bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of mult-omics and nucleotide metabolism reprogramming signature analysis reveals gastric cancer immunological and prognostic features
Authors: Chen Shaofei , Wang Zhiyong 
Published: June 2024

Abstract
Background
Gastric cancer is a frequent and lethal solid tumor that has a poor prognosis and treatment result. Reprogramming of nucleotide metabolism is a characteristic of cancer development and progression.

Methods
We used a variety of machine learning techniques to create a novel nucleotide metabolism-related index (NMRI) using gastric cancer sample data obtained from the TCGA and GEO databases. This index is based on genes associated to nucleotide metabolism. Gastric cancer patients were categorized into high and low NMRI groups based on NMRI results. The clinical features, tumor immune microenvironment, response to chemotherapy, and response to immunotherapy were then thoroughly examined. In vitro experiments were then used to confirm the biological role of SERPINE1 in gastric cancer.

Results
The four nucleotide metabolism-related genes that make up NMRI (GAMT, ORC1, CNGB3, and SERPINE1) were verified in an external dataset and are a valid predictor of prognosis for patients with gastric cancer. The high NMRI group was more responsive to immunotherapy and had greater levels of immune cell infiltration than the low NMRI group. The proliferation and migration of stomach cancer was shown to be decreased by SERPINE1 knockdown in vitro.

Conclusions
This study's NMRI can reliably predict a patient's prognosis for stomach cancer and pinpoint the patient group that will benefit from immunotherapy, offering important new information on the clinical treatment of stomach cancer.
Platelet-derived circFAM13B associated with anti-platelet responsiveness of ticagrelor in patients with acute coronary syndrome
Authors: Zou Yuting , Wang Yuyan , Yao Yanzhu , Wu Yangxun , Lv Chao , Yin Tong 
Published: June 2024

Abstract
Background
Platelet is enriched with Circular RNAs (circRNAs), with circFAM13B rank among the 10 most abundant circRNAs in platelets. The aim of the present study was to evaluate the predictive value of platelet-derived circFAM13B for the antiplatelet responsiveness and efficacy of ticagrelor in patients with acute coronary syndrome (ACS).

Methods
Consecutive ACS patients treated with ticagrelor were enrolled, and the antiplatelet responsiveness of 3 days of ticagrelor maintenance treatment was assessed by measuring the adenosine diphosphate (ADP)-induced platelet inhibition rate (ADP%) using thromboelastography. The expression of circFAM13B in the patients’ platelets was analyzed by quantitative real-time polymerase chain reaction. The correlation between circFAM13B expression and ticagrelor antiplatelet responsiveness, as well as the independent contribution of circFAM13B to the composite of adverse ischemic events during a follow-up period of at least 12 months was evaluated.

Results
A total of 129 eligible ACS patients treated with ticagrelor were enrolled in the study. A negative correlation was found between the expression of circFAM13B and the ADP% value (r = -0.41, P < 0.001). Patients with ADP% ≥ 76% had a significantly lower level of circFAM13B compared to those with ADP% < 76% (adjusted P = 0.009). Receiver operating characteristic curve analysis demonstrated that combining circFAM13B expression > 1.05 with clinical risk factors could effectively predict the risk of adverse ischemic events (AUC = 0.81, 95% CI: 0.69 to 0.92, P < 0.001). Kaplan-Meier survival analysis showed that patients with circFAM13B > 1.05 had a significantly higher risk of adverse ischemic events compared to those with circFAM13B ≤ 1.05 (P = 0.003). Multivariate logistic hazard analysis identified circFAM13B > 1.05 as an independent risk factor for adverse ischemic events in in ticagrelor-treated ACS patients (adjusted OR: 5.60, 95% CI: 1.69–18.50; P = 0.005).

Conclusions
Platelet-derived circFAM13B could be utilized for predicting the antiplatelet responsiveness and efficacy of ticagrelor in patients with ACS.
Extracellular vesicles released by host epithelial cells during Pseudomonas aeruginosa infection function as homing beacons for neutrophils
Authors: Ayilam Ramachandran Rajalakshmy , Lemoff Andrew , Robertson Danielle M. 
Published: June 2024

Abstract
Background
Pseudomonas aeruginosa (PA) is an opportunistic pathogen that can cause sight threatening infections in the eye and fatal infections in the cystic fibrosis airway. Extracellular vesicles (EVs) are released by host cells during infection and by the bacteria themselves; however, there are no studies on the composition and functional role of host-derived EVs during PA infection of the eye or lung. Here we investigated the composition and capacity of EVs released by PA infected epithelial cells to modulate innate immune responses in host cells.

Methods
Human telomerase immortalized corneal epithelial cells (hTCEpi) cells and human telomerase immortalized bronchial epithelial cells (HBECs) were treated with a standard invasive test strain of Pseudomonas aeruginosa, PAO1, for 6 h. Host derived EVs were isolated by qEV size exclusion chromatography. EV proteomic profiles during infection were compared using mass spectrometry and functional studies were carried out using hTCEpi cells, HBECs, differentiated neutrophil-like HL-60 cells, and primary human neutrophils isolated from peripheral blood.

Results
EVs released from PA infected corneal epithelial cells increased pro-inflammatory cytokine production in naïve corneal epithelial cells and induced neutrophil chemotaxis independent of cytokine production. The EVs released from PA infected bronchial epithelial cells were also chemotactic although they failed to induce cytokine secretion from naïve HBECs. At the proteomic level, EVs derived from PA infected corneal epithelial cells exhibited lower complexity compared to bronchial epithelial cells, with the latter having reduced protein expression compared to the non-infected control.

Conclusions
This is the first study to comprehensively profile EVs released by corneal and bronchial epithelial cells during Pseudomonas infection. Together, these findings show that EVs released by PA infected corneal and bronchial epithelial cells function as potent mediators of neutrophil migration, contributing to the exuberant neutrophil response that occurs during infection in these tissues.
Mechanisms underlying neutrophils adhesion to triple-negative breast cancer cells via CD11b-ICAM1 in promoting breast cancer progression
Authors: Yang Chenghui , Li Lili , Ye Zhiqiang , Zhang Anqi , Bao Yunjia , Wu Xue , Ren Guohong , Jiang Chao , Wang Ouchen , Wang Zhen 
Published: June 2024

Abstract
Background
Triple-negative breast cancer (TNBC) is recognized as the most aggressive and immunologically infiltrated subtype of breast cancer. A high circulating neutrophil-to-lymphocyte ratio (NLR) is strongly linked to a poor prognosis among patients with breast cancer, emphasizing the critical role of neutrophils. Although the involvement of neutrophils in tumor metastasis is well documented, their interactions with primary tumors and tumor cells are not yet fully understood.

Methods
Clinical data were analyzed to investigate the role of neutrophils in breast cancer. In vivo mouse model and in vitro co-culture system were used for mechanism researches. Blocking experiments were further performed to identify therapeutic agents against TNBC.

Results
TNBC cells secreted GM-CSF to sustain the survival of mature neutrophils and upregulated CD11b expression. Through CD11b, neutrophils specifically binded to ICAM1 on TNBC cells, facilitating adhesion. Transcriptomic sequencing combined with human and murine functional experiments revealed that neutrophils, through direct CD11b-ICAM1 interactions, activated the MAPK signaling pathway in TNBC cells, thereby enhancing tumor cell invasion and migration. Atorvastatin effectively inhibited ICAM1 expression in tumor cells, and tumor cells with ICAM1 knockout or treated with atorvastatin were unresponsive to neutrophil activation. The MAPK pathway and MMP9 expression were significantly inhibited in the tumor tissues of TNBC patients treated with atorvastatin.

Conclusions
Targeting CD11b-ICAM1 with atorvastatin represented a potential clinical approach to reduce the malignant characteristics of TNBC.

Graphical Abstract
Trends and off-label utilization of antipsychotics in children and adolescents from 2016 to 2021 in China: a real-world study
Authors: Zhaojian Wang , Meizhu Jiang , Jun Hong , Shanshan Guo , Jiping Huo , Zhigang Zhao , Ying Gong , Cao Li 
Published: June 2024

Abstract
Background
Global antipsychotic usage, including off-label prescriptions, has increased in recent decades. However, trends in China, particularly for children and adolescents, remain unclear. This study explored these trends from 2016 to 2021 and identified factors associated with off-label prescriptions.

Methods
In this retrospective study, we analyzed on-label and off-label prescriptions based on drug information approved by the China National Medical Products Administration. To identify factors associated with off-label prescriptions, we conducted multivariate logistic regression analysis.

Results
Our study included 48,258 antipsychotic prescriptions, 52.4% (25,295) of which were prescriptions for males. Of these, 61.7% (29,813) were off-label. Over time, the number of antipsychotics and the percentage of off-label prescriptions for children and adolescents overall increased from 2016 to 2021. The use of atypical antipsychotics increased, whereas that of typical antipsychotics decreased. For off-label usage, all of the factors in our study were associated with off-label usage, including age, sex, year, region, department, reimbursement, antipsychotic type, drug expense, number of polypharmacy and diagnoses. Additionally, tiapride (15.8%) and aripiprazole (18.6%) were the most common typical and atypical antipsychotics, respectively. For pediatric diseases, common diagnoses included mood or affective disorders (31.7%) and behavioral and emotional disorders, with onset usually occurring in childhood and adolescence (29.1%). Furthermore, a depressive state was the most common diagnosis for which antipsychotic polypharmacy was used for treatment.

Conclusion
In this retrospective study, off-label antipsychotic prescriptions were common, with trends generally increasing among children and adolescents from 2016 to 2021. However, there is a lack of evidence supporting off-label usage, thus emphasizing the need for studies on the efficacy and safety of these treatments.
Disagreements in risk of bias assessment for randomized controlled trials in hypertension-related Cochrane reviews
Authors: Yao Yi , Shen Jing , Luo Jianzhao , Li Nian , Liao Xiaoyang , Zhang Yonggang 
Published: June 2024

Abstract
Background
The inter-reviewer reliability of the risk of bias (RoB) assessment lacked agreement in previous studies. It is important to analyse these disagreements to improve the repeatability of RoB assessment. The objective of the study was to evaluate the frequency and reasons for disagreements in RoB assessments for randomised controlled trials (RCTs) that were included in multiple Cochrane reviews in the field of hypertension.

Methods
A cross-sectional study was employed. We retrieved any RCTs that had been included in multiple Cochrane reviews in the field of hypertension from ARCHIE. The results of the RoB assessments were extracted, and the distributions of agreements and possible reasons for disagreement were analyzed.

Results
Twenty-six Cochrane reviews were included in this study. A total of 78 RCTs appeared in more than one Cochrane review. The level of agreement ranged from domain to domain. “Blinding of outcome assessment” showed a reasonably high level of agreement (94.9%), while “incomplete outcome data”, “selective outcome reporting” and “other sources of bias” showed moderate levels of agreement (74.6%, 79.2% and 75.6%, respectively). However, the domains of “allocation concealment”, “random sequence generation” and “blinding of participants and personnel” showed low levels of agreement (24.4%, 23.5%, and 47.4%, respectively). In the domains of “allocation concealment” and “blinding of participants and personnel”, the agreement group had higher proportion of publication year ≤ 1996 than the disagreement group (P = 0.008 and P < 0.001, respectively). In the “blinding of participants and personnel”, the impact factor was higher in the agreement group (P < 0.001). By analyzing the support text, we found that the most likely reason for disagreement was extracting different information from the same RCT.

Conclusion
For Cochrane reviews in the field of hypertension using the 2011 version of the RoB tool, there was a large disagreement in the RoB assessment. It is suggested that the results of RoB assessments in systematic reviews that used the 2011 version of the RoB tool need to be interpreted with caution. More accurate information from RCTs needs to be collected when we synthesize clinical evidence.
Studying harms of interventions with an equity lens in randomized trials
Authors: Li Tianjing , Mayo-Wilson Evan , Shaughnessy Daniel , Qureshi Riaz 
Published: June 2024

AbstractEquity and health equity are fundamental pillars in fostering a just and inclusive society. While equity underscores fairness in resource allocation and opportunity, health equity aims to eradicate avoidable health disparities among social groups. The concept of harms in interventions—undesirable consequences associated with the use of interventions—often varies across populations due to biological and social factors, necessitating a nuanced understanding. An equity lens reveals disparities in harm distribution, urging researchers and policymakers to address these differences in their decision-making processes. Furthermore, interventions, even well-intentioned ones, can inadvertently exacerbate disparities, emphasizing the need for comprehensive harm assessment. Integrating equity considerations in research practices and trial methodologies, through study design or through practices such as inclusive participant recruitment, is pivotal in advancing health equity. By prioritizing interventions that address disparities and ensuring inclusivity in research, we can foster a more equitable healthcare system.
Diabetic microenvironment deteriorates the regenerative capacities of adipose mesenchymal stromal cells
Authors: Ahmed Sara M. , Elkhenany Hoda A. , Ahmed Toka A. , Ghoneim Nehal I. , Elkodous Mohamed Abd , Mohamed Rania Hassan , Magdeldin Sameh , Osama Aya , Anwar Ali Mostafa , Gabr Mahmoud M. , El-Badri Nagwa 
Published: June 2024

Abstract
Background
Type 2 diabetes is an endocrine disorder characterized by compromised insulin sensitivity that eventually leads to overt disease. Adipose stem cells (ASCs) showed promising potency in improving type 2 diabetes and its complications through their immunomodulatory and differentiation capabilities. However, the hyperglycaemia of the diabetic microenvironment may exert a detrimental effect on the functionality of ASCs. Herein, we investigate ASC homeostasis and regenerative potential in the diabetic milieu.

Methods
We conducted data collection and functional enrichment analysis to investigate the differential gene expression profile of MSCs in the diabetic microenvironment. Next, ASCs were cultured in a medium containing diabetic serum (DS) or normal non-diabetic serum (NS) for six days and one-month periods. Proteomic analysis was carried out, and ASCs were then evaluated for apoptosis, changes in the expression of surface markers and DNA repair genes, intracellular oxidative stress, and differentiation capacity. The crosstalk between the ASCs and the diabetic microenvironment was determined by the expression of pro and anti-inflammatory cytokines and cytokine receptors.

Results
The enrichment of MSCs differentially expressed genes in diabetes points to an alteration in oxidative stress regulating pathways in MSCs. Next, proteomic analysis of ASCs in DS revealed differentially expressed proteins that are related to enhanced cellular apoptosis, DNA damage and oxidative stress, altered immunomodulatory and differentiation potential. Our experiments confirmed these data and showed that ASCs cultured in DS suffered apoptosis, intracellular oxidative stress, and defective DNA repair. Under diabetic conditions, ASCs also showed compromised osteogenic, adipogenic, and angiogenic differentiation capacities. Both pro- and anti-inflammatory cytokine expression were significantly altered by culture of ASCs in DS denoting defective immunomodulatory potential. Interestingly, ASCs showed induction of antioxidative stress genes and proteins such as SIRT1, TERF1, Clusterin and PKM2.

Conclusion
We propose that this deterioration in the regenerative function of ASCs is partially mediated by the induced oxidative stress and the diabetic inflammatory milieu. The induction of antioxidative stress factors in ASCs may indicate an adaptation mechanism to the increased oxidative stress in the diabetic microenvironment.
The efficacy of self-monitoring of blood glucose (SMBG) intervention package through a subscription model among type-2 diabetes mellitus in Malaysia: a preliminary trial
Authors: Johari Sa’ida Munira , Razalli Nurul Huda , Chua Kai Jia , Shahar Suzana 
Published: June 2024

AbstractBackgroundThe aim of this study was to determine the effect of a Self-Monitoring Blood Glucose (SMBG) intervention package through a subscription model in improving HbA1c and health parameters among type-2 diabetes mellitus (T2DM) individuals in Malaysia.MethodsThis is a quasi-experimental study involving a total number of 111 individuals with T2DM (mean age 57.0 ± 11.7 years, 61% men) who were assigned to intervention (n = 51) and control (n = 60) groups. The intervention group participants were the subscribers of SugO365 program which provided a personalized care service based on self-recorded blood glucose values. Subscribers received a Contour®Plus One glucometer which can connect to Health2Sync mobile app to capture all blood glucose readings as well as physical and virtual follow up with dietitians, nutritionists, and pharmacists for 6 months. Outcome measures were body weight, body mass index (BMI), random blood glucose (RBG), glycated haemoglobin (HbA1c) and health-related quality of life (HRQoL, assessed by SF-36 questionnaire). Data were measured at baseline, third and sixth months.ResultsRepeated-measure analysis of covariance showed significant improvement in HbA1c level (ƞp2 = 0.045, p = 0.008) in the intervention (baseline mean 7.7% ± 1.1%; end mean 7.3% ± 1.3%) as compared to control (baseline mean 7.7% ± 0.9%; end mean 8.1% ± 1.6%) group. Similar trend was observed for Role Emotional domain of the quality of life (ƞp2 = 0.047, p = 0.023) in the intervention (baseline mean 62.8 ± 35.1, end mean 86.3 ± 21.3) compared to control (baseline mean group 70.5 ± 33.8; end mean 78.4 ± 27.3) group. Negative association was found in HbA1c changes using Z-score and Physical Function domain (r = − 0.217, p = 0.022).ConclusionA 6 months SMBG intervention package through a subscription model improved blood glucose control as measured by HbA1c and health-related quality of life, particularly the Role Emotional domain. Elevated HbA1c levels are correlated with decreased physical function.There is a need to further examine the efficacy of SMBG intervention package using a larger sample and a longer period of intervention and to determine its cost efficacy.
J-shaped relationship between stress hyperglycemia ratio and 90-day and 180-day mortality in patients with a first diagnosis of acute myocardial infarction: analysis of the MIMIC-IV database
Authors: Hu Ben , Chen Xinghua , Wang Yuhui , Wei Xing , Feng Jun , Hou Linlin 
Published: June 2024

Abstract
Aims
The Stress Hyperglycemia Ratio (SHR) potently predicts adverse outcomes in patients with cardiovascular and cerebrovascular diseases. However, the relationship between SHR and short-term mortality risk in patients with a first diagnosis of acute myocardial infarction (AMI) remains contentious. This study sought to understand better the relationship between SHR and short-term mortality risk in patients with a first diagnosis of AMI.

Methods
We conducted a cohort study using data from 1961 patients with a first diagnosis of AMI from the MIMIC-IV (version 2.2) database. Patients were divided into three groups based on SHR tertiles. The Cox proportional hazards model and a two-segmented Cox proportional hazards model were used to elucidate the nonlinear relationship between SHR in patients with a first diagnosis of AMI and mortality.

Results
Of the surveyed population, 175 patients (8.92%) died within 90 days, and 210 patients (10.71%) died within 180 days. After multivariate adjustments, elevated SHR levels were significantly and non-linearly associated with a higher risk of 90-day and 180-day mortality in patients with a first diagnosis of AMI, showing a J-shaped correlation with an inflection point at 0.9. Compared to participants with SHR levels below the inflection point, those with higher SHR levels had a fivefold increased risk of 90-day mortality (hazard ratio [HR] 5.74; 95% confidence interval [CI] 3.19, 10.33) and a fourfold increased risk of 180-day mortality (HR 4.56; 95% CI 2.62, 7.95). In the subgroup analysis, patients with pre-diabetes mellitus (pre-DM) and higher SHR levels had increased 90-day (HR 6.90; 95% CI  1.98, 24.02) and 180-day mortality risks (HR 5.30; 95% CI  1.96, 14.27).

Conclusion
In patients with a first diagnosis of AMI, there is a J-shaped correlation between SHR and 90-day and 180-day mortality, with an adverse prognostic inflection point of SHR at 0.9.
Spontaneous intercostal artery bleeding occurring simultaneously in numerous vessels during antithrombotic therapy with mechanical circulatory support: a case report
Authors: Ohtaka Kazuto , Ohtake Setsuyuki , Ishii Yu , Kaku Saya , Takeuchi Yuta , Mizota Tomoko , Yamamura Yoshiyuki , Ichinokawa Masaomi , Yoshioka Tatsuya , Tamoto Eiji , Murakawa Katsuhiko , Ono Koichi , Kato Tatsuya 
Published: June 2024

Abstract
Background
Intercostal artery bleeding often occurs in a single vessel; in rare cases, it can occur in numerous vessels, making it more difficult to manage.

Case presentation
A 63-year-old Japanese man was admitted to the emergency department owing to sudden chest and back pain, dizziness, and nausea. Emergency coronary angiography revealed myocardial infarction secondary to right coronary artery occlusion. After intra-aortic balloon pumping, percutaneous coronary intervention was performed in the right coronary artery. At 12 hours following percutaneous coronary intervention, the patient developed new-onset left anterior chest pain and hypotension. Contrast-enhanced computed tomography revealed 15 sites of contrast extravasation within a massive left extrapleural hematoma. Emergency angiography revealed contrast leakage in the left 6th to 11th intercostal arteries; hence, transcatheter arterial embolization was performed. At 2 days after transcatheter arterial embolization, his blood pressure subsequently decreased, and contrast-enhanced computed tomography revealed the re-enlargement of extrapleural hematoma with multiple sites of contrast extravasation. Emergency surgery was performed owing to persistent bleeding. No active arterial hemorrhage was observed intraoperatively. Bleeding was observed in various areas of the chest wall, and an oxidized cellulose membrane was applied following ablation and hemostasis. The postoperative course was uneventful.

Conclusion
We report a case of spontaneous intercostal artery bleeding occurring simultaneously in numerous vessels during antithrombotic therapy with mechanical circulatory support that was difficult to manage. As bleeding from numerous vessels may occur during antithrombotic therapy, even without trauma, appropriate treatments, such as transcatheter arterial embolization and surgery, should be selected in patients with such cases.