bluuebunny/crossref_metadata_2025 huggingface dataset:
A protocol for the formative evaluation of the implementation of patient-reported outcome measures in child and adolescent mental health services as part of a learning health system
Authors: McCabe Erin , Dyson Michele , McNeil Deborah , Hindmarch Whitney , Ortega Iliana , Arnold Paul D. , Dimitropoulos Gina , Clements Ryan , Santana Maria J. , Zwicker Jennifer D.
Published: July 2024

Background

Mental health conditions affect one in seven young people and research suggests that current mental health services are not meeting the needs of most children and youth. Learning health systems are an approach to enhancing services through rapid, routinized cycles of continuous learning and improvement. Patient-reported outcome measures provide a key data source for learning health systems. They have also been shown to improve outcomes for patients when integrated into routine clinical care. However, implementing these measures into health systems is a challenging process. This paper describes a protocol for a formative evaluation of the implementation of patient-reported measures in a newly operational child and adolescent mental health centre in Calgary, Canada. The purpose is to optimize the collection and use of patient-reported outcome measures. Our specific objectives are to assess the implementation progress, identify barriers and facilitators to implementation, and explore patient, caregivers and clinician experiences of using these measures in routine clinical care.

Methods

This study is a mixed-methods, formative evaluation using the Consolidated Framework for Implementation Research. Participants include patients and caregivers who have used the centre’s services, as well as leadership, clinical and support staff at the centre. Focus groups and semi-structured interviews will be conducted to assess barriers and facilitators to the implementation and sustainability of the use of patient-reported outcome measures, as well as individuals’ experiences with using these measures within clinical care. The data generated by the patient-reported measures over the first five months of the centre’s operation will be analyzed to understand implementation progress, as well as validity of the chosen measures for the centres’ population.

Discussion

The findings of this evaluation will help to identify and address the factors that are affecting the successful implementation of patient-reported measures at the centre. They will inform the co-design of strategies to improve implementation with key stakeholders, which include patients, clinical staff, and leadership at the centre. To our knowledge, this is the first study of the implementation of patient-reported outcome measures in child and adolescent mental health services and our findings can be used to enhance future implementation efforts in similar settings.
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

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

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

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

Dihydroorotase (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

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

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

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

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

Research 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.
Construction and application of medication reminder system: intelligent generation of universal medication schedule
Authors: Huang Hangxing , Zhang Lu , Yang Yongyu , Huang Ling , Lu Xikui , Li Jingyang , Yu Huimin , Cheng Shuqiao , Xiao Jian
Published: July 2024

Background

Patients with chronic conditions need multiple medications daily to manage their condition. However, most patients have poor compliance, which affects the effectiveness of treatment. To address these challenges, we establish a medication reminder system for the intelligent generation of universal medication schedule (UMS) to remind patients with chronic diseases to take medication accurately and to improve safety of home medication.

Methods

To design medication time constraint with one drug (MTCOD) for each drug and medication time constraint with multi-drug (MTCMD) for each two drugs in order to better regulate the interval and time of patients’ medication. Establishment of a medication reminder system consisting of a cloud database of drug information, an operator terminal for medical staff and a patient terminal.

Results

The cloud database has a total of 153,916 pharmaceutical products, 496,708 drug interaction data, and 153,390 pharmaceutical product-ingredient pairs. The MTCOD data was 153,916, and the MTCMD data was 8,552,712. An intelligent UMS medication reminder system was constructed. The system can read the prescription information of patients and provide personalized medication guidance with medication timeline for chronic patients. At the same time, patients can query medication information and get remote pharmacy guidance in real time.

Conclusions

Overall, the medication reminder system provides intelligent medication reminders, automatic drug interaction identification, and monitoring system, which is helpful to monitor the entire process of treatment in patients with chronic diseases.
Efficient production of itaconic acid from the single-carbon substrate methanol with engineered Komagataella phaffii
Authors: Severinsen Manja Mølgaard , Bachleitner Simone , Modenese Viola , Ata Özge , Mattanovich Diethard
Published: July 2024

Background

Amidst the escalating carbon dioxide levels resulting from fossil fuel consumption, there is a pressing need for sustainable, bio-based alternatives to underpin future global economies. Single-carbon feedstocks, derived from CO2, represent promising substrates for biotechnological applications. Especially, methanol is gaining prominence for bio-production of commodity chemicals.

Results

In this study, we show the potential of Komagataella phaffii as a production platform for itaconic acid using methanol as the carbon source. Successful integration of heterologous genes from Aspergillus terreus (cadA, mttA and mfsA) alongside fine-tuning of the mfsA gene expression, led to promising initial itaconic acid titers of 28 g·L−1 after 5 days of fed-batch cultivation. Through the combined efforts of process optimization and strain engineering strategies, we further boosted the itaconic acid production reaching titers of 55 g·L−1 after less than 5 days of methanol feed, while increasing the product yield on methanol from 0.06 g·g−1 to 0.24 g·g−1.

Conclusion

Our results highlight the potential of K. phaffii as a methanol-based platform organism for sustainable biochemical production.
TGFβ signaling pathway is altered by HLA-B27 expression, resulting in pathogenic consequences relevant for spondyloarthritis
Authors: Lauraine Marc , de Taffin de Tilques Maxence , Melamed-Kadosh Dganit , Cherqaoui Bilade , Rincheval Vincent , Prevost Erwan , Rincheval-Arnold Aurore , Cela Eneida , Admon Arie , Guénal Isabelle , Araujo Luiza M. , Breban Maxime
Published: July 2024

Background

Association of HLA-B27 with spondyloarthritis (SpA) has been known for 50 years, but still remains unexplained. We recently showed that HLA-B27 expressed in wing imaginal disc from HLA-B27/human-β2 microglobulin (hβ2m) transgenic Drosophila deregulated bone morphogenetic protein (BMP) pathway by interacting physically with type I BMP receptor (BMPR1) Saxophone (Sax), leading to crossveinless phenotype.

Methods

Genetic interaction was studied between activin/transforming growth factor β (TGFβ) pathway and HLA-B27/hβ2m in transgenic Drosophila wings. The HLA-B27-bound peptidome was characterized in wing imaginal discs. In mesenteric lymph node (mLN) T cells from HLA-B27/hβ2m rat (B27 rat), physical interaction between HLA-B27 and activin receptor-like kinase-2 (ALK2), ALK3 and ALK5 BMPR1s, phosphorylation of small mothers against decapentaplegic (SMADs) and proteins of the non-canonical BMP/TGFβ pathways induced by its ligands, and the transcript level of target genes of the TGFβ pathway, were evaluated.

Results

In HLA-B27/hβ2m transgenic Drosophila, inappropriate signalling through the activin/TGFβ pathway, involving Baboon (Babo), the type I activin/TGFβ receptor, contributed to the crossveinless phenotype, in addition to deregulated BMP pathway. We identified peptides bound to HLA-B27 with the canonical binding motif in HLA-B27/hβ2m transgenic Drosophila wing imaginal disc. We demonstrated specific physical interaction, between HLA-B27/hβ2m and mammalian orthologs of Sax and Babo, i.e. ALK2 and ALK5 (i.e. TGFβ receptor I), in the mLN cells from B27 rat. The magnitude of phosphorylation of SMAD2/3 in response to TGFβ1 was increased in T cells from B27 rats, showing evidence for deregulated TGFβ pathway. Accordingly, expression of several target genes of the pathway was increased in T cells from B27 rats, in basal conditions and/or after TGFβ exposure, including Foxp3, Rorc, Runx1 and Maf. Interestingly, Tgfb1 expression was reduced in naive T cells from B27 rats, even premorbid, an observation consistent with a pro-inflammatory pattern.

Conclusions

This study shows that HLA-B27 alters the TGFβ pathways in Drosophila and B27 rat. Given the importance of this pathway in CD4 + T cells differentiation and regulation, its disturbance could contribute to the abnormal expansion of pro-inflammatory T helper 17 cells and altered regulatory T cell phenotype observed in B27 rats.
Comparative evaluation of disease dynamics in wild boar and domestic pigs experimentally inoculated intranasally with the European highly virulent African swine fever virus genotype II strain “Armenia 2007”
Authors: Sánchez-Cordón Pedro J. , Lean Fabian Z. X. , Batten Carrie , Steinbach Falko , Neimanis Aleksija , Le Potier Marie-Frédérique , Wikström-Lassa Emil , Wynne Felicity , Strong Rebecca , McCleary Stephen , Crooke Helen , Gavier-Widén Dolores , Núñez Alejandro
Published: July 2024

Since the reintroduction of African swine fever virus (ASFV) in Europe in 2007 and its subsequent spread to Asia, wild boar has played a crucial role in maintaining and disseminating the virus. There are significant gaps in the knowledge regarding infection dynamics and disease pathogenesis in domestic pigs and wild boar, particularly at the early infection stage. We aimed to compare domestic pigs and wild boar infected intranasally to mimic natural infection with one of the original highly virulent genotype II ASFV isolates (Armenia 2007). The study involved euthanising three domestic pigs and three wild boar on days 1, 2, 3, and 5 post-infection, while four domestic pigs and four wild boar were monitored until they reached a humane endpoint. The parameters assessed included clinical signs, macroscopic lesions, viremia levels, tissue viral load, and virus shedding in nasal and rectal swabs from day 1 post-infection. Compared with domestic pigs, wild boar were more susceptible to ASFV, with a shorter incubation period and earlier onset of clinical signs. While wild boar reached a humane endpoint earlier than domestic pigs did, the macroscopic lesions were comparatively less severe. In addition, wild boar had earlier viremia, and the virus was also detected earlier in tissues. The medial retropharyngeal lymph nodes were identified as key portals for ASFV infection in both subspecies. No viral genome was detected in nasal or rectal swabs until shortly before reaching the humane endpoint in both domestic pigs and wild boar, suggesting limited virus shedding in acute infections.
Frailty and its association with long-term mortality among community-dwelling older adults aged 75 years and over
Authors: Lewis Maor , Heymann Anthony , Zacay Galia , Justo Dan
Published: July 2024

Background

Frailty, a significant risk factor for adverse outcomes and mortality, poses an emerging challenge with profound implications for public health and clinical practice. The measurement of frailty offers potential enhancements in healthcare services for older adults. The prevalence of frailty and its association with long-term mortality in a nationwide, unselected population of community-dwelling older adults, particularly those aged 75 and over, has not been previously studied on a large scale in Israel.

Methods

A retrospective cohort study was conducted at Meuhedet Health Maintenance Organization, Israel’s third largest healthcare service provider, serving 1,276,000 people (13.8% of Israelis). The prevalence of frailty and its association with all-cause mortality were studied among older adults aged 75 years and over who were followed for 2–8 years. Frailty, defined by the cumulative deficit method, utilized clinical data from the preceding 10-year period, comprising 28 chronic diseases and age-related health deficits.

Results

The cohort included 43,737 older adults, with a median age of 77 years (IQR 75–82 years); among them, 19,300 (44.1%) were males. Overall, 19,396 (44.3%) older adults were frail: 12,260 (28.0%) mildly frail, 5,533 (12.7%) moderately frail and 1,603 (3.7%) severely frail. During the follow-up period 15,064 (34.4%) older adults died: 4,782 (39.0%) mildly frail, 3,016 (54.5%) moderately frail and 1,080 (67.4%) severely frail. Cox regression analysis demonstrated that mortality was associated with severe frailty (HR 2.63, 95%CI 2.45–2.80), moderate frailty (HR 2.05, 95%CI 1.96–2.14), and mild frailty (HR 1.45, 95%CI 1.39–1.51), independent of age, gender, and population sector. Among patients aged 90 years and over, no significant differences in cumulative survival were found between those with moderate and severe frailty (p = 0.408).

Conclusions

Frailty is prevalent among community-dwelling Israeli older adults aged 75 years and over, and it is associated with long-term mortality. Considering its association with long-term mortality across frailty levels until the age of 90, early identification and intervention for frailty are recommended within this population. Policymakers should consider the use of the cumulative deficit method for evaluating frailty at both the population health and clinical levels.
STAR-RIS-assisted key generation method in quasi-static environment
Authors: Ma Yang , Chen Liquan , Lu Tianyu , Song Yufan , Cao Kailin
Published: July 2024

In this paper, we introduce a new method to solve the low-entropy problem in a quasi-static environment. We utilize a simultaneous transmission and reflection reconfigurable intelligent surface (STAR-RIS) that transmits and reflects incoming signals to users located on different sides of the surface. Specifically, we design the flow of multi-user channel probing when STAR-RIS is assisted, analyze and derive the analytical expression of the secret key capacity (SKC) of STAR-RIS-assisted system from the perspective of information theory, and finally analyze how to maximize the SKC and sum of all users under three different working protocols of STAR-RIS. The simulation results show that: (1) STAR-RIS can achieve better SKC performance than the conventional reflection/transmission RIS; and (2) the SKC is determined by the number of STAR-RIS elements, correlation coefficient, pilot length and RIS-reflected channel quality, and the time switching protocol can obtain higher SKC than the energy splitting protocol and mode switching protocol.
Sustainable entrepreneurship through customer satisfaction and reuse intention of online food delivery applications: insights from China
Authors: Jingzu Gao , Siyu Long , Mengling Wu , Yang Qing , Al Mamun Abdullah , Hayat Naeem
Published: July 2024

Advancements in the online food delivery market in China have resulted from the rapid development and popularity of mobile communications and smartphones, which are currently applied by mobile and online application developers to restaurants and food delivery services for high sales revenue and fulfilment of Chinese consumers at home. The current work aims to thoroughly examine the four information quality dimensions (i.e. intrinsic quality, contextual quality, representational quality and accessibility quality), perceived ease of use, perceived usefulness, and perceived convenience and their subsequent implications on user satisfaction and reuse intention of online food delivery applications. By analysing the roles of these factors, we underscore how innovative technology and entrepreneurial strategies can drive customer engagement and satisfaction in the rapidly evolving online food delivery market. The theoretical model proposed in this study was tested through partial least square structural equation modelling (PLS-SEM). Resultantly, intrinsic quality, contextual quality, representational quality, accessibility quality, perceived usefulness, and perceived ease of use showed a positive and statistically significant effect on user satisfaction, whereas contextual, representational, and accessibility quality, perceived usefulness, perceived convenience, and customer satisfaction positively and significantly affected users’ intention to reuse the online food delivery applications. The key determinant of reuse intention was customers’ personal satisfaction. In order to improve the continuous usage intention of online food delivery applications, application developers and the food industry should therefore focus on providing accurate and up-to-date information, which is expected to boost user satisfaction and reuse intentions.
Evaluation of postoperative results after a presurgical optimisation programme
Authors: García Sánchez Francisco , Mudarra García Natalia
Published: July 2024

Background

Presurgical optimisation programmes decrease the risk of postoperative complications, reduce hospital stays and speed up patient recovery. They usually involve a multidisciplinary team addressing physical, nutritional and psychosocial issues. The objective of this study was to assess the results of implementing a presurgical optimisation programme led by a liaison nurse in patients undergoing major surgery in a primary general hospital.

Methods

An observational, retrospective, descriptive, cross-sectional, comparative study based on the revision of patients’ health records undergoing major surgery between January 2019 and December 2022. Patients entering the presurgical optimisation programme (intervention group) were compared with patients receiving usual medical care (control group). The presurgical optimisation programme consisted of oral nutritional supplementation, physical exercise, strengthening of lung capacity and psychological and emotional support. Frequency (%) of surgery complications and use of healthcare resources (duration of hospitalisation, time spent in the intensive care unit (ICU), and readmission) at day 30 were recorded. Descriptive statistics were applied.

Results

Two hundred eleven patients (58.5% men, mean age: 65.76 years (SD 11.5), 75.2%. non-smokers; mean body mass index (BMI): 28.32 (SD 5.38); mean Nutritional Risk Score (NRS) 3.71 (SD 1.35; oncology diagnosis: 88.6%) were included: 135 in the intervention group, and 76 in the control group. The average duration of the presurgical optimisation programme was 20 days (SD 5). Frequency of postoperative complications was 25% (n = 33) in the intervention group and 52.6% (n = 40) in the control group (p < 0.001) [odds ratio (OR) = 3.4; 95% confidence interval (CI) (1.8; 6.2)]. 14.5% (n = 19) of patients in the intervention group and 34.2% (n = 26) in the control group had remote postoperative complications [OR = 3.1; 95% CI (1.6; 6.2)]. Patients in the intervention group spent fewer days in the hospital [mean 8.34 (SD 6.70) vs 11.63 (SD 10.63)], and there were fewer readmissions at 30 days (7.6% vs 19.7%) compared with the control group.

Conclusions

A presurgical optimisation programme led by a liaison nurse decreases the rate of immediate and late surgical complications and reduces hospital stays and readmissions in patients undergoing major surgery.
Stone–Geary meets CES: the properties of an extended linear expenditure system
Authors: Sancho Ferran
Published: July 2024

The structure of demand plays a fundamental role in shaping economic equilibrium. In computable general equilibrium analysis, comparative statics allow us to simulate how policies or external adjustments impact the equilibrium state. The results of these simulations are significantly influenced by the nature of the adopted demand structure. Typically, homothetic demand structures are frequently used for simplicity in these equilibrium models, but they do not accurately capture demand behavior. In this text, we study the properties of a demand system that eliminates demand constraints often found in general equilibrium models. Specifically, we first explore the characteristics of a demand system that generalizes the standard Stone–Geary linear demand structure. Second, we illustrate its possibilities with an empirical application using available Spanish data.
Redundancy in microbiota-mediated suppression of the soybean cyst nematode
Authors: Hussain Muzammil , Xuan Peixue , Xin Yi , Ma Haikun , Zhou Yahan , Wen Shihui , Hamid M. Imran , Wan Tianyu , Hu Jianyang , Li Yuezhong , Kang Seogchan , Liu Xingzhong , Xiang Meichun
Published: July 2024

Background

Soybean cyst nematodes (SCN) as animal parasites of plants are not usually interested in killing the host but are rather focused on completing their life cycle to increase population, resulting in substantial yield losses. Remarkably, some agricultural soils after long-term crop monoculture show a significant decline in SCN densities and suppress disease in a sustainable and viable manner. However, relatively little is known about the microbes and mechanisms operating against SCN in such disease-suppressive soils.

Results

Greenhouse experiments showed that suppressive soils (S) collected from two provinces of China and transplantation soils (CS, created by mixing 10% S with 90% conducive soils) suppressed SCN. However, SCN suppressiveness was partially lost or completely abolished when S soils were treated with heat (80 °C) and formalin. Bacterial community analysis revealed that the specific suppression in S and CS was mainly associated with the bacterial phylum Bacteroidetes, specifically due to the enrichment of Chitinophaga spp. and Dyadobacter sp., in the cysts. SCN cysts colonized by Chitinophaga spp. showed dramatically reduced egg hatching, with unrecognizable internal body organization of juveniles inside the eggshell due to chitinase activity. Whereas, Dyadobacter sp. cells attached to the surface coat of J2s increased soybean resistance against SCN by triggering the expression of defence-associated genes. The disease-suppressive potential of these bacteria was validated by inoculating them into conducive soil. The Dyadobacter strain alone or in combination with Chitinophaga strains significantly decreased egg densities after one growing cycle of soybeans. In contrast, Chitinophaga strains alone required more than one growing cycle to significantly reduce SCN egg hatching and population density.

Conclusion

This study revealed how soybean monoculture for decades induced microbiota homeostasis, leading to the formation of SCN-suppressive soil. The high relative abundance of antagonistic bacteria in the cyst suppressed the SCN population both directly and indirectly. Because uncontrolled proliferation will likely lead to quick demise due to host population collapse, obligate parasites like SCN may have evolved to modulate virulence/proliferation to balance these conflicting needs.
A network model of stress contagion: evidence from the vocational classroom
Authors: Kärner Tobias , Shkoza Livia , Pohlmeier Winfried
Published: July 2024

Purpose

Our study focuses on stress contagion in vocational school classes, examining how students’ stress experiences affect their spatial classmates. For this purpose, we apply a novel formal network model that allows us to differentiate between endogenous and exogenous peer effects in the stress contagion process. Using the network model, we investigate effects on students’ stress levels, considering the stress and coping experiences of spatial peers as well as didactic-methodological context factors.

Methods

We test our statistical model using secondary data collected in a study involving 53 students from two classes at a public German vocational training school. The students’ experiences of stress (time pressure, pressure to succeed) and coping strategies (understanding of the subject matter, self-confidence) were captured using the experience sampling method, while classroom characteristics (e.g., teacher instruction, cooperative work) were recorded through video-based analysis of lessons. Utilizing the panel data, we employ maximum likelihood estimation to assess the spatial peer effects model for both classrooms.

Results

Among other findings, all model specifications revealed significant peer effects for both stress measures, indicating that the higher the stress experience of immediate peers in the classroom, the higher the individual stress experienced by the students. Concerning the considered context factors, we found, for example, that increased cooperative work leads to higher levels of stress experience.

Conclusion

From a substantive perspective, our results underscore the role of peer-to-peer contagion in the vocational classroom and thus suggest a nuanced examination of cooperative practices. From a research methodology perspective, our approach illustrates how various methods (such as experience sampling, video-based classroom observation, and spatial network information) complement and enrich each other, highlighting the added value of our network analytical approach