bluuebunny/crossref_metadata_2025_split huggingface dataset:
Building bridges: evaluating policymakers' research capacities, engagement, and utilization in health policymaking within the Kuwaiti context: a cross-sectional study
Authors: Alhenaidi Abdulaziz , Al-Haqan Asmaa , Alfarhan Heba , Alaradi Limya , Elsherif Mohamed , Kelendar Hisham 
Published: July 2024

Abstract
Background
Health policymaking is a critical aspect of governmental decision-making that shapes the well-being of populations. In the Middle East and North Africa, particularly in Kuwait, limited attention has been given to exploring the research capacities, engagement, and utilization among health policymakers. This study aims to bridge this gap by investigating how Kuwaiti health policymakers incorporate evidence-based research into the formulation of health-related policies.

Methods
This cross-sectional study targeted health policymakers in leadership positions within the Kuwait Ministry of Health (MOH). Using the Seeking, Engaging with and Evaluating Research (SEER) questionnaire, participants' capacities, engagement, and use of research were assessed. The targeted sample was all health policymakers in leadership positions, starting from the head of departments and above. The questionnaire comprises four domains, 14 sections, and 50 questions and utilizes Likert and binary scales, with aggregate scores predicting engagement actions and research use. The data were collected between March and July 2023. All the statistical analyses were performed using SPSS v27, and the numerical and categorical variables were analyzed using appropriate statistical tests, including t-tests, ANOVA, and Pearson's correlation.

Results
Out of 205 policymakers, 88 participated (42.9% response rate): predominantly male (51.1%) and married (78.4%). The mean age was 49.84 ± 7.28 years, with a mean MOH tenure of 24.39 ± 6.80 years. Participants demonstrated high value for research (mean score 4.29 ± 0.55) and expressed confidence in the research utilization. Organizational emphasis on research use exhibited nuanced perceptions, identifying areas where MOH support may be lacking. Access to research resources and processes for policy development guidance were highlighted as challenges.

Conclusions
This study provides crucial insights into the research capacities and engagement of Kuwaiti health policymakers. It emphasizes the need for targeted interventions to align individual perceptions with organizational expectations, address confidence disparities, and enhance collaborative efforts. Organizational investments are crucial for fostering a dynamic research ecosystem to improve evidence-based policy development in Kuwait's healthcare landscape.
Discovery of a novel hybrid coumarin-hydroxamate conjugate targeting the HDAC1-Sp1-FOSL2 signaling axis for breast cancer therapy
Authors: Zhu Sujie , Zhu Wenjing , Zhao Kaihua , Yu Jie , Lu Wenxia , Zhou Rui , Fan Shule , Kong Weikaixin , Yang Feifei , Shan Peipei 
Published: July 2024

Abstract
Background
Breast cancer is one of the most lethal cancers in women. Despite significant advances in the diagnosis and treatment of breast cancer, many patients still succumb to this disease, and thus, novel effective treatments are urgently needed. Natural product coumarin has been broadly investigated since it reveals various biological properties in the medicinal field. Accumulating evidence indicates that histone deacetylase inhibitors (HDACIs) are promising novel anti-breast cancer agents. However, most current HDACIs exhibit only moderate effects against solid tumors and are associated with severe side effects. Thus, to develop more effective HDACIs for breast cancer therapy, hydroxamate of HDACIs was linked to coumarin core, and coumarin-hydroxamate hybrids were designed and synthesized.

Methods
A substituted coumarin moiety was incorporated into the classic hydroxamate HDACIs by the pharmacophore fusion strategy. ZN444B was identified by using the HDACI screening kit and cell viability assay. Molecular docking was performed to explore the binding mode of ZN444B with HDAC1. Western blot, immunofluorescent staining, cell viability, colony formation and cell migration and flow cytometry assays were used to analyze the anti-breast cancer effects of ZN444B in vitro. Orthotopic studies in mouse models were applied for preclinical evaluation of efficacy and toxicity in vivo. Proteomic analysis, dual-luciferase reporter assay, chromatin immunoprecipitation, co-immunoprecipitation, immunofluorescent staining assays along with immunohistochemical (IHC) analysis were used to elucidate the molecular basis of the actions of ZN444B.

Results
We synthesized and identified a novel coumarin-hydroxamate conjugate, ZN444B which possesses promising anti-breast cancer activity both in vitro and in vivo. A molecular docking model showed that ZN444B binds to HDAC1 with high affinity. Further mechanistic studies revealed that ZN444B specifically decreases FOS-like antigen 2 (FOSL2) mRNA levels by inhibiting the deacetylase activity of HDAC1 on Sp1 at K703 and abrogates the binding ability of Sp1 to the FOSL2 promoter. Furthermore, FOSL2 expression positively correlates with breast cancer progression and metastasis. Silencing FOSL2 expression decreases the sensitivity of breast cancer cells to ZN444B treatment. In addition, ZN444B shows no systemic toxicity in mice.

Conclusions
Our findings highlight the potential of FOSL2 as a new biomarker and therapeutic target for breast cancer and that targeting the HDAC1-Sp1-FOSL2 signaling axis with ZN444B may be a promising therapeutic strategy for breast cancer.
Endometrial senescence is mediated by interleukin 17 receptor B signaling
Authors: Kawamura Keiko , Matsumura Yumiko , Kawamura Teruhiko , Araki Hiromitsu , Hamada Norio , Kuramoto Kazutaka , Yagi Hiroshi , Onoyama Ichiro , Asanoma Kazuo , Kato Kiyoko 
Published: July 2024

Abstract
Background
We previously identified Il17RB, a member of the IL17 superfamily, as a candidate marker gene for endometrial aging. While IL17RB has been linked to inflammation and malignancies in several organ systems, its function in the endometrium has not been investigated and is thus poorly understood. In the present study, we performed a functional analysis of this receptor with the aim of determining the effects of its age-associated overexpression on the uterine environment.

Methods
We analyzed IL17RB-related signaling pathways and downstream gene expression in an immortalized human endometrial glandular epithelial cell line (“hEM”) forced to express the receptor via lentiviral transduction (“IL17RB-hEM”). We also prepared endometrial organoids from human endometrial tissue sourced from hysterectomy patients (“patient-derived EOs”) and exposed them to cytokines that are upregulated by IL17RB expression to investigate changes in organoid-forming capacity and senescence markers. We analyzed RNA-seq data (GEO accession number GSE132886) from our previous study to identify the signaling pathways associated with altered IL17RB expression. We also analyzed the effects of the JNK pathway on organoid-forming capacity.

Results
Stimulation with interleukin 17B enhanced the NF-κB pathway in IL17RB-hEM, resulting in significantly elevated expression of the genes encoding the senescence associated secretory phenotype (SASP) factors IL6, IL8, and IL1β. Of these cytokines, IL1β inhibited endometrial organoid growth. Bioinformatics analysis showed that the JNK signaling pathway was associated with age-related variation in IL17RB expression. When IL17RB-positive cells were cultured in the presence of IL17B, their organoid-forming capacity was slightly but non-significantly lower than in unexposed IL17RB-positive cells, but when IL17B was paired with a JNK inhibitor (SP600125), it was restored to control levels. Further, IL1β exposure significantly reduced organoid-forming capacity and increased p21 expression in endometrial organoids relative to non-exposure (control), but when IL1β was paired with SP600125, both indicators were restored to levels comparable to the control condition.

Conclusions
We have revealed an association between IL17RB, whose expression increases in the endometrial glandular epithelium with advancing age, and cellular senescence. Using human endometrial organoids as in vitro model, we found that IL1β inhibits cell proliferation and leads to endometrial senescence via the JNK pathway.
Dihydroorotase MoPyr4 is required for development, pathogenicity, and autophagy in rice blast fungus
Authors: Wang Jing-Yi , Cai Ying-Ying , Li Lin , Zhu Xue-Ming , Shen Zi-Fang , Wang Zi-He , Liao Jian , Lu Jian-Ping , Liu Xiao-Hong , Lin Fu-Cheng 
Published: July 2024

AbstractDihydroorotase (DHOase) is the third enzyme in the six enzymatic reaction steps of the endogenous pyrimidine nucleotide de novo biosynthesis pathway, which is a metabolic pathway conserved in both bacteria and eukaryotes. However, research on the biological function of DHOase in plant pathogenic fungi is very limited. In this study, we identified and named MoPyr4, a homologous protein of Saccharomyces cerevisiae DHOase Ura4, in the rice blast fungus Magnaporthe oryzae and investigated its ability to regulate fungal growth, pathogenicity, and autophagy. Deletion of MoPYR4 led to defects in growth, conidiation, appressorium formation, the transfer and degradation of glycogen and lipid droplets, appressorium turgor accumulation, and invasive hypha expansion in M. oryzae, which eventually resulted in weakened fungal pathogenicity. Long-term replenishment of exogenous uridine-5’-phosphate (UMP) can effectively restore the phenotype and virulence of the ΔMopyr4 mutant. Further study revealed that MoPyr4 also participated in the regulation of the Pmk1-MAPK signaling pathway, co-localized with peroxisomes for the oxidative stress response, and was involved in the regulation of the Osm1-MAPK signaling pathway in response to hyperosmotic stress. In addition, MoPyr4 interacted with MoAtg5, the core protein involved in autophagy, and positively regulated autophagic degradation. Taken together, our results suggested that MoPyr4 for UMP biosynthesis was crucial for the development and pathogenicity of M. oryzae. We also revealed that MoPyr4 played an essential role in the external stress response and pathogenic mechanism through participation in the Pmk1-MAPK signaling pathway, peroxisome-related oxidative stress response mechanism, the Osm1-MAPK signaling pathway and the autophagy pathway.
Impact of physical activity on caloric and macronutrient intake in children and adolescents: a systematic review and meta-analysis of randomized controlled trials
Authors: Hahn Heiko , Friedel Manuel , Niessner Claudia , Zipfel Stephan , Mack Isabelle 
Published: July 2024

Abstract
Background
Physical activity is widely promoted to maintain and improve health across all ages. Investigating how physical activity affects subsequent food intake provides insight into the factors that contribute to maintaining energy balance and effective weight management.

Objective
This systematic review and meta-analysis summarizes the evidence on the effect of acute physical activity on subsequent food intake in children and adolescents.

Methods
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA) were applied. Randomized controlled trials (RCTs) objectively measuring post-exercise energy intake in children and adolescents aged 5 to 18 years were included. Studies with self-reported food intake were excluded. The databases PubMed, Web of Science and Cochrane Library were searched for RCTs, and the data were summarized at a qualitative and quantitative level. Version 2 of the Cochrane risk-of-bias tool for randomized trials was used to assess risk of bias. Changes in energy intake were examined with random effects meta-analysis. (PROSPERO: CRD42022324259).

Results
Out of 9582 studies, 22 RCTs with cross-over design remained eligible for meta-analysis. The primary outcome was post-intervention energy intake up to the next 24 h. Heterogeneity of studies was moderate, with an I2 of 57%. The median (interquartile range, IQR) energy expended while exercising was 240 (158) kcal. Meta-analysis of 41 study arms (exercise n = 780 and control n = 478) showed no differences in total energy intake between the exercise and control group with a mean difference MD = 23.31 [-27.54, 74.15] kcal. No subgroup differences were found. Macronutrient intake and appetite sensations where not substantially affected.

Conclusion
Engaging in exercise is a suitable means of raising activity-induced energy expenditure, without causing any noticeable changes in food intake or hunger within a single day.
Effects of increasing the availability of vegetarian options on main meal choices, meal offer satisfaction and liking: a pre-post analysis in a French university cafeteria
Authors: Arrazat Laura , Cambriels Claire , Noan Christine Le , Nicklaus Sophie , Marty Lucile 
Published: July 2024

Abstract
Background
Changing the food environment is an important public health lever for encouraging sustainable food choices. Targeting the availability of vegetarian main meals served in cafeterias substantially affects food choice, but acceptability has never been assessed. We examined the effects of an availability intervention at a French university cafeteria on students’ main meal choices, meal offer satisfaction and liking.

Methods
A four-week controlled trial was conducted in a university cafeteria in Dijon, France. During the two-week control period, vegetarian main meals constituted 24% of the offer. In the subsequent two-week intervention period, this proportion increased to 48%, while all the other menu items remained unchanged. Students were not informed of the change. Student choices were tracked using production data, and daily paper ballots were used to assess student satisfaction with the meal offer and liking of the main meal they chose (score range [1;5]). Nutritional quality, environmental impact, and cost of production of meal choices were calculated for each lunchtime. Food waste was measured over 4 lunchtimes during control and intervention periods. An online questionnaire collected student feedback at the end of the study.

Results
Doubling availability of vegetarian main meals significantly increased the likelihood of choosing vegetarian options (OR = 2.57, 95% CI = [2.41; 2.74]). Responses of the paper ballots (n = 18,342) indicated slight improvements in meal offer satisfaction from 4.05 ± 0.92 to 4.07 ± 0.93 (p = 0.028) and in liking from 4.09 ± 0.90 to 4.13 ± 0.92 (p < 0.001) during control and intervention periods, respectively. The end-of-study questionnaire (n = 510) revealed that only 6% of students noticed a change the availability of vegetarian main meals. The intervention led to a decrease in the environmental impact of the main meals chosen, a slight decrease in nutritional quality, a slight increase in meal costs and no change in food waste.

Conclusions
Doubling availability of vegetarian main meals in a university cafeteria resulted in a twofold increase in their selection, with students reporting being more satisfied and liking the main meals more during the intervention period. These results suggest that serving an equal proportion of vegetarian and nonvegetarian main meals could be considered in French university cafeterias to tackle environmental issues.

Trial registration
Study protocol and analysis plan were pre-registered on the Open Science Framework (https://osf.io/pf3x7/).
Tumoral periprostatic adipose tissue exovesicles-derived miR-20a-5p regulates prostate cancer cell proliferation and inflammation through the RORA gene
Authors: Sánchez-Martin Silvia , Altuna-Coy Antonio , Arreaza-Gil Verónica , Bernal-Escoté Xana , Fontgivell Joan Francesc Garcia , Ascaso-Til Helena , Segarra-Tomás José , Ruiz-Plazas Xavier , Chacón Matilde R. 
Published: July 2024

Abstract
Background
From the first steps of prostate cancer (PCa) initiation, tumours are in contact with the most-proximal adipose tissue called periprostatic adipose tissue (PPAT). Extracellular vesicles are important carriers of non-coding RNA such as miRNAs that are crucial for cellular communication. The secretion of extracellular vesicles by PPAT may play a key role in the interactions between adipocytes and tumour. Analysing the PPAT exovesicles (EVs) derived-miRNA content can be of great relevance for understanding tumour progression and aggressiveness.

Methods
A total of 24 samples of human PPAT and 17 samples of perivesical adipose tissue (PVAT) were used. EVs were characterized by western blot and transmission electron microscopy (TEM), and uptake by PCa cells was verified by confocal microscopy. PPAT and PVAT explants were cultured overnight, EVs were isolated, and miRNA content expression profile was analysed. Pathway and functional enrichment analyses were performed seeking potential miRNA targets. In vitro functional studies were evaluated using PCa cells lines, miRNA inhibitors and target gene silencers.

Results
Western blot and TEM revealed the characteristics of EVs derived from PPAT (PPAT-EVs) samples. The EVs were up taken and found in the cytoplasm of PCa cells. Nine miRNAs were differentially expressed between PPAT and PVAT samples. The RORA gene (RAR Related Orphan Receptor A) was identified as a common target of 9 miRNA-regulated pathways. In vitro functional analysis revealed that the RORA gene was regulated by PPAT-EVs-derived miRNAs and was found to be implicated in cell proliferation and inflammation.

Conclusion
Tumour periprostatic adipose tissue is linked to PCa tumour aggressiveness and could be envisaged for new therapeutic strategies.
miR-223 accelerates lipid droplets clearance in microglia following spinal cord injury by upregulating ABCA1
Authors: Ou Zhilin , Cheng Yongquan , Ma Hao , Chen Kai , Lin Qiong , Chen Jiayu , Guo Ruqin , Huang Zhiping , Cheng Qixian , Alaeiilkhchi Nima , Zhu Qingan , Huang Zucheng , Jiang Hui 
Published: July 2024

Abstract
Background
Spinal cord injury (SCI) is characterized by extensive demyelination and inflammatory responses. Facilitating the clearance of lipid droplets (LDs) within microglia contributes to creating a microenvironment that favors neural recovery and provides essential materials for subsequent remyelination. Therefore, investigating MicroRNAs (miRNAs) that regulate lipid homeostasis after SCI and elucidating their potential mechanisms in promoting LDs clearance in microglia have become focal points of SCI research.

Methods
We established a subacute C5 hemicontusion SCI model in mice and performed transcriptomic sequencing on the injury epicenter to identify differentially expressed genes and associated pathways. Confocal imaging was employed to observe LDs accumulation. Multi-omics analyses were conducted to identify differentially expressed mRNA and miRNA post-SCI. Pathway enrichment analysis and protein-protein interaction network construction were performed using bioinformatics methods, revealing miR-223-Abca1 as a crucial miRNA-mRNA pair in lipid metabolism regulation. BV2 microglia cell lines overexpressing miR-223 were engineered, and immunofluorescence staining, western blot, and other techniques were employed to assess LDs accumulation, relevant targets, and inflammatory factor expression, confirming its role in regulating lipid homeostasis in microglia.

Results
Histopathological results of our hemicontusion SCI model confirmed LDs aggregation at the injury epicenter, predominantly within microglia. Our transcriptomic analysis during the subacute phase of SCI in mice implicated ATP-binding cassette transporter A1 (Abca1) as a pivotal gene in lipid homeostasis, cholesterol efflux and microglial activation. Integrative mRNA-miRNA multi-omics analysis highlighted the crucial role of miR-223 in the neuroinflammation process following SCI, potentially through the regulation of lipid metabolism via Abca1. In vitro experiments using BV2 cells overexpressing miR-223 demonstrated that elevated levels of miR-223 enhance ABCA1 expression in myelin debris and LPS-induced BV2 cells. This promotes myelin debris degradation and LDs clearance, and induces a shift toward an anti-inflammatory M2 phenotype.

Conclusions
In summary, our study unveils the critical regulatory role of miR-223 in lipid homeostasis following SCI. The mechanism by which this occurs involves the upregulation of ABCA1 expression, which facilitates LDs clearance and myelin debris degradation, consequently alleviating the lipid burden, and inhibiting inflammatory polarization of microglia. These findings suggest that strategies to enhance miR-223 expression and target ABCA1, thereby augmenting LDs clearance, may emerge as appealing new clinical targets for SCI treatment.
Comparative analysis of optional hunting behavior in Cricetinae hamsters using the data compression approach
Authors: Levenets J. , Panteleeva S. , Reznikova Zh. , Gureeva A. , Kupriyanov V. , Feoktistova N. , Surov A. 
Published: July 2024

AbstractResearch into the hunting behavior in members of the Cricetidae family offers an opportunity to reveal what changes in the predatory behavioral sequences occur when a rodent species shifts from an omnivorous to a predatory lifestyle. The study tests the following hypotheses: are there phylogenetic differences in the divergence of species’ predatory lifestyles in hamsters or do ecological factors lead to shaping their hunting behavior? We applied the data compression approach for performing comparative analysis of hunting patterns as biological “texts.” The study presents a comparative analysis of hunting behaviors in five Cricetinae species, focusing on the new data obtained for the desert hamster Phodopus roborovskii whose behavior has never been studied before. The hunting behavior of P. roborovskii appeared to be the most variable one. In contrast, behavioral sequences in P. campbelli and Allocricetulus curtatus display more significant order and predictability of behavior during hunting. Optional hunting behavior in the most ancient species P. roborovskii displayed similarities with obligate patterns in “young” Allocricetulus species. It thus turned out to be the most advanced hunter among members of the Phodopus genus. Differences in hunting sequences among Phodopus representatives suggest that the hunting behavior of these species, despite its optional mode, was subject to selection during species splitting within the genus. These results did not reveal the role played by phylogenetic differences in the divergence of species’ predatory lifestyles. They suggested that ecological conditions are the main factors in speciation of the hunting behavior in hamsters.