bluuebunny/crossref_metadata_2025 huggingface dataset:
Materializing the metaphor: Theorizing the food desert as a sociospatial–legal instrument in the production of space
Authors: Zurawski Erica
Published: May 2023

In June of 2022, the United States Department of Agriculture (USDA) announced a new framework to address and transform the food system, including a commitment to increase funding to the Healthy Food Financing Initiative (HFFI) to the tune of $155 million to address “food deserts.” This investment is perplexing given the decade of scholarship and activism critiquing the food desert concept and its tendency to invite supply-side, corporate food retail development, of which the HFFI is emblematic. Bringing legal geographies to critical food studies, this article argues that the food desert concept, as invoked, spatialized, and abstracted by the USDA, is better understood as a socio-spatial-legal instrument imbricated in the production of space. First, this article attends to the USDA's use of the food desert as a guiding metaphor in the production of abstract space, highlighting the dominant characterizations of abstract space—fragmentation, homogenization, and hierarchy. Second, this article traces how this abstraction is materialized through US legislation and policy aimed at “fixing food deserts,” most readily through the HFFI. In the context of extensive scholarship that has criticized the prioritization of capital development and food retail, this analysis engages radical food geography praxis to outline a new terrain for struggle, namely where the discursive comingles with and co-constitutes the legal and spatial. From this analytical vantage point, this article demonstrates how the food desert concept, through US law and policy, is made material and spatial in ways that reproduce inequitable food landscapes and foreclose more radical approaches to food equity. Beyond the context of the food desert concept, this analysis offers an account of how discourse is rendered material, and the consequences therein.
Non-hypertrophic chondrogenesis of mesenchymal stem cells through mechano-hypoxia programing
Authors: Li David Xinzheyang , Ma Zhiyao , Szojka Alexander RA , Lan Xiaoyi , Kunze Melanie , Mulet-Sierra Aillette , Westover Lindsey , Adesida Adetola B
Published: May 2023

Cartilage tissue engineering aims to generate functional replacements to treat cartilage defects from damage and osteoarthritis. Human bone marrow-derived mesenchymal stem cells (hBM-MSC) are a promising cell source for making cartilage, but current differentiation protocols require the supplementation of growth factors like TGF-β1 or −β3. This can lead to undesirable hypertrophic differentiation of hBM-MSC that progress to bone. We have found previously that exposing engineered human meniscus tissues to physiologically relevant conditions of the knee (mechanical loading and hypoxia; hence, mechano-hypoxia conditioning) increased the gene expression of hyaline cartilage markers, SOX9 and COL2A1, inhibited hypertrophic marker COL10A1, and promoted bulk mechanical property development. Adding further to this protocol, we hypothesize that combined mechano-hypoxia conditioning with TGF-β3 growth factor withdrawal will promote stable, non-hypertrophic chondrogenesis of hBM-MSC embedded in an HA-hydrogel. We found that the combined treatment upregulated many cartilage matrix- and development-related markers while suppressing many hypertrophic- and bone development-related markers. Tissue level assessments with biochemical assays, immunofluorescence, and histochemical staining confirmed the gene expression data. Further, mechanical property development in the dynamic compression treatment shows promise toward generating functional engineered cartilage through more optimized and longer culture conditions. In summary, this study introduced a novel protocol to differentiate hBM-MSC into stable, cartilage-forming cells.
Big data analytics implementation issues: A case study of a large bank in Malaysia
Authors: Siew Eu-Gene , Farouk Firdous Mohd
Published: May 2023

This case study discusses the concept of big data analytics, which involves managing and analyzing large, complex data to discover patterns and insights. Implementing big data analytics has many benefits, such as improving decision-making processes, enhancing accounting processes and compliance, boosting marketing campaigns, and providing better credit risk assessment procedures. This case study aims for the student to understand the challenges of big data analytics implementation in a Malaysian commercial bank. Students take on the role of a Senior IT Manager who needs to consider solutions to the implementation problems. Although the team proposed using cloud-based services as a solution to these issues, the CEO expressed concerns about security risks and requested other alternative solutions. The team has also been requested to come up with solutions to the data quality issues experienced by the case study bank.
Sustaining telecare consultations in nurse-led clinics: Perceptions of stroke patients and advanced practice nurses: A qualitative study
Authors: Wong Arkers Kwan Ching , Bayuo Jonathan , Wong Frances Kam Yuet , Kwok Vivian Wai Yan , Tong Danny Wah Kun , Kwong Man King , Yuen Bernard Man Kam , Fong Ching Sing , Chan Shun Tim , Chan Rinis Sin Yi , Li Wah Chun
Published: May 2023

Objective

The ongoing pandemic has accentuated the use of telecare services; however, only limited progress has been made in understanding the barriers and facilitators to using these services. In order to move towards sustaining such essential services, the present study aimed to ascertain the experiences of stroke survivors and healthcare providers regarding the utilization of a post-stroke telecare service in Hong Kong.

Methods

Interpretive description was employed for this study. Semi-structured discussions and interviews were undertaken with nine stroke survivors and four stroke nurses who delivered the telecare services. The principles of thematic analysis were inductively followed to analyse the data. The Standards for Reporting Qualitative Research checklist was used to guide the reporting of the data.

Results

Three themes emerged: (a) pre-existing post-discharge service pathways; (b) push factors/facilitators for telecare usage; and (c) barriers to telecare usage. Overall, the telecare service was considered a significant alternative and one that complements conventional face-to-face follow-ups. Stroke survivors were motivated to use the service because it was convenient and flexible. However, significant barriers exist, including technical issues and a lack of guidelines and training opportunities for healthcare providers.

Conclusions

Although telecare is still evolving, several factors drive stroke survivors to use the service. Attention needs to be paid to the emerging barriers to improve long-term usage of the service. Clear guidelines are needed to underpin the development and implementation of telecare services.
Effect of an educational intervention to increase stroke awareness among Italian high school students: A prospective study in Tuscany
Authors: Di Carlo Antonio , Baldereschi Marzia , Bovis Francesca , Piccardi Benedetta , Linoli Giovanni , Orlandi Giovanni , Volpi Gino , Chiti Alberto , Tassi Rossana , Brescia Alfonso , Inzitari Domenico
Published: May 2023

Introduction:

Stroke in young people shares traditional modifiable risk factors with older groups, and greatly affects quality of life. However, evidence on the effectiveness of educational interventions in young populations, aiming at spreading stroke knowledge and enhancing prevention, is still scarce. We evaluated baseline knowledge of stroke and possible improvements after an educational intervention among Italian high school students, also considering differences related to sex and type of school.

Subjects and methods:

Using a mixed educational strategy, a prospective evaluation of stroke knowledge was performed in five humanities and sciences (lyceums) and five vocational high schools of Tuscany (students of the 12th and 13th grade). A baseline assessment with a structured questionnaire (21 questions) was followed by a standardized oral presentation, using audiovisual materials. After 3 months, the same questionnaire was re-administered to evaluate the long-term impact of the educational intervention.

Results:

Overall, 573 students (50.8% males; age range, 17–19 years) were enrolled; 288 (50.3%) were from lyceums and 285 (49.7%) from vocational schools. Follow-up participation was 97.2%. Baseline performances were comparable between groups for most variables examined. At 3 months, all groups showed a significant improvement from baseline regarding reaction to a stroke event, identification of stroke risk factors, such as smoking (from 62.9% to 83.7%; p < 0.001) and alcohol abuse (from 49.6% to 67.2%; p < 0.001), and symptoms. Knowledge of the existence of stroke units and thrombolysis increased from 25.4% to 60.7% ( p < 0.001) and from 35.8% to 84.0% ( p < 0.001), respectively.

Conclusions:

Our educational intervention improved stroke awareness in high school students. The effects persisted after 3 months. Improved knowledge in young populations may reduce stroke burden in adult life, increase timely access to therapies, and spread knowledge across families.
Mini-Publics as an innovation in spatial governance
Authors: Durrant Daniel , Cohen Tom
Published: May 2023

Mini-publics—deliberative fora made up of randomly selected, representative groups of citizens—have attracted considerable interest as a means of resolving perceived weaknesses in existing forms of governance. In this paper, we consider the use of a mini-public or citizens’ assembly to constitute an ad hoc governance space based on the Travel to Work Area of Cambridge in the United Kingdom rather than working within the existing local government boundaries within which transport infrastructure is usually governed. Through this case study, we explore the question of embedding mini-publics in the wider processes of policy and decision-making. More specifically this is the question of the extent to which they ought to be permitted to inform and even assume responsibility for local-level transport policy decisions. We argue that, if they are to become more widely used, then it will be necessary to understand the practices associated with such democratic experiments and their potential to transform existing governance networks in contested areas of spatial policy.
An Answer to Spivak’s Can the Subaltern Speak? A Study of Marginalized Women’s Autobiographies
Authors: Imran Muhammad , Tilwani Shouket Ahmad , Morve Roshan K.
Published: May 2023

This article discusses marginalized women’s resistance to patriarchal norms in a male-dominated Afghan society. This study analyses the literary modes of selected autobiographies—Fawzia Koofi’s The Favored Daughter, Sarina Sarwari’s Sokhan-i Del-i Yek Zan (Words from the Heart of a Woman) and Hadisa Osmani’s Pursuing My Dreams as an Afghan Woman—with Spivak’s essay ‘Can the Subaltern Speak?’ In this article, Spivak’s idea of subaltern has been deconstructed and needs to be re-read and understood in the context of Afghan women’s autobiographies. In answer to Spivak, yes, the subaltern can speak to resist patriarchal voices, speak against women’s subjugated situation and talk about women’s emancipation. This can be demonstrated by examining Afghan women’s autobiographies. Afghan women’s autobiographies focus on women’s courage and emancipation to resist social victimization and verbal and physical violence. It further states that numerous contemporary Afghan women have highlighted women’s issues due to the absence of a strong feminist voice. Therefore, it demonstrates Afghan women’s gradual awakening, as well as their resolution to resist victimization, subjugation, oppression and violence in a patriarchal and culturally complex male-dominant society. Hence, the present study appraises Afghan women’s struggle to give them recognition and a contribution to the literature, giving a positive light to other women. These women are promoting awareness and giving a feminist message as a women’s strong voice is necessary for a progressive and gender-equality-based society. Afghan women’s writing testifies to finding an answer to Spivak’s question, ‘Can the Subaltern Speak?’
Content validity of an item bank to assess intervention characteristic determinants of implementing evidence-based practices
Authors: Jones Salene M.W. , Shrey Aditya , Weiner Bryan J.
Published: May 2023

Background

Barriers and facilitators, collectively called determinants, of evidence-based practice implementation are key to identifying the best strategies for promoting implementation. Assessing determinants before implementation can help tailor strategies to those that would be most effective. Current measures of determinants are not comparable across implementation settings and implementation scientists and practitioners often have to create their own measures. This study was the first step in creating determinants item banks that are usable across settings and focused on intervention characteristics. We aimed to establish the content validity of the item bank.

Method

This study used a concurrent mixed methods approach. Items for assessing intervention characteristic determinants were first identified through systematic reviews. Implementation scientists then completed a survey where they provided both quantitative and qualitative feedback on the items. Finally, three experts with both clinical and implementation experience provided feedback on redundancy and representativeness.

Results

The systematic reviews identified over 1,959 items so subsequent steps were limited to focus on intervention characteristic determinants (271 items) such as adaptability of the practice. Based on feedback from thirty implementation scientists, the items were reduced to 92 but an additional 53 were added, most due to qualitative feedback. Items were also rewritten based on qualitative results. Three experts reviewed the remaining 145 items. Based on their feedback, the number of items was reduced to 109.

Conclusions

Creating a determinants item bank was feasible and the final items had content validity. The next steps include testing reliability and validity in a larger sample of clinicians implementing evidence-based practices.
Crowd science and science skepticism
Authors: Acar Oguz A
Published: May 2023

Science skepticism is widespread and on the rise. It is a strong threat to public well-being and global sustainability. In this paper, I argue that crowd science is a promising and underutilized tool to fight this threat. Drawing on recent behavioral research in marketing, I identify several positive psychological consequences of crowd science initiatives—both for the participants and observers of these initiatives—which could in turn promote stronger trust in science.
Trauma-Informed Classroom Management in Music Education: A Literature Review
Authors: Bauman-Field Betty
Published: May 2023

Students who have experienced trauma may be especially likely to present challenging behaviors in the classroom. With an increase of trauma-affected students in music classrooms, it is important for music educators to consider classroom management (CM) practices that support trauma-affected students’ healing without triggering students’ trauma responses. In this review of literature, I discuss childhood trauma and trauma-informed positive education (TIPE), research-supported CM strategies in music education, and the ways in which these CM practices do or do not support the trauma-informed approach outlined by TIPE. In addition, I provide my own definition for trauma-informed CM in music education and suggest implications for the music education field.
Metabolic adaptation to tyrosine kinase inhibition in leukemia stem cells
Authors: Qiu Shaowei , Sheth Vipul , Yan Chengcheng , Liu Juan , Chacko Balu K. , Li Hui , Crossman David K. , Fortmann Seth D. , Aryal Sajesan , Rennhack Ashley , Grant Maria B. , Welner Robert S. , Paterson Andrew J. , Wende Adam R. , Darley-Usmar Victor M. , Lu Rui , Locasale Jason W. , Bhatia Ravi
Published: May 2023

Tyrosine kinase inhibitors (TKIs) are very effective in treating chronic myelogenous leukemia (CML), but primitive, quiescent leukemia stem cells persist as a barrier to the cure. We performed a comprehensive evaluation of metabolic adaptation to TKI treatment and its role in CML hematopoietic stem and progenitor cell persistence. Using a CML mouse model, we found that glycolysis, glutaminolysis, the tricarboxylic acid cycle, and oxidative phosphorylation (OXPHOS) were initially inhibited by TKI treatment in CML-committed progenitors but were restored with continued treatment, reflecting both selection and metabolic reprogramming of specific subpopulations. TKI treatment selectively enriched primitive CML stem cells with reduced metabolic gene expression. Persistent CML stem cells also showed metabolic adaptation to TKI treatment through altered substrate use and mitochondrial respiration maintenance. Evaluation of transcription factors underlying these changes helped detect increased HIF-1 protein levels and activity in TKI-treated stem cells. Treatment with an HIF-1 inhibitor in combination with TKI treatment depleted murine and human CML stem cells. HIF-1 inhibition increased mitochondrial activity and reactive oxygen species (ROS) levels, reduced quiescence, increased cycling, and reduced the self-renewal and regenerating potential of dormant CML stem cells. We, therefore, identified the HIF-1–mediated inhibition of OXPHOS and ROS and maintenance of CML stem cell dormancy and repopulating potential as a key mechanism of CML stem cell adaptation to TKI treatment. Our results identify a key metabolic dependency in CML stem cells persisting after TKI treatment that can be targeted to enhance their elimination.
Comparative proteomic analysis of glomerular proteins in IgA nephropathy and IgA vasculitis with nephritis
Authors: Kaga Hajime , Matsumura Hirotoshi , Saito Ayano , Saito Masaya , Abe Fumito , Suzuki Takehiro , Dohmae Naoshi , Odaka Masafumi , Komatsuda Atsushi , Wakui Hideki , Takahashi Naoto
Published: May 2023

Background

IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAVN) are related glomerular diseases characterized by marked similarities in immunological and histological findings. We herein performed a comparative proteomic analysis of glomerular proteins in IgAN and IgAVN.

Methods

We used renal biopsy specimens from 6 IgAN patients without nephrotic syndrome (NS) (IgAN-I subgroup), 6 IgAN patients with NS (IgAN-II subgroup), 6 IgAVN patients with 0–8.0% of glomeruli with crescent formation (IgAVN-I subgroup), 6 IgAVN patients with 21.2–44.8% of glomeruli with crescent formation (IgAVN-II subgroup), 9 IgAVN patients without NS (IgAVN-III subgroup), 3 IgAVN patients with NS (IgAN-IV subgroup), and 5 control cases. Proteins were extracted from laser microdissected glomeruli and analyzed using mass spectrometry. The relative abundance of proteins was compared between groups. An immunohistochemical validation study was also performed.

Results

More than 850 proteins with high confidence were identified. A principal component analysis revealed a clear separation between IgAN and IgAVN patients and control cases. In further analyses, 546 proteins that were matched with ≥ 2 peptides were selected. The levels of immunoglobulins (IgA, IgG, and IgM), complements (C3, C4A, C5, and C9), complement factor H-related proteins (CFHR) 1 and 5, vitronectin, fibrinogen chains, and transforming growth factor-β inducible gene-h3 were higher (> 2.6 fold) in the IgAN and IgAVN subgroups than in the control group, whereas hornerin levels were lower (< 0.3 fold). Furthermore, C9 and CFHR1 levels were significantly higher in the IgAN group than in the IgAVN group. The abundance of some podocyte-associated proteins and glomerular basement membrane (GBM) proteins was significantly less in the IgAN-II subgroup than in the IgAN-I subgroup as well as in the IgAVN-IV subgroup than in the IgAVN-III subgroup. Among the IgAN and IgAVN subgroups, talin 1 was not detected in the IgAN-II subgroup. This result was supported by immunohistochemical findings.

Conclusions

The present results suggest shared molecular mechanisms for glomerular injury in IgAN and IgAVN, except for enhanced glomerular complement activation in IgAN. Differences in the protein abundance of podocyte-associated and GBM proteins between IgAN and IgAVN patients with and without NS may be associated with the severity of proteinuria.
Lipo-MGN nanoparticle hypoxia attenuation-mediated single-dose radiotherapy- and pH/ROS-responsive T1 contrast magnetic resonance imaging in hepatocellular carcinoma
Authors: Thomas Reju George , Kim Subin , Nagareddy Raveena , Vijayan Veena , Pullickal Ansuja Mathew , Yoon Mee Sun , Park In Kyu , Jeong Yong Yeon
Published: May 2023

Tumor hypoxia is an important factor for developing resistance to radiation therapy (RT) and presents a bleak prognosis in cancer patients undergoing treatment for RT resistant hepatocellular carcinoma. Here, we present the synthesis of liposome-coated Mn3O4 (MGN) nanoparticles (Lipo-MGN) and investigation of their therapeutic potential with RT utilizing a HepG2 cancer model. According to in vitro research, Lipo-MGN effectively produced oxygen in the presence of H2O2 and significantly reduced the expression of HIF-1 in human HepG2 cells that were under hypoxic conditions. Lipo-MGN reversed the radio-resistance brought on by hypoxia and increased cell damage. When Lipo-MGN and RT were administered together in a HepG2 xenograft mice model, the tumor growth was delayed more than with RT alone. As determined by MR imaging, liposome-MGN also exhibited T1 contrast enhancement in tumor. According to these findings, Lipo-MGNs may increase the impact of RT by focusing tumor hypoxia. Hypoxic, radioresistant HepG2 cancer may be treated with Lipo-MGN in clinical studies.
Influencing factors of interprofessional collaboration in multifactorial fall prevention interventions: a qualitative systematic review
Authors: Muusse J. S. C. , Zuidema R. , van Scherpenseel M. C. , Velde S. J. te
Published: May 2023

Background

With the ageing population worldwide, falls are becoming a severe and growing health problem. Interprofessional multifactorial fall prevention interventions (FPIs) have effectively prevented falls in community-dwelling older adults. However, the implementation of FPIs often fails due to a lack of interprofessional collaboration. Therefore, gaining insight into the influencing factors of interprofessional collaboration in multifactorial FPI’s for older adults living in the community is essential. Consequently, our aim was to provide an overview of factors influencing interprofessional collaboration in multifactorial FPIs for community-dwelling older adults.

Methods

This qualitative systematic literature research was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Pubmed, CINAHL, and Embase electronic databases have been systematically searched for eligible articles, with a qualitative design. The quality was appraised using the Checklist for Qualitative Research by the Joann Briggs Institute. The findings were inductively synthesized using a meta-aggregative approach. Confidence in the synthesized findings was established using the ConQual methodology.

Results

Five articles were included. Analysis of the included studies resulted in 31 influencing factors for interprofessional collaboration, which were labelled as findings. These findings were summarized in ten categories and combined into five synthesized findings. Results showed that communication, role clarity, information sharing, organization, and interprofessional aim influence interprofessional collaboration in multifactorial FPIs.

Conclusions

This review provides a comprehensive summary of findings on interprofessional collaboration, specifically in the context of multifactorial FPIs. Knowledge in this area is considerably relevant given the multifactorial nature of falls, which demands an integrated, multidomain approach, including both health and social care. The results can be utilized as a fundament for developing effective implementation strategies aiming to improve interprofessional collaboration between health and social care professionals working in multifactorial FPIs in the community.
Magnitude and predictors of unfavorable management outcome in surgically treated patients with intestinal obstruction in Ethiopia: a systematic review and meta-analysis
Authors: Adane Fentahun , Dessalegn Megbar
Published: May 2023

Background

Unless an emergency surgical intervention is conducted, intestinal obstruction may result in high morbidity and mortality. In Ethiopia, the magnitude and predictors of unfavorable management outcomes in surgically treated patients with intestinal obstruction are highly variable and inconsistent. The aim of this study was; therefore, to estimate the overall prevalence of unfavorable management outcome and its predictors among surgically treated patients with intestinal obstruction in Ethiopia.

Method

We searched articles from databases from June 1, 2022, to August 30, 2022. Cochrane Q test statistics and I2 tests were applied. We used a random-effect meta-analysis model to overcome the impact of heterogeneity among the included studies. In addition, the association between risk factors and unfavorable management outcome in surgically treated patients with intestinal obstruction was investigated.

Results

This study included a total of twelve articles. The pooled prevalence of unfavorable management outcome in surgically treated patients with intestinal obstruction was 20.22% (95% CI: 17.48–22.96). According to a sub-group analysis by region, Tigray region had the highest prevalence of poor management outcome, which was 25.78% (95% CI: 15.69–35.87). Surgical site infection was the most commonly reported symptom of poor management outcome (8.63%; 95% CI: 5.62, 11.64). The length of postoperative hospital stays (95% CI: 3.02, 29.08), duration of illness (95% CI: 2.44, 6.12), presence of comorbidity (95% CI: 2.38, 10.11), dehydration (95% CI: 2.07, 17.40), and type of intraoperative procedure (95% CI: 2.12, 6.97) were all significantly associated with unfavorable management outcome of intestinal obstruction among surgically treated patients in Ethiopia.

Conclusion

According to this study, the magnitude of unfavorable management outcome was high among surgically treated patients in Ethiopia. Unfavorable management outcome was significantly associated with the length of postoperative hospital stays, duration of illness, comorbidity, dehydration, and type of intraoperative procedure. Medical, surgical and public health measures are pivotal to reduce unfavorable management outcome in surgically treated intestinal obstruction patients in Ethiopia.
Association between plant-based diets and metabolic syndrome in obese adults from Iran: a cross-sectional study
Authors: Vajdi Mahdi , Karimi Arash , Tousi Ayda Zahiri , Hosseini Babak , Nikniaz Zeinab , Farhangi Mahdieh Abbasalizad
Published: May 2023

Background

Metabolic syndrome (MetS) is a common chronic disease with several complications. Given that, studies on the association of plant-based diet indices (PDIs) with risk of MetS among adults with obesity, are limited, we aimed to examine the association between PDIs (including overall PDI, healthy PDI (hPDI), unhealthy PDI (uPDI)) and MetS in Iranian adults with obesity.

Methods

In Tabriz, Iran, a total of 347 adults between the ages of 20 and 50 participated in this cross-sectional research study. We created an overall PDI, hPDI, and uPDI from validated semi-quantitative food-frequency questionnaire (FFQ) data. To investigate the association between hPDI, overall PDI, uPDI, and MetS and its components, a binary logistic regression analysis was performed.

Results

The average age was 40.78 ± 9.23 years, and the average body mass index was 32.62 ± 4.80 kg/m2. There was no significant association between overall PDI (OR: 0.87; 95% CI: 0.54–1.47), hPDI (OR: 0.82; 95% CI: 0.48–1.40), and uPDI (OR: 0.83; 95% CI: 0.87–2.46) with MetS, even after adjustment for confounders. Moreover, our findings showed that participants with the highest adherence to uPDI had a higher chance of hyperglycemia (OR: 2.50; 95% CI: 1.13–5.52). Also, this association was significant in the first (OR: 2.51; 95% CI: 1.04–6.04) and second (OR: 2.58; 95% CI: 1.05–6.33) models, after controlling for covariates. However, in both adjusted and crude models, we did not find a significant association between hPDI and PDI scores and MetS components such as high triglyceride, high waist circumference, low High-density lipoprotein cholesterol, raised blood pressure, and hyperglycemia. Moreover, those in the top tertile of uPDI had higher fasting blood sugar and insulin levels when compared with those in the first tertile, and subjects in the last tertile of hPDI compared with participants in the first tertile had lower weight, waist-to-hip ratio, and fat-free mass.

Conclusion

We found a direct significant association between uPDI and odds of hyperglycemia in the whole population of study. Future large-scale, prospective studies on PDIs and the MetS are necessary to confirm these findings.
Identification of the characteristics of infiltrating immune cells in pulpitis and its potential molecular regulation mechanism by bioinformatics method
Authors: Wang Jing , Qiao Junxia , Ma Lili , Li Xin , Wei Chengshi , Tian Xiufen , Liu Kun
Published: May 2023

Objective

The inflammation of dental pulp will also trigger an immune response. The purpose of this study is to demonstrate the immune cell’s function and explore their regulatory molecules and signal pathways in pulpitis.

Method

The CIBERSORTx method was used to quantitatively analyze 22 types of immune cells infiltrating in the GSE77459 dataset of dental pulp tissues. The immune-related differential genes (IR-DEGs) were further screened and enriched for the GO and KEGG pathways. Protein–protein interaction (PPI) networks were constructed and the hub IR-DEGs were screened. Finally, we constructed the regulatory network of hub genes.

Results

The GSE77459 dataset screened 166 IR-DEGs and was enriched for three signal pathways involved in pulpitis development: chemokine signaling, TNF signaling, and NF-κB signaling. Significant differences in immune cell infiltration were observed between normal and inflamed dental pulp. The proportions of M0 macrophages, neutrophils, and follicular helper T cells were significantly higher than that of the normal dental pulp, while the proportions of resting mast cells, resting dendritic cells, CD8 T cells, and monocytes were significantly lower. The random forest algorithm concluded that M0 macrophages and neutrophils were the two most important immune cells. We identified five immune-related hub genes IL-6, TNF-α, IL-1β, CXCL8, and CCL2. In addition, IL-6, IL-1β, and CXCL8 are highly correlated with M0 macrophages and neutrophils, and the five hub genes have many shared regulatory molecules: four miRNAs and two lncRNAs, three transcription factors.

Conclusion

Immune cell infiltration plays an important role in pulpitis among which M0 macrophages and neutrophils are the most significant immune cells. IL-6, TNF-α, IL-1, CXCL8, and CCL2 may be essential molecule of the immune response regulation network in pulpitis. This will help us understand the immune regulatory network in pulpitis.
Inositol possesses antifibrotic activity and mitigates pulmonary fibrosis
Authors: Li Ji-Min , Chang Wen-Hsin , Li Linhui , Yang David C. , Hsu Ssu-Wei , Kenyon Nicholas J. , Chen Ching-Hsien
Published: May 2023

Background

Myo-inositol (or inositol) and its derivatives not only function as important metabolites for multiple cellular processes but also act as co-factors and second messengers in signaling pathways. Although inositol supplementation has been widely studied in various clinical trials, little is known about its effect on idiopathic pulmonary fibrosis (IPF). Recent studies have demonstrated that IPF lung fibroblasts display arginine dependency due to loss of argininosuccinate synthase 1 (ASS1). However, the metabolic mechanisms underlying ASS1 deficiency and its functional consequence in fibrogenic processes are yet to be elucidated.

Methods

Metabolites extracted from primary lung fibroblasts with different ASS1 status were subjected to untargeted metabolomics analysis. An association of ASS1 deficiency with inositol and its signaling in lung fibroblasts was assessed using molecular biology assays. The therapeutic potential of inositol supplementation in fibroblast phenotypes and lung fibrosis was evaluated in cell-based studies and a bleomycin animal model, respectively.

Results

Our metabolomics studies showed that ASS1-deficient lung fibroblasts derived from IPF patients had significantly altered inositol phosphate metabolism. We observed that decreased inositol-4-monophosphate abundance and increased inositol abundance were associated with ASS1 expression in fibroblasts. Furthermore, genetic knockdown of ASS1 expression in primary normal lung fibroblasts led to the activation of inositol-mediated signalosomes, including EGFR and PKC signaling. Treatment with inositol significantly downregulated ASS1 deficiency-mediated signaling pathways and reduced cell invasiveness in IPF lung fibroblasts. Notably, inositol supplementation also mitigated bleomycin-induced fibrotic lesions and collagen deposition in mice.

Conclusion

These findings taken together demonstrate a novel function of inositol in fibrometabolism and pulmonary fibrosis. Our study provides new evidence for the antifibrotic activity of this metabolite and suggests that inositol supplementation may be a promising therapeutic strategy for IPF.
SOLVe: a closed-loop system focused on protective mechanical ventilation
Authors: von Platen Philip , Pickerodt Philipp A. , Russ Martin , Taher Mahdi , Hinken Lea , Braun Wolfgang , Köbrich Rainer , Pomprapa Anake , Francis Roland C. E. , Leonhardt Steffen , Walter Marian
Published: May 2023

Background

Mechanical ventilation is an essential component in the treatment of patients with acute respiratory distress syndrome. Prompt adaptation of the settings of a ventilator to the variable needs of patients is essential to ensure personalised and protective ventilation. Still, it is challenging and time-consuming for the therapist at the bedside. In addition, general implementation barriers hinder the timely incorporation of new evidence from clinical studies into routine clinical practice.

Results

We present a system combing clinical evidence and expert knowledge within a physiological closed-loop control structure for mechanical ventilation. The system includes multiple controllers to support adequate gas exchange while adhering to multiple evidence-based components of lung protective ventilation. We performed a pilot study on three animals with an induced ARDS. The system achieved a time-in-target of over 75 % for all targets and avoided any critical phases of low oxygen saturation, despite provoked disturbances such as disconnections from the ventilator and positional changes of the subject.

Conclusions

The presented system can provide personalised and lung-protective ventilation and reduce clinician workload in clinical practice.
Dysregulated endothelial cell markers in systemic lupus erythematosus: a systematic review and meta-analysis
Authors: Bergkamp S. C. , Wahadat M. J. , Salah A. , Kuijpers T. W. , Smith V. , Tas S. W. , van den Berg J. M. , Kamphuis S. , Schonenberg-Meinema D.
Published: May 2023

Objectives

To perform a systematic literature review and meta-analysis on endothelial cell (EC) markers that are involved and dysregulated in systemic lupus erythematosus (SLE) in relation to disease activity, as EC dysregulation plays a major role in the development of premature atherosclerosis in SLE.

Methods

Search terms were entered into Embase, MEDLINE, Web of Science, Google Scholar and Cochrane. Inclusion criteria were 1) studies published after 2000 reporting measurements of EC markers in serum and/or plasma of SLE patients (diagnosed according to ACR/SLICC criteria), 2) English language peer reviewed articles, and 3) disease activity measurement. For meta-analysis calculations, the Meta-Essentials tool by Erasmus Research Institute and of Management (ERIM) was used. Only those EC markers, which were 1) reported in at least two articles and 2) reported a correlation coefficient (i.e. Spearman’s rank or Pearson’s) between the measured levels of the EC marker and disease activity were included. For meta-analyses, a fixed effect model was used.

Results

From 2133 hits, 123 eligible articles were selected. The identified SLE-related endothelial markers were involved in EC activation, EC apoptosis, disturbed angiogenesis, defective vascular tone control, immune dysregulation and coagulopathy. Meta-analyses of primarily cross-sectional studies showed significant associations between marker levels and disease activity for the following endothelial markers: Pentraxin-3, Thrombomodulin, VEGF, VCAM-1, ICAM-1, IP-10 and MCP-1. Dysregulated EC markers without associations with disease activity were: Angiopoeitin-2, vWF, P-Selectin, TWEAK and E-Selectin.

Conclusions

We provide a complete literature overview for dysregulated EC markers in SLE comprising a wide range of different EC functions. SLE-induced EC marker dysregulation was seen with, but also without, association with disease activity. This study provides some clarity in the eminent complex field of EC markers as biomarkers for SLE. Longitudinal data on EC markers in SLE are now needed to guide us more in unravelling the pathophysiology of premature atherosclerosis and cardiovascular events in SLE patients.
Metabolomic investigation of urinary extracellular vesicles for early detection and screening of lung cancer
Authors: Yang Qinsi , Luo Jiaxin , Xu Hao , Huang Liu , Zhu Xinxi , Li Hengrui , Yang Rui , Peng Bo , Sun Da , Zhu Qingfu , Liu Fei
Published: May 2023

Lung cancer is a prevalent cancer type worldwide that often remains asymptomatic in its early stages and is frequently diagnosed at an advanced stage with a poor prognosis due to the lack of effective diagnostic techniques and molecular biomarkers. However, emerging evidence suggests that extracellular vesicles (EVs) may promote lung cancer cell proliferation and metastasis, and modulate the anti-tumor immune response in lung cancer carcinogenesis, making them potential biomarkers for early cancer detection. To investigate the potential of urinary EVs for non-invasive detection and screening of patients at early stages, we studied metabolomic signatures of lung cancer. Specifically, we conducted metabolomic analysis of 102 EV samples and identified metabolome profiles of urinary EVs, including organic acids and derivatives, lipids and lipid-like molecules, organheterocyclic compounds, and benzenoids. Using machine learning with a random forest model, we screened for potential markers of lung cancer and identified a marker panel consisting of Kanzonol Z, Xanthosine, Nervonyl carnitine, and 3,4-Dihydroxybenzaldehyde, which exhibited a diagnostic potency of 96% for the testing cohort (AUC value). Importantly, this marker panel also demonstrated effective prediction for the validation set, with an AUC value of 84%, indicating the reliability of the marker screening process. Our findings suggest that the metabolomic analysis of urinary EVs provides a promising source of non-invasive markers for lung cancer diagnostics. We believe that the EV metabolic signatures could be used to develop clinical applications for the early detection and screening of lung cancer, potentially improving patient outcomes.
Pro-inflammatory activity of long noncoding RNA FOXD2-AS1 in Achilles tendinopathy
Authors: Ke Xiaoting , Zhang Wenjie
Published: May 2023

Achilles tendinopathy is a prevalent clinical problem that plagues athletes and general populations. Achilles tendon healing is a complex process, and so far, there is no successful long-term solution to Achilles tendinopathy in the field of microsurgery due to its poor natural regeneration ability. Limitations in understanding the pathogenesis of Achilles tendon development and Achilles tendon injury hinder clinical treatment developments. There is an increasing demand for innovative conservative treatments that can improve Achilles tendon injury. In this study, a Sprague–Dawley rat model of Achilles tendinopathy was established. Lentiviral vectors that interfere with the expression of FOXD2-AS1, miR-21-3p, or PTEN were injected every 3 days. Rats were euthanized after 3 weeks, and the effect of FOXD2-AS1, miR-21-3p, or PTEN on Achilles tendon healing was analyzed by histological observation, biomechanical test, and examinations of inflammatory factors and tendon markers. As measured, downregulating FOXD2-AS1 or upregulating miR-21-3p improved histological structure, suppressed inflammation, promoted the expression of tendon markers, and optimized the biomechanical properties of Achilles tendon. Upregulating PTEN was capable of reversing the promoting effect of inhibition of FOXD2-AS1 on Achilles tendon healing. As concluded, deficiency of FOXD2-AS1 accelerates the healing of Achilles tendon injury and improves tendon degeneration by regulating the miR-21-3p/PTEN axis and promoting the activation of the PI3K/AKT signaling pathway.
Ankyrin2 is essential for neuronal morphogenesis and long-term courtship memory in Drosophila
Authors: Schwartz Silvia , Wilson Sarah J , Hale Tracy K , Fitzsimons Helen L
Published: May 2023

Dysregulation of HDAC4 expression and/or nucleocytoplasmic shuttling results in impaired neuronal morphogenesis and long-term memory in Drosophila melanogaster. A recent genetic screen for genes that interact in the same molecular pathway as HDAC4 identified the cytoskeletal adapter Ankyrin2 (Ank2). Here we sought to investigate the role of Ank2 in neuronal morphogenesis, learning and memory. We found that Ank2 is expressed widely throughout the Drosophila brain where it localizes predominantly to axon tracts. Pan-neuronal knockdown of Ank2 in the mushroom body, a region critical for memory formation, resulted in defects in axon morphogenesis. Similarly, reduction of Ank2 in lobular plate tangential neurons of the optic lobe disrupted dendritic branching and arborization. Conditional knockdown of Ank2 in the mushroom body of adult Drosophila significantly impaired long-term memory (LTM) of courtship suppression, and its expression was essential in the γ neurons of the mushroom body for normal LTM. In summary, we provide the first characterization of the expression pattern of Ank2 in the adult Drosophila brain and demonstrate that Ank2 is critical for morphogenesis of the mushroom body and for the molecular processes required in the adult brain for the formation of long-term memories.
Paternal genetic effects of cadmium exposure during pregnancy on hormone synthesis disorders in ovarian granulosa cells of offspring
Authors: Sun Yi , Liu Zhangpin , Zhang Wenchang , Lin Hao , Li Qingyu , Liu Chenchen , Zhang Chenyun
Published: May 2023

The aim of this study was to investigate the paternal genetic intergenerational and transgenerational genetic effects of cadmium (Cd) exposure during pregnancy on estradiol (E2) and progesterone (Pg) synthesis in the ovarian granulosa cells (GCs) of offspring. Pregnant SD rats were intragastrically exposed to CdCl2 (0, 0.5, 2.0, 8.0 mg/kg) from days 1 to 20 to produce the F1 generation, F1 males were mated with newly purchased females to produce the F2 generation, and the F3 generation was obtained in the same way. Using this model, Cd-induced hormone synthesis disorders in GCs of F1 have been observed [8]. In this study, altered serum E2 and Pg levels in both F2 and F3 generations showed a nonmonotonic dose‒response relationship. In addition, hormone synthesis-related genes (Star, Cyp11a1, Cyp17a1, Cyp19a1, Sf-1) and miRNAs were observed to be altered in both F2 and F3. No differential changes in DNA methylation modifications of hormone synthesis-related genes were observed, and only the Adcy7 was hypomethylated. In summary, paternal genetic intergenerational and transgenerational effects exist in ovarian GCs E2 and Pg synthesis disorders induced by Cd during pregnancy. In F2, the upregulation of StAR and CYP11A1, and changes in the miR-27a-3p, miR-27b-3p, and miR-146 families may be important, while changes in the miR-10b-5p and miR-146 families in F3 may be important.
SPON1 is an independent prognostic biomarker for ovarian cancer
Authors: Miyakawa Ryoya , Kobayashi Makoto , Sugimoto Kotaro , Endo Yuta , Kojima Manabu , Kobayashi Yasuyuki , Furukawa Shigenori , Honda Tsuyoshi , Watanabe Takafumi , Asano Shigeyuki , Soeda Shu , Hashimoto Yuko , Fujimori Keiya , Chiba Hideki
Published: May 2023

Background

Ovarian cancer has the worst outcome among gynecological malignancies; therefore, biomarkers that could contribute to the early diagnosis and/or prognosis prediction are urgently required. In the present study, we focused on the secreted protein spondin-1 (SPON1) and clarified the prognostic relevance in ovarian cancer.

Methods

We developed a monoclonal antibody (mAb) that selectively recognizes SPON1. Using this specific mAb, we determined the expression of SPON1 protein in the normal ovary, serous tubal intraepithelial carcinoma (STIC), and ovarian cancer tissues, as well as in various normal adult tissues by immunohistochemistry, and verified its clinicopathological significance in ovarian cancer.

Results

The normal ovarian tissue was barely positive for SPON1, and no immunoreactive signals were detected in other healthy tissues examined, which was in good agreement with data obtained from gene expression databases. By contrast, upon semi-quantification, 22 of 242 ovarian cancer cases (9.1%) exhibited high SPON1 expression, whereas 64 (26.4%), 87 (36.0%), and 69 (28.5%) cases, which were designated as SPON1-low, possessed the moderate, weak, and negative SPON1 expression, respectively. The STIC tissues also possessed SPON1-positive signals. The 5-year recurrence-free survival (RFS) rate in the SPON1-high group (13.6%) was significantly lower than that in the SPON1-low group (51.2%). In addition, high SPON1 expression was significantly associated with several clinicopathological variables. Multivariable analysis revealed that high SPON1 was an independent prognostic factor for RFS of ovarian cancer.

Conclusions

SPON1 represents a prognostic biomarker for ovarian cancer, and the anti-SPON1 mAb could be valuable as an outcome predictor.