bluuebunny/crossref_metadata_2025 huggingface dataset:
RISK MANAGEMENT IN THE SYSTEM OF ENSURING ECONOMIC SECURITY OF ORGANIZATIONS
Authors:   Financial University under the Government of the Russian Federation, Moscow, Russian Federation, TURGAEVA A.A.
Published: April 2024

Task. Risk management, as an independent part of the science of «management», is actively studied by analysts and other researchers. The modern development of risk management is determined by the need for the practical implementation of optimal and effective procedures aimed at managing the risks of the organization. The problem is that risks directly affect the state of economic security of the enterprise, while the enterprise does not always have an understanding of «what risk management is, what is its connection with ensuring the economic security of the organization». The purpose of the study is to form such an understanding and clarify a number of existing statements in this area. Model. The author reveals the essence of the category «risk management» and conducts a study of the close connection with the concept of «economic security of an organization». Conclusions. Risk management seems to be an adaptation toolkit for enterprise risk management, including ensuring balanced and optimal business development in order to ensure a high level of economic security of the organization. Practical significance. Popularizing risk management in organizations as an effective tool in solving problems related to risk management will draw the attention of company management to the practical orientation of risk management procedures to ensure economic security and their effectiveness and efficiency in practice. Originality. The modern directions of development of risk management are clarified in order to ensure the economic security of the organization.
SUBJECT COMPOSITION OF PARTICIPANTS IN LEGAL RELATIONS ARISING WHEN USING INNOVATIVE (UNMANNED) VEHICLES IN BUSINESS ACTIVITIES
Authors:   Financial University under the Government of the Russian Federation, Moscow, Russian Federation, SERGEEV A.M. , DEMCHENKO M.V.
Published: April 2024

The subject of research is the composition of the participants in the legal relationship on the use of an unmanned vehicle. The article breaks off with a general overview of attempts to settle these legal relations, which are fundamentally new both for the Russian legal system and the economy as a whole. At the same time, central attention is paid to their subject composition. The study states that the legal regulation of relations on the use of unmanned vehicles is haphazard. A single regulatory legal act has not yet been adopted, and by-laws have an extremely heterogeneous subject of legal regulation, including civil, administrative and other aspects. This leads to significant problems of legal technique, the result of which in the future will be difficulties in law enforcement practice. An analysis of the civil component of the use of unmanned vehicles shows that the potential of the current civil legislation to regulate relevant relations is far from exhausted. The range of subjects for the use of an unmanned vehicle coincides with the subjects of classical relations for the transportation or rental of vehicles. In this regard, changes to the Civil Code of the Russian Federation, its additions by new subjects of legal relations or new contractual structures are undesirable at the current stage.
The Role of Transcranial-Color-Doppler in the Management of Basilar Artery Stenosis: Case Series and Systematic Review of Literature
Authors: Filidei Marta , Di Schino Chiara , Allegritti Massimiliano , Costanti Danilo , Morandini Ilaria , Riva Alice , Viticchi Giovanna , Colosimo Carlo , Caproni Stefano
Published: April 2024

Managing vertebrobasilar (VB) stroke, particularly basilar artery occlusion (BAO), presents challenges due to diverse clinical presentations and intricate diagnostics, risking delays in acute-phase reperfusion therapies. The diagnostic complexities of VB stroke prompt questions about whether presentation tempo influences outcomes. For non-urgent cases of basilar artery stenosis (BAS) lacking guidelines, clinical management becomes case-dependent. Current options include aggressive medical therapy (AMT) and percutaneous transluminal angioplasty and/or stenting (PTAS). However, the choice of PTAS remains debated, with recent trials observing higher-than-expected recurrence rates, particularly in intracranial stenosis. Understanding hemodynamic status is crucial in predicting stroke risk, especially in atherosclerotic VB disease. Recent studies highlighted the role of distal flow status in predicting stroke risk, emphasizing the importance of hemodynamic assessment beyond anatomic measures. Neurosonology, especially transcranial color-coded duplex sonography (TCCS), emerges as a valuable tool for assessing hemodynamics. Despite TCCS being operator-dependent and technically challenging for BAS evaluation, it effectively detects significant hemodynamic changes, providing real-time information on collateral flow. This review explores the potential role of TCCS in managing BA hemodynamic failure in VB stroke, with particular regard to the selection of BAS patients who may benefit from PTAS.
Application of potassium fertilizer and plant growth regulators to the growth and productivity of purple sweet potato
Authors: Sulistyowati Desty Dwi , Widiyono Wahyu
Published: April 2024

The study aimed to determine the effect of plant growth regulators and potassium fertilizer on the growth and productivity of three clones of purple sweet potato. The experiment was conducted at IPB University experimental station in Leuwikopo Dramaga Bogor for seven months. The study used a split-plot design with three factors and three replications. The first factor was as a subplot, namely plant growth regulators (PGR) application which consisted of two levels of without PGR (S0) and with PGR (S1) concentration of 2 cc l-1 of water (2,000 ppm). The second factor was as a subplot, namely rates of potassium chloride fertilizer (60, 120, 180 kg ha-1 K2O). The third factor as the main plot was sweet potato clones of (K1) Ayamurasaki, (K2) RIS-03063-05, and (K3) MSU 03028-10. The concentration of 2,000 ppm PGR did not significantly affect growth and tuber yield components. Potassium chloride K2O of 60 kg ha-1 up to 180 kg ha-1 did not significantly affect growth and tuber yield components. MSU 03028-10 clone had the highest total tuber yield (1537.8), healthy tuber (1529.9), unmarketable tuber (740.3), and small tuber (709.0). MSU 03028-10 clones have the longest stem length and the largest number of leaves 3-12 WAP. This study indicates that the MSU 03028-10 clone produces better growth and productivity than other clones.
Energy Modelling in Sierra Leone: Data-in-Brief
Authors: Kiley Fynn , Caulker David , Collier William , Fields Neve , Blyth William , Quiros-Tortos Jairo , Howells Mark
Published: April 2024

Energy systems modelling plays a pivotal role in understanding and optimizing complex energy systems. By integrating various factors such as energy demand, supply, infrastructure, and environmental considerations, energy systems modelling provides valuable insights for policymakers, industry stakeholders, and researchers. This can be key to informing stakeholder and policy decisions and facilitate the mobilisation of capital and market development to support the development of the energy sector. This article presents the data, assumptions, and related calculations used for the development of a national scale power system model for Sierra Leone. The focus of the model was a techno-economic analysis of specific hydropower expansion plans. Where possible, this data has been collected from publicly available sources such as scientific literature, feasibility studies, international databases, data from existing modelling efforts in Sierra Leone, and local stakeholders. The collection of the data, development of the model, and creation of scenarios was done in collaboration with the Ministry of Energy in Sierra Leone and verified by a broad range of stakeholders. The following paper outlines the key data presented in the full database which can be accessed through the URL found in the Specifications Table. The URL also contains the Reference Energy System (RES) used in this study.
Desenho Universal para Aprendizagem na prática maker: promovendo a inclusão e a diversidade
Authors: Casagrande Keli , Aparecida Vieira Leociléa
Published: April 2024

O estudo intitulado "Desenho Universal para Aprendizagem na prática maker: promovendo a inclusão e a diversidade” tem por objetivo principal analisar como a abordagem inclusiva baseada no Desenho Universal para Aprendizagem (DUA) pode ampliar o acesso dos alunos a experiências educacionais relevantes no contexto das práticas maker. Para isso, buscou-se integrar o conhecimento teórico e prático, capturando detalhes significativos do ambiente educacional e do processo de ensino e aprendizagem. Os objetivos específicos foram: identificar desafios e oportunidades na integração das propostas maker com o DUA e analisar as experiências dos alunos em relação à implementação das propostas maker com uma perspectiva inclusiva. O estudo é de natureza exploratória-descritiva, abordagem qualitativa e do tipo pesquisa-ação, com foco na observação e análise interpretativa dos fenômenos. O campo de pesquisa foi uma Sala de Recursos da Rede Municipal de Curitiba, com dois grupos de alunos (com 3 e 4 alunos, respectivamente), na faixa etária entre oito a doze anos. O estudo conclui de que há a necessidade de considerar a diversidade de estilos de aprendizagem, necessidades individuais e características dos alunos para garantir um ambiente educacional verdadeiramente inclusivo e acessível e de que é preciso aprofundar a compreensão sobre melhores ações pedagógicas para implementar e avaliar intervenções educacionais inclusivas no contexto das práticas maker.
Trabalho colaborativo: reorganização das práticas escolares numa perspectiva inclusiva
Authors: Daiana Aparecida Teles Vieira de Lima  , Everton Schwartz da Silva  , Janaíne Gonçalves de Oliveira  , Josiele Regiane Grossklaus Senff  , Sandra Salete de Camargo Silva
Published: April 2024

O estudo é vinculado ao Programa de Pós-Graduação, Mestrado Profissional em Educação Inclusiva (PROFEI) e ao Espaço de Estudos e Pesquisas em Educação, Direito e Inclusão (EPEDIN) da Universidade Estadual do Paraná - Campus União da Vitória. Considerando a relevância do trabalho colaborativo, a pergunta que permeia o problema da pesquisa é: Como repensar as práticas escolares para atender as diferenças em uma perspectiva inclusiva? Nesse sentido, a pesquisa objetiva evidenciar como o trabalho colaborativo contribui com a reorganização escolar, efetivando práticas pedagógicas inclusivas. O referencial teórico do estudo da temática proposta, de cunho qualitativo bibliográfico, respalda-se nas obras dos(as) autores(as) Damiani (2008), Roldão (2007), Mendes (2023) e Libâneo; Oliveira; Toschi (2012); Lück (2011). A fim de propiciar ambientes adequados e inclusivos, a escola vem passando por um processo de revisão quanto a sua estrutura e organização pedagógica. No entanto, um ambiente que acolha as diferenças e oportunize a todos(as) o acesso ao currículo requer a participação de todos(as) os(as) responsáveis no processo de escolarização dos(as) estudantes. Desta forma, é necessário desenvolver uma cultura colaborativa, em que os(as) profissionais partilham seus saberes e responsabilidades, promovendo um apoio mútuo, na busca de um objetivo comum.
A inclusão escolar de alunos com Altas Habilidades/Superdotação no Ensino Médio: o que dizem as pesquisas
Authors: Edna Ribeiro Bellini  , Andreia Nakamura Bondezan  , Cleudet de Assis Scherer
Published: April 2024

O presente artigo tem como objetivo apresentar como vem se delineando a inclusão educacional dos alunos com Altas Habilidades/Superdotação na etapa conclusiva da Educação Básica, o Ensino Médio. Para o desenvolvimento deste trabalho utilizou-se como método de pesquisa a revisão bibliográfica de literatura. A base de dados selecionada para o desenvolvimento deste artigo foi a Biblioteca Digital Brasileira de Teses e Dissertações (BDTD), por meio dos seguintes descritores: Superdotação e Ensino Médio. A partir dessa pesquisa pode-se verificar que ainda são poucas as publicações científicas brasileiras que abordam a inclusão do aluno com altas habilidades/superdotação, em especial, no ensino médio. As pesquisas analisadas enfatizam que há necessidade de políticas públicas, em âmbito nacional, para que os alunos com Altas Habilidades/Superdotação saiam da invisibilidade. Também destacam que é necessário urgência de investimentos financeiros para a formação continuada em serviço dos professores para a compreensão das especificidades deste alunado que, desta forma, promova mudanças nas práticas pedagógicas.
Cushioning mechanism of the metatarsals during landing for the skateboarding ollie maneuver
Authors: Wu Yusen , Wang Haichun , Deng Cheng , Guo Yangyu , Zhu Xiaolan
Published: April 2024

Skateboarding is an Olympic event with frequent jumping and landing, where the cushioning effect by the foot structure (from the arch, metatarsals, etc.) and damping performance by sports equipment (shoes, insoles, etc.) can greatly affect an athlete’s sports performance and lower the risk of limb injury. Skateboarding is characterized by the formation of a “man–shoe–skateboard system,” which makes its foot cushioning mechanism different from those of other sports maneuvers, such as basketball vertical jump and gymnastics broad jump. Therefore, it is necessary to clarify the cushioning mechanism of the foot structure upon landing on a skateboard. To achieve this, a multibody finite element model of the right foot, shoe, and skateboard was created using Mimics, Geomagic, and ANSYS. Kinetic data from the ollie maneuver were used to determine the plantar pressure and Achilles tendon force at three characteristics (T1, T2, and T3). The stress and strain on the foot and metatarsals (MT1–5) were then simulated. The simulation results had an error of 6.98% compared to actual measurements. During landing, the force exerted on the internal soft tissues tends to increase. The stress and strain variations were highest on MT2, MT3, and MT4. Moreover, the torsion angle of MT1 was greater than those of the other metatarsals. Additionally, the displacements of MT2, MT3, and MT4 were higher than those of the other parts. This research shows that skateboarders need to absorb the ground reaction force through the movements of the MTs for ollie landing. The soft tissues, bones, and ligaments in the front foot may have high risks of injury. The developed model serves as a valuable tool for analyzing the foot mechanisms in skateboarding; furthermore, it is crucial to enhance cushioning for the front foot during the design of skateboard shoes to reduce potential injuries.
Microphysiological systems as models for immunologically ‘cold’ tumors
Authors: Gaebler Daniela , Hachey Stephanie J. , Hughes Christopher C. W.
Published: April 2024

The tumor microenvironment (TME) is a diverse milieu of cells including cancerous and non-cancerous cells such as fibroblasts, pericytes, endothelial cells and immune cells. The intricate cellular interactions within the TME hold a central role in shaping the dynamics of cancer progression, influencing pivotal aspects such as tumor initiation, growth, invasion, response to therapeutic interventions, and the emergence of drug resistance. In immunologically ‘cold’ tumors, the TME is marked by a scarcity of infiltrating immune cells, limited antigen presentation in the absence of potent immune-stimulating signals, and an abundance of immunosuppressive factors. While strategies targeting the TME as a therapeutic avenue in ‘cold’ tumors have emerged, there is a pressing need for novel approaches that faithfully replicate the complex cellular and non-cellular interactions in order to develop targeted therapies that can effectively stimulate immune responses and improve therapeutic outcomes in patients. Microfluidic devices offer distinct advantages over traditional in vitro 3D co-culture models and in vivo animal models, as they better recapitulate key characteristics of the TME and allow for precise, controlled insights into the dynamic interplay between various immune, stromal and cancerous cell types at any timepoint. This review aims to underscore the pivotal role of microfluidic systems in advancing our understanding of the TME and presents current microfluidic model systems that aim to dissect tumor-stromal, tumor-immune and immune-stromal cellular interactions in various ‘cold’ tumors. Understanding the intricacies of the TME in ‘cold’ tumors is crucial for devising effective targeted therapies to reinvigorate immune responses and overcome the challenges of current immunotherapy approaches.
Comparison of short-term efficacy of two bipolar radiofrequency ablation forceps for rheumatic heart disease concomitant with atrial fibrillation
Authors: Zhang Ning , Hou Ming , Mei Bo , Liu Yong , Lai Ying-long
Published: April 2024

Background

Currently, the bipolar radiofrequency ablation forceps manufactured by AtriCure are the main instrument for surgical ablation in patients with rheumatic heart disease (RHD) concomitant with atrial fibrillation (AF). The bipolar radiofrequency ablation forceps by Med-Zenith has a greater advantage in price compared with AtriCure. However, few studies have been reported on the comparison of their clinical efficacy. The aim of this study is to compare the short-term clinical efficacy of the two ablation forceps for RHD concomitant with AF.

Methods

Clinical data of 167 patients with RHD concomitant with AF admitted to the Department of Cardiac Major Vascular Surgery, Affiliated Hospital of North Sichuan Medical College, were retrospectively analyzed, and the restoration efficacy of sinus rhythm (SR) and cardiac function after surgery were compared with two ablation forceps.

Results

The end-systolic diameter of the right atrium and the end-systolic diameter of the left atrium in the patients of both groups at each postoperative time point decreased compared with that of the preoperative period (P < 0.05), and the left ventricular ejection fraction started to improve significantly at 6 months after surgery compared with that of the preoperative period (P < 0.05). There was no difference between the two groups of patients in the comparison of the aforementioned indicators at different points in time (P > 0.05). At 12 months postoperatively, the SR maintenance rate in using the ablation forceps by Med-Zenith (73.3%) was lower than that for AtriCure (86.4%) and the cumulative recurrence rate of AF in using the Med-Zenith ablation forceps was greater than that for AtriCure.

Conclusions

The two bipolar radiofrequency ablation forceps compared in the study are safe and effective in treating patients of RHD concomitant with AF, and the ablation forceps by AtriCure may be more effective in restoring SR in the short term.
Sustaining mental health and wellbeing programmes in schools: recommendations from an online roundtable
Authors: March Anna , Stapley Emily , Hayes Daniel , Moore Darren , Deighton Jessica
Published: April 2024

Despite recent investments in school-based mental health and wellbeing promotion in England, the sustainability of mental health interventions remains a substantial challenge. This article brings together potential solutions to sustaining interventions in schools, drawing on insights from an online roundtable discussion held in July 2022. Facilitated by researchers and informed by recent research on barriers and facilitators to sustaining school-based mental health interventions, 16 participants came together to discuss challenges and solutions. Participants included school staff, policy makers, educational psychologists, researchers and mental health intervention developers. The discussion explored the need for accountability at all levels (e.g., from school leaders to policy makers and Ofsted) and the potential value of engaging schools more consistently with academic evidence. Participants also discussed the importance of creating a healthy and sustainable ecosystem for interventions (underscoring the significance of staff wellbeing, adequate resourcing, and longer-term funding commitments), and moving beyond separate, isolated interventions. The findings offer a range of recommendations for school decision makers, mental health researchers, intervention developers, and those working in the wider system around schools.
Osteoporosis in Parkinson’s disease and the role of lean body mass: a cross-sectional study in a Brazilian tertiary center
Authors: Lima Danielle Pessoa , Chagas-Neto Francisco Abaeté das , Gomes de Luna João Rafael , Martins Yasmin de Oliveira , de Almeida Samuel Brito , Feitosa Camila Ximenes , Gradvohl Leticia Brasil , Rosa Isabele Dantas , Lopes Fábia Karine de Moura , Aragão Luciana Felipe Férrer , Viana-Júnior Antonio Brazil , Augusto Kristopherson Lustosa , Roriz-Filho Jarbas de Sá , d’Alva Catarina Brasil , Montenegro-Júnior Renan Magalhães , Braga-Neto Pedro
Published: April 2024

Background

Parkinson’s disease (PD) is the second most common neurodegenerative illness and has the highest increase rate in recent years. There is growing evidence to suggest that PD is linked to higher osteoporosis rates and risk of fractures.

Objective

This study aims to estimate the prevalence and factors associated with osteoporosis as defined by the National Osteoporosis Foundation (NOF) and World Health Organization in patients with mild to moderate PD.

Methods

We performed a cross-sectional study at a tertiary public hospital in Fortaleza, Brazil, dating from May 2021 until April 2022. The study sample was comprised of patients with mild to moderate PD who were at least 40 years old and who had the ability to walk and stand unassisted. Bone Mineral Density (BMD) of both the hip (neck of the femur) and the lumbar spine were obtained via properly calibrated Dual Energy X-ray Absorptiometry (DXA) scanning. The FRAX (Fracture Risk Assessment Tool) score was used to determine a person’s 10-year risk of major osteoporotic fracture. The Revised European Working Group on Sarcopenia in Older People (EWGSOP 2) was used as a basis to confirm a sarcopenia diagnosis with the following parameters: low muscle strength gauged by handgrip strength and low muscle quantity by DXA. Physical performance was carefully evaluated by using the Short Physical Performance Battery test. Osteoporosis and osteopenia were diagnosed following the NOF guidelines and WHO recommendations.

Results

We evaluated 107 patients in total, of whom 45 (42%) were women. The group’s mean age was 68 ± 9 years, and the mean disease time span was 9.9 ± 6.0 years and mean motor UPDRS was 43 ± 15. We found that 42.1% and 34.6% of the sample had osteopenia and osteoporosis following NOF criteria, respectively, and 43% and 33.6% following the WHO recommendations. Lower lean appendicular mass was associated to osteopenia and osteoporosis in multinomial logistic regression analysis in both diagnostic criteria.

Conclusion

Our findings provide additional evidence for the protective role of lean mass against osteoporosis in patients with PD.
Charging station service scope division and real-time pricing strategy based on the strongest occupation method
Authors: Yang Xian , Tang Xiafei , Chen Yuxiang , Wu Jialong , Tan Yudong
Published: April 2024

With the rapid construction of charging stations (CSs), charging station operators need to enhance their core competitiveness by precisely planning their service areas and formulating reasonable and effective pricing strategies. However, the regional competition among multiple charging station operators is generally ignored. In the traditional model, the service scope of CSs appears as regular circles, which is inconsistent with the market distribution law. In response to the irregular relationship between the dynamic service scope of CSs and the real-time charging price, a charging station service scope (CSSS) model is proposed by introducing the variable service field strength (SFS). First, the competitiveness of CSs is evaluated quantitatively, and the SFS of CSs is defined to describe the service scope of CSs by the strongest occupation method. Second, the impact of the charging price on the charging demand is analyzed based on the CSSS division model. In addition, the revenue of charging station operators and the stability of the power grid are considered to establish a real-time pricing optimization model. Finally, the numerical simulation is operated in Furong District of Changsha. It is shown that the proposed method effectively achieves more profits for charging stations and decreases the average power deviation of the whole region.
Synthesizing foundations in evolutionary morphology and a plea for conceptual explicitness regarding homology concepts
Authors: Göpel Torben
Published: April 2024

Morphology, the scientific discipline dealing with description and comparison of organismal form, is one of the oldest disciplines in biology and traditionally strongly linked to the concept of homology. With morphological data being used and morphological knowledge being applied in other (younger) biological disciplines, morphology has often been degraded to an only auxiliary discipline or a mere set of methods serving those other disciplines. While this notion has been wrong all along, the last decades have seen a renaissance of morphology mostly due to significant leaps in imaging techniques and the advent of 3D digital data. Modern large-scale morphological endeavors in what is called phenomics and new means of functional analyses underline the fruitfulness of morphological research. Furthermore, morphology has been revisited on a conceptual level leading to a “re-philosophication” of morphology acknowledging its nature as explanatory science. Based on Richter and Wirkner’s research program of Evolutionary Morphology, this essay expands the conceptual framework to identify entities and processes vital for morphology as independent scientific discipline. With no unified homology concept in sight (and maybe not even desired), following the emergence of bio-ontologies in morphology, a plea is made for conceptual explicitness which acknowledges the plurality of homology concepts but enables intersubjective transfer.
Unveiling the menace: a thorough review of potential pandemic fungal disease
Authors: Jafarlou Mahdi
Published: April 2024

Fungal diseases have emerged as a significant global health threat, with the potential to cause widespread outbreaks and significant morbidity and mortality. Anticipating future pandemic fungal diseases is essential for effective preparedness and response strategies. This comprehensive literature review aims to provide a comprehensive analysis of the existing research on this topic. Through an extensive examination of scholarly articles, this review identifies potential fungal pathogens that have the potential to become pandemics in the future. It explores the factors contributing to the emergence and spread of these fungal diseases, including climate change, globalization, and antimicrobial resistance. The review also discusses the challenges in diagnosing and treating these diseases, including limited access to diagnostic tools and antifungal therapies. Furthermore, it examines the strategies and interventions that can be employed to mitigate the impact of future pandemic fungal diseases, such as improved surveillance systems, public health education, and research advancements. The findings of this literature review contribute to our understanding of the potential risks posed by fungal diseases and provide valuable insights for public health professionals and policymakers in effectively preparing for and responding to future pandemic outbreaks. Overall, this review emphasizes the importance of proactive measures and collaborative efforts to anticipate and mitigate the impact of future pandemic fungal diseases.
Identification of Dof transcription factors in Dendrobium huoshanense and expression pattern under abiotic stresses
Authors: Gu Fangli , Zhang Wenwu , Wang Tingting , He Xiaomei , Chen Naifu , Zhang Yingyu , Song Cheng
Published: April 2024

Introduction: DNA-binding with one finger (Dof) transcription factors (TFs) are a unique family of TFs found in higher plants that regulate plant responses to light, hormones, and abiotic stresses. The specific involvement of Dof genes in the response to environmental stresses remains unknown in D. huoshanense.

Methods: A total of 22 Dof family genes were identified from the D. huoshanense genome.

Results: Chromosome location analysis showed that DhDof genes were distributed on 12 chromosomes, with the largest number of Dof genes located on chromosome 8. The phylogenetic tree revealed that DhDofs could be categorized into 11 distinct subgroups. In addition to the common groups, DhDof4, DhDof5, DhDof17, and the AtDof1.4 ortholog were clustered into the B3 subgroup. Group E was a newly identified branch, among which DhDof6, DhDof7, DhDof8, and DhDof9 were in an independent branch. The conserved motifs and gene structure revealed the differences in motif number and composition of DhDofs. The dof domain near the N-terminus was highly conserved and contained a C2-C2-type zinc finger structure linked with four cysteines. Microsynteny and interspecies collinearity revealed gene duplication events and phylogenetic tree among DhDofs. Large-scale gene duplication had not occurred among the DhDofs genes and only in one pair of genes on chromosome 13. Synteny blocks were found more often between D. huoshanense and its relatives and less often between Oryza sativa and Arabidopsis thaliana. Selection pressure analysis indicated that DhDof genes were subject to purifying selection. Expression profiles and correlation analyses revealed that the Dof gene under hormone treatments showed several different expression patterns. DhDof20 and DhDof21 had the highest expression levels and were co-expressed under MeJA induction. The cis-acting element analysis revealed that each DhDof had several regulatory elements involved in plant growth as well as abiotic stresses. qRT-PCR analysis demonstrated that DhDof2 was the main ABA-responsive gene and DhDof7 was the main cold stress-related gene. IAA suppressed the expression of some Dof candidates, and SA inhibited most of the candidate genes.

Discussion: Our results may provide new insights for the further investigation of the Dof genes and the screening of the core stress-resistance genes.
Development of 42 marker panel for in-depth study of cancer associated fibroblast niches in breast cancer using imaging mass cytometry
Authors: Røgenes Hanna , Finne Kenneth , Winge Ingeborg , Akslen Lars A. , Östman Arne , Milosevic Vladan
Published: April 2024

Imaging Mass Cytometry (IMC) is a novel, and formidable high multiplexing imaging method emerging as a promising tool for in-depth studying of tissue architecture and intercellular communications. Several studies have reported various IMC antibody panels mainly focused on studying the immunological landscape of the tumor microenvironment (TME). With this paper, we wanted to address cancer associated fibroblasts (CAFs), a component of the TME very often underrepresented and not emphasized enough in present IMC studies. Therefore, we focused on the development of a comprehensive IMC panel that can be used for a thorough description of the CAF composition of breast cancer TME and for an in-depth study of different CAF niches in relation to both immune and breast cancer cell communication. We established and validated a 42 marker panel using a variety of control tissues and rigorous quantification methods. The final panel contained 6 CAF-associated markers (aSMA, FAP, PDGFRa, PDGFRb, YAP1, pSMAD2). Breast cancer tissues (4 cases of luminal, 5 cases of triple negative breast cancer) and a modified CELESTA pipeline were used to demonstrate the utility of our IMC panel for detailed profiling of different CAF, immune and cancer cell phenotypes.
The C1q and gC1qR axis as a novel checkpoint inhibitor in cancer
Authors: Ghebrehiwet Berhane , Zaniewski Michal , Fernandez Audrey , DiGiovanni Mathew , Reyes Tiana N. , Ji Ping , Savitt Anne G. , Williams Jennie L. , Seeliger Markus A. , Peerschke Ellinor I. B.
Published: April 2024

Understanding at the molecular level of the cell biology of tumors has led to significant treatment advances in the past. Despite such advances however, development of therapy resistance and tumor recurrence are still unresolved major challenges. This therefore underscores the need to identify novel tumor targets and develop corresponding therapies to supplement existing biologic and cytotoxic approaches so that a deeper and more sustained treatment responses could be achieved. The complement system is emerging as a potential novel target for cancer therapy. Data accumulated to date show that complement proteins, and in particular C1q and its receptors cC1qR/CR and gC1qR/p33/HABP1, are overexpressed in most cancer cells and together are involved not only in shaping the inflammatory tumor microenvironment, but also in the regulation of angiogenesis, metastasis, and cell proliferation. In addition to the soluble form of C1q that is found in plasma, the C1q molecule is also found anchored on the cell membrane of monocytes, macrophages, dendritic cells, and cancer cells, via a 22aa long leader peptide found only in the A-chain. This orientation leaves its 6 globular heads exposed outwardly and thus available for high affinity binding to a wide range of molecular ligands that enhance tumor cell survival, migration, and proliferation. Similarly, the gC1qR molecule is not only overexpressed in most cancer types but is also released into the microenvironment where it has been shown to be associated with cancer cell proliferation and metastasis by activation of the complement and kinin systems. Co-culture of either T cells or cancer cells with purified C1q or anti-gC1qR has been shown to induce an anti-proliferative response. It is therefore postulated that in the tumor microenvironment, the interaction between C1q expressing cancer cells and gC1qR bearing cytotoxic T cells results in T cell suppression in a manner akin to the PD-L1 and PD-1 interaction.
Irreversible electroporation promotes a pro-inflammatory tumor microenvironment and anti-tumor immunity in a mouse pancreatic cancer model
Authors: Imran Khan Mohammad , Brock Rebecca M. , Beitel-White Natalie , Powar Manali , Orr Katie , Aycock Kenneth N. , Alinezhadbalalami Nastaran , Salameh Zaid S. , Eversole Paige , Tintera Benjamin , Markov Madanick Justin , Hendricks-Wenger Alissa , Coutermarsh-Ott Sheryl , Davalos Rafael V. , Allen Irving C.
Published: April 2024

Pancreatic cancer is a significant cause of cancer-related mortality and often presents with limited treatment options. Pancreatic tumors are also notorious for their immunosuppressive microenvironment. Irreversible electroporation (IRE) is a non-thermal tumor ablation modality that employs high-voltage microsecond pulses to transiently permeabilize cell membranes, ultimately inducing cell death. However, the understanding of IRE’s impact beyond the initiation of focal cell death in tumor tissue remains limited. In this study, we demonstrate that IRE triggers a unique mix of cell death pathways and orchestrates a shift in the local tumor microenvironment driven, in part, by reducing the myeloid-derived suppressor cell (MDSC) and regulatory T cell populations and increasing cytotoxic T lymphocytes and neutrophils. We further show that IRE drives induce cell cycle arrest at the G0/G1 phase in vitro and promote inflammatory cell death pathways consistent with pyroptosis and programmed necrosis in vivo. IRE-treated mice exhibited a substantial extension in progression-free survival. However, within a span of 14 days, the tumor immune cell populations reverted to their pre-treatment composition, which resulted in an attenuation of the systemic immune response targeting contralateral tumors and ultimately resulting in tumor regrowth. Mechanistically, we show that IRE augments IFN- γ signaling, resulting in the up-regulation of the PD-L1 checkpoint in pancreatic cancer cells. Together, these findings shed light on potential mechanisms of tumor regrowth following IRE treatment and offer insights into co-therapeutic targets to improve treatment strategies.
Association between serum antinuclear antibody and rheumatoid arthritis
Authors: Liu Fang , Wang Xiu-Qin , Zou Jian-Wen , Li Ming , Pan Cui-Cui , Si Yuan-Quan
Published: April 2024

Background

The relationship between serum antinuclear antibody (ANA) and rheumatoid arthritis (RA) remains unknown. Therefore, we aimed to evaluate whether serum ANA was associated with an increased risk of RA in a case–control study.

Methods

Patients with rheumatoid arthritis hospitalized at Shandong Provincial Hospital from January 2018 to December 2022 were recruited as the case group, and patients with other types of arthritis and healthy people at the same time were taken as the control group. Antinuclear antibody (ANA) was detected by indirect immunofluorescence assays. Propensity score matching was employed to construct a cohort of patients exhibiting comparable baseline characteristics. The relationship between serum ANA and the risk of rheumatoid arthritis was analyzed by logistic regression analysis.

Results

A total of 1,175 patients with RA and 1,662 control subjects were included in this study. After adjusting for potential confounding factors in the propensity-score matched cohort, the risk of RA gradually increased with rising of ANA titers. When ANA titers were divided into three groups (1:100, 1:320, and 1:1,000), the OR (95% CI) for ANA titers from low to high was 3.95 (3.01, 5.18), 16.63 (9.44, 29.30), and 17.34 (9.53, 31.54), respectively, compared to those when ANA was negative. The ANA patterns closely related to the occurrence of RA include nuclear homogeneous, nuclear speckled, and cytoplasmic speckled. Among them, the positive rate of nuclear homogeneous was the highest, which accounted for 42.64%. The OR (95% CI) of ANA patterns including nuclear homogeneous, nuclear speckled, and cytoplasmic speckled was 16.81 (11.46, 24.65), 3.40 (2.49, 4.63), and 3.09 (1.77, 5.40), respectively.

Conclusion

There was a curve relation between ANA titer and RA, and the higher the ANA titer, the higher the probability of RA. However, there was no statistical difference in probability of RA for 1:320 versus 1:1,000 ANA titers. The most important kind of ANA pattern in the blood of RA patients was nuclear homogeneous. These findings suggest that ANA may be a novel risk marker for RA.
Microglial repopulation restricts ocular inflammation and choroidal neovascularization in mice
Authors: Song Yinting , Liao Yuefeng , Liu Tong , Chen Yanxian , Wang Fei , Zhou Zixia , Zhang Weili , Li Jinying
Published: April 2024

Introduction

Age-related macular degeneration (AMD) is a prevalent, chronic and progressive retinal degenerative disease characterized by an inflammatory response mediated by activated microglia accumulating in the retina. In this study, we demonstrate the therapeutically effects and the underlying mechanisms of microglial repopulation in the laser-induced choroidal neovascularization (CNV) model of exudative AMD.

Methods

The CSF1R inhibitor PLX3397 was used to establish a treatment paradigm for microglial repopulation in the retina. Neovascular leakage and neovascular area were examined by fundus fluorescein angiography (FFA) and immunostaining of whole-mount RPE-choroid-sclera complexes in CNV mice receiving PLX3397. Altered cellular senescence was measured by beta-galactosidase (SA-β-gal) activity and p16INK4a expression. The effect and mechanisms of repopulated microglia on leukocyte infiltration and the inflammatory response in CNV lesions were analyzed.

Results

We showed that ten days of the CSF1R inhibitor PLX3397 treatment followed by 11 days of drug withdrawal was sufficient to stimulate rapid repopulation of the retina with new microglia. Microglial repopulation attenuated pathological choroid neovascularization and dampened cellular senescence in CNV lesions. Repopulating microglia exhibited lower levels of activation markers, enhanced phagocytic function and produced fewer cytokines involved in the immune response, thereby ameliorating leukocyte infiltration and attenuating the inflammatory response in CNV lesions.

Discussion

The microglial repopulation described herein are therefore a promising strategy for restricting inflammation and choroidal neovascularization, which are important players in the pathophysiology of AMD.
Lipid nanoparticle composition for adjuvant formulation modulates disease after influenza virus infection in quadrivalent influenza vaccine vaccinated mice
Authors: Jangra Sonia , Lamoot Alexander , Singh Gagandeep , Laghlali Gabriel , Chen Yong , Ye Tingting , García-Sastre Adolfo , De Geest Bruno G. , Schotsaert Michael
Published: April 2024

There are considerable avenues through which currently licensed influenza vaccines could be optimized. We tested influenza vaccination in a mouse model with two adjuvants: Sendai virus-derived defective interfering (SDI) RNA, a RIG-I agonist; and an amphiphilic imidazoquinoline (IMDQ-PEG-Chol), a TLR7/8 agonist. The negatively charged SDI RNA was formulated into lipid nanoparticles (LNPs) facilitating direct delivery of SDI RNA to the cytosol, where RIG-I sensing induces inflammatory and type I interferon responses. We previously tested SDI RNA and IMDQ-PEG-Chol as standalone and combination adjuvants for influenza and SARS-CoV-2 vaccines. Here, we tested two different ionizable lipids, K-Ac7-Dsa and S-Ac7-Dog, for LNP formulations. The LNPs were incorporated with SDI RNA to determine its potential as a combination adjuvant with IMDQ-PEG-Chol by evaluating the host immune response to vaccination and infection in immunized BALB/c mice. Adjuvanticity of IMDQ-PEG-Chol with and without empty or SDI-loaded LNPs was validated with quadrivalent inactivated influenza vaccine (QIV), showing robust induction of antibody titers and T-cell responses. Depending on the adjuvant combination and LNP formulation, humoral and cellular vaccine responses could be tailored towards type 1 or type 2 host responses with specific cytokine profiles that correlated with the protective responses to viral infection. The extent of protection conferred by different vaccine/LNP/adjuvant combinations was tested by challenging mice with a vaccine-matched strain of influenza A virus A/Singapore/gp1908/2015 IVR-180 (H1N1). Groups that received either LNP formulated with SDI or IMDQ-PEG-Chol, or both, showed very low levels of viral replication in their lungs at 5 days post-infection (DPI). These studies provide evidence that the combination of vaccines with LNPs and/or adjuvants promote antigen-specific cellular responses that can contribute to protection upon infection. Interestingly, we observed differences in humoral and cellular responses to vaccination between different groups receiving K-Ac7-Dsa or S-Ac7-Dog lipids in LNP formulations. The differences were also reflected in inflammatory responses in lungs of vaccinated animals to infection, depending on LNP formulations. Therefore, this study suggests that the composition of the LNPs, particularly the ionizable lipid, plays an important role in inducing inflammatory responses in vivo, which is important for vaccine safety and to prevent adverse effects upon viral exposure.
Mechanism of electro-acupuncture in alleviating intestinal injury in septic mice via polyamine-related M2-macrophage polarization
Authors: Xu Xinyi , Huang Xianglong , Xiao Lu , Wang Jiabao , Yang Xiaokun , Wu Yifan
Published: April 2024

Objective

The objective of this study was to investigate the impact of electro-acupuncture (EA) on sepsis-related intestinal injury and its relationship with macrophage polarization.

Methods

A sepsis model was established using cecal ligation and puncture (CLP) to assess the effectiveness of EA. The extent of pathological injury was evaluated using Chiu’s score, the expression of ZO-1 and Ocludin, and the impact on macrophage polarization was examined through flow cytometry and immunofluorescence staining. The expression of spermidine, one type of polyamine, and ornithine decarboxylase (ODC) was measured using ELISA and PCR. Once the efficacy was determined, a polyamine depletion model was created, and the role of polyamines was reassessed by evaluating efficacy and observing macrophage polarization.

Results

EA treatment reduced the Chiu’s score and increased the expression of ZO-1 and Ocludin in the intestinal tissue of septic mice. It inhibited the secretion of IL-1β and TNF-α, promoted the polarization of M2-type macrophages, increased the secretion of IL-10, and upregulated the expression of Arg-1, spermidine, and ODC. However, after depleting polyamines, the beneficial effects of EA on alleviating intestinal tissue damage and modulating macrophage polarization disappeared.

Conclusion

The mechanism underlying the alleviation of intestinal injury associated with CLP-induced sepsis by EA involves with the promotion of M2-type macrophage polarization mediated by spermidine expression.
Dimethyl fumarate alleviates allergic asthma by strengthening the Nrf2 signaling pathway in regulatory T cells
Authors: Cen Yanhong , Li Fangfang , Li Yikui , Zhang Kaimin , Riaz Farooq , Zhao Kuaile , Wei Ping , Pan Fan
Published: April 2024

Allergic asthma is a widely prevalent inflammatory condition affecting people across the globe. T cells and their secretory cytokines are central to the pathogenesis of allergic asthma. Here, we have evaluated the anti-inflammatory impact of dimethyl fumarate (DMF) in allergic asthma with more focus on determining its effect on T cell responses in allergic asthma. By utilizing the ovalbumin (OVA)-induced allergic asthma model, we observed that DMF administration reduced the allergic asthma symptoms and IgE levels in the OVA-induced mice model. Histopathological analysis showed that DMF treatment in an OVA-induced animal model eased the inflammation in the nasal and bronchial tissues, with a particular decrease in the infiltration of immune cells. Additionally, RT-qPCR analysis exhibited that treatment of DMF in an OVA-induced model reduced the expression of inflammatory cytokine (IL4, IL13, and IL17) while augmenting anti-inflammatory IL10 and Foxp3 (forkhead box protein 3). Mechanistically, we found that DMF increased the expression of Foxp3 by exacerbating the expression of nuclear factor E2-related factor 2 (Nrf2), and the in-vitro activation of Foxp3+ Tregs leads to an escalated expression of Nrf2. Notably, CD4-specific Nrf2 deletion intensified the allergic asthma symptoms and reduced the in-vitro iTreg differentiation. Meanwhile, DMF failed to exert protective effects on OVA-induced allergic asthma in CD4-specific Nrf2 knock-out mice. Overall, our study illustrates that DMF enhances Nrf2 signaling in T cells to assist the differentiation of Tregs, which could improve the anti-inflammatory immune response in allergic asthma.