bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined metabolome and transcriptome reveal HmF6’H1 regulating simple coumarin accumulation against powdery mildew infection in Heracleum moellendorffii Hance
Authors: Liu Hanbing , Wang Yiran , Chang QinZheng , Li Qiubi , Fang Jiahui , Cao Ning , Tong Xuejiao , Jiang Xinmei , Yu Xihong , Cheng Yao
Published: June 2024

Background

Powdery mildew, caused by Eeysiphe heraclei, seriously threatens Heracleum moellendorffii Hance. Plant secondary metabolites are essential to many activities and are necessary for defense against biotic stress. In order to clarify the functions of these metabolites in response to the pathogen, our work concentrated on the variations in the accumulation of secondary metabolites in H. moellendorffii during E. heraclei infection.

Results

Following E. heraclei infection, a significant upregulation of coumarin metabolites—particularly simple coumarins and associated genes was detected by RNA-seq and UPLC-MS/MS association analysis. Identifying HmF6’H1, a Feruloyl CoA 6’-hydroxylase pivotal in the biosynthesis of the coumarin basic skeleton through ortho-hydroxylation, was a significant outcome. The cytoplasmic HmF6’H1 protein was shown to be able to catalyze the ortho-hydroxylation of p-coumaroyl-CoA and caffeoyl-CoA, resulting in the formation of umbelliferone and esculetin, respectively. Over-expression of the HmF6’H1 gene resulted in increased levels of simple coumarins, inhibiting the biosynthesis of furanocoumarins and pyranocoumarins by suppressing PT gene expression, enhancing H. moellendorffii resistance to powdery mildew.

Conclusions

These results established HmF6’H1 as a resistance gene aiding H. moellendorffii in combatting E. heraclei infection, offering additional evidence of feruloyl-CoA 6’-hydroxylase role in catalyzing various types of simple coumarins. Therefore, this work contributes to our understanding of the function of simple coumarins in plants’ defense against powdery mildew infection.
Morbidity profile and pharmaceutical management of adult outpatients between primary and tertiary care levels in Sri Lanka: a dual-centre, comparative study
Authors: Alwis Inosha , Rajapaksha Buwanaka , Jayasanka Chanuka , Dharmaratne Samath D.
Published: June 2024

Background

Outpatient care is central to both primary and tertiary levels in a health system. However, evidence is limited on outpatient differences between these levels, especially in South Asia. This study aimed to describe and compare the morbidity profile (presenting morbidities, comorbidities, multimorbidity) and pharmaceutical management (patterns, indicators) of adult outpatients between a primary and tertiary care outpatient department (OPD) in Sri Lanka.

Methods

A comparative study was conducted by recruiting 737 adult outpatients visiting a primary care and a tertiary care facility in the Kandy district. A self-administered questionnaire and a data sheet were used to collect outpatient and prescription data. Following standard categorisations, Chi-square tests and Mann‒Whitney U tests were employed for comparisons.

Results

Outpatient cohorts were predominated by females and middle-aged individuals. The median duration of presenting symptoms was higher in tertiary care OPD (10 days, interquartile range: 57) than in primary care (3 days, interquartile range: 12). The most common systemic complaint in primary care OPD was respiratory symptoms (32.4%), whereas it was dermatological symptoms (30.2%) in tertiary care. The self-reported prevalence of noncommunicable diseases (NCDs) was 37.9% (95% CI: 33.2–42.8) in tertiary care OPD and 33.2% (95% CI: 28.5–38.3) in primary care; individual disease differences were significant only for diabetes (19.7% vs. 12.8%). The multimorbidity in tertiary care OPD was 19.0% (95% CI: 15.3–23.1), while it was 15.9% (95% CI: 12.4–20.0) in primary care. Medicines per encounter at primary care OPD (3.86, 95% CI: 3.73–3.99) was higher than that at tertiary care (3.47, 95% CI: 3.31–3.63). Medicines per encounter were highest for constitutional and respiratory symptoms in both settings. Overall prescribing of corticosteroids (62.7%), vitamin supplements (45.8%), anti-allergic (55.3%) and anti-asthmatic (31.3%) drugs was higher in the primary care OPD, and the two former drugs did not match the morbidity profile. The proportion of antibiotics prescribed did not differ significantly between OPDs. Subgroup analyses of drug categories by morbidity largely followed these overall differences.

Conclusions

The morbidities between primary and tertiary care OPDs differed in duration and type but not in terms of multimorbidity or most comorbidities. Pharmaceutical management also varied in terms of medicines per encounter and prescribed categories. This evidence supports planning in healthcare and provides directions for future research in primary care.
An exploration of Northern Ireland general practice pharmacists’ views on their role in general practice: a cross-sectional survey
Authors: Hassan Abrar H. F. , Barry Heather E. , Hughes Carmel M.
Published: June 2024

Background

There is limited research examining the views of general practice pharmacists (GPPs) on their role and their impact in general practice. The aim of this study was to explore GPPs’ views regarding this role and its potential impact within general practice in Northern Ireland (NI).

Methods

A paper-based self-administered questionnaire was mailed to 319 general practices in NI in 2022, directed to the GPP who spent most time at the practice. A variety of closed and open questions were included in six sections. Responses to closed questions were analysed descriptively whilst open question responses were analysed using content analysis. To ascertain associations between variables (e.g. GPP prescribing status, working arrangements and aspects of collaboration with GPPs), Fisher’s exact test was employed with an a priori significance level of p < 0.05.

Results

155 responses were received equating to a response rate of 48.5%. Most participants (72.3%) were female, independent prescribers (71%), and 64.5% were currently using their independent prescriber qualification. Services that were provided by most GPPs were medication reconciliation (99.4%) and medication reviews (97.4%). The most common method of communication between GPPs and general practitioners (GPs) was face-to-face (89.0%). Telephone was the most common method of communication between GPPs, community pharmacists (97.4%) and patients (98.7%). Most GPPs (> 80%) showed positive attitudes towards collaboration with GPs and those who worked in multiple practices were more likely to agree with the Attitudes Towards Collaboration Instrument for pharmacists (ATCI-P) statements compared to those who worked in a single practice (p < 0.05). Less than 40% (36.8%) of GPPs agreed that patients were aware of the role they provided. The majority of GPPs (80.6%) expressed positive views on their impact on primary care. Analysis of the free-text comments revealed the need for more GPP patient-facing activities, GPP-specific training, and promotion of the GPP role.

Conclusion

The findings indicated that GPPs had largely positive views about their role and their impact on primary care. The results may be helpful for practices and service commissioners. Further research is necessary to explore the perspectives of patients regarding the role of the GPP and to enhance patients’ awareness of the GPP.
Nocturia and frailty in older adults: a scoping review
Authors: Komleva Yulia , Gollasch Maik , König Maximilian
Published: June 2024

Background

More than one in two older people wake up several times a night to urinate. Far from being a minor inconvenience, nocturia is associated with poor health outcomes. Given the importance of sleep as a foundation for resilience and healthy ageing, nocturia may promote the development of frailty, which is inextricably linked to physical decline, disability, and mortality.

The aim of this scoping review was to collate published evidence on the relationship between nocturia and frailty, using the methodological framework of Arksey and O'Malley, together with the Joanna Briggs Institute methodology as guidance (OSF registration: osf.io/d5ct7).

Methods

Relevant publications were retrieved via PubMed, Embase, the Cochrane Library and Google Scholar. The Rayyan tool was used to facilitate the screening process. Data were extracted by two independent reviewers. 250 publications were initially identified, of which 87 met the eligibility criteria.

Results

Most of the evidence came from cross-sectional studies, most of which had been published within the last 5 years. The researchers were diverse, with 27% having a geriatric background. Only few publications established a clear association between nocturia and frailty. Other topics included: the association between nocturia and poor sleep quality and duration; the association between sleep and frailty; the association between frailty, multimorbidity, and age-related changes in the lower urinary tract.

Conclusion

The findings emphasize the increasing interest and interdisciplinary nature of research into the relationship between frailty, nocturia, lower urinary tract symptoms, and sleep disturbances. Further research is required to enhance understanding, establish causality, and identify potential therapeutic approaches.
Longitudinal dynamic single-cell mass cytometry analysis of peripheral blood mononuclear cells in COVID-19 patients within 6 months after viral RNA clearance
Authors: Zhou Diwenxin , Zhao Shuai , He Keting , Liu Qiuhong , Zhang Fen , Pu Zhangya , Xiao Lanlan , Zhang Lingjian , Chen Shangci , Qian Xiaohan , Wu Xiaoxin , Shen Yangfan , Yu Ling , Zhang Huafen , Jin Jiandi , Xu Min , Wang Xiaoyan , Zhu Danhua , Xie Zhongyang , Xu Xiaowei
Published: June 2024

This study investigates the longitudinal dynamic changes in immune cells in COVID-19 patients over an extended period after recovery, as well as the interplay between immune cells and antibodies. Leveraging single-cell mass spectrometry, we selected six COVID-19 patients and four healthy controls, dissecting the evolving landscape within six months post-viral RNA clearance, alongside the levels of anti-spike protein antibodies. The T cell immunophenotype ascertained via single-cell mass spectrometry underwent validation through flow cytometry in 37 samples. Our findings illuminate that CD8 + T cells, gamma-delta (gd) T cells, and NK cells witnessed an increase, in contrast to the reduction observed in monocytes, B cells, and double-negative T (DNT) cells over time. The proportion of monocytes remained significantly elevated in COVID-19 patients compared to controls even after six-month. Subpopulation-wise, an upsurge manifested within various T effector memory subsets, CD45RA + T effector memory, gdT, and NK cells, whereas declines marked the populations of DNT, naive and memory B cells, and classical as well as non-classical monocytes. Noteworthy associations surfaced between DNT, gdT, CD4 + T, NK cells, and the anti-S antibody titer. This study reveals the changes in peripheral blood mononuclear cells of COVID-19 patients within 6 months after viral RNA clearance and sheds light on the interactions between immune cells and antibodies. The findings from this research contribute to a better understanding of immune transformations during the recovery from COVID-19 and offer guidance for protective measures against reinfection in the context of viral variants.
Smoking patterns and the intention to quit in German cancer patients: a cross-sectional study
Authors: Bokemeyer Frederike , Lebherz Lisa , Bokemeyer Carsten , Gali Kathleen , Schulz Holger , Bleich Christiane
Published: June 2024

Background

Continued smoking after a cancer diagnosis can be associated with lower treatment tolerance, poorer outcomes, and reduced quality of life compared to non-smoking cancer patients or to those who have quit. Yet about 60% of patients continue to smoke after being diagnosed and find it difficult to quit. To address this problem, it is necessary to identify current and past smoking patterns (e.g., frequency of use, types of tobacco products) and determine whether there is motivation to quit. Similarly, factors associated with continued smoking should be identified. These data will provide the basis for the development of smoking cessation programs tailored to the needs of cancer patients.

Methods

A questionnaire was distributed to cancer patients older than 18 years in a German Comprehensive Cancer Center. Participating cancer patients were divided into three main groups: 1) patients who stopped smoking before being diagnosed with cancer (Ex-before); 2) patients who stopped smoking after a cancer diagnosis (Ex-after); and 3) patients who currently smoke cigarettes (CS). Sociodemographic, medical, and psychosocial data were collected, as well as smoking patterns and the motivation to quit smoking.

Results

About half of patients (51%) who smoked before diagnosis continue to smoke after a cancer diagnosis. Being diagnosed with a tobacco-related cancer type was associated with a decreased probability of continued smoking. Patients with tobacco-related tumors and receiving positive support in burdensome situations were more likely to have a higher cigarette dependence. Of all CS, 59.1% had intention to quit, and 22.7% reported having taken action to quit.

The support by a smoking cessation program was considered important. CS were willing to spend up to €100 for support and were open to multiple sessions per week, group sessions, one-on-one sessions and/or online support.

Conclusion

These findings underscore the importance of educating cancer patients about the consequences of smoking and to provide them with support to quit. Identified risk factors may further help to recognize cancer patients with high risk of continued smoking after diagnosis.

Trial Registration

The study was registered at OSF (https://osf.io/3c9km) and published as a study protocol at “https://bmjopen.bmj.com/content/13/4/e069570”.
Diet, lifestyle factors, comorbidities, and hepatocellular carcinoma risk in a middle eastern country: a case-control study
Authors: Almohaid Shaimaa , Akhtar Saeed
Published: June 2024

Background

Hepatocellular Carcinoma (HCC) can be classified as one of the most common malignancies worldwide. There is scarcity of the published data on the risk factors for HCC in the Gulf Cooperation Council countries specifically Kuwait. Therefore, this case-control study sought to examine the risk factors associated with HCC in Kuwait.

Methods

Fifty-three histopathologically confirmed HCC cases were recruited from the Kuwait Cancer Control Center Registry. One hundred ninety-six controls (1:4 ratio) were selected from medical and/ or surgical outpatient’s clinics at all six public hospitals of Kuwait. A structured questionnaire was used to collect the data both from cases and controls through face-to-face interviews. A multivariable logistic regression model was fitted to the case-control data. Adjusted odds ratios (ORadj) and their 95% confidence intervals (CI) were computed using the parameters’ estimates of the final model and used for interpretation of the model.

Results

The HCC cases compared with the controls were 41.6 times more likely to have had the history of non-alcoholic fatty liver disease (NAFLD) (ORadj = 41.6; 95% CI: 8.9–193.5; p < 0.001). The cases compared with the controls were more likely to have reported the history of heavy alcohol drinking (ORadj = 14.2; 95% CI: 1.2–173.4; p = 0.038). Furthermore, compared with the controls, the HCC cases tended to frequently consume milk and/or milk substitutes (≥ 3 glass/ week) (ORadj = 7.2; 95% CI: 1.2–43.4). Conversely however, there was a significant protective effect if the participants reportedly have had regularly used olive oil in their routine diet as a source of fat (ORadj = 0.17; 95% CI: 0.04–0.80) or regularly used non-steroid anti-inflammatory drugs (NSAIDs) (ORadj = 0.20; 95% CI: 0.05–0.71).

Conclusions

This study showed that heavy alcohol consumption, NAFLD history, and excessive consumption of milk/ milk substitutes were associated with a significantly increased HCC risk. Conversely however, regular use of olive oil in the diet as a source of fat or regular use of NSAIDs had a significantly protective effect against HCC risk. Adapting healthy dietary habits and preventing/ treating NAFLD may minimize the HCC risk. Future research with a larger sample size may contemplate validating the results of this study and unraveling additional risk factors contributing to HCC risk. The resultant data may help design and implement evidence-based educational programs for the prevention of HCC in this and other similar settings.
PRDX1 exerts a photoprotection effect by inhibiting oxidative stress and regulating MAPK signaling on retinal pigment epithelium
Authors: Wen Xiao-Ying , Yang Na , Gao Yang , Ma Wei-na , Fu Yan , Geng Ren-fei , Zhang Yue-ling
Published: June 2024

Background

The purpose of this study was to investigate the photoprotection effect of peroxiredoxin 1 (PRDX1) protein in ultraviolet B (UVB) irradiation-induced damage of retinal pigment epithelium (RPE) and its possible molecular mechanism.

Methods

ARPE-19 cell viability and apoptosis were assessed by MTT assay and flow cytometry, respectively. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the PRDX1 expression. The corresponding kits were employed to measure the levels or activities of lactate dehydrogenase (LDH), 8-hydroxy-2-deoxyguanosine (8-OHdG), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD). Western blotting was applied to examine PRDX1 expression and mitogen-activated protein kinase (MAPK) signaling pathway-related proteins.

Results

After exposure to 20 mJ/cm2 intensity of UVB irradiation for 24 h, ARPE-19 cells viability was decreased, the leakage degree of LDH and 8-OHdG were increased, and cell apoptosis was elevated. The expression of PRDX1 was significantly down-regulated in UVB-induced ARPE-19 cells. The low expression of PRDX1 was involved in high irradiation intensity. Overexpression of PRDX1 increased cell activity, decreased cell apoptosis, and LDH as well as 8-OHdG leakage in UVB-induced ARPE-19 cells. In addition to alleviating UVB-induced cell damage, PRDX1 overexpression also inhibited UVB-induced oxidative stress (down-regulation of ROS and MDA levels, up-regulation of GSH-Px and SOD activities) and the activation of MAPK signaling pathway in ARPE-19 cells.

Conclusion

PRDX1 exerts a photoprotection effect on RPE by attenuating UVB-induced cell damage and inhibiting oxidative stress, which can be attributed to the inhibition of MAPK signaling pathway activation.
Prevalence of dental carries and its association with breastfeeding duration among young children in Addis Ababa, Ethiopia
Authors: Tesfay Marta Yemane , Delbiso Tefera Darge
Published: June 2024

Background

Breastfeeding is a crucial feeding practices that significantly contributes to the healthy development of children. However, the effect of breastfeeding duration on caries risk is unclear, as different studies have found different results. This study aims to assess the prevalence of dental caries and its association with breastfeeding duration among young children aged 12–36 months in selected health facilities of Addis Ababa, Ethiopia.

Methods

A cross-sectional study among 380 children aged 12–36 months from 11 health centers in Addis Ababa was conducted. Questionnaires and dental examinations were used to collect data. Dental caries was measured by the deft (decayed–extracted–filled teeth) index. Binary logistic regression was used to assess the association between dental caries and duration of breastfeeding, after adjusting for the confounders.

Results

The prevalence of dental caries was 53.4% (95% CI: 48.3, 58.5%), with 13.7% having high caries and 39.7% having low caries. Breastfeeding duration was not significantly associated with dental carries, after adjusting for confounders. However, sugar intake, older age, mothers’ unemployment, and not being in marital union are risk factors for dental caries development.

Conclusions

Promotion of healthy diet, especially limiting intake of sugar and sweets, and integration of oral health into primary health care programs are recommended. Further research using longitudinal design or meta-analysis is recommended to establish more concise evidence on the association between breastfeeding duration and dental caries.
Metabolomic insights into pulmonary fibrosis: a mendelian randomization study
Authors: Tang Wuyinuo , Jiang Huanyu , Wu Xinhui , Wu Guanyi , Zhao Chenchong , Lin Wenbo , Zhu Ying , Jiang Guowei , Chen Xiuhua , Huang Hang , He Lvyuan
Published: June 2024

Background

This study leverages a two-sample Mendelian Randomization (MR) approach to explore the causal relationships between 1,400 metabolites and pulmonary fibrosis, using genetic variation as instrumental variables. By adhering to stringent criteria for instrumental variable selection, the research aims to uncover metabolic pathways that may influence the risk and progression of pulmonary fibrosis, providing insights into potential therapeutic targets.

Methods

Utilizing data from the OpenGWAS project, which includes a significant European cohort, and metabolite GWAS data from the Canadian Longitudinal Aging Study (CLSA), the study employs advanced statistical methods. These include inverse variance weighting (IVW), weighted median estimations, and comprehensive sensitivity analyses conducted using the R software environment to ensure the robustness of the causal inferences.

Results

The study identified 62 metabolites with significant causal relationships with pulmonary fibrosis, highlighting both risk-enhancing and protective metabolic factors. This extensive list of metabolites presents a broad spectrum of potential therapeutic targets and biomarkers for early detection, underscoring the metabolic complexity underlying pulmonary fibrosis.

Conclusions

The findings from this MR study significantly advance our understanding of the metabolic underpinnings of pulmonary fibrosis, suggesting that alterations in specific metabolites could influence the risk and progression of the disease. These insights pave the way for the development of novel diagnostic and therapeutic strategies, emphasizing the potential of metabolic modulation in managing pulmonary fibrosis.
Resting-state brain plasticity is associated with the severity in cervical spondylotic myelopathy
Authors: Tan Yongming , Shao Ziwei , Wu Kaifu , Zhou Fuqing , He Laichang
Published: June 2024

Objective

To investigate the brain mechanism of non-correspondence between imaging presentations and clinical symptoms in cervical spondylotic myelopathy (CSM) patients and to test the utility of brain imaging biomarkers for predicting prognosis of CSM.

Methods

Forty patients with CSM (22 mild-moderate CSM, 18 severe CSM) and 25 healthy controls (HCs) were recruited for rs-fMRI and cervical spinal cord diffusion tensor imaging (DTI) scans. DTI at the spinal cord (level C2/3) with fractional anisotropy (FA) and degree centrality (DC) were recorded. Then one-way analysis of covariance (ANCOVA) was conducted to detect the group differences in the DC and FA values across the three groups. Pearson correlation analysis was then separately performed between JOA with FA and DC.

Results

Among them, degree centrality value of left middle temporal gyrus exhibited a progressive increase in CSM groups compared with HCs, the DC value in severe CSM group was higher compared with mild-moderate CSM group. (P < 0.05), and the DC values of the right superior temporal gyrus and precuneus showed a decrease after increase. Among them, DC values in the area of precuneus in severe CSM group were significantly lower than those in mild-moderate CSM and HCs. (P < 0.05). The fractional anisotropy (FA) values of the level C2/3 showed a progressive decrease in different clinical stages, that severe CSM group was the lowest, significantly lower than those in mild-moderate CSM and HCs (P < 0.05). There was negative correlation between DC value of left middle temporal gyrus and JOA scores (P < 0.001), and the FA values of dorsal column in the level C2/3 positively correlated with the JOA scores (P < 0.001).

Conclusion

Structural and functional changes have taken place in the cervical spinal cord and brain of CSM patients. The Brain reorganization plays an important role in maintaining the symptoms and signs of CSM, aberrant DC values in the left middle temporal gyrus may be the possible mechanism of inconsistency between imaging findings and clinical symptoms. Degree centrality is a potentially useful prognostic functional biomarker in cervical spondylotic myelopathy.
Predicting herb-disease associations using network-based measures in human protein interactome
Authors: Wang Seunghyun , Lee Hyun Chang , Lee Sunjae
Published: June 2024

Background

Natural herbs are frequently used to treat diseases or to relieve symptoms in many countries. Moreover, as their safety has been proven for a long time, they are considered as main sources of new drug development. However, in many cases, the herbs are still prescribed relying on ancient records and/or traditional practices without scientific evidences. More importantly, the medicinal efficacy of the herbs has to be evaluated in the perspective of MCMT (multi-compound multi-target) effects, but most efforts focus on identifying and analyzing a single compound experimentally. To overcome these hurdles, computational approaches which are based on the scientific evidences and are able to handle the MCMT effects are needed to predict the herb-disease associations.

Results

In this study, we proposed a network-based in silico method to predict the herb-disease associations. To this end, we devised a new network-based measure, WACP (weighted average closest path length), which not only quantifies proximity between herb-related genes and disease-related genes but also considers compound compositions of each herb. As a result, we confirmed that our method successfully predicts the herb-disease associations in the human protein interactome (AUROC = 0.777). In addition, we observed that our method is superior than the other simple network-based proximity measures (e.g. average shortest and closest path length). Additionally, we analyzed the associations between Brassica oleracea var. italica and its known associated diseases more specifically as case studies. Finally, based on the prediction results of the WACP, we suggested novel herb-disease pairs which are expected to have potential relations and their literature evidences.

Conclusions

This method could be a promising solution to modernize the use of the natural herbs by providing the scientific evidences about the molecular associations between the herb-related genes targeted by multiple compounds and the disease-related genes in the human protein interactome.
Exploring potential circRNA biomarkers for cancers based on double-line heterogeneous graph representation learning
Authors: Zhang Yi , Wang ZhenMei , Wei Hanyan , Chen Min
Published: June 2024

Background

Compared with the time-consuming and labor-intensive for biological validation in vitro or in vivo, the computational models can provide high-quality and purposeful candidates in an instant. Existing computational models face limitations in effectively utilizing sparse local structural information for accurate predictions in circRNA-disease associations. This study addresses this challenge with a proposed method, CDA-DGRL (Prediction of CircRNA-Disease Association based on Double-line Graph Representation Learning), which employs a deep learning framework leveraging graph networks and a dual-line representation model integrating graph node features.

Method

CDA-DGRL comprises several key steps: initially, the integration of diverse biological information to compute integrated similarities among circRNAs and diseases, leading to the construction of a heterogeneous network specific to circRNA-disease associations. Subsequently, circRNA and disease node features are derived using sparse autoencoders. Thirdly, a graph convolutional neural network is employed to capture the local graph network structure by inputting the circRNA-disease heterogeneous network alongside node features. Fourthly, the utilization of node2vec facilitates depth-first sampling of the circRNA-disease heterogeneous network to grasp the global graph network structure, addressing issues associated with sparse raw data. Finally, the fusion of local and global graph network structures is inputted into an extra trees classifier to identify potential circRNA-disease associations.

Results

The results, obtained through a rigorous five-fold cross-validation on the circR2Disease dataset, demonstrate the superiority of CDA-DGRL with an AUC value of 0.9866 and an AUPR value of 0.9897 compared to existing state-of-the-art models. Notably, the hyper-random tree classifier employed in this model outperforms other machine learning classifiers.

Conclusion

Thus, CDA-DGRL stands as a promising methodology for reliably identifying circRNA-disease associations, offering potential avenues to alleviate the necessity for extensive traditional biological experiments. The source code and data for this study are available at https://github.com/zywait/CDA-DGRL.
How does psychosocial safety climate cross-level influence work engagement and job burnout: the roles of organization-based self-esteem and psychological detachment
Authors: Yuan Tongshuang , Ren Hui , Yin Xin , Liang Leilei , Fei Junsong , Liu Xiaoying , Zheng Chengbin , Wang Huimin , Gao Jiaying , Mei Songli , Li Hongyan
Published: June 2024

Background

Existing researches on nurses’ work engagement and job burnout have mostly stayed at the individual level, and limited researches test the cross-level effects of psychosocial safety climate (PSC). The study aimed to explore the cross-level mediating effect of organization-based self-esteem (OBSE) and the moderating effect of psychological detachment between the relationship of PSC and work engagement and job burnout in nurses.

Methods

The cross-sectional study was conducted during November to December 2022 at a tertiary hospital in a northeastern province of China. Data was collected from 1832 nurses through an online questionnaire. Correlation analyses and hierarchical linear modeling were used to test study hypotheses.

Results

The results showed that PSC was positively associated with work engagement, and negatively associated with job burnout. OBSE mediated the effect of PSC on work engagement, as well as job burnout. Additionally, psychological detachment played a moderating role between PSC and work engagement, but no moderating effect was found between PSC and job burnout.

Conclusions

PSC at the organizational level increases work engagement and reduces job burnout by stimulating nurses’ high levels of OBSE. Psychological detachment, as a situational factor, enhances the positive influence of PSC on work engagement. The implementation of measures to improve the PSC levels of the organization, and the levels of OBSE and psychological detachment among nurses could help to promote their good work performance.
Differences in the knowledge, attitudes, and needs of caregivers and healthcare providers regarding palliative care: a cross-sectional investigation in pediatric settings in China
Authors: Lin Xi , Qulian Guo , Bai Yongqi , Liu Qin
Published: June 2024

Background

Countries abroad have implemented pediatric palliative treatment for several years; however, complete pediatric palliative treatment guidelines and legal guidance remain lacking in China, making the implementation of palliative care difficult.

Purpose

This study aimed to understand the current situation, similarities, and differences in the knowledge, attitudes, and needs of caregivers and healthcare providers regarding palliative care for children.

Methods

This cross-correlation study collected data from pediatric and neonatal intensive care units of four hospitals in China. The participants comprised 180 caregivers and 172 healthcare providers. The measurement tools included the palliative care knowledge scale, palliative care attitude scale, and pediatric palliative care needs scale. This study adhered to the STROBE reporting guidelines.

Results

Significant differences in palliative care knowledge, attitudes, and needs were observed between caregivers and healthcare providers (p < 0.005). Pediatric healthcare providers demonstrated higher knowledge and positive attitudes regarding palliative care than caregivers. Needs for communication in general and relief from pain and other symptoms of caregivers were higher than those of healthcare providers (p < 0.001). Furthermore, palliative care attitude and needs of healthcare providers were positively correlated with each other (r = 0.212, p < 0.005).

Conclusion

Pediatric healthcare providers and caregivers demonstrated different perceptions of needs for palliative care. The results of this study can serve as a reference for the future development of guidelines related to children’s needs and related interventions.
Resistin predicts disease severity and survival in patients with pulmonary arterial hypertension
Authors: Gao Li , Skinner John , Nath Tanmay , Lin Qing , Griffiths Megan , Damico Rachel L. , Pauciulo Michael W. , Nichols William C. , Hassoun Paul M. , Everett Allen D. , Johns Roger A.
Published: June 2024

Background

Abnormal remodeling of distal pulmonary arteries in patients with pulmonary arterial hypertension (PAH) leads to progressively increased pulmonary vascular resistance, followed by right ventricular hypertrophy and failure. Despite considerable advancements in PAH treatment prognosis remains poor. We aim to evaluate the potential for using the cytokine resistin as a genetic and biological marker for disease severity and survival in a large cohort of patients with PAH.

Methods

Biospecimens, clinical, and genetic data for 1121 adults with PAH, including 808 with idiopathic PAH (IPAH) and 313 with scleroderma-associated PAH (SSc-PAH), were obtained from a national repository. Serum resistin levels were measured by ELISA, and associations between resistin levels, clinical variables, and single nucleotide polymorphism genotypes were examined with multivariable regression models. Machine-learning (ML) algorithms were applied to develop and compare risk models for mortality prediction.

Results

Resistin levels were significantly higher in all PAH samples and PAH subtype (IPAH and SSc-PAH) samples than in controls (P < .0001) and had significant discriminative abilities (AUCs of 0.84, 0.82, and 0.91, respectively; P < .001). High resistin levels (above 4.54 ng/mL) in PAH patients were associated with older age (P = .001), shorter 6-min walk distance (P = .001), and reduced cardiac performance (cardiac index, P = .016). Interestingly, mutant carriers of either rs3219175 or rs3745367 had higher resistin levels (adjusted P = .0001). High resistin levels in PAH patients were also associated with increased risk of death (hazard ratio: 2.6; 95% CI: 1.27–5.33; P < .0087). Comparisons of ML–derived survival models confirmed satisfactory prognostic value of the random forest model (AUC = 0.70, 95% CI: 0.62–0.79) for PAH.

Conclusions

This work establishes the importance of resistin in the pathobiology of human PAH. In line with its function in rodent models, serum resistin represents a novel biomarker for PAH prognostication and may indicate a new therapeutic avenue. ML-derived survival models highlighted the importance of including resistin levels to improve performance. Future studies are needed to develop multi-marker assays that improve noninvasive risk stratification.
Si-Wu-Tang alleviates metabolic dysfunction-associated fatty liver disease by inhibiting ACSL4-mediated arachidonic acid metabolism and ferroptosis in MCD diet-fed mice
Authors: Xue Xiaoyong , Wang Le , Wu Ruiyu , Li Yufei , Liu Runping , Ma Zhi , Jia Kexin , Zhang Yinhao , Li Xiaojiaoyang
Published: June 2024

Background

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent chronic liver disease worldwide. Si-Wu-Tang (SWT), a traditional Chinese medicine decoction has shown therapeutic effects on various liver diseases. However, the hepatoprotective effects and underlying mechanism of SWT on MAFLD remain unclear.

Methods

First, a methionine-choline-deficient (MCD) diet-fed mice model was used and lipidomic analysis and transcriptomic analysis were performed. The contents of total iron ions, ferrous ions, and lipid peroxidation were detected and Prussian blue staining was performed to confirm the protective effects of SWT against ferroptosis. Finally, chemical characterization and network pharmacological analysis were employed to identify the potential active ingredients.

Results

Serological and hepatic histopathological findings indicated SWT's discernible therapeutic impact on MCD diet-induced MAFLD. Lipidomic analysis revealed that SWT improved intrahepatic lipid accumulation by inhibiting TG synthesis and promoting TG transport. Transcriptomic analysis suggested that SWT ameliorated abnormal FA metabolism by inhibiting FA synthesis and promoting FA β-oxidation. Then, ferroptosis phenotype experiments revealed that SWT could effectively impede hepatocyte ferroptosis, which was induced by long-chain acyl-CoA synthetase 4 (ACSL4)-mediated esterification of arachidonic acid (AA). Finally, chemical characterization and network pharmacological analysis identified that paeoniflorin and other active ingredients might be responsible for the regulative effects against ferroptosis and MAFLD.

Conclusion

In conclusion, our study revealed the intricate mechanism through which SWT improved MCD diet-induced MAFLD by targeting FA metabolism and ferroptosis in hepatocytes, thus offering a novel therapeutic approach for the treatment of MAFLD and its complications.

Graphical Abstract
Short-term effects of the strengthening families Program (SFP 10–14) in Brazil: a cluster randomized controlled trial
Authors: Sanchez Zila M. , Valente Juliana Y. , Gubert Fabiane A. , Galvão Patrícia P. O. , Cogo-Moreira Hugo , Rebouças Lidiane N. , dos Santos Miguel Henrique S. , Melo Márcia H. S. , Caetano Sheila C.
Published: June 2024

Introduction

This study reports the evaluation of the short-term effects of the Strengthening Families Program (SFP 10–14), adapted as Famílias Fortes (Strong Families) in Brazil, on preventing adolescent drug use and improving parenting behaviors.

Methods

A two-arm, parallel cluster randomized controlled trial was conducted in 60 Social Assistance Reference Centers (SARC) from 12 Brazilian municipalities. In each city, the SARC were randomly assigned to the intervention or control group. A total of 805 families participated in the study, each contributing data from one parent or legal guardian and one adolescent totaling 1,610 participants. Data collection occurred before intervention implementation and 6 months after baseline collection. Data were analyzed using multilevel mixed-effects modeling with repeated measures in two different paradigms: Intention to Treat (ITT) and Per protocol (PP). The study was registered in the Brazilian Ministry of Health Register of Clinical Trials (REBEC), under protocol no. RBR-5hz9g6z.

Results

Considering the ITT paradigm, the program reduced the chance of parents and legal guardians being classified as negligent by 60% (95%CI 0.21; 0.78), increased the use of nonviolent discipline by caregivers (Coef 0.33, 95%CI 0.01; 0.64) and decreased the chance of adults exposing adolescents to their drunken episodes by 80% (95%CI 0.06; 0.54). No program effects were observed on outcomes related to adolescent drug use. Similar results were found for the PP paradigm.

Conclusion

The positive effects on family outcomes suggest preventive potential of the program among the Brazilian population. Long-term evaluations are necessary to verify if the program can also achieve the drug use reduction goals not observed in the short term.
Subclinical patterns of disordered eating behaviors in the daily life of adolescents and young adults from the general population
Authors: Peschel Stephanie K. V. , Sigrist Christine , Voss Catharina , Fürtjes Sophia , Berwanger Johanna , Ollmann Theresa M. , Kische Hanna , Rückert Frank , Koenig Julian , Beesdo-Baum Katja
Published: June 2024

Background

Disordered eating behaviors (DEBs), a risk factor for the development of eating disorders (EDs), are prevalent in young people and different DEBs frequently co-occur. Previous studies on DEB-patterns have largely used traditional retrospective questionnaires to assess DEBs. In addition, most previous studies did not specifically exclude individuals with clinical EDs, which limits current knowledge concerning purely subclinical patterns of DEBs. In the present study, we aimed to explore phenotypes and group sizes of subclinical patterns of DEBs reported in everyday life via smartphone-based ecological momentary assessment (EMA) in adolescents and young adults from the general population without lifetime EDs. In secondary analyses, we further aimed to investigate whether DEB-patterns would be associated with additional previously identified risk factors for ED-development.

Methods

EMA was conducted in a community sample of 14–21-year-olds from Dresden, Germany, over four days for up to eight times a day and covered engagement in four DEBs: skipping eating, restrained eating, eating large amounts of food, and loss-of-control eating. Data were analyzed from N = 966 individuals without lifetime EDs with an EMA compliance rate of at least 50% (81.9% of the total sample; average compliance: 84.6%). Latent profile analyses were performed to identify subclinical patterns of DEBs, stratified by sex. Associations between symptomatic profiles and ED-risk factors were tested via regression analyses.

Results

Based on theoretical deliberations, statistical indices, interpretability, and parsimony, a three-profile solution, namely no DEBs, high-mixed DEBs, and low-mixed DEBs, was selected for both sexes. Both symptomatic profiles in both sexes were associated with more unfavorable manifestations in additional ED risk factors compared to the no DEBs profile, with the highest number of associations being observed in the female high-mixed profile.

Conclusions

The present findings suggest that problematic manifestations of DEBs in young people may occur even in the absence of an ED diagnosis and that they are associated with additional risk factors for EDs, warranting increased efforts in targeted prevention, early identification and intervention in order to counteract symptom progression.
CD151-enriched migrasomes mediate hepatocellular carcinoma invasion by conditioning cancer cells and promoting angiogenesis
Authors: Zhang Kangnan , Zhu Zhenhua , Jia Rongrong , Wang NA , Shi Min , Wang Yugang , Xiang Shihao , Zhang Qinghui , Xu Ling
Published: June 2024

Background

The tetraspanin family plays a pivotal role in the genesis of migrasomes, and Tetraspanin CD151 is also implicated in neovascularization within tumorous contexts. Nevertheless, research pertaining to the involvement of CD151 in hepatocellular carcinoma (HCC) neovascularization and its association with migrasomes remains inadequate.

Methods

To investigate the correlation between CD151 and migrasome marker TSPAN4 in liver cancer, we conducted database analysis using clinical data from HCC patients. Expression levels of CD151 were assessed in HCC tissues and correlated with patient survival outcomes. In vitro experiments were performed using HCC cell lines to evaluate the impact of CD151 expression on migrasome formation and cellular invasiveness. Cell lines with altered CD151 expression levels were utilized to study migrasome generation and in vitro invasion capabilities. Additionally, migrasome function was explored through cellular aggregation assays and phagocytosis studies. Subsequent VEGF level analysis and tissue chip experiments further confirmed the role of CD151 in mediating migrasome involvement in angiogenesis and cellular signal transduction.

Results

Our study revealed a significant correlation between CD151 expression and migrasome marker TSPAN4 in liver cancer, based on database analysis of clinical samples. High expression levels of CD151 were closely associated with poor survival outcomes in HCC patients. Experimentally, decreased CD151 expression led to reduced migrasome generation and diminished in vitro invasion capabilities, resulting in attenuated in vivo metastatic potential. Migrasomes were demonstrated to facilitate cellular aggregation and phagocytosis, thereby promoting cellular invasiveness. Furthermore, VEGF-enriched migrasomes were implicated in signaling and angiogenesis, accelerating HCC progression.

Conclusions

In summary, our findings support the notion that elevated CD151 expression promotes migrasome formation, and migrasomes play a pivotal role in the invasiveness and angiogenesis of liver cancer cells, thereby facilitating HCC progression. This finding implies that migrasomes generated by elevated CD151 expression may constitute a promising high-priority target for anti-angiogenic therapy in HCC, offering crucial insights for the in-depth exploration of migrasome function and a renewed comprehension of the mechanism underlying liver cancer metastasis.
Sex differences in treatments and outcomes of patients with cardiogenic shock: a systematic review and epidemiological meta-analysis
Authors: Fisher Thomas , Hill Nicole , Kalakoutas Antonis , Lahlou Assad , Rathod Krishnaraj , Proudfoot Alastair , Warren Alex
Published: June 2024

Background

Women are at higher risk of mortality from many acute cardiovascular conditions, but studies have demonstrated differing findings regarding the mortality of cardiogenic shock in women and men. To examine differences in 30-day mortality and mechanical circulatory support use by sex in patients with cardiogenic shock.

Main body

Cochrane Central, PubMed, MEDLINE and EMBASE were searched in April 2024. Studies were included if they were randomised controlled trials or observational studies, included adult patients with cardiogenic shock, and reported at least one of the following outcomes by sex: raw mortality, adjusted mortality (odds ratio) or use of mechanical circulatory support. Out of 4448 studies identified, 81 met inclusion criteria, pooling a total of 656,754 women and 1,018,036 men. In the unadjusted analysis for female sex and combined in-hospital and 30-day mortality, women had higher odds of mortality (Odds Ratio (OR) 1.35, 95% confidence interval (CI) 1.26–1.44, p < 0.001). Pooled unadjusted mortality was 35.9% in men and 40.8% in women (p < 0.001). When only studies reporting adjusted ORs were included, combined in-hospital/30-day mortality remained higher in women (OR 1.10, 95% CI 1.06–1.15, p < 0.001). These effects remained consistent across subgroups of acute myocardial infarction- and heart failure- related cardiogenic shock. Overall, women were less likely to receive mechanical support than men (OR = 0.67, 95% CI 0.57–0.79, p < 0.001); specifically, they were less likely to be treated with intra-aortic balloon pump (OR = 0.79, 95% CI 0.71–0.89, p < 0.001) or extracorporeal membrane oxygenation (OR = 0.84, 95% 0.71–0.99, p = 0.045). No significant difference was seen with use of percutaneous ventricular assist devices (OR = 0.82, 95% CI 0.51–1.33, p = 0.42).

Conclusion

Even when adjusted for confounders, mortality for cardiogenic shock in women is approximately 10% higher than men. This effect is seen in both acute myocardial infarction and heart failure cardiogenic shock. Women with cardiogenic shock are less likely to be treated with mechanical circulatory support than men. Clinicians should make immediate efforts to ensure the prompt diagnosis and aggressive treatment of cardiogenic shock in women.