bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome profiling and proteomic validation reveals targets of the androgen receptor signaling in the BT-474 breast cancer cell line
Authors: Vasiliou Stella K. , Filippou Panagiota S. , Clotet-Freixas Sergi , Soosaipillai Antoninus , Batruch Ihor , Viktor Tsianos Foivos , Konvalinka Ana , Diamandis Eleftherios P. 
Published: May 2022

Abstract
Background
Accumulating evidence suggests that the androgen receptor (AR) and its endogenous ligands influence disease progression in breast cancer (BCa). However, AR-mediated changes in BCa differ among the various BCa subtypes according to their hormone receptor profile [i.e., presence/absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2, (HER2)]. Thus, we explored the androgen-regulated transcriptomic changes in the ER+PR+HER2+ BCa cell line, BT-474, and compared them with PR-mediated changes.

Methods
We performed RNA sequencing analysis in treated BT-474 cells with dihydrotestosterone (DHT) and progesterone. Validation of the top ten differentially androgen-regulated genes and a number of other genes found in enriched signaling pathways was performed by qRT-PCR in BT-474 and other BCa cell lines. In addition, a parallel reaction monitoring targeted proteomic approach was developed to verify selected transcripts at the protein level.

Results
In total 19,450 transcripts were detected, of which 224 were differentially regulated after DHT treatment. The increased expression of two well-known androgen-regulated genes, KLK2 (p < 0.05) and KLK3 (p < 0.001), confirmed the successful androgen stimulation in BT-474 cells. The transcription factor, ZBTB16, was the most highly upregulated gene, with ~ 1000-fold change (p < 0.001). Pathway enrichment analysis revealed downregulation of the DNA replication processes (p < 0.05) and upregulation of the androgen signaling and fatty acid metabolism pathways (p < 0.05). Changes related to progesterone treatment showed opposite effects in gene expression than DHT treatment. Similar expression profiles were observed among other BCa cell lines expressing high levels of AR (ZR75.1 and MBA-MB-453). The parallel reaction monitoring targeted proteomic analysis further confirmed that altered protein expression (KLK3, ALOX15B) in the supernatant and cell lysate of DHT-treated BT-474 cells, compared to control cells.

Discussion
Our findings suggest that AR modulates the metabolism of BT-474 cells by affecting the expression of a large number of genes and proteins. Based on further pathway analysis, we suggest that androgen receptor acts as a tumor suppressor in the BT-474 cells.
Optimized sample preparation and data analysis for TMT proteomic analysis of cerebrospinal fluid applied to the identification of Alzheimer’s disease biomarkers
Authors: Weiner Sophia , Sauer Mathias , Visser Pieter Jelle , Tijms Betty M. , Vorontsov Egor , Blennow Kaj , Zetterberg Henrik , Gobom Johan 
Published: May 2022

AbstractBackgroundCerebrospinal fluid (CSF) is an important biofluid for biomarkers of neurodegenerative diseases such as Alzheimer’s disease (AD). By employing tandem mass tag (TMT) proteomics, thousands of proteins can be quantified simultaneously in large cohorts, making it a powerful tool for biomarker discovery. However, TMT proteomics in CSF is associated with analytical challenges regarding sample preparation and data processing. In this study we address those challenges ranging from data normalization over sample preparation to sample analysis.MethodUsing liquid chromatography coupled to mass-spectrometry (LC–MS), we analyzed TMT multiplex samples consisting of either identical or individual CSF samples, evaluated quantification accuracy and tested the performance of different data normalization approaches. We examined MS2 and MS3 acquisition strategies regarding accuracy of quantification and performed a comparative evaluation of filter-assisted sample preparation (FASP) and an in-solution protocol. Finally, four normalization approaches (median, quantile, Total Peptide Amount, TAMPOR) were applied to the previously published European Medical Information Framework Alzheimer’s Disease Multimodal Biomarker Discovery (EMIF-AD MBD) dataset.ResultsThe correlation of measured TMT reporter ratios with spiked-in standard peptide amounts was significantly lower for TMT multiplexes composed of individual CSF samples compared with those composed of aliquots of a single CSF pool, demonstrating that the heterogeneous CSF sample composition influences TMT quantitation. Comparison of TMT reporter normalization methods showed that the correlation could be improved by applying median- and quantile-based normalization. The slope was improved by acquiring data in MS3 mode, albeit at the expense of a 29% decrease in the number of identified proteins. FASP and in-solution sample preparation of CSF samples showed a 73% overlap in identified proteins. Finally, using optimized data normalization, we present a list of 64 biomarker candidates (clinical AD vs. controls, p < 0.01) identified in the EMIF-AD cohort.ConclusionWe have evaluated several analytical aspects of TMT proteomics in CSF. The results of our study provide practical guidelines to improve the accuracy of quantification and aid in the design of sample preparation and analytical protocol. The AD biomarker list extracted from the EMIF-AD cohort can provide a valuable basis for future biomarker studies and help elucidate pathogenic mechanisms in AD.
Diabetes risk loci-associated pathways are shared across metabolic tissues
Authors: Bouland Gerard A. , Beulens Joline W. J. , Nap Joey , van der Slik Arno R. , Zaldumbide Arnaud , ’t Hart Leen M. , Slieker Roderick C. 
Published: May 2022

Abstract
Aims/hypothesis
Numerous genome-wide association studies have been performed to understand the influence of genetic variation on type 2 diabetes etiology. Many identified risk variants are located in non-coding and intergenic regions, which complicates understanding of how genes and their downstream pathways are influenced. An integrative data approach will help to understand the mechanism and consequences of identified risk variants.

Methods
In the current study we use our previously developed method CONQUER to overlap 403 type 2 diabetes risk variants with regulatory, expression and protein data to identify tissue-shared disease-relevant mechanisms.

Results
One SNP rs474513 was found to be an expression-, protein- and metabolite QTL. Rs474513 influenced LPA mRNA and protein levels in the pancreas and plasma, respectively. On the pathway level, in investigated tissues most SNPs linked to metabolism. However, in eleven of the twelve tissues investigated nine SNPs were linked to differential expression of the ribosome pathway. Furthermore, seven SNPs were linked to altered expression of genes linked to the immune system. Among them, rs601945 was found to influence multiple HLA genes, including HLA-DQA2, in all twelve tissues investigated.

Conclusion
Our results show that in addition to the classical metabolism pathways, other pathways may be important to type 2 diabetes that show a potential overlap with type 1 diabetes.
Seed inoculation with antagonistic bacteria limits occurrence of E. coli O157:H7gfp + on baby spinach leaves
Authors: Karlsson Maria E. , Uhlig Elisabeth , Håkansson Åsa , Alsanius Beatrix W. 
Published: May 2022

Abstract
Backround
During the last decades, outbreaks of foodborne illnesses have increasingly been linked to fresh and/or minimally processed fruit and vegetables. Enterohemorrhagic Escherichia coli was the causal agent for major outbreaks in Europe with leafy green vegetables and sprouts. To improve food safety, microbial antagonism has received attention during recent years and could be one of the solution to prevent contamination of food borne pathogens on fresh produce. Here we investigate the antagonistic effect of three bacterial strains (Pseudomonas orientalis, P. flavescens and Rhodococcus sp.) isolated from spinach leaves against E. coli O157:H7gfp + under laboratory and greenhouse conditions.

Results
Our results shows that significantly less culturable E.coli O157:H7gfp + were retrieved from the spinach canopy subjected to antagonist seed treatment than canopy inoculation. Seeds inoculated with Rhodococcus sp. significantly reduced growth of E. coli O157:H7gfp + compared with the other antagonists. The result from the in vitro study shows a significant reduction of growth of E. coli O157:H7gfp+, but only after 44 h when E. coli O157:H7gfp + was propagated in a mixture of spent media from all three antagonists.

Conclusions
The antagonistic effect on phyllospheric E.coli O157:H7gfp + observed after seed inoculation with Rhodococcus sp. might be an indication of induced resistance mechanism in the crop. In addition, there was a small reduction of culturable E.coli O157:H7gfp + when propagated in spent media from all three antagonists. Nutritional conditions rather than metabolites formed by the three chosen organisms appear to be critical for controlling E. coli O157:H7gfp+.
Outcomes and risk factors for delayed-onset postoperative respiratory failure: a multi-center case-control study by the University of California Critical Care Research Collaborative (UC3RC)
Authors: Stocking Jacqueline C. , Drake Christiana , Aldrich J. Matthew , Ong Michael K. , Amin Alpesh , Marmor Rebecca A. , Godat Laura , Cannesson Maxime , Gropper Michael A. , Romano Patrick S. , Sandrock Christian , Bime Christian , Abraham Ivo , Utter Garth H. 
Published: May 2022

Abstract
Background
Few interventions are known to reduce the incidence of respiratory failure that occurs following elective surgery (postoperative respiratory failure; PRF). We previously reported risk factors associated with PRF that occurs within the first 5 days after elective surgery (early PRF; E-PRF); however, PRF that occurs six or more days after elective surgery (late PRF; L-PRF) likely represents a different entity. We hypothesized that L-PRF would be associated with worse outcomes and different risk factors than E-PRF.

Methods
This was a retrospective matched case-control study of 59,073 consecutive adult patients admitted for elective non-cardiac and non-pulmonary surgical procedures at one of five University of California academic medical centers between October 2012 and September 2015. We identified patients with L-PRF, confirmed by surgeon and intensivist subject matter expert review, and matched them 1:1 to patients who did not develop PRF (No-PRF) based on hospital, age, and surgical procedure. We then analyzed risk factors and outcomes associated with L-PRF compared to E-PRF and No-PRF.

Results
Among 95 patients with L-PRF, 50.5% were female, 71.6% white, 27.4% Hispanic, and 53.7% Medicare recipients; the median age was 63 years (IQR 56, 70). Compared to 95 matched patients with No-PRF and 319 patients who developed E-PRF, L-PRF was associated with higher morbidity and mortality, longer hospital and intensive care unit length of stay, and increased costs. Compared to No-PRF, factors associated with L-PRF included: preexisiting neurologic disease (OR 4.36, 95% CI 1.81–10.46), anesthesia duration per hour (OR 1.22, 95% CI 1.04–1.44), and maximum intraoperative peak inspiratory pressure per cm H20 (OR 1.14, 95% CI 1.06–1.22).

Conclusions
We identified that pre-existing neurologic disease, longer duration of anesthesia, and greater maximum intraoperative peak inspiratory pressures were associated with respiratory failure that developed six or more days after elective surgery in adult patients (L-PRF). Interventions targeting these factors may be worthy of future evaluation.
Effect of intratracheal dexmedetomidine combined with ropivacaine on postoperative sore throat: a prospective randomised double-blinded controlled trial
Authors: Niu Jingyi , Hu Rui , Yang Na , He Yan , Sun Hao , Ning Rende , Yu Junma 
Published: May 2022

Abstract
Background
The present study aimed to investigate whether intratracheal dexmedetomidine combined with ropivacaine reduces the severity and incidence of postoperative sore throat after tracheal intubation under general anaesthesia.

Methods
Two hundred patients with American Society of Anaesthesiologists physical status I-II who were subjected to general anaesthesia were randomly divided into four groups, namely, Group D, Group R, Group DR and Group S; these groups received intratracheal dexmedetomidine (1 µg/kg), 0.8% ropivacaine (40 mg), dexmedetomidine (1 µg/kg) combined with 0.8% ropivacaine (40 mg) and normal saline before endotracheal intubation, respectively. The primary outcomes were the incidence and grade of sore throat and hoarseness at 2 h and 24 h after surgery. Moreover, the modified Observer's Assessment of Alertness/Sedation Scale results were recorded at each time point. The secondary outcomes were intraoperative haemodynamic fluctuations, intraoperative anaesthetic drug requirements, and adverse reactions during and after surgery. The patients’ vital signs before induction, before superficial anaesthesia, after superficial anaesthesia, before intubation, after intubation, and 1 min after intubation were recorded. The use of anaesthetic drugs and occurrence of adverse effects were also recorded.

Results
The incidence and severity of sore throat were significantly lower in Group DR than in the other three groups 2 h after the operation, but they were only significantly lower in Group DR than in the control group 24 h after the operation. Moreover, compared with Group S and Group D, Group DR exhibited more stable haemodynamics during intubation. The doses of remifentanil and propofol were significantly lower in Group DR than in the other groups.

Conclusion
The combined use of dexmedetomidine and ropivacaine for surface anaesthesia before intubation significantly reduced the incidence and severity of postoperative sore throat. This treatment also decreased anaesthetic drug requirements and intraoperative haemodynamic fluctuations and caused no adverse effects.

Trial registration
This clinical research was registered at the Chinese Clinical Trial Registry (ChiCTR1900022907, Registration date 30/04/2019).
Synergistic prognostic value of coronary distensibility index and fractional flow reserve based cCTA for major adverse cardiac events in patients with Coronary artery disease
Authors: Zhu Xiao-long , Pang Zhi-ying , Jiang Wei , Dong Ting-yu 
Published: May 2022

Abstract
Background
Coronary distensibility index (CDI), as an early predictor of cardiovascular diseases, has the potential to complement coronary computed tomography angiography (cCTA)-derived fractional flow reserve (CT-FFR) for predicting major adverse cardiac events (MACEs). Thus, the prognostic value of CT-FFR combined with CDI for MACEs is worth exploring.

Methods
Patients with a moderate or severe single left anterior descending coronary artery stenosis were included and underwent FFR and CDI analysis based on cCTA, followed up at least 1 year, and recorded MACEs. Multivariate logistic regression analysis was performed to determine independent predictors of MACEs. The area under of receiver operating characteristic (ROC) curve was used to evaluated evaluate the diagnostic performance of CT-FFR, CDI, and a combination of the two.

Results
All the vessel-specific data were from LAD. 150 patients were analysed. 55 (37%) patients experienced MACEs during follow-up. Patients with CT-FFR ≤ 0.8 had higher percentage of MACEs compared with CT-FFR > 0.8 (56.3% vs.7.3%, p < 0.05). Patients’ CDI was significantly decreased in MACEs group compared with non-MACEs group (p < 0.05). Multivariate analysis revealed that diabetes (p = 0.025), triglyceride (p = 0.015), CT-FFR ≤ 0.80 (p = 0.038), and CDI (p < 0.001) are independent predictors of MACEs. According to ROC curve analysis, CT-FFR combined CDI showed incremental diagnostic performance over CT-FFR alone for prediction of MACEs (AUC = 0.831 vs. 0.656, p = 0.0002).

Conclusion
Our study provides initial evidence that combining CDI with CT-FFR shows incremental discriminatory power for MACEs over CT-FFR alone, independent of clinical risk factors. Diabetes and triglyceride are also associated with MACEs.
Novel biomarkers of inflammation in heart failure with preserved ejection fraction: analysis from a large prospective cohort study
Authors: Carris Nicholas W. , Mhaskar Rahul , Coughlin Emily , Bracey Easton , Tipparaju Srinivas M. , Halade Ganesh V. 
Published: May 2022

Abstract
Background
Heart failure with preserved ejection fraction (HFpEF) is a syndrome with a heterogeneous cluster of causes, including non-resolving inflammation, endothelial dysfunction, and multi-organ defects. The present study’s objective was to identify novel predictors of HFpEF.

Methods
The study analyzed the Multi-Ethnic Study of Atherosclerosis (MESA) to assess the association of specific markers of inflammation with new onset of HFpEF (interleukin-2 [IL-2], matrix metalloproteinase 3 [MMP3], large low-density lipoprotein cholesterol [LDL-C], and medium high-density lipoprotein cholesterol [HDL-C]). The study included men and women 45 to 84 years of age without cardiovascular disease at baseline. The primary outcome was the multivariate association of the hypothesized markers of inflammation with new-onset of HFpEF versus participants without new-onset heart failure. Participants with missing data were excluded.

Results
The present analysis included 6814 participants, 53% female, with a mean age of 62 years. Among the entire cohort, HFpEF was diagnosed in 151 (2.2%) participants and heart failure with reduced ejection fraction (HFrEF) was diagnosed in 146 (2.1%) participants. Participants were followed for the outcome of heart failure for a median 13.9 years. Baseline IL-2 was available for 2861 participants. The multivariate analysis included 2792 participants. Of these, 2668 did not develop heart failure, 62 developed HFpEF, 47 developed HFrEF, and 15 developed unclassified heart failure. In the multivariate regression model, IL-2 was associated with new-onset HFpEF (OR, 1.00058; 95% confidence interval, 1.00014 to 1.00102, p = 0.009) but not new-onset HFrEF. In multivariate analysis, MMP3, large LDL-C, and medium HDL-C were not associated with HFpEF or HFrEF.

Conclusion
These findings portend IL-2 as an important component of suboptimal inflammation in the pathogenesis of HFpEF.
The pre-ablation triglyceride-glucose index predicts late recurrence of atrial fibrillation after radiofrequency ablation in non-diabetic adults
Authors: Tang Qinghui , Guo Xiao-Gang , Sun Qi , Ma Jian 
Published: May 2022

Abstract
Background
Current prognostic risk scoring systems and biomarkers are routinely used as non-invasive methods for assessing late recurrence of atrial fibrillation (AF) in patients who have undergone radiofrequency catheter ablation (RFCA). This study aimed to investigate the predictive value of the triglyceride-glucose (TyG) index for late AF recurrence after RFCA in non-diabetic patients.

Methods
In total, 275 patients with AF who underwent RFCA at the Fuwai hospital (Beijing, China) between January 2016 and December 2018 were enrolled in this study. During follow up, patients were divided into late and non-late AF recurrence groups, based on whether they had experienced late AF recurrence determined by electrocardiography (ECG) examine or 48 h Holter monitoring. The TyG index was calculated using the following equation: ln [fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2].

Results
During a median follow-up of 26.1 months, late AF recurrence event rates significantly increased in the highest TyG index tertile group (tertile 3) compared to the lowest group (tertile 1) (54% versus 12%, respectively; p < 0.001). The mean TyG index was higher in the late AF recurrence group compared to the non- late AF recurrence group (9.42 ± 0.6 versus 8.68 ± 0.70, respectively; p < 0.001). On multivariate Cox regression analysis, the pre-ablation TyG index was an independent risk factor for late recurrence of AF after RFCA (hazard ratio [HR] 2.015 [95% confidence interval (CI): 1.408–4.117]; p = 0.009). Receiver operating characteristic (ROC) curve analysis revealed that TyG index was a significant predictor of late AF recurrence after RFCA, with an area under the ROC curve (AUC) of 0.737 (95% CI: 0.657–0.816; p < 0.001). In addition, the AUC of left atrial diameter (LAD) was 0.780 (95%CI: 0.703–0.857, p < 0.001). Finally, the TyG index positively correlated with LAD (r = 0.133, p = 0.027), high sensitivity C-reactive protein (r = 0.132, p = 0.028) and N-terminal pro B-type natriuretic peptide (r = 0.291, p < 0.001) levels.

Conclusions
An elevated pre-ablation TyG index was associated with an increased risk of late AF recurrence after RFCA in non-diabetic patients. The TyG index may be potentially useful as a novel biomarker for the risk stratification of late AF recurrence in non-diabetic patients.
The sham effect of invasive interventions in chronic coronary syndromes: a systematic review and meta-analysis
Authors: Palma Catarina , David Cláudio , Fernandes Ricardo M. , Pinto Fausto J. , Costa João , Ferreira Joaquim J. , Caldeira Daniel 
Published: May 2022

Abstract
Background
Some patients with chronic coronary syndromes undergo invasive procedures but the efficacy of such interventions remains to be robustly established by randomised sham-controlled trials (RCTs).

Purpose
To determine the sham effect in patients with chronic coronary syndromes enrolled in RCTs by performing a systematic review and meta-analysis.

Methods
In April 2022, we performed a literature search for published patient-blind RCTs (CENTRAL, MEDLINE®, PsycINFO, and reference lists) with sham procedures, reporting the pre-post effects in the invasive sham arm among patients with Canadian cardiovascular society (CCS) angina or angina equivalents.

Results
16 RCTs were included with 546 patients in the sham arm. Pooled results showed that sham interventions were associated with: improvement of 7% (95% CI 2–11%; I2 = 0%) in exercise time; decrease of 0.78 (95% CI − 1.10 to − 0.47; I2 = 75%) in CCS angina class; decrease of 53% (95% CI 24–71%; I2 = 96%) and 25% (95% CI 20–29%; I2 = 0%) in anginal episodes and nitroglycerine (NTG) use, respectively. Pooled results also showed an improvement in the physical functioning, angina frequency, treatment satisfaction, and disease perception domains of the Seattle Angina Questionnaire (SAQ).

Conclusion
Sham interventions in patients with chronic coronary syndromes were associated with a significant decrease in anginal episodes, NTG use, and CCS angina class and increased SAQ quality of life and exercise time. These results highlight the need for previous non sham-controlled trials to be interpreted with caution, and the importance of new invasive interventions to be evaluated versus a sham procedure.