bluuebunny/crossref_metadata_2025 huggingface dataset:
An Assessment of Austrian School Students’ Mental Health and Their Wish for Support: A Mixed Methods Approach
Authors: Haider Katja , Humer Elke , Weber Magdalena , Pieh Christoph , Ghorab Tiam , Dale Rachel , Dinhof Carina , Gächter Afsaneh , Probst Thomas , Jesser Andrea
Published: March 2023

The mental health of school students has been severely impacted by the aftermath of the COVID-19 pandemic. The present study used a mixed methods approach to assess students’ mental health and examine their wishes for support to improve their psychological well-being. We further investigated gender and age group differences in the amount of clinically relevant mental health problems and the roles that mental health and gender had on desired support. Between April and May 2022, a total of 616 Austrian students aged between 14 and 20 participated in a cross-sectional online survey (77.4% female; 19.8% male; 2.8% non-binary) assessing wishes for support regarding mental well-being and mental health indicators (depression: PHQ-9; anxiety: GAD-7; insomnia: ISI; stress: PSS-10; eating disorders: SCOFF; alcohol abuse: CAGE). A wish for support was expressed by 46.6% of the students. Qualitative content analysis revealed that the two most important categories of desired support types were “professional help” and “someone to talk to”. The group of students with a wish for support in general significantly more often showed clinically relevant depression, anxiety, insomnia, eating disorders, or high stress symptoms. Students that wished for professional help significantly more often exceeded the cut-off for clinically relevant depression, anxiety, and high stress. Those who wished for someone to talk to significantly more often exceeded the cut-off for clinically relevant eating disorders. The results indicate a great need for support for young people’s mental health problems and that this need is even more urgent for students.
Associations between Socioeconomic Status and Psychological Distress: An Analysis of Disaggregated Latinx Subgroups Using Data from the National Health Interview Survey
Authors: McSorley Anna-Michelle Marie , Bacong Adrian Matias
Published: March 2023

Differences in socioeconomic status (SES), including income, education, and employment, continue to be significant contributors to health disparities in the United States (US), including disparities in mental health outcomes. Despite the size and diversity of the Latinx population, there is a lack of literature describing differences in mental health outcomes, including psychological distress, for Latinx subgroups (e.g., Dominican, Puerto Rican, Cuban). Therefore, we used pooled data from the 2014–2018 National Health Interview Survey to examine variations in psychological distress among Latinx subgroups as compared to other Latinx subgroups and non-Latinx whites. Additionally, we conducted regression analyses and tested whether race/ethnicity modified the relationship between SES indicators and psychological distress. Findings indicate that individuals categorized as Dominican and Puerto Rican were among the Latinx subgroups with the highest levels of psychological distress when compared to other Latinx subgroups and non-Latinx whites. Additionally, results demonstrate that SES indicators, such as higher levels of income and education, were not necessarily significantly associated with lower levels of psychological distress for all Latinx subgroups when compared to non-Latinx whites. Our findings discourage the practice of making broad generalizations about psychological distress or its associations with SES indicators to all Latinx subgroups using results garnered from the aggregate Latinx category.
How Do Repeated Viewings in Forest Landscapes Influence Young People’s Visual Behaviors and Cognitive Evaluations?
Authors: Wu Mengyun , Gao Yu , Zhang Zhi , Zhang Bo , Meng Huan , Zhang Weikang , Zhang Tong
Published: March 2023

Background: With the spread of the COVID-19 epidemic, it has gradually become normal to periodically visit and enjoy forest landscape resources in the suburbs of cities. For designers and managers of forest landscapes, exploring change in the visual behaviors and cognitive evaluations of people who repeatedly view forest landscapes and the characteristics of this change will aid the design and sustainable utilization of forest landscape resources in the suburbs of cities. Purpose: From the perspective of users’ preferences for forest landscape space, this study explored the changes in visual behavior characteristics and psychological preference characteristics for individuals who repeatedly view forest landscapes and their drivers under different preferences. Methods: This study collected data from 52 graduate and undergraduate students. We used a difference test to compare the differences in the visual behavior coincidence degree and the changes in psychological evaluations; a descriptive statistical analysis to explore young peoples’ likes and dislikes of landscape elements; and Spearman correlation analysis to explore the correlation between the psychological evaluations and visual behaviors. Main results: 1. At the second viewing, the participants’ regression behavior tended to decrease for various spaces, and they were more inclined to view areas that they had not viewed before. In addition, at the second viewing, the degree of fixation behavior coincidence was generally low, and there were obvious differences across spaces; 2. The participants’ feature evaluations and comprehensive evaluations for landscapes did not change significantly with their increased familiarity with the spaces; 3. There was a significant positive correlation between the participants’ psychological evaluations of landscape stimuli and the degree of fixation coincidence when viewing the spaces, among which the rate of distant clarity and the degree of fixation behavior coincidence were significantly and positively correlated. Meanwhile, at the second viewing, the number of favorite elements in the lookout space, which belongs to high-preference spaces, noticeably increased.
The Impact of COVID-19 on New Kidney Cancer Diagnosis: Stage and Treatment in Northern Italy
Authors: Mangone Lucia , Marinelli Francesco , Bonfante Giulia , Bisceglia Isabella , Morabito Fortunato , Masini Cristina , Bergamaschi Franco Antonio Mario , Pinto Carmine
Published: March 2023

This study aims to evaluate the impact of COVID-19 on new renal carcinoma (RC) diagnoses using data from the Reggio Emilia Cancer Registry in 2018–2020. A total of 293 RCs were registered, with roughly 100 cases yearly. The distribution by age shows a significant decrease in the 30–59 age group (33.7% in 2018, 24.8% in 2019, and 19.8% in 2020). The incidence of Stage I was 59.4%, 46.5%, and 58.2% in 2018, 2019, and 2020, respectively, whereas the Stage II rate had values of 6.9%, 7.9%, and 2.2% in the years 2018, 2019, and 2020, respectively. Slight non-significant variations were observed in Stages III and IV. Surgery was performed in 83.2% of cases in 2018, 78.2% in 2019, and 82.4% in 2020; the surgery distribution by stage showed no significant differences. Chemotherapy showed an increase in 2020, which was statistically significant only for Stage IV. The gender incidence trends over the last 25 years showed an increase in the male sex in the first period; then, a decline was documented, likely due to a decrease in cigarette consumption. In females, the trend was constant. The RC mortality trend significantly dropped in both genders over the entire study period.
Lessons Learned—The Impact of the Third Wave of the COVID-19 Pandemic on German Waldorf Parents’ Support Needs and Their Rating of Children’s Health-Related Quality of Life: A Cross-Sectional Online Survey
Authors: Vagedes Jan , Michael Karin , Sobh Mohsen , Islam Mohammad O. A. , Kuderer Silja , Jeske Christian , Kaman Anne , Martin David , Vagedes Katrin , Erhart Michael , Ravens-Sieberer Ulrike , Zdražil Tomáš
Published: March 2023

Background: COVID-19-related lockdowns and homeschooling have imposed a substantial burden on school-aged children and parents. Waldorf education is a reform-educational concept. Little is known about the situation of German Waldorf families under pandemic conditions. Methods: A cross-sectional, online, parent-proxy survey was conducted regarding the third pandemic wave. The primary outcome was parents’ support needs, assessed with questions from the German COPSY (COVID-19 and PSYchological Health) study; the secondary outcome was children’s HRQoL (KIDSCREEN-10, proxy version). Results: We analyzed questionnaires from 431 parents of 511 Waldorf students aged 7 to 17 years. While 70.8% of Waldorf parents (WPs) reported a general need for support in dealing with their children, 59.9% of COPSY parents (CPs) indicated this need. WPs’ support needs in dealing with their children’s academic demands were similar to CPs’ needs but relatively higher in terms of dealing with emotions and moods, behavior, and relationships within the family. WPs sought support mainly from school and teachers (65.6%). Support needs were high, although WPs rated their children’s HRQoL higher than CPs. Conclusions: Our results underline the substantial pandemic-related burden on families across school types. WPs participating in this survey gave evidence that supports should focus on academic demands as well as psychosocial issues.
Health System Factors Affecting the Experience of Non-Invasive Ventilation Provision of People with Neuromuscular Disorders in New Zealand
Authors: Perry Meredith A. , Jones Bernadette , Jenkins Matthew , Devan Hemakumar , Neill Alister , Ingham Tristram
Published: March 2023

Non-invasive ventilation (NIV) is a critical therapy for many patients with neuromuscular disorders (NMD), supporting those with respiratory failure to achieve adequate respiration and improve their quality of life. The aim of this study was to explore the experiences of access to, consent, uptake, maintenance and safe use of non-invasive ventilation by people with NMD. Semi-structured individual interviews were conducted with 11 people with NMD, each using NIV for more than 12 months. A critical realism ontological paradigm with contextualism epistemology guided the Reflexive Thematic Analysis. An Equity of Health Care Framework underpinned the analysis. Three themes were interpreted: Uptake and informed consent for NIV therapy; Practicalities of NIV; and Patient-clinician relationships. We identified issues at the system, organization and health professional levels. Conclusions: We recommend the development of national service specifications with clear standards and dedicated funding for patients with NMD and call on the New Zealand Ministry of Health to proactively investigate and monitor the variations in service delivery identified. The specific areas of concern for patients with NMD suggest the need for NMD-related NIV research and service provision responsive to the distinct needs of this population.
Influence of Environmental Exposure to Steel Waste on Endocrine Dysregulation and PER3 Gene Polymorphisms
Authors: Coutinho Gilvania Barreto Feitosa , Moreira Maria de Fátima Ramos , Fischer Frida Marina , dos Santos Maria Carolina Reis , Feitosa Lucas Ferreira , de Azevedo Sayonara Vieira , Borges Renato Marçullo , Nascimento-Sales Michelle , Christoffolete Marcelo Augusto , Santa-Marinha Marden Samir , Valente Daniel , Teixeira Liliane Reis
Published: March 2023

Objective: To evaluate the association between environmental exposure to the following chemical substances: cadmium (Cd), lead (Pb), nickel (Ni), manganese (Mn), benzene (BZN), and toluene (TLN), and Period Circadian Regulator 3 (PER3) gene variable number of tandem repeats (VNTR) polymorphisms, according to chronotype in a population living in a steel residue-contaminated area. Methods: This assessment comprises a study conducted from 2017 to 2019 with 159 participants who completed health, work, and Pittsburgh sleep scale questionnaires. Cd, Pb, Ni, Mn, BZN, and TLN concentrations in blood and urine were determined by Graphite Furnace Atomic Absorption Spectrometry (GFAAS) and Headspace Gas Chromatography (GC), and genotyping was carried out using Polymerase Chain Reaction (PCR). Results: A total of 47% of the participants were afternoon chronotype, 42% were indifferent, and 11% were morning chronotype. Insomnia and excessive sleepiness were associated with the indifferent chronotype, while higher urinary manganese levels were associated with the morning chronotype (Kruskal–Wallis chi-square = 9.16; p < 0.01). In turn, the evening chronotype was associated with poorer sleep quality, higher lead levels in blood, and BZN and TLN levels in urine (χ2 = 11.20; p < 0.01) in non-occupationally exposed individuals (χ2 = 6.98; p < 0.01) as well as the highest BZN (χ2 = 9.66; p < 0.01) and TLN (χ2 = 5.71; p < 0.01) levels detected in residents from the influence zone 2 (far from the slag). Conclusion: Mn, Pb, benzene, and toluene contaminants may have influenced the different chronotypes found in the steel residue-exposed population.
Mamwi Gidaanjitoomin/Together We Build It: A Systematic Review of Traditional Indigenous Building Structures in North America and Their Potential Application in Contemporary Designs to Promote Environment and Well-Being
Authors: Mashford-Pringle Angela , Fu Ruofan , Stutz Sterling
Published: March 2023

(1) Background: Housing has long been recognized as an essential determinant of health. Our sense of home goes beyond physical shelter and is associated with personal or collective connections with spaces and places. However, modern architecture has gradually lost its connections between people and places; (2) Methods: We examined traditional Indigenous architecture and how it can be utilized in contemporary settings to restore connections to promote the environment, health, and well-being. (3) Results: We found that traditional Indigenous building structures may be the best manifestation of the Indigenous interconnected and holistic worldviews in North America, containing thousands of years of knowledge and wisdom about the land and the connection between humans and the environment, which is the foundation of reciprocal well-being; (4) Conclusions: Learning from the traditional structures, we proposed that modern architects should consider the past, present, and future in every endeavor and design and to utilize traditional knowledge as a crucial source of inspiration in creating works that are beneficial for both current and future generations by taking collectivism, health and well-being, and the environment into consideration in designs.
Nurses’ Perceptions of Ethical Conflicts When Caring for Patients with COVID-19
Authors: Caro-Alonso Pedro Ángel , Rodríguez-Martín Beatriz , Rodríguez-Almagro Julián , Chimpén-López Carlos , Romero-Blanco Cristina , Casado Naranjo Ignacio , Hernández-Martínez Antonio , López-Espuela Fidel
Published: March 2023

The COVID-19 pandemic has caused ethical challenges and dilemmas in care decisions colliding with nurses’ ethical values. This study sought to understand the perceptions and ethical conflicts faced by nurses working on the frontline during the first and second waves of the COVID-19 pandemic and the main coping strategies. A qualitative phenomenological study was carried out following Giorgi’s descriptive phenomenological approach. Data were collected through semi-structured interviews until data saturation. The theoretical sample included 14 nurses from inpatient and intensive care units during the first and second waves of the pandemic. An interview script was used to guide the interviews. Data were analyzed following Giorgi’s phenomenological method using Atlas-Ti software. Two themes were identified: (1) ethical conflicts on a personal and professional level; and (2) coping strategies (active and autonomous learning, peer support and teamwork, catharsis, focusing on care, accepting the pandemic as just another work situation, forgetting the bad situations, valuing the positive reinforcement, and humanizing the situation). The strong professional commitment, teamwork, humanization of care, and continuous education have helped nurses to deal with ethical conflicts. It is necessary to address ethical conflicts and provide psychological and emotional support for nurses who have experienced personal and professional ethical conflicts during COVID-19.
Advancing Access to Quality LGBTQIA+ Health Care: Gender Discrimination, Socio-Cultural, and Mental Health Issues: A Mixed-Method Study
Authors: Argyriadis Alexandros , Fradelos Evangelos C. , Argyriadi Agathi , Ziegler Erin , Kaba Evridiki
Published: March 2023

Recent research highlights the lack of knowledge and reduced skills of health care professionals in communicating with people from the LGBTQIA+ community. This often occurs due to reduced continuing education on social issues in the health sector. The purpose of this research was to study the readiness of health care professionals to manage the social and mental health issues of the LGBTQIA+ community. In particular, the cultural competence of health care professionals targeted at gender identity, the recognition of the level of mastery of soft skills, and the relevant experiences of the participants were studied. For the purposes of conducting this research, a mixed methodology was used to pursue an in-depth study of human beliefs, attitudes, perceptions, ideas, and experiences. More specifically, a previously validated research tool was used to measure cultural competence and assess soft skills. At the same time, interviews were conducted with health care professionals for a more complete understanding of their skills and attitudes. The study comprised a quantitative study involving 479 health care professionals and a qualitative study involving 20 health care professionals, with results from each study. The results showed that the health care professionals’ knowledge of the LGBTQIA+ community is sufficient, but their skills and attitudes towards gender diversity are limited. In addition, the level of acquisition of soft skills by health care professionals is low, and there is insufficient training for health care professionals with regards to social issues. In conclusion, a targeted and structured educational intervention for health care professionals is required to avoid future unfortunate behaviours, and to ensure that the health care provided to healthy and sick populations, regardless of sexual orientation, is adequate.
The Theoretical Lineage and Evolutionary Logic of Research on the Environmental Behavior of Family Firms: A Literature Review
Authors: Geng Limin , Lu Xueyuan , Zhang Can
Published: March 2023

Family firms research is becoming one of the most important and promising areas for theoretical innovation in management practice. Corporate environmental behavior has attracted widespread academic attention, but the research on the environmental behavior of family firms is obviously insufficient, and the relevant research results are still in a fragmented state. In this paper, we review and summarize the existing research on the environmental behavior of family firms from three aspects: the research dimensions, the influencing factors, and the influencing effects, and try to sort out the theoretical lineage and evolutionary logic of the environmental behavior of family firms. From the existing research results, the research on the influencing factors and effects of family firms’ environmental behavior is at the stage of strife, and there is a lack of in-depth and systematic research on the mechanisms affecting the environmental behavior of family firms and the changes of their effects. In the future, we can explore how to apply or integrate multiple theories simultaneously for complementary explanations, so as to provide a reference for the government to formulate targeted policies to stimulate and regulate the environmental behaviors of family firms.
Extracellular Vesicles: The Future of Diagnosis in Solid Organ Transplantation?
Authors: Romero-García Nekane , Huete-Acevedo Javier , Mas-Bargues Cristina , Sanz-Ros Jorge , Dromant Mar , Badenes Rafael , Borrás Consuelo
Published: March 2023

Solid organ transplantation (SOT) is a life-saving treatment for end-stage organ failure, but it comes with several challenges, the most important of which is the existing gap between the need for transplants and organ availability. One of the main concerns in this regard is the lack of accurate non-invasive biomarkers to monitor the status of a transplanted organ. Extracellular vesicles (EVs) have recently emerged as a promising source of biomarkers for various diseases. In the context of SOT, EVs have been shown to be involved in the communication between donor and recipient cells and may carry valuable information about the function of an allograft. This has led to an increasing interest in exploring the use of EVs for the preoperative assessment of organs, early postoperative monitoring of graft function, or the diagnosis of rejection, infection, ischemia-reperfusion injury, or drug toxicity. In this review, we summarize recent evidence on the use of EVs as biomarkers for these conditions and discuss their applicability in the clinical setting.
Kinase Inhibitor VvBKI1 Interacts with Ascorbate Peroxidase VvAPX1 Promoting Plant Resistance to Oomycetes
Authors: Lv Junli , Wu Wei , Ma Tao , Yang Bohan , Khan Asaf , Fu Peining , Lu Jiang
Published: March 2023

Downy mildew caused by oomycete pathogen Plasmopara viticola is a devastating disease of grapevine. P. viticola secretes an array of RXLR effectors to enhance virulence. One of these effectors, PvRXLR131, has been reported to interact with grape (Vitis vinifera) BRI1 kinase inhibitor (VvBKI1). BKI1 is conserved in Nicotiana benthamiana and Arabidopsis thaliana. However, the role of VvBKI1 in plant immunity is unknown. Here, we found transient expression of VvBKI1 in grapevine and N. benthamiana increased its resistance to P. viticola and Phytophthora capsici, respectively. Furthermore, ectopic expression of VvBKI1 in Arabidopsis can increase its resistance to downy mildew caused by Hyaloperonospora arabidopsidis. Further experiments revealed that VvBKI1 interacts with a cytoplasmic ascorbate peroxidase, VvAPX1, an ROS-scavenging protein. Transient expression of VvAPX1 in grape and N. benthamiana promoted its resistance against P. viticola, and P. capsici. Moreover, VvAPX1 transgenic Arabidopsis is more resistant to H. arabidopsidis. Furthermore, both VvBKI1 and VvAPX1 transgenic Arabidopsis showed an elevated ascorbate peroxidase activity and enhanced disease resistance. In summary, our findings suggest a positive correlation between APX activity and resistance to oomycetes and that this regulatory network is conserved in V. vinifera, N. benthamiana, and A. thaliana.
CoNiCrMo Particles, but Not TiAlV Particles, Activate the NLRP3 Inflammasome in Periprosthetic Cells
Authors: Brunken Fenna , Senft Tristan , Herbster Maria , Relja Borna , Bertrand Jessica , Lohmann Christoph H.
Published: March 2023

Aseptic loosening is the main reason for arthroplasty failure. The wear particles generated at the tribological bearings are thought to induce an inflammatory tissue response, leading to bone loss and the subsequent loosening of the implant. Different wear particles have been shown to activate the inflammasome, thereby contributing to an inflammatory milieu in the direct vicinity of the implant. The aim of this study was to investigate whether the NLRP3 inflammasome is activated by different metal particles in vitro and in vivo. Three different cell lines representing periprosthetic cell subsets (MM6, MG63 and Jurkat) were incubated with different amounts of TiAlV or CoNiCrMo particles. The activation of the NLRP3 inflammasome was determined through the detection of the caspase 1 cleavage product p20 in a Western blot. The formation of the inflammasome was also investigated in vivo using immunohistological staining for ASC in primary synovial tissues as well as tissues containing TiAlV and CoCrMo particles and in vitro after the stimulation of the cells. The results show that the CoCrMo particles induced ASC more markedly, as a readout for inflammasome formation in vivo, compared to TiAlV particular wear. The CoNiCrMo particles also induced ASC-speck formation in all the tested cell lines, which was not induced by the TiAlV particles. The Western blot shows that NRLP3 inflammasome activation, measured through caspase 1 cleavage, was increased only by the CoNiCrMo particles in the MG63 cells. We conclude from our data that the activation of the inflammasome is mainly driven by CoNiCrMo particles and less by TiAlV particles, indicating that different inflammatory pathways are activated by the different alloys.
Anti-Inflammatory, Antimicrobial, Antioxidant and Photoprotective Investigation of Red Propolis Extract as Sunscreen Formulation in Polawax Cream
Authors: Valverde Thalita Marcolan , Soares Bruna Nayane Goncalves de Souza , Nascimento Andréa Mendes do , Andrade Ângela Leão , Sousa Lucas Resende Dutra , Vieira Paula Melo de Abreu , Santos Vagner Rodrigues , Seibert Janaína Brandão , Almeida Tatiane Cristine Silva de , Rodrigues Caio Fabrini , Oliveira Samantha Roberta Machado de , Martins Flaviano dos Santos , Júnior Jeronimo Geraldo Ferreira , Santos Viviane Martins Rebello dos
Published: March 2023

Many activities have been described for propolis, including, antiviral, antibacterial, antifungal, anti-inflammatory, immunoregulatory, antioxidant and wound healing properties. Recently, propolis has been highlighted due to its potential application in the pharmaceutical and cosmetic industries, motivating a better understanding of its antioxidant and anti-inflammatory activities. Propolis and its main polyphenolic compounds presented high antioxidant activity, and effectiveness as broad spectrum UVB and UVA photoprotection sunscreens. Through a qualitative phytochemical screening, the ethanolic red propolis extracts (EEPV) (70% at room temperature and 70% at a hot temperature) presented a positive result for flavonoids and terpenoids. It presented an antioxidant activity for reducing 50% of DPPH of 17 and 12 μg/mL for extraction at room temperature and at a hot temperature, respectively. The UPLC-QTOF-MS/MS analysis allowed the annotation of 40 substances for EEPV-Heated and 42 substances for EEPV-Room Temperature. The IC50 results of the ABTS scavenging activity was 4.7 μg/mL for both extractions, at room temperature and at a hot temperature. Additionally, we also evaluated the cytotoxic profile of propolis extracts against macrophage (RAW 264.7 cells) and keratinocytes (HaCaT cells), which showed non-cytotoxic doses in cell viability assays even after a long period of exposure. In addition, propolis extracts showed antibacterial activity for Gram-positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis), demonstrating potential biological activity for the creation of formulations aimed at disease control and prevention.
Insights from Spatial Measures of Intolerance to Identifying Pathogenic Variants in Developmental and Epileptic Encephalopathies
Authors: Silk Michael , de Sá Alex , Olshansky Moshe , Ascher David B.
Published: March 2023

Developmental and epileptic encephalopathies (DEEs) are a group of epilepsies with early onset and severe symptoms that sometimes lead to death. Although previous work successfully discovered several genes implicated in disease outcomes, it remains challenging to identify causative mutations within these genes from the background variation present in all individuals due to disease heterogeneity. Nevertheless, our ability to detect possible pathogenic variants has continued to improve as in silico predictors of deleteriousness have advanced. We investigate their use in prioritising likely pathogenic variants in epileptic encephalopathy patients’ whole exome sequences. We showed that the inclusion of structure-based predictors of intolerance improved upon previous attempts to demonstrate enrichment within epilepsy genes.
Differential Transcriptome Responses in Human THP-1 Macrophages Following Exposure to T98G and LN-18 Human Glioblastoma Secretions: A Simplified Bioinformatics Approach to Understanding Patient-Glioma-Specific Effects on Tumor-Associated Macrophages
Authors: Scobie Micaela R. , Abood Abdullah , Rice Charles D.
Published: March 2023

A common theme in glioma disease progression is robust infiltration of immune cells within the tumor microenvironment, resulting in a state of chronic inflammation. This disease state is characterized by an abundance of CD68+ microglia and CD163+ bone marrow-derived macrophages with the greater the percentage of CD163+ cells, the poorer the prognosis. These macrophages are “cold,” in that their phenotype is of an alternatively activated state (M0-M2-like) supporting tumor growth rather than being engaged with classically activated, pro-inflammatory, and anti-tumor activities, referred to as “hot”, or M1-like. Herein, we have developed an in vitro approach that uses two human glioma cell lines, T98G and LN-18, which exhibit a variety of differing mutations and characteristics, to demonstrate their disparate effects on differentiated THP-1 macrophages. We first developed an approach to differentiating THP-1 monocytes to macrophages with mixed transcriptomic phenotypes we regard as M0-like macrophages. We then found that supernatants from the two different glioma cell lines induced different gene expression profiles in THP-1 macrophages, suggesting that from patient to patient, gliomas may be considered as different diseases. This study suggests that in addition to standard glioma treatment modalities, transcriptome profiling of the effects of cultured glioma cells on a standard THP-1 macrophage in vitro model may lead to future druggable targets that aim to reprogram tumor-associated macrophages towards an anti-tumor phenotype.
A Comprehensive and Integrative Approach to MeCP2 Disease Transcriptomics
Authors: Trostle Alexander J. , Li Lucian , Kim Seon-Young , Wang Jiasheng , Al-Ouran Rami , Yalamanchili Hari Krishna , Liu Zhandong , Wan Ying-Wooi
Published: March 2023

Mutations in MeCP2 result in a crippling neurological disease, but we lack a lucid picture of MeCP2′s molecular role. Individual transcriptomic studies yield inconsistent differentially expressed genes. To overcome these issues, we demonstrate a methodology to analyze all modern public data. We obtained relevant raw public transcriptomic data from GEO and ENA, then homogeneously processed it (QC, alignment to reference, differential expression analysis). We present a web portal to interactively access the mouse data, and we discovered a commonly perturbed core set of genes that transcends the limitations of any individual study. We then found functionally distinct, consistently up- and downregulated subsets within these genes and some bias to their location. We present this common core of genes as well as focused cores for up, down, cell fraction models, and some tissues. We observed enrichment for this mouse core in other species MeCP2 models and observed overlap with ASD models. By integrating and examining transcriptomic data at scale, we have uncovered the true picture of this dysregulation. The vast scale of these data enables us to analyze signal-to-noise, evaluate a molecular signature in an unbiased manner, and demonstrate a framework for future disease focused informatics work.
NETs Promote Inflammatory Injury by Activating cGAS-STING Pathway in Acute Lung Injury
Authors: Zhao Jie , Zhen Ningxin , Zhou Qichao , Lou Jian , Cui Wei , Zhang Gensheng , Tian Baoping
Published: March 2023

Acute respiratory distress syndrome (ARDS) threatens the survival of critically ill patients, the mechanisms of which are still unclear. Neutrophil extracellular traps (NETs) released by activated neutrophils play a critical role in inflammatory injury. We investigated the role of NETs and the underlying mechanism involved in acute lung injury (ALI). We found a higher expression of NETs and cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) in the airways, which was reduced by Deoxyribonuclease I (DNase I) in ALI. The administration of the STING inhibitor H-151 also significantly relieved inflammatory lung injury, but failed to affect the high expression of NETs in ALI. We isolated murine neutrophils from bone marrow and acquired human neutrophils by inducing HL-60 to differentiate. After the PMA interventions, exogenous NETs were obtained from such extracted neutrophils. Exogenous NETs intervention in vitro and in vivo resulted in airway injury, and such inflammatory lung injury was reversed upon degrading NETs with or inhibiting cGAS-STING with H-151 as well as siRNA STING. In conclusion, cGAS-STING participates in regulating NETs-mediated inflammatory pulmonary injury, which is expected to be a new therapeutic target for ARDS/ALI.
Repeated Application and Removal of Polyisocyanopeptide Hydrogel Wound Dressings in a Splinted Full-Thickness Wound Model
Authors: Op ‘t Veld Roel C. , Joosten Lieke , Laverman Peter , Bronkhorst Ewald M. , Jansen John A. , Walboomers X. Frank , Wagener Frank A. D. T. G.
Published: March 2023

Polyisocyanopeptide (PIC) hydrogels are proposed as promising wound dressings. These gels are thermo-sensitive, allow application as a cold liquid, and rely on gelation through body heat. It is supposed that the gel can be easily removed by reversing the gelation and washing it away with a cold irrigation solution. The impact on wound healing of the regular application and removal of PIC dressings is compared to a single application of PIC and the clinically used Tegaderm™ in murine splinted full-thickness wounds for up to 14 days. SPECT/CT analysis of 111In-labelled PIC gels showed that, on average, 58% of the PIC gel could be washed out of the wounds with the employed method, which is, however, heavily influenced by personal technique. Evaluation with photography and (immuno-)histology showed that wounds in which PIC dressings were regularly removed and replaced were smaller at 14 days post-injury but performed on par with the control treatment. Moreover, the encapsulation of PIC in wound tissue was less severe and occurred less often when PIC was regularly refreshed. In addition, no morphological damage related to the removal procedure was observed. Thus, PIC gels are atraumatic and perform similarly to currently employed wound dressing materials, offering possible future benefits for both clinicians and patients.
In Vitro Antiviral and Anti-Inflammatory Activities of N-Acetylglucosamine: Development of an Alternative and Safe Approach to Fight Viral Respiratory Infections
Authors: Marchetti Magda , De Berardis Barbara , Bigioni Irene , Mariano Alessia , Superti Fabiana , Scotto d’Abusco Anna
Published: March 2023

Viral respiratory tract infections (RTIs) are responsible for significant morbidity and mortality worldwide. A prominent feature of severe respiratory infections, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is the cytokine release syndrome. Therefore, there is an urgent need to develop different approaches both against viral replication and against the consequent inflammation. N-acetylglucosamine (GlcNAc), a glucosamine (GlcN) derivative, has been developed as an immunomodulatory and anti-inflammatory inexpensive and non-toxic drug for non-communicable disease treatment and/or prevention. Recent studies have suggested that GlcN, due to its anti-inflammatory activity, could be potentially useful for the control of respiratory virus infections. Our present study aimed to evaluate in two different immortalized cell lines whether GlcNAc could inhibit or reduce both viral infectivity and the inflammatory response to viral infection. Two different viruses, frequent cause of upper and lower respiratory tract infections, were used: the H1N1 Influenza A virus (IAV) (as model of enveloped RNA virus) and the Human adenovirus type 2 (Adv) (as model of naked DNA virus). Two forms of GlcNAc have been considered, bulk GlcNAc and GlcNAc in nanoform to overcome the possible pharmacokinetic limitations of GlcNAc. Our study suggests that GlcNAc restricts IAV replication but not Adv infection, whereas nano-GlcNAc inhibits both viruses. Moreover, GlcNAc and mainly its nanoformulation were able to reduce the pro-inflammatory cytokine secretion stimulated by viral infection. The correlation between inflammatory and infection inhibition is discussed.
Characterization and Vaccine Potential of Outer Membrane Vesicles from Photobacterium damselae subsp. piscicida
Authors: Teixeira Alexandra , Loureiro Inês , Lisboa Johnny , Oliveira Pedro N. , Azevedo Jorge E. , dos Santos Nuno M. S. , do Vale Ana
Published: March 2023

Photobacterium damselae subsp. piscicida (Phdp) is a Gram-negative fish pathogen with worldwide distribution and broad host specificity that causes heavy economic losses in aquaculture. Although Phdp was first identified more than 50 years ago, its pathogenicity mechanisms are not completely understood. In this work, we report that Phdp secretes large amounts of outer membrane vesicles (OMVs) when cultured in vitro and during in vivo infection. These OMVs were morphologically characterized and the most abundant vesicle-associated proteins were identified. We also demonstrate that Phdp OMVs protect Phdp cells from the bactericidal activity of fish antimicrobial peptides, suggesting that secretion of OMVs is part of the strategy used by Phdp to evade host defense mechanisms. Importantly, the vaccination of sea bass (Dicentrarchus labrax) with adjuvant-free crude OMVs induced the production of anti-Phdp antibodies and resulted in partial protection against Phdp infection. These findings reveal new aspects of Phdp biology and may provide a basis for developing new vaccines against this pathogen.
Molecular Structure of Phosphoserine Aminotransferase from Saccharomyces cerevisiae
Authors: Jang Jiyeon , Chang Jeong Ho
Published: March 2023

Phosphoserine aminotransferase (PSAT) is a pyridoxal 5′-phosphate-dependent enzyme involved in the second step of the phosphorylated pathway of serine biosynthesis. PSAT catalyzes the transamination of 3-phosphohydroxypyruvate to 3-phosphoserine using L-glutamate as the amino donor. Although structural studies of PSAT have been performed from archaea and humans, no structural information is available from fungi. Therefore, to elucidate the structural features of fungal PSAT, we determined the crystal structure of Saccharomyces cerevisiae PSAT (ScPSAT) at a resolution of 2.8 Å. The results demonstrated that the ScPSAT protein was dimeric in its crystal structure. Moreover, the gate-keeping loop of ScPSAT exhibited a conformation similar to that of other species. Several distinct structural features in the halide-binding and active sites of ScPSAT were compared with its homologs. Overall, this study contributes to our current understanding of PSAT by identifying the structural features of fungal PSAT for the first time.
Overexpression of LjPLT3 Enhances Salt Tolerance in Lotus japonicus
Authors: Liu Jiao , Liu Leru , Tian Lu , Xu Shaoming , Wu Guojiang , Jiang Huawu , Chen Yaping
Published: March 2023

Intracellular polyols are used as osmoprotectants by many plants under environmental stress. However, few studies have shown the role of polyol transporters in the tolerance of plants to abiotic stresses. Here, we describe the expression characteristics and potential functions of Lotus japonicus polyol transporter LjPLT3 under salt stress. Using LjPLT3 promoter-reporter gene plants showed that LjPLT3 was expressed in the vascular tissue of L. japonicus leaf, stem, root, and nodule. The expression was also induced by NaCl treatment. Overexpression of LjPLT3 in L. japonicus modified the growth rate and saline tolerance of the transgenic plants. The OELjPLT3 seedlings displayed reduced plant height under both nitrogen-sufficient and symbiotic nitrogen fixation conditions when 4 weeks old. The nodule number of OELjPLT3 plants was reduced by 6.7–27.4% when 4 weeks old. After exposure to a NaCl treatment in Petri dishes for 10 days, OELjPLT3 seedlings had a higher chlorophyll concentration, fresh weight, and survival rate than those in the wild type. For symbiotic nitrogen fixation conditions, the decrease in nitrogenase activity of OELjPLT3 plants was slower than that of the wild type after salt treatment. Compared to the wild type, both the accumulation of small organic molecules and the activity of antioxidant enzymes were higher under salt stress. Considering the concentration of lower reactive oxygen species (ROS) in transgenic lines, we speculate that overexpression of LjPLT3 in L. japonicus might improve the ROS scavenging system to alleviate the oxidative damage caused by salt stress, thereby increasing plant salinity tolerance. Our results will direct the breeding of forage legumes in saline land and also provide an opportunity for the improvement of poor and saline soils.
A Multi-Stage Bioprocess for the Expansion of Rodent Skin-Derived Schwann Cells in Computer-Controlled Bioreactors
Authors: Walsh Tylor , Abraham Brett , Chu Tak-Ho , Biernaskie Jeff , Midha Rajiv , Kallos Michael S.
Published: March 2023

Regenerative therapies for the treatment of peripheral nerve and spinal cord injuries can require hundreds of millions of autologous cells. Current treatments involve the harvest of Schwann cells (SCs) from nerves; however, this is an invasive procedure. Therefore, a promising alternative is using skin-derived Schwann cells (Sk-SCs), in which between 3–5 million cells can be harvested from a standard skin biopsy. However, traditional static planar culture is still inefficient at expanding cells to clinically relevant numbers. As a result, bioreactors can be used to develop reproducible bioprocesses for the large-scale expansion of therapeutic cells. Here, we present a proof-of-concept SC manufacturing bioprocess using rat Sk-SCs. With this integrated process, we were able to simulate a feasible bioprocess, taking into consideration the harvest and shipment of cells to a production facility, the generation of the final cell product, and the cryopreservation and shipment of cells back to the clinic and patient. This process started with 3 million cells and inoculated and expanded them to over 200 million cells in 6 days. Following the harvest and post-harvest cryopreservation and thaw, we were able to maintain 150 million viable cells that exhibited a characteristic Schwann cell phenotype throughout each step of the process. This process led to a 50-fold expansion, producing a clinically relevant number of cells in a 500 mL bioreactor in just 1 week, which is a dramatic improvement over current methods of expansion.
Genome-Wide Identification and Characterization of Copper Chaperone for Superoxide Dismutase (CCS) Gene Family in Response to Abiotic Stress in Soybean
Authors: Jiao Shuang , Feng Rui , He Yu , Cao Fengming , Zhao Yue , Zhou Jingwen , Zhai Hong , Bai Xi
Published: March 2023

Copper Chaperone For Superoxide Dismutase (CCS) genes encode copper chaperone for Superoxide dismutase (SOD) and dramatically affect the activity of SOD through regulating copper delivery from target to SOD. SOD is the effective component of the antioxidant defense system in plant cells to reduce oxidative damage by eliminating Reactive oxygen species (ROS), which are produced during abiotic stress. CCS might play an important role in abiotic stress to eliminate the damage caused by ROS, however, little is known about CCS in soybean in abiotic stress regulation. In this study, 31 GmCCS gene family members were identified from soybean genome. These genes were classified into 4 subfamilies in the phylogenetic tree. Characteristics of 31 GmCCS genes including gene structure, chromosomal location, collinearity, conserved domain, protein motif, cis-elements, and tissue expression profiling were systematically analyzed. RT-qPCR was used to analyze the expression of 31 GmCCS under abiotic stress, and the results showed that 5 GmCCS genes(GmCCS5, GmCCS7, GmCCS8, GmCCS11 and GmCCS24) were significantly induced by some kind of abiotic stress. The functions of these GmCCS genes in abiotic stress were tested using yeast expression system and soybean hairy roots. The results showed that GmCCS7/GmCCS24 participated in drought stress regulation. Soybean hairy roots expressing GmCCS7/GmCCS24 showed improved drought stress tolerance, with increased SOD and other antioxidant enzyme activities. The results of this study provide reference value in-depth study CCS gene family, and important gene resources for the genetic improvement of soybean drought stress tolerance.
Intracoronary Imaging of Coronary Atherosclerotic Plaque: From Assessment of Pathophysiological Mechanisms to Therapeutic Implication
Authors: Gurgoglione Filippo Luca , Denegri Andrea , Russo Michele , Calvieri Camilla , Benatti Giorgio , Niccoli Giampaolo
Published: March 2023

Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality worldwide. Several cardiovascular risk factors are implicated in atherosclerotic plaque promotion and progression and are responsible for the clinical manifestations of coronary artery disease (CAD), ranging from chronic to acute coronary syndromes and sudden coronary death. The advent of intravascular imaging (IVI), including intravascular ultrasound, optical coherence tomography and near-infrared diffuse reflectance spectroscopy has significantly improved the comprehension of CAD pathophysiology and has strengthened the prognostic relevance of coronary plaque morphology assessment. Indeed, several atherosclerotic plaque phenotype and mechanisms of plaque destabilization have been recognized with different natural history and prognosis. Finally, IVI demonstrated benefits of secondary prevention therapies, such as lipid-lowering and anti-inflammatory agents. The purpose of this review is to shed light on the principles and properties of available IVI modalities along with their prognostic significance.
Anoxia Rapidly Induces Changes in Expression of a Large and Diverse Set of Genes in Endothelial Cells
Authors: Antonelli Antonella , Scarpa Emanuele Salvatore , Bruzzone Santina , Astigiano Cecilia , Piacente Francesco , Bruschi Michela , Fraternale Alessandra , Di Buduo Christian A. , Balduini Alessandra , Magnani Mauro
Published: March 2023

Sinusoidal endothelial cells are the predominant vascular surface of the bone marrow and constitute the functional hematopoietic niche where hematopoietic stem and progenitor cells receive cues for self-renewal, survival, and differentiation. In the bone marrow hematopoietic niche, the oxygen tension is usually very low, and this condition affects stem and progenitor cell proliferation and differentiation and other important functions of this region. Here, we have investigated in vitro the response of endothelial cells to a marked decrease in O2 partial pressure to understand how the basal gene expression of some relevant biological factors (i.e., chemokines and interleukins) that are fundamental for the intercellular communication could change in anoxic conditions. Interestingly, mRNA levels of CXCL3, CXCL5, and IL-34 genes are upregulated after anoxia exposure but become downmodulated by sirtuin 6 (SIRT6) overexpression. Indeed, the expression levels of some other genes (such as Leukemia Inhibitory Factor (LIF)) that were not significantly affected by 8 h anoxia exposure become upregulated in the presence of SIRT6. Therefore, SIRT6 mediates also the endothelial cellular response through the modulation of selected genes in an extreme hypoxic condition.