bluuebunny/crossref_metadata_2025_split huggingface dataset:
A discriminant analysis of plasma metabolomics for the assessment of metabolic responsiveness to red raspberry consumption
Authors: Barbe Valentin , de Toro-Martín Juan , San-Cristobal Rodrigo , Garneau Véronique , Pilon Geneviève , Couture Patrick , Roy Denis , Couillard Charles , Marette André , Vohl Marie-Claude 
Published: March 2023

BackgroundMany studies show that the intake of raspberries is beneficial to immune-metabolic health, but the responses of individuals are heterogeneous and not fully understood.MethodsIn a two-arm parallel-group, randomized, controlled trial, immune-metabolic outcomes and plasma metabolite levels were analyzed before and after an 8-week red raspberry consumption. Based on partial least squares discriminant analysis (PLS-DA) on plasma xenobiotic levels, adherence to the intervention was first evaluated. A second PLS-DA followed by hierarchical clustering was used to classify individuals into response subgroups. Clinical immune and metabolic outcomes, including insulin resistance (HOMA-IR) and sensitivity (Matsuda, QUICKI) indices, during the intervention were assessed and compared between response subgroups.ResultsTwo subgroups of participants, type 1 responders (n = 17) and type 2 responders (n = 5), were identified based on plasma metabolite levels measured during the intervention. Type 1 responders showed neutral to negative effects on immune-metabolic clinical parameters after raspberry consumption, and type 2 responders showed positive effects on the same parameters. Changes in waist circumference, waist-to-hip ratio, fasting plasma apolipoprotein B, C-reactive protein and insulin levels as well as Matsuda, HOMA-IR and QUICKI were significantly different between the two response subgroups. A deleterious effect of two carotenoid metabolites was also observed in type 1 responders but these variables were significantly associated with beneficial changes in the QUICKI index and in fasting insulin levels in type 2 responders. Increased 3-ureidopropionate levels were associated with a decrease in the Matsuda index in type 2 responders, suggesting that this metabolite is associated with a decrease in insulin sensitivity for those subjects, whereas the opposite was observed for type 1 responders.ConclusionThe beneficial effects associated with red raspberry consumption are subject to inter-individual variability. Metabolomics-based clustering appears to be an effective way to assess adherence to a nutritional intervention and to classify individuals according to their immune-metabolic responsiveness to the intervention. This approach may be replicated in future studies to provide a better understanding of how interindividual variability impacts the effects of nutritional interventions on immune-metabolic health.
Ketogenic diet alleviates renal fibrosis in mice by enhancing fatty acid oxidation through the free fatty acid receptor 3 pathway
Authors: Qiu Yang , Hu Xiaofan , Xu Cong , Lu Chenqi , Cao Rui , Xie Yanan , Yang Jun 
Published: March 2023

IntroductionThe ketogenic diet (KD), as a dietary intervention, has gained importance in the treatment of solid organ structural remodeling, but its role in renal fibrosis has not been explored.MethodsMale C57BL/6 mice were fed a normal diet or a KD for 6 weeks prior to unilateral ureteral obstruction (UUO), a well-established in vivo model of renal fibrosis in rodents. Seven days after UUO, serum and kidney samples were collected. Serum β-hydroxybutyrate (β-OHB) concentrations and renal fibrosis were assessed. NRK52E cells were treated with TGFβ1, a fibrosis-inducing cytokine, and with or without β-OHB, a ketone body metabolized by KD, to investigate the mechanism underlying renal fibrosis.ResultsKD significantly enhanced serum β-OHB levels in mice. Histological analysis revealed that KD alleviated structural destruction and fibrosis in obstructed kidneys and reduced the expression of the fibrosis protein markers α-SMA, Col1a1, and Col3a1. Expression of the rate-limiting enzymes involved in fatty acid oxidation (FAO), Cpt1a and Acox1, significantly decreased after UUO and were upregulated by KD. However, the protective effect of KD was abolished by etomoxir (a Cpt1a inhibitor). Besides, our study observed that KD significantly suppressed UUO-induced macrophage infiltration and the expression of IL-6 in the obstructive kidneys. In NRK52E cells, fibrosis-related signaling was increased by TGFβ1 and reduced by β-OHB. β-OHB treatment restored the impaired expression of Cpt1a. The effect of β-OHB was blocked by siRNA targeting free fatty acid receptor 3 (FFAR3), suggesting that β-OHB might function through the FFAR3-dependent pathway.DiscussionOur results highlight that KD attenuates UUO-induced renal fibrosis by enhancing FAO via the FFAR3-dependent pathway, which provides a promising dietary therapy for renal fibrosis.
Deciphering the origin of total estrogenic activity of complex mixtures
Authors: Debon Emma , Gentili Bastien , Latado Hélia , Serrant Patrick , Badoud Flavia , Ernest Marion , Christinat Nicolas , Bessaire Thomas , Schilter Benoit , Marin-Kuan Maricel 
Published: March 2023

IntroductionIdentifying compounds with endocrine properties in food is getting increasingly important. Current chemical analysis methodology is mainly focused on the identification of known substances without bringing insight for biological activity. Recently, the application of bioassays has been promoted for their potential to detect unknown bioactive substances and to provide information on possible interactions between molecules. From the toxicological perspective, measuring endocrine activity cannot inform on endocrine disruption and/or health risks without sufficient knowledge on the nature of the responsible factors.MethodsThe present study addresses a promising approach using High Performance Thin-Layer Chromatography (HPTLC) coupled to bioassays were analyzed using the Liquid Chromatography Mass-Spectrometry (LC-MS). The estrogen receptor activation was assessed using the transcription activation Estrogen Receptor Alpha Chemical Activated LUciferase gene eXpression assay (ERα- CALUX) and the HPTLC coupled to the Estrogen Screen Yeast assay (p-YES).ResultsSeven isoflavones were identified in the soy isolates. Estrogen receptor activation was assessed for both, the identified isoflavones and the soy isolates with ERα-CALUX test. Correlation between the soy isolates extracts and the identified isoflavones was shown. Moreover, p-YES revealed the presence of an estrogenic bioactive zone. Analysis of the bioactive zone through LCHRMS highlighted signals corresponding to several isoflavones already detected in the isolates as well as two additional ones. For all detected isoflavones, an estrogenic activity dose-response was established in both bioassays.ConclusionFinally, genistein, daidzein, and naringenin were found as the most active substances. A concordance analysis integrating the analytical and bioassay data indicated that genistein and daidzein were the drivers of the estrogenic activity of these soy protein isolates. Altogether, these data suggest that the integration of HPTLC-bioassay together with chemical analysis is a powerful approach to characterize the endocrine activity of complex mixtures.
Tim3 and PD-1 as a therapeutic and prognostic targets in colorectal cancer: Relationship with sidedness, clinicopathological parameters, and survival
Authors: Mokhtari Zahra , Rezaei Marzieh , Sanei Mohammad Hossein , Dehghanian Amirreza , Faghih Zahra , Heidari Zahra , Tavana Shirin 
Published: March 2023

BackgroundColorectal cancer (CRC) is a heterogeneous disease that complicates predicting patients’ prognosis and their response to treatment. CRC prognosis is influenced by the tumor microenvironment (TME). The immune system is a critical component of the TME. Programmed cell death receptor 1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (Tim3) are inhibitory immune checkpoints that regulate immune response and may provide prognostic power. However, the effect of their expressions and co-expressions on the CRC prognosis remains unclear. Accordingly, this study aimed to investigate the prognostic value of the CD8, CD3, PD-1, Tim3 expression, and PD-1/Tim3 co-expression in patients with CRC.Materials and MethodsOne hundred and thirty six patients with CRC who underwent curative surgery were enrolled in the study. Immunohistochemical staining was performed for PD-1, Tim3, CD8, and CD3, and the expression of each marker was evaluated in the center of the tumor (CT), invasive margin (IM), and adjacent normal-like tissue.ResultOur results indicated that high expression of PD-1 in IM was significantly associated with lower TNM stage, T-stage, M-stage, lack of metastasis, the presence of tertiary lymphoid structure (TLS), lack of recurrence (in the left-sided tumors), and larger tumor size (in right-sided tumors) (P&lt;0.05). High expression of PD-1 in IM was also associated with improved overall survival (OS) in a subgroup of patients with high CD8 expression. High Tim3 expression in CT was associated with higher M-stage (M1) (in left-sided CRCs) (P&lt;0.05). It was also associated with decreased OS in total cohort and left-sided CRCs and represented an independent prognostic factor for CRC patients in multivariate analysis. PD-1 and Tim3 co-expression had no synergistic effects on predicting OS.ConclusionOur findings suggest that the clinicopathological and prognostic significance of immune system-related markers such as CD8, PD-1, and Tim3 depends on the primary tumor sides. We also showed that Tim3 could act as a prognostic factor and therapeutic target in CRC. This marker is probably a more preferred target for immunotherapy than PD-1, especially in left-sided CRCs.
Outcome of the first 200 patients with prostate cancer treated with MRI-Linac at Assuta MC
Authors: Gelbart Pridan Or , Ben David Merav Akiva , Zalmanov Svetlana , Lipski Yoav , Grinberg Vladislav , Levin Daphne , Apter Sara , Guindi Michal , Epstein Dan , Radus Roman , Arsenault Orit , Hod Keren , Tamami Qusai , Pfeffer Raphael 
Published: March 2023

BackgroundWe present our experience with MR-guided stereotactic body radiotherapy (SBRT) for 200 consecutive patients with prostate cancer with minimum 3-month follow-up.MethodsTreatment planning included fusion of the 0.35-Tesla planning MRI with multiparametric MRI and PET-PSMA for Group Grade (GG) 2 or higher and contour review with an expert MRI radiologist. No fiducials or rectal spacers were used. Prescription dose was 36.25 Gy in 5 fractions over 2 weeks to the entire prostate with 3-mm margins. Daily plan was adapted if tumor and organs at risk (OAR) doses differed significantly from the original plan. The prostate was monitored during treatment that was automatically interrupted if the target moved out of the PTV range.ResultsMean age was 72 years. Clinical stage was T1c, 85.5%; T2, 13%; and T3, 1.5%. In addition, 20% were GG1, 50% were GG2, 14.5% were GG3, 13% were GG4, and one patient was GG5. PSA ranged from 1 to 77 (median, 6.2). Median prostate volume was 57cc, and 888/1000 (88%) fractions required plan adaptation. The most common acute GU toxicity was Grade I, 31%; dysuria and acute gastrointestinal toxicity were rare. Three patients required temporary catheterization. Prostate size of over 100cc was associated with acute fatigue, urinary hesitance, and catheter insertion. Prostate Specific Antigen (PSA) decreased in 99% of patients, and one patient had regional recurrence.ConclusionMR-guided prostate SBRT shows low acute toxicity and excellent short-term outcomes. Real-time MRI ensures accurate positioning and SBRT delivery.
Epidemiology and mortality predictors for severe childhood community-acquired pneumonia in ICUs: A retrospective observational study
Authors: Cao Lu , Ji Zhaohua , Zhang Peng , Wang Jingwen 
Published: March 2023

BackgroundTo identify the epidemiology and mortality predictors of severe childhood community-acquired pneumonia (CAP) and evaluate the influence of medications on clinical outcomes in the real world.MethodsWe conducted a multicenter retrospective observational study among children aged ≤5 years with severe CAP, separately comparing the detailed information between those who experienced in-hospital death and those who survived in three different age groups. A multivariate logistic regression model was used to determine mortality predictors.ResultsA total of 945 children were recruited: 341 young children aged 2–59 months, 47 infants aged 29 days to 2 months, and 557 neonates aged less than 28 days. A total of 88 deaths occurred (9.3%). There was low adherence to antimicrobial guidelines in the group aged 2–59 months, and carbapenems widely served as initial empirical regimens. However, analysis of all three age groups showed that the efficacy of antibacterial drugs with initial empirical selection grades higher than those recommended by the guidelines was not better than that of antibacterial drugs with grades recommended by the guidelines. In multivariate analyses, very severe pneumonia (odds ratio (OR): 3.48; 95% confidence interval (CI): 1.36–8.93), lower birth weight (OR: 4.64; 95% CI: 1.78–12.20), severe underweight (OR: 6.06; 95% CI: 2.34–15.63), mechanical ventilation (OR: 2.58; 95% CI: 1.00–6.62; OR: 15.63; 95% CI 3.25–76.92), a higher number of comorbidities (OR: 8.40; 95% CI: 1.89–37.04), comorbidities including anemia (OR: 5.24; 95% CI: 2.33–11.76) and gastrointestinal hemorrhage (OR: 3.79; 95% CI: 1.36–10.53), and the use of sedative-hypnotics (OR: 2.60; 95% CI: 1.14–5.95) were independent risk factors for death; infants treated with probiotics had a lower mortality rate (OR: 0.14; 95% CI: 0.06–0.33).ConclusionsSevere CAP remains a primary cause of death in children under 5 years of age. Clinical characteristics, comorbidities and medications are evidently associated with death. Importantly, we should pay particular attention to the identification of mortality predictors and establish prophylactic measures to reduce mortality.
Pediatric Crohn's disease diagnosis aid via genomic analysis and machine learning
Authors: Zheng Zhiwei , Zhan Sha , Zhou Yongmao , Huang Ganghua , Chen Pan , Li Baofei 
Published: March 2023

IntroductionDetermination of pediatric Crohn's disease (CD) remains a major diagnostic challenge. However, the rapidly emerging field of artificial intelligence has demonstrated promise in developing diagnostic models for intractable diseases.MethodsWe propose an artificial neural network model of 8 gene markers identified by 4 classification algorithms based on Gene Expression Omnibus database for diagnostic of pediatric CD.ResultsThe model achieved over 85% accuracy and area under ROC curve value in both training set and testing set for diagnosing pediatric CD. Additionally, immune infiltration analysis was performed to address why these markers can be integrated to develop a diagnostic model.ConclusionThis study supports further clinical facilitation of precise disease diagnosis by integrating genomics and machine learning algorithms in open-access database.
Spider venom-derived peptide JZTX-14 prevents migration and invasion of breast cancer cells via inhibition of sodium channels
Authors: Wu Wenfang , Yin Yuan , Feng Peihao , Chen Gong , Pan Liangyu , Gu Panyang , Zhou Siqin , Lin Fulong , Ji Siyu , Zheng Chunbing , Deng Meichun 
Published: March 2023

Nav1.5 channel is crucial for the proliferation and migration of breast cancer cells. In this study, we investigated the anticancer effect of JZTX-14, a natural peptide considered an effective antagonist of Nav1.5. First, we successfully isolated and purified the 31 amino acid peptide JZTX-14 containing three pairs of disulfide bonds from spider venom and synthesised JZTX-14 by solid phase synthesis. We then predicted their physiochemical properties and structures in the peptide database. Further, we investigated the effects of natural and synthetic JZTX-14 on the proliferation and migration of MDA-MB-231 breast cancer cells via modulation of sodium current through the Nav1.5 channel. The results showed that both synthetic and natural JZTX-14 inhibited Nav1.5 currents, indicating the successful synthesis of JZTX-14. However, JZTX-14 did not affect MDA-MB-231 cell proliferation but inhibited its migration. Transcriptome analysis revealed that JZTX-14 downregulated S100A4 and FBXO2 and upregulated SERPINB2 in MDA-MB-231 cells. Western blot analysis demonstrated an increased level of the epithelial marker, E-cadherin, and decreased levels of the mesenchymal markers, N-cadherin and vimentin, and matrix metalloproteinase (MMP2), indicating the possible underlying mechanism of the inhibition of MDA-MB-231 cell migration by JZTX-14. This study provides a new target for inhibiting breast cancer metastasis and identifies a potent natural peptide for treating Triple-negative breast cancer.
Metabonomic analysis of the anti-hepatic fibrosis effect of Ganlong capsules
Authors: Lv ChangLing , Li YinRui , Ou Ling , Zhou Jie , Peng Fang , Wu DingYu 
Published: March 2023

Context: Hepatic fibrosis is a progressive condition, often attributed to metabolic disorders, which may promote cirrhosis and liver cancer. Ganlong capsules derived from Periplaneta Americana have been shown to have a therapeutic effect on liver fibrosis but little is known about the molecular mechanisms involved.Objective: To investigate the metabolic modulations produced by Ganlong capsules in liver fibrosis.Methods: A carbon tetrachloride- (CCl4) treated rat model of liver fibrosis was constructed and Ganlong capsules administered. Levels of serum liver enzymes and pathological changes to the liver were evaluated. Non-targeted metabolomics of liver, serum and urine were used to investigate metabolic regulatory mechanisms.Results:Ganlong capsules reduced serum levels of liver enzymes and improved pathological changes in the rat model of fibrosis. Non-targeted metabolomics showed that Ganlong capsules ameliorated pathways of glycerophospholipid, linoleic acid, pyrimidine, glycine, butyric acid, valine, serine, threonine and arachidonic acid metabolism and biosynthesis of leucine and isoleucine. Such pathways influence the development of CCl4-induced liver fibrosis.Conclusion:Ganlong capsules had an anti-fibrotic hepatoprotective effect and regulated lipid, butyric acid, amino acid and arachidonic acid metabolism.
Association of thiamine administration and prognosis in critically ill patients with heart failure
Authors: Yang Rui , Huang Jiasheng , Zhao Yumei , Wang Jia , Niu Dongdong , Ye Enlin , Yue Suru , Hou Xuefei , Cui Lili , Wu Jiayuan 
Published: March 2023

Background: Thiamine deficiency is common in patients with heart failure, and thiamine supplement can benefit these patients. However, the association between thiamine administration and prognosis among critically ill patients with heart failure remains unclear. Thus, this study aims to prove the survival benefit of thiamine use in critically ill patients with heart failure.Methods: A retrospective cohort analysis was performed on the basis of the Medical Information Mart of Intensive Care-Ⅳ database. Critically ill patients with heart failure were divided into the thiamine and non-thiamine groups depending on whether they had received thiamine therapy or not during hospitalization. The association between thiamine supplement and in-hospital mortality was assessed by using the Kaplan−Meier (KM) method and Cox proportional hazard models. A 1:1 nearest propensity-score matching (PSM) and propensity score-based inverse probability of treatment weighting (IPW) were also performed to ensure the robustness of the findings.Results: A total of 7,021 patients were included in this study, with 685 and 6,336 in the thiamine and non-thiamine groups, respectively. The kaplan−meier survival curves indicated that the thiamine group had a lower in-hospital mortality than the none-thiamine group. After adjusting for various confounders, the Cox regression models showed significant beneficial effects of thiamine administration on in-hospital mortality among critically ill patients with heart failure with a hazard ratio of 0.78 (95% confidence interval: 0.67–0.89) in the fully adjusted model. propensity-score matching and probability of treatment weighting analyses also achieved consistent results.Conclusion: Thiamine supplement is associated with a decreased risk of in-hospital mortality in critically ill patients with heart failure who are admitted to the ICU. Further multicenter and well-designed randomized controlled trials with large sample sizes are necessary to validate this finding.
Random effects modelling versus logistic regression for the inclusion of cluster-level covariates in propensity score estimation: A Monte Carlo simulation and registry cohort analysis
Authors: Du Mike , Prats-Uribe Albert , Khalid Sara , Prieto-Alhambra Daniel , Strauss Victoria Y. 
Published: March 2023

Purpose: Surgeon and hospital-related features, such as volume, can be associated with treatment choices and outcomes. Accounting for these covariates with propensity score (PS) analysis can be challenging due to the clustered nature of the data. We studied six different PS estimation strategies for clustered data using random effects modelling (REM) compared with logistic regression.Methods: Monte Carlo simulations were used to generate variable cluster-level confounding intensity [odds ratio (OR) = 1.01–2.5] and cluster size (20–1,000 patients per cluster). The following PS estimation strategies were compared: i) logistic regression omitting cluster-level confounders; ii) logistic regression including cluster-level confounders; iii) the same as ii) but including cross-level interactions; iv), v), and vi), similar to i), ii), and iii), respectively, but using REM instead of logistic regression. The same strategies were tested in a trial emulation of partial versus total knee replacement (TKR) surgery, where observational versus trial-based estimates were compared as a proxy for bias. Performance metrics included bias and mean square error (MSE).Results: In most simulated scenarios, logistic regression, including cluster-level confounders, led to the lowest bias and MSE, for example, with 50 clusters × 200 individuals and confounding intensity OR = 1.5, a relative bias of 10%, and MSE of 0.003 for (i) compared to 32% and 0.010 for (iv). The results from the trial emulation also gave similar trends.Conclusion: Logistic regression, including patient and surgeon-/hospital-level confounders, appears to be the preferred strategy for PS estimation.
A machine learning approach to identifying suicide risk among text-based crisis counseling encounters
Authors: Broadbent Meghan , Medina Grespan Mattia , Axford Katherine , Zhang Xinyao , Srikumar Vivek , Kious Brent , Imel Zac 
Published: March 2023

IntroductionWith the increasing utilization of text-based suicide crisis counseling, new means of identifying at risk clients must be explored. Natural language processing (NLP) holds promise for evaluating the content of crisis counseling; here we use a data-driven approach to evaluate NLP methods in identifying client suicide risk.MethodsDe-identified crisis counseling data from a regional text-based crisis encounter and mobile tipline application were used to evaluate two modeling approaches in classifying client suicide risk levels. A manual evaluation of model errors and system behavior was conducted.ResultsThe neural model outperformed a term frequency-inverse document frequency (tf-idf) model in the false-negative rate. While 75% of the neural model’s false negative encounters had some discussion of suicidality, 62.5% saw a resolution of the client’s initial concerns. Similarly, the neural model detected signals of suicidality in 60.6% of false-positive encounters.DiscussionThe neural model demonstrated greater sensitivity in the detection of client suicide risk. A manual assessment of errors and model performance reflected these same findings, detecting higher levels of risk in many of the false-positive encounters and lower levels of risk in many of the false negatives. NLP-based models can detect the suicide risk of text-based crisis encounters from the encounter’s content.