptoms in multiple sclerosis patients
Authors: Sacco Rosaria , Maino Paolo , Koetsier Eva , Disanto Giulio , Renard Julien , Digesu Alex , Gobbi Claudio , Zecca Chiara
Published: November 2023

Background and purpose

Lower urinary tract symptoms (LUTS) significantly affect quality of life (QoL) of multiple sclerosis (MS) patients, and pharmacotherapy has limited efficacy. We investigated efficacy and safety of the implantable StimRouter neuromodulation system for treating refractory LUTS in MS.

Methods

This prospective, single‐center, clinical trial was conducted at the Multiple Sclerosis Center of Lugano, Switzerland, involving MS patients treated with self‐administered percutaneous tibial nerve stimulation delivered by StimRouter over 24 weeks. Changes in video‐urodynamic parameters as well as LUTS severity were measured by Overactive Bladder Questionnaire (OAB‐q), QoL using the Multiple Sclerosis Quality of Life (MSQoL‐54), and treatment satisfaction using a 1–10 visual analogue scale. Adverse events were also recorded.

Results

Of 23 MS patients recruited, six had neurogenic detrusor overactivity (NDO), five had detrusor sphincter dyssynergia (DSD), and 12 had both NDO and DSD. Of patients with NDO, median bladder volume at first uninhibited contraction significantly increased from baseline to week 24 (median = 136 mL, interquartile range [IQR] = 101–244 mL vs. 343 mL, IQR = 237–391 mL; β = 138.2, p = 0.001). No significant changes of urodynamic parameters were found in patients with DSD. OAB‐q symptom scores progressively decreased, and OAB‐q quality of life scores increased (β = −0.50, p < 0.001 and β = 0.47, p < 0.001, respectively), whereas MSQoL‐54 scores did not significantly change (β = 0.24, p = 0.084) in the overall population. Treatment satisfaction was overall high (median = 8, IQR = 6–9). No serious adverse events were recorded.

Conclusions

StimRouter represents a minimally invasive, magnetic resonance imaging‐compatible, self‐administered neuromodulation device leading to objective and subjective improvements of OAB symptoms and related QoL in MS patients with refractory LUTS.
Caregivers' burden and deep brain stimulation for Parkinson disease: A systematic review of qualitative studies
Authors: Cavallieri Francesco , Ghirotto Luca , Sireci Francesca , Parmeggiani Margherita , Pedroni Cristina , Mardones Felipe Andres , Bassi Maria Chiara , Fioravanti Valentina , Fraix Valérie , Moro Elena , Valzania Franco
Published: November 2023

Background and purpose

The impact of subthalamic nucleus deep brain stimulation (STN‐DBS) on caregivers' burden is understudied. We perform a systematic review and meta‐synthesis aggregating qualitative studies involving partners of people with Parkinson disease (PwP) to explore their experiences and unmet needs.

Methods

A systematic review for retrieving qualitative studies included six databases: MEDLINE, Embase, CINAHL, Cochrane, PsycInfo, and Scopus. Inclusion criteria were as follows: (i) studies on the experience of caregivers of PwP in the context of STN‐DBS, (ii) English peer‐reviewed articles, and (iii) qualitative or mixed methods studies reporting caregivers' quotations. After the appraisal of included studies, we performed meta‐synthesis of qualitative findings. Descriptive themes and conceptual elements related to PwP partners' experiences and unmet needs were generated.

Results

A total of 1108 articles were screened, and nine articles were included. Three categories were identified: (i) dealing with Parkinson disease (PD) every day (the starting situation characterized by the impact of PD on ordinary life; the limitations to partners' socialization; partners' efforts in stepping aside for love and care activities), (ii) facing life changes with STN‐DBS (the feeling of being unprepared for changes; the fear and concern due to loved ones' behavioral changes; struggling to find an explanation for those changes), and (iii) rebuilding the role of caregiver and partner after STN‐DBS.

Conclusions

This meta‐synthesis elucidates concerns, challenges, and unmet needs of partners of PwP who underwent STN‐DBS. It is important to provide them with information, education, and adequate support to face these challenges. Professionals need to involve partners in the care and decision process, because STN‐DBS‐related outcomes do not depend solely on the well‐being of PwP but also on the well‐being of individuals surrounding them.
Exosomes derived from human dermal fibroblasts (HDFn‐Ex) alleviate DNCB‐induced atopic dermatitis (AD) via PPARα
Authors: Jang You Na , Lee Jung Ok , Lee Jung Min , Park A. Yeon , Kim Yu Jin , Kim Su Young , Seok Joon , Yoo Kwang Ho , Kim Beom Joon
Published: November 2023

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Skin barrier dysfunction is the initial step in the development of AD. Recently, exosomes have been considered as potential cell‐free medicine for skin defects such as aging, psoriasis and wounds. The aim of this study was to investigate the effects of human dermal fibroblast‐neonatal‐derived exosome (HDFn‐Ex) on AD. HDFn‐Ex increased the expression of peroxisome proliferator activated receptor α (PPARα) and alleviated the 1‐chloro‐2,4‐dinitrobenzene (DNCB)‐mediated downregulation of filaggrin, involucrin, loricrin, hyaluronic acid synthase 1 (HAS1) and HAS2 in human keratinocyte HaCaT cells. However, these effects were inhibited by the PPARα antagonist GW6471. In the artificial skin model, HDFn‐Ex significantly inhibited DNCB‐induced epidermal hyperplasia and the decrease in filaggrin and HAS1 levels via a PPARα. In the DNCB‐induced AD‐like mouse model, HDFn‐Ex administration reduced epidermis thickening and mast cell infiltration into the dermis compared to DNCB treatment. Moreover, the decreases in PPARα, filaggrin and HAS1 expression, as well as the increases in IgE and IL4 levels induced by DNCB treatment were reversed by HDFn‐Ex. These effects were blocked by pre‐treatment with GW6471. Furthermore, HDFn‐Ex exhibited an anti‐inflammatory effect by inhibiting the DNCB‐induced increases in IκBα phosphorylation and TNF‐α expression. Collectively, HDFn‐Ex exhibited a protective effect on AD. Notably, these effects were regulated by PPARα. Based on our results, we suggest that HDFn‐Ex is a potential candidate for treating AD by recovering skin barrier dysfunction and exhibiting anti‐inflammatory activity.
Patient headache questionnaires can improve headache diagnosis and treatment in children
Authors: Szperka Christina L. , Witzman Stephanie , Ostapenko Svetlana , Farrar John T. , Hsu Jesse Yenchih , Malavolta Carrie P. , Bunney Janille D. , Bange Erin M. , Patterson Gentile Carlyn , Velasquez Gerardo , Marquez de Prado Blanca , Cosico Mahgenn , Lee Meyeon , Pojomovsky McDonnell Pamela , Prelack Marisa S. , Chadehumbe Madeline A. , Stephenson Donna J. , Kichula Elizabeth A. , Tomaine Scott C. , Hershey Andrew D.
Published: November 2023

Objective

To examine trends in diagnosis of headache and migraine in a large pediatric neurology cohort, and test whether an electronic health record (EHR)‐integrated headache questionnaire can increase specificity of diagnosis and likelihood of prescribing migraine treatment.

Background

Under‐diagnosis of migraine contributes to the burden of disease. As we founded our Pediatric Headache Program in 2013, we recognized that the proportion of patients with headache who were given a diagnosis of migraine was much lower than expected.

Methods

We developed a patient headache questionnaire, initially on paper (2013–2014), then in an electronic database (2014–2016), and finally integrated into our electronic health record (pilot: 2016, full: May 2017). We compared diagnoses and prescribed treatments for new patients who were given a headache diagnosis, looking at trends in the proportion of patients given specific diagnoses (migraine, etc.) versus the non‐specific diagnosis, “headache.” Next, we conducted a prospective cohort study to test for association between provider use of the form and the presence of a specific diagnosis, then for an association between specific diagnosis and prescription of migraine treatment.

Results

Between July 2011 and December 2022 the proportion of new headache patients who were given a diagnosis of migraine increased 9.7% and non‐specific headache diagnoses decreased 21.0%. In the EHR cohort (June 2017–December 2022, n = 15,122), use of the provider form increased the rate of specific diagnosis to 87.2% (1839/2109) compared to 75.5% (5708/7560) without a patient questionnaire, nearly doubling the odds of making a specific diagnosis (odds ratio [OR] 1.90, 95% confidence interval [CI]: 1.65–2.19). Compared to those given only a non‐specific headache diagnosis who were prescribed a migraine therapy 53.7% (1766/3286) of the time, 75.3% (8914/11836) of those given a specific diagnosis received a migraine therapy, more than doubling the odds of prescription (OR 2.39, 95% CI: 2.20–2.60).

Conclusions

Interventions to improve specificity of diagnosis were effective and led to increased rates of prescription of migraine treatments. These results have been sustained over several years. This headache questionnaire was adapted into the Foundation system of EpicCare, so it is broadly available as a clinical and research tool for institutions that use this EHR software.
CARIN' about migrants through news? Linking migrant deservingness to traditional and digital media consumption
Authors: De Coninck David , Duque Maria , Schwartz Seth J. , d'Haenens Leen
Published: November 2023

In recent years, public discourse and political actors have increasingly used a deservingness rhetoric to refer to the arrival and permanent settlement of migrant groups. However, scholars have drawn on the concept of deservingness without developing a clear theoretical framework for it. Following our recent work on the migrant deservingness framework, in the present study we use the CARIN criteria (Control, Attitude, Reciprocity, Identity, Need) to establish the extent to which host nationals in eight nations impose conditions towards accepting permanent settlement among migrants. Specifically, we examine the links of these deservingness perceptions with news media consumption in seven European countries and Colombia using online survey panel data (N = 12,142). Our findings indicate that consuming news via commercial television and in popular newspapers, in particular, is linked to greater conditionality regarding migrant settlement. Consuming public television or quality news sources is only weakly linked to (reduced) conditionality. We discuss these findings using the migrant deservingness framework.
Recurrent Lupus Vulgaris Following Repeated BCG (Bacillus Calmette Guèrin) Vaccination
Authors: Şaşmaz Rüstem , Altinyazar H. Cevdet , Tatlican Semih , Eskioğlu Fatma , Yurtsever Pinar
Published: November 2023

We report a case of lupus vulgaris following BCG (Bacillus Calmette Guèrin) vaccination on the right shoulder. The patient had a history of lupus vulgaris on his left shoulder that developed following BCG vaccination and was treated successfully eight years ago.
Growth Factors, Signal Transduction, and Cellular Responses
Authors: Shen John T. , Falanga Vincent
Published: November 2023

The extraordinary advances in the field of growth factors and signal transduction have created new and promising therapeutic interventions. We intend to explain the difficult nomenclatures associated with growth factors and their mechanisms of action.