Metabolic and Pharmacokinetic Profiling Studies of N, N-Dimethylaniline-Heliamine in Rats by UHPLC-Q-Orbitrap MS/MS.

Cardiovascular disease is the first cause of death worldwide and kills more people each year than any other cause of death. N, N-dimethylaniline-heliamine (DH), a synthetic tetrahydroisoquinoline alkaloid, has shown notable antiarrhythmic activity. However, the metabolic processes and pharmacokinetic characteristics of DH in rats have not been studied. This study aims to identify its metabolites, as well as develop and validate a rapid and efficient bioanalytical method for quantifying DH in rat plasma over a wide range of concentrations. Its metabolites were characterized in silico, in vitro, and in vivo. A series of 16 metabolites were identified, of which 12 were phase I metabolites and 4 were phase II metabolites. A low probability of DH binding to DNA, protein, and glutathione is predicted by the in silico model. The main metabolic processes of DH were demethylation, dehydrogenation, glucuronidation, and sulfation. Concentration-time profiles were generated by analyzing the plasma, and the outcomes were analyzed via non-compartmental analysis to identify the pharmacokinetic parameters. Among the detected parameters were the volume of distribution, estimated at 126,728.09 ± 56,867.09 mL/kg, clearance at 30,148.65 ± 15,354.27 mL/h/kg, and absolute oral bioavailability at 16.11%. The plasma distribution volume of DH was substantially higher than the overall plasma volume of rats, which suggests that DH has a specific tissue distribution in rats. This study suggests that DH is appropriately bioavailable and excreted via a variety of routes and has low toxicity.

Social Vulnerability and Compliance With World Health Organization Advice on Protective Behaviors Against COVID-19 in African and Asia Pacific Countries: Factor Analysis to Develop a Social Vulnerability Index.

BACKGROUND: COVID-19 protective behaviors are key interventions advised by the World Health Organization (WHO) to prevent COVID-19 transmission. However, achieving compliance with this advice is often challenging, particularly among socially vulnerable groups. OBJECTIVE: We developed a social vulnerability index (SVI) to predict individuals' propensity to adhere to the WHO advice on protective behaviors against COVID-19 and identify changes in social vulnerability as Omicron evolved in African countries between January 2022 and August 2022 and Asia Pacific countries between August 2021 and June 2022. METHODS: In African countries, baseline data were collected from 14 countries (n=15,375) during the first Omicron wave, and follow-up data were collected from 7 countries (n=7179) after the wave. In Asia Pacific countries, baseline data were collected from 14 countries (n=12,866) before the first Omicron wave, and follow-up data were collected from 9 countries (n=8737) after the wave. Countries' socioeconomic and health profiles were retrieved from relevant databases. To construct the SVI for each of the 4 data sets, variables associated with COVID-19 protective behaviors were included in a factor analysis using polychoric correlation with varimax rotation. Influential factors were adjusted for cardinality, summed, and min-max normalized from 0 to 1 (most to least vulnerable). Scores for compliance with the WHO advice were calculated using individuals' self-reported protective behaviors against COVID-19. Multiple linear regression analyses were used to assess the associations between the SVI and scores for compliance to WHO advice to validate the index. RESULTS: In Africa, factors contributing to social vulnerability included literacy and media use, trust in health care workers and government, and country income and infrastructure. In Asia Pacific, social vulnerability was determined by literacy, country income and infrastructure, and population density. The index was associated with compliance with the WHO advice in both time points in African countries but only during the follow-up period in Asia Pacific countries. At baseline, the index values in African countries ranged from 0.00 to 0.31 in 13 countries, with 1 country having an index value of 1.00. The index values in Asia Pacific countries ranged from 0.00 to 0.23 in 12 countries, with 2 countries having index values of 0.79 and 1.00. During the follow-up phase, the index values decreased in 6 of 7 African countries and the 2 most vulnerable Asia Pacific countries. The index values of the least vulnerable countries remained unchanged in both regions. CONCLUSIONS: In both regions, significant inequalities in social vulnerability to compliance with WHO advice were observed at baseline, and the gaps became larger after the first Omicron wave. Understanding the dimensions that influence social vulnerability to protective behaviors against COVID-19 may underpin targeted interventions to enhance compliance with WHO recommendations and mitigate the impact of future pandemics among vulnerable groups.

LncRNA HOTTIP as a diagnostic biomarker for acute respiratory distress syndrome in patients with sepsis and to predict the short-term clinical outcome: a case-control study.

BACKGROUND: The present research aims to investigate the clinical diagnostic value of LncRNA HOXA distal transcript antisense RNA (HOTTIP) in acute respiratory distress syndrome (ARDS) of sepsis and its predictive significance for mortality. METHODS: One hundred eighteenth patients with sepsis and 96 healthy individuals were enrolled. RT-qPCR to examine HOTTIP levels. The incidence of ARDS and death was recorded. The diagnostic significance of HOTTIP in sepsis ARDS was examined using ROC and logistic regression analysis. The correlation between HOTTIP and disease severity was evaluated using Pearson's coefficients. Kaplan-Meier analysis and COX regression were employed to examine the predictive significance of mortality. Validation of HOTTIP target miRNA by dual-luciferase assay. RESULTS: HOTTIP was persistently up-regulated in patients with ARDS sepsis than in patients without ARDS patients (P < 0.05). HOTTIP was a risk factor for the development of ARDS, which could be diagnosed in ARDS patients from non-ARDS patients (AUC = 0.847). Both the SOFA score (r = 0.6793) and the APACHE II score (r = 0.6384) were positively correlated with the HOTTIP levels. Furthermore, serum HOTTIP was an independent predictor of short-term mortality (HR = 4.813. 95%CI: 1.471-15.750, P = 0.009) and noticeably predicted the occurrence of short-term death (log rank = 0.020). miR-574-5p, a target miRNA for HOTTIP, was reduced in patients with sepsis ARDS and negatively correlated with HOTTIP. CONCLUSIONS: The presence of HOTTIP serves as a diagnostic biomarker for the occurrence of ARDS, exhibits correlation with disease severity, and provides predictive value of short-term mortality in sepsis patients. HOTTIP may be involved in ARDS progression by targeting miR-574-5p.

Prospective observational study to validate a next-generation sequencing blood RNA signature to predict early kidney transplant rejection.

The objective of this study was to validate the performance of Tutivia, a peripheral blood gene expression signature, in predicting early acute rejection (AR) post-kidney transplant. Recipients of living or deceased donor kidney transplants were enrolled in a nonrandomized, prospective, global, and observational study (NCT04727788). The main outcome was validation of the area under the curve (AUC) of Tutivia vs serum creatinine at biopsy alone, or Tutivia + serum creatinine at biopsy. Of the 151 kidney transplant recipients, the mean cohort age was 53 years old, and 64% were male. There were 71% (107/151) surveillance/protocol biopsies and 29% (44/151) for-cause biopsies, with a 31% (47/151) overall rejection rate. Tutivia (AUC 0.69 [95% CI: 0.59-0.77]) and AUC of Tutivia + creatinine at biopsy (0.68 [95% CI: 0.59-0.77]) were greater than the AUC of creatinine at biopsy alone (0.51.4 [95% CI: 0.43-0.60]). Applying a model cut-off of 50 (scale 0-100) generated a high- and low-risk category for AR with a negative predictive value of 0.79 (95% CI: 0.71-0.86), a positive predictive value of 0.60 (95% CI: 0.45-0.74), and an odds ratio of 5.74 (95% CI: 2.63-12.54). Tutivia represents a validated noninvasive approach for clinicians to accurately predict early AR, beyond the current standard of care.

Neutrophil extracellular traps-related signature predicts the prognosis and immune infiltration in gastric cancer.

Introduction: Gastric cancer (GC) is the fifth most prevalent cancer globally, with the third highest case fatality rate. Neutrophil extracellular traps (NETs) are a reticulated structure of DNA, histones, and antimicrobial peptides produced by active neutrophils that trap pathogens. Even though NETs are associated with poorer recurrence-free survival (RFS) and overall survival (OS), the specifics of this interaction between NETs and cancer cells are yet unknown. Methods: The keywords "neutrophil extracellular traps and gastric cancer" were used in the GEO database for retrieval, and the GSE188741 dataset was selected to obtain the NETs-related gene. 27 NETs-related genes were screened by univariate Cox regression analysis (p < 0.05). 27 NETs-related genes were employed to identify and categorize NETs-subgroups of GC patients under the Consensus clustering analysis. 808 GC patients in TCGA-STAD combined with GES84437 were randomly divided into a training group (n = 403) and a test group (n = 403) at a ratio of 1:1 to validate the NETs-related signature. Results: Based on Multivariate Cox regression and LASSO regression analysis to develop a NETs-related prognosis model. We developed a very specific nomogram to improve the NETs-clinical score's usefulness. Similarly, we also performed a great result in pan-cancer study with NETs-score. Low NETs scores were linked to higher MSI-H (microsatellite instability-high), mutation load, and immune activity. The cancer stem cell (CSC) index and chemotherapeutic treatment sensitivity were also connected to the NET score. Our comprehensive analysis of NETs in GC suggests that NETs have a role in the tumor microenvironment, clinicopathological features, and prognosis. Discussion: The NETs-score risk model provides a basis for better prognosis and therapy outcomes in GC patients.

Circulating mir-483-5p as a novel diagnostic biomarker for acute coronary syndrome and its predictive value for the clinical outcome after PCI.

BACKGROUND: MicroRNA (miRNA) plays a critical function in the progression of acute coronary syndrome (ACS) and is associated with major adverse cardiovascular events (MACEs) after undergoing percutaneous coronary intervention (PCI). This research was designed to probe the diagnostic accuracy of miR-483-5p in patients with ACS and its predictive value of MACEs. METHODS: 118 patients with ACS (40 with unstable angina pectoris [UAP] and 78 with acute myocardial infarction [AMI]) and 75 healthy controls were enrolled. Serum miR-483-5p was detected in the subjects by reverse transcription-quantitative real-time PCR (RT-qPCR). ROC curve and logistic regression models were employed to estimate the diagnosis. Patients were monitored for 6 months after PCI to document the occurrence of MACEs. Kaplan-Meier survival was conducted to explore the predictive significance of miR-483-5p for the MACEs. RESULTS: Serum miR-483-5p levels were higher in ACS patients and associated with SYNTAX score and Gensini score. miR-483-5p was effective in identifying ACS patients from healthy individuals (AUC = 0.919) and AMI patients from ACS patients (AUC = 0.867), demonstrating a high diagnostic value, proven by logistic regression (OR = 9.664, 95%CI = 4.462-20.928, P < 0.001). The prevalence of MACEs during follow-up were 24.58%, and a higher prevalence of MACEs were observed in patients with elevated miR-483-5p (P = 0.01). miR-483-5p was also an effective predictor of MACE occurrence (HR = 5.955, 95%CI = 1.928-18.389, P = 0.002). CONCLUSION: Expression of serum miR-483-5p can be utilized as a non-invasive marker for diagnosing ACS and predicting the onset of MACE after PCI.

Clinical frailty scale is useful in predicting return-to-home in patients admitted due to coronavirus disease.

BACKGROUND: The spread of the novel severe acute respiratory syndrome coronavirus 2 infection has been prolonged, with the highly contagious Omicron variant becoming the predominant variant by 2022. Many patients admitted to dedicated coronavirus disease 2019 (COVID-19) wards (COVID-19 treatment units) develop disuse syndrome while being treated in the hospital, and their ability to perform activities of daily living declines, making it difficult for hospitals to discharge them. This study aimed to investigate the relationship between the degree of frailty and home discharge of patients admitted to a COVID-19 treatment units. METHODS: This study retrospectively examined the in-patient medical records of 138 patients (82.7 ± 7.6 years old) admitted to a COVID-19 treatment unit from January to December 2022. The end-point was to determine the patients' ability to be discharged from the unit directly to home; such patients were classified into the 'Home discharge' group and compared with those in the 'Difficulty in discharge' group. The degree of frailty was determined based on the Clinical Frailty Scale (CFS), and the relationship with the endpoint was analysed. A receiver operating characteristic (ROC) curve was created and the cut-off value was calculated with the possibility of home discharge as the state variable and CFS as the test variable. Logistic regression analysis was conducted with the possibility of home discharge as the dependent variable and CFS as the independent variable. RESULTS: There were 75 patients in the Home discharge group and 63 in the Difficulty in discharge group. ROC analysis showed a CFS cut-off value of 6 or more, with a sensitivity of 70.7% and a specificity of 84.1%. The results of the logistic regression analysis showed a significant correlation between possibility of home discharge and CFS even after adjusting for covariates, with an odds ratio of 13.44. CONCLUSIONS: Based on the evaluation of the degree of frailty conducted in the COVID-19 treatment unit, it was possible to accurately predict whether a patient could be discharged directly to home after treatment CFS could be an effective screening tool to easily detect patients requiring ongoing hospitalisation even after the acute phase of treatment.

ADAM19 and TUBB1 Correlate with Tumor Infiltrating Immune Cells and Predicts Prognosis in Osteosarcoma.

BACKGROUND: Osteosarcoma is the most common type of primary malignant bone tumor. INTRODUCTION: This study aimed to explore potential key prognostic genes and their roles in osteosarcoma. METHODS: Three microarray datasets for osteosarcoma were downloaded from the GEO database. Differentially expressed genes (DEGs) were screened by the Limma package. Functional enrichment analysis was performed based on DAVID, GeneMANIA, and Metascape databases. Prognostic value of DEGs was elevated by survival analysis. CIBERSORT was used to assess the infiltrating abundance of 22 immune cells, followed by the Pearson correlation analysis between immune cells and prognosis-related genes. Gene set enrichment analysis and drug-gene interactions prediction were performed for prognosis-related genes. RESULTS: A total of 8 common up-regulated DEGs and 13 common down-regulated DEGs were screened in the GSE36001 and GSE56001 datasets. Enrichment analysis showed these DEGs were implicated in platelet activation, SMAD protein phosphorylation, lymphocyte/leukocyte/T cells activation, and cell migration. Survival analysis indicated that elevated expression of ADAM19 and TUBB1 were associated with a favorable prognosis. CIBERSORT algorithm revealed the higher infiltrating level of CD8 T cells, macrophages M0, and M2 in osteosarcoma. ADAM19 expression positively correlated with naïve B cells and negatively correlated with activated dendritic cells infiltrating abundance. TUBB1 expression positively correlated with gamma delta T cells while negatively correlated with helper follicular T cells infiltrating abundance. A total of 56 drugs were found to target TUBB1. CONCLUSION: ADAM19 and TUBB1 could be prognostic biomarkers in osteosarcoma. Both their expression correlates with tumor infiltrating immune cells. TUBB1 was a multi-drug target that might be a therapeutic target in osteosarcoma.

Risk Factors of Sudden Cardiac Arrest during the Postoperative Period in Patient Undergoing Heart Valve Surgery.

BACKGROUND: Sudden cardiac arrest (SCA) is the sudden cessation of normal cardiac activity with hemodynamic collapse. This usually leads to sudden cardiac death (SCD) when cardiopulmonary resuscitation is not undertaken. In patients undergoing heart valve surgery, postoperative SCA is a complication with a high risk of death, cerebral hypoxia and multiple organ dysfunction syndrome (MODS). Therefore, knowledge of the predictors of postoperative SCA is extremely important as it enables the identification of patients at risk of this complication and the application of the special surveillance and therapeutic management in this group of patients. The aim of the study was to evaluate the usefulness of selected biomarkers in predicting postoperative SCA in patients undergoing heart valve surgery. METHODS: This prospective study was conducted on a group of 616 consecutive patients with significant valvular heart disease that underwent elective valve surgery with or without coronary artery bypass surgery. The primary end-point at the intra-hospital follow-up was postoperative SCA. The secondary end-point was death from all causes in patients with postoperative SCA. Patients were observed until discharge from the hospital or until death. Logistic regression was used to assess the relationships between variables. RESULTS: The postoperative SCA occurred in 14 patients. At multivariate analysis, only NT-proBNP (odds ratio (OR) 1.022, 95% confidence interval (CI) 1.012-1.044; p = 0.03) remained independent predictors of the primary end-point. Age and NT-proBNP were associated with an increased risk of death in patients with postoperative SCA. CONCLUSIONS: The results of the presented study indicate that SCA in the early postoperative period in patients undergoing heart valve surgery is an unpredictable event with high mortality. The potential predictive ability of the preoperative NT-proBNP level for the occurrence of postoperative SCA and death in patients after SCA demonstrated in the study may indicate that the overloaded and damaged myocardium in patients undergoing heart valve surgery is particularly sensitive to non-physiological conditions prevailing in the perioperative period, which may cause serious hemodynamic disturbances in the postoperative period and lead to death.

Predictability and transferability of local biodiversity environment relationships.

Background: Biodiversity varies in space and time, and often in response to environmental heterogeneity. Indicators in the form of local biodiversity measures-such as species richness or abundance-are common tools to capture this variation. The rise of readily available remote sensing data has enabled the characterization of environmental heterogeneity in a globally robust and replicable manner. Based on the assumption that differences in biodiversity measures are generally related to differences in environmental heterogeneity, these data have enabled projections and extrapolations of biodiversity in space and time. However so far little work has been done on quantitatively evaluating if and how accurately local biodiversity measures can be predicted. Methods: Here I combine estimates of biodiversity measures from terrestrial local biodiversity surveys with remotely-sensed data on environmental heterogeneity globally. I then determine through a cross-validation framework how accurately local biodiversity measures can be predicted within ("predictability") and across similar ("transferability") biodiversity surveys. Results: I found that prediction errors can be substantial, with error magnitudes varying between different biodiversity measures, taxonomic groups, sampling techniques and types of environmental heterogeneity characterizations. And although errors associated with model predictability were in many cases relatively low, these results question-particular for transferability-our capability to accurately predict and project local biodiversity measures based on environmental heterogeneity. I make the case that future predictions should be evaluated based on their accuracy and inherent uncertainty, and ecological theories be tested against whether we are able to make accurate predictions from local biodiversity data.

Cerebrospinal fluid exosomal miR-152-3p predicts the occurrence of subarachnoid haemorrhage and regulates vascular smooth muscle cell dysfunction.

INTRODUCTION: Ruptured intracranial aneurysm (RA) can lead to subarachnoid haemorrhage (SAH). This study was to explore the predictive value of cerebrospinal fluid (CSF) derived exosome miR-152-3p and its regulatory role in the human vascular smooth muscle cells (HVSMCs). MATERIAL AND METHODS: Real-time quantitative polymerase reaction was carried out to detect CSF exosome miR-152-3p in 66 patients with unruptured intracranial aneurysms (UA), 69 patients with RA, and 68 patients with hydrocephalus. Clinical predictive value of SAH occurrence was assessed using receiver operating characteristic curve (ROC) and logistics regression analysis. Cell Counting Kit-8 and Transwell were employed to detect the proliferation and migration of HVSMCs. The binding relationship between miR-152-3p and PTEN was confirmed by the dual-luciferase reporter assay. RESULTS: Compared with hydrocephalus, exosome miR-152-3p was lower in patients with intracranial aneurysms, and among them, RA was lower than in patients with UA (p < 0.001). ROC confirmed that exosome miR-152-3p not only distinguishes patients with UA from patients with hydrocephalus but also predicts SAH in patients with intracranial aneurysms. Logistic regression analysis showed that miR-152-3p (OR = 0.039, 95% CI = 0.015-0.106, p < 0.001) and aneurysm size (OR = 2.701, 95% CI = 1.045-6.890, p = 0.040) were independent predictors of progression for UA to RA. Increased miR-152-3p inhibited the proliferation and migration of HVSMCs. PTEN was the direct target gene of miR-152-3p, which was elevated in CSF-derived exosomes and negatively correlated with miR-152-3p levels. CONCLUSIONS: Our study confirmed that the CSF-derived exosome miR-152-3p was a feasible predictor of SAH and was involved in the dysfunction of HVSMCs.

Circulating miR-342-5p serves as a diagnostic biomarker in patients with carotid artery stenosis and predicts the occurrence of the cerebral ischemic event.

BACKGROUND: Carotid artery stenosis (CAS) is an important risk factor for cerebral ischemia events (CIE). Previous studies have shown that microRNAs (miRNAs) are involved in the occurrence and development of CAS. AIMS: The purpose of this study was to reveal the clinical diagnostic value of miR-342-5p for asymptomatic CAS (ACAS) and to evaluate its predictive value for the occurrence of CIE in patients. METHODS: A total of 92 ACAS patients and 86 healthy controls were enrolled as subjects. The expression level of serum miR-342-5p was detected by qRT-PCR. The receiver operating characteristic (ROC) curve was used to detect the diagnostic value of miR-342-5p in ACAS. Kaplan-Meier survival and Cox regression analysis assessed the predictive value of miR-342-5p for the occurrence of CIE in ACAS patients. RESULTS: The level of serum miR-342-5p in ACAS patients was significantly higher than that in healthy controls (P < 0.05). ROC curve showed the high diagnostic value of serum miR-342-5p, which could distinguish ACAS patients from healthy controls. Multivariate Cox regression analysis confirmed that miR-342-5p was an independent predictor (HR = 5.512, 95%CI = 1.370-22.176, P = 0.016). What is more, Kaplan-Meier analysis confirmed that patients with high miR-342-5p expression develop more CIE (log-rank, P = 0.020). CONCLUSIONS: miR-342-5p was significantly overexpressed in ACAS. And the upregulation of serum miR-342-5p is a valuable diagnostic biomarker and can predict the occurrence of CIE.

A Five-MicroRNA Signature Predicts the Prognosis in Nasopharyngeal Carcinoma.

BACKGROUND: There is no effective prognostic signature that could predict the prognosis of nasopharyngeal carcinoma (NPC). METHODS: We constructed a prognostic signature based on five microRNAs using random forest and Least Absolute Shrinkage And Selection Operator (LASSO) algorithm on the GSE32960 cohort (N = 213). We verified its prognostic value using three independent external validation cohorts (GSE36682, N = 62; GSE70970, N = 246; and TCGA-HNSC, N = 523). Through principal component analysis, receiver operating characteristic curve analysis, and C-index calculation, we confirmed the predictive accuracy of this prognostic signature. RESULTS: We calculated the risk score based on the LASSO algorithm and divided the patients into high- and low-risk groups according to the calculated optimal cutoff value. The patients in the high-risk group tended to have a worse prognosis outcome and chemotherapy response. The time-dependent receiver operating characteristic curve showed that the 1-year overall survival rate of the five-microRNA signature had an area under the curve of more than 0.83. A functional annotation analysis of the five-microRNA signature showed that the patients in the high-risk group were usually accompanied by activation of DNA repair and MYC-target pathways, while the patients in the low-risk group had higher immune-related pathway signals. CONCLUSIONS: We constructed a five-microRNA prognostic signature, which could accurately predict the prognosis of nasopharyngeal carcinoma, and constructed a nomogram that could conveniently predict the overall survival of patients.

Brain-environment alignment during movie watching predicts fluid intelligence and affective function in adulthood.

BOLD fMRI studies have provided compelling evidence that the human brain demonstrates substantial moment-to-moment fluctuations in both activity and functional connectivity (FC) patterns. While the role of brain signal variability in fostering cognitive adaptation to ongoing environmental demands is well-documented, the relevance of moment-to-moment changes in FC patterns is still debated. Here, we adopt a graph theoretical approach in order to shed light on the cognitive-affective implications of FC variability and associated profiles of functional network communication in adulthood. Our goal is to identify brain communication pathways underlying FC reconfiguration at multiple timescales, thereby improving understanding of how faster perceptually bound versus slower conceptual processes shape neural tuning to the dynamics of the external world and, thus, indirectly, mold affective and cognitive responding to the environment. To this end, we used neuroimaging and behavioural data collected during movie watching by the Cambridge Center for Ageing and Neuroscience (N = 642, 326 women) and the Human Connectome Project (N = 176, 106 women). FC variability evoked by changes to both the concrete perceptual and the more abstract conceptual representation of an ongoing situation increased from young to older adulthood. However, coupling between variability in FC patterns and concrete environmental features was stronger at younger ages. FC variability (both moment-to-moment/concrete featural and abstract conceptual boundary-evoked) was associated with age-distinct profiles of network communication, specifically, greater functional integration of the default mode network in older adulthood, but greater informational flow across neural networks implicated in environmentally driven attention and control (cingulo-opercular, salience, ventral attention) in younger adulthood. Whole-brain communication pathways anchored in default mode regions relevant to episodic and semantic context creation (i.e., angular and middle temporal gyri) supported FC reconfiguration in response to changes in the conceptual representation of an ongoing situation (i.e., narrative event boundaries), as well as stronger coupling between moment-to-moment fluctuations in FC and concrete environmental features. Fluid intelligence/abstract reasoning was directly linked to levels of brain-environment alignment, but only indirectly associated with levels of FC variability. Specifically, stronger coupling between moment-to-moment FC variability and concrete environmental features predicted poorer fluid intelligence and greater affectively driven environmental vigilance. Complementarily, across the adult lifespan, higher fluid (but not crystallised) intelligence was related to stronger expression of the network communication profile underlying momentary and event boundary-based FC variability during youth. Our results indicate that the adaptiveness of dynamic FC reconfiguration during naturalistic information processing changes across the lifespan due to the associated network communication profiles. Moreover, our findings on brain-environment alignment complement the existing literature on the beneficial consequences of modulating brain signal variability in response to environmental complexity. Specifically, they imply that coupling between moment-to-moment FC variability and concrete environmental features may index a bias towards perceptually-bound, rather than conceptual processing, which hinders affective functioning and strategic cognitive engagement with the external environment.

Predicting Masaoka-Koga Clinical Stage of Thymic Epithelial Tumors Using Preoperative Spectral Computed Tomography Imaging.

OBJECTIVES: To investigate the utility of spectral computed tomography (CT) parameters for the prediction of the preoperative Masaoka-Koga stage of thymic epithelial tumors (TETs). MATERIALS AND METHODS: Fifty-four patients with TETs, aged from 37 to 73 years old, an average age of 55.56 ± 9.79 years, were included in the study.According to the Masaoka-Koga staging method, there were 19 cases of stage I, 15 cases of stage II, 8 cases of stage III, and 12 cases of stage IV disease. All patients underwent dual-phase enhanced energy spectral CT scans. Regions of interest (ROIs) were defined in sections of the lesion with homogeneous density, the thoracic aorta at the same level as the lesion, the outer fat layer of the lesion, and the anterior chest wall fat layer. The single-energy CT value at 40-140 keV, iodine concentration, and energy spectrum curve of all lesion and thoracic aorta were obtained. The energy spectrum CT parameters of the lesions, extracapsular fat of the lesions, and anterior chest wall fat in stage I and stage II were obtained. The energy spectrum CT parameters of the lesions, enlarged lymph nodes and intravascular emboli in the 3 groups were obtained. The slope of the energy spectrum curve and the normalized iodine concentration were calculated. RESULTS: In stage I lesions, there was a statistically significant difference between the slope of the energy spectrum curve for the lesion and those of the fat outside the lesion and the anterior chest wall in the arteriovenous phase (P<0.001, P<0.001). The energy spectrum curve of the tumor parenchyma was the opposite of that of the extracapsular fat. In stage II lesions, there was a statistically significant difference between the slope of the energy spectrum curve for the anterior chest wall and those of the lesion and the fat outside the lesion in the arteriovenous phase(P<0.001, P<0.001). The energy spectrum curve of the tumor parenchyma was consistent with that of the extracapsular fat. Distinction between stage I and II tumors be evaluated by comparing the energy spectrum curves of the mass and the extracapsular fat of the mass. The accuracy rate of is 79.4%. For stages III and IV, there was no significant difference in the slope of the energy spectrum curve of the tumor parenchyma, metastatic lymph node, and intravascular embolism (P>0.05). The energy spectrum curve of the tumor parenchyma was consistent with that of the enlarged lymph nodes and intravascular emboli. The two radiologists have strong consistency in evaluating TETs Masaoka-Koga staging, The Kappa coefficient is 0.873,(95%CI:0.768-0.978). CONCLUSION: Spectral CT parameters, especially the energy spectrum curve and slope, are valuable for preoperative TET and can be used in preoperative staging prediction.

Individual Brain Metabolic Connectome Indicator Based on Jensen-Shannon Divergence Similarity Estimation Predicts Seizure Outcomes of Temporal Lobe Epilepsy.

Objective: We aimed to use an individual metabolic connectome method, the Jensen-Shannon Divergence Similarity Estimation (JSSE), to characterize the aberrant connectivity patterns and topological alterations of the individual-level brain metabolic connectome and predict the long-term surgical outcomes in temporal lobe epilepsy (TLE). Methods: A total of 128 patients with TLE (63 females, 65 males; 25.07 ± 12.01 years) who underwent Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) imaging were enrolled. Patients were classified either as experiencing seizure recurrence (SZR) or seizure free (SZF) at least 1 year after surgery. Each individual's metabolic brain network was ascertained using the proposed JSSE method. We compared the similarity and difference in the JSSE network and its topological measurements between the two groups. The two groups were then classified by combining the information from connection and topological metrics, which was conducted by the multiple kernel support vector machine. The validation was performed using the nested leave-one-out cross-validation strategy to confirm the performance of the methods. Results: With a median follow-up of 33 months, 50% of patients achieved SZF. No relevant differences in clinical features were found between the two groups except age at onset. The proposed JSSE method showed marked degree reductions in IFGoperc.R, ROL. R, IPL. R, and SMG. R; and betweenness reductions in ORBsup.R and IOG. R; meanwhile, it found increases in the degree analysis of CAL. L and PCL. L, and in the betweenness analysis of PreCG.R, IOG. R, PoCG.R, PCL. L and PCL.R. Exploring consensus significant metabolic connections, we observed that the most involved metabolic motor networks were the INS-TPOmid.L, MTG. R-SMG. R, and MTG. R-IPL.R pathways between the two groups, and yielded another detailed individual pathological connectivity in the PHG. R-CAU.L, PHG. R-HIP.L, TPOmid.L-LING.R, TPOmid.L-DCG.R, MOG. R-MTG.R, MOG. R-ANG.R, and IPL. R-IFGoperc.L pathways. These aberrant functional network measures exhibited ideal classification performance in predicting SZF individuals from SZR ones at a sensitivity of 75.00%, a specificity of 92.79%, and an accuracy of 83.59%. Conclusion: The JSSE method indicator can identify abnormal brain networks in predicting an individual's long-term surgical outcome of TLE, thus potentially constituting a clinically applicable imaging biomarker. The results highlight the biological meaning of the estimated individual brain metabolic connectome.

The use of planned behavior theory in predicting cigarette smoking among Waterpipe smokers.

BACKGROUND: Waterpipe and cigarette smoking have been found to be associated with each other as cigarette smokers were more likely to be waterpipe users than non-cigarette smokers. Also, waterpipe smokers were likely to be former daily cigarette users. The aim of this study is to examine the likelihood of waterpipe use leading to cigarette use among current waterpipe users using theory of planned behavior. METHODS: Four hundred six current waterpipe smokers who initially had started tobacco use with the waterpipe were recruited from 15 waterpipe lounges in 2015. From a total of 70 waterpipe lounges in Riyadh, the 15 waterpipe lounges were selected randomly and participants were also selected randomly inside each waterpipe lounge based on the table or section number. The survey was developed using the Qualtrics Online Survey Software and participants completed a survey using iPad tablets. RESULTS: Cigarette smoking and intention to smoke cigarettes were predicted by attitude and perceived behavioral control. There was no direct effect of subjective norm on the cigarette use behavior, yet subjective norm had a statistically significant indirect effect on intentions through attitude and perceived behavioral control. CONCLUSIONS: The findings of this study could be useful in prevention/intervention programs aimed at reducing tobacco smoking behaviors among waterpipe users. Intervention programs might be directed at the attitude and perceived behavioral control by targeting underlying behavioral and control beliefs. The theory of planned behavior provided solid explanations of intention to use cigarettes among waterpipe smokers.

High expression of CPNE3 predicts adverse prognosis in acute myeloid leukemia.

CPNE3, a member of a Ca2+ -dependent phospholipid-binding protein family, was identified as a ligand of ERBB2 and has a more general role in carcinogenesis. Here, we identified the prognostic significance of CPNE3 expression in acute myeloid leukemia (AML) patients based on two datasets. In the first microarray dataset (n = 272), compared to low CPNE3 expression (CPNE3low ), high CPNE3 expression (CPNE3high ) was associated with adverse overall survival (OS, P < 0.001) and event-free survival (EFS, P < 0.001). In the second independent group of AML patients (TCGA dataset, n = 179), CPNE3high was also associated with adverse OS and EFS (OS, P = 0.01; EFS, P = 0.036). Notably, among CPNE3high patients, those received allogenic hematopoietic cell transplantation (HCT) had longer OS and EFS than those with chemotherapy alone (allogeneic HCT, n = 40 vs chemotherapy, n = 46), but treatment modules played an insignificant role in the survival of CPNE3low patients (allogeneic HCT, n = 32 vs chemotherapy, n = 54). These results indicated that CPNE3high is an independent, adverse prognostic factor in AML and might guide treatment decisions towards allogeneic HCT. To understand its inherent mechanisms, we investigated genome-wide gene/microRNA expression signatures and cell signaling pathways associated with CPNE3 expression. In conclusion, CPNE3high is an adverse prognostic biomarker for AML. Its effect may be attributed to the distinctive genome-wide gene/microRNA expression and related cell signaling pathways.

Dyspnea as an independent predictor of mortality.

BACKGROUND AND AIM: Dyspnea is a common and easily elicited presenting complaint in patients seen by physicians who evaluate and take care of chronic respiratory disorders. Although dyspnea is subjective and tends to increase with age or reduced lung function, it appears to be reproducible as a symptom and often signifies serious underlying disease. METHODS: Systematic review of longitudinal studies with dyspnea as the exposure and mortality as the outcome; age, smoking and lung function had to be controlled for to be included in the review. In addition, a minimum sample size at baseline of 500 subjects was required for each study. RESULTS: From over 3000 potential references, 10 longitudinal studies met all criteria and were included. All 10 studies suggested that dyspnea was an independent predictor of mortality with point estimates by odds ratio, rate ratio or hazard ratios ranging from 1.3 up to 2.9-fold greater than baseline. All 10 studies had actual or implied 95% confidence interval bands greater than the null value of one. CONCLUSION: Dyspnea, a symptom, predicts mortality and is a proxy for underlying diseases, most often of heart and lung. Therefore, chronic dyspnea needs to be evaluated as to etiology to allow for treatment to minimize morbidity and mortality when possible.

Escala de Blatchford modificada en la hemorragia digestiva alta no varicosa / Modified Blatchford Scale for non-variceal upper gastrointestinal bleeding

Introducción: las escalas pronósticas tienen una amplia utilización en el diagnóstico, tratamiento y seguimiento del paciente con hemorragia digestiva alta no varicosa. Objetivo: determinar la capacidad predictiva de los elementos clínicos componentes de la escala de Blatchford modificada para identificar a los pacientes con mayor probabilidad de presentar estigmas de sangrado activo o reciente, durante la endoscopia urgente.Métodos: estudio observacional, analítico y prospectivo. Se incluyeron todos los pacientes, 188, atendidos en el Centro de Urgencias del Hospital Militar Central Dr. Luis Díaz Soto, desde el 1ro. de enero al 31 de diciembre de 2012. Se realizó una estimación del riesgo por cada uno de los componentes de la escala. Se calculó el valor predictivo mediante curva ROC. Se determinaron la sensibilidad y especificidad del punto de corte igual a 1. Resultados: de los pacientes estudiados, 61 (32,4 por ciento) presentaron estigmas de sangrado activo o reciente. La mayor probabilidad de estigmas se encontró en casos con tensión arterial sistólica ≤ 90 mmHg (RR: 7,53; IC 95 por ciento 2,31-24,48; p= 0,001), frecuencia cardiaca ≥ 100 lat/min (RR: 5,49; IC 95 por ciento 2,78-10,83; p= 0,001) y hemoglobina ≤ 10 g/dL (RR: 4,39; IC 95 por ciento 2,17-8,89; p= 0,001). La capacidad predictiva de la escala de Blatchford fue buena (c= 0,729; IC 95 por ciento 0,652-0,807; p= 001). El punto de corte 1 mostró una sensibilidad de 11,81 por ciento y una especificidad de 98,36 por ciento. Conclusiones: se confirma el valor de la escala de Blatchford abreviada para predecir la presencia de estigmas de sangrado activo o reciente durante el estudio endoscópico en pacientes con sangrado digestivo alto no varicoso(AU)

Introduction: prognostic scales have a wide use in the diagnosis, treatment and monitoring patients with non-variceal upper gastrointestinal bleeding. Objective: determine the predictive ability of clinical component elements of Blatchford modified scale to identify patients most likely to have stigmata of active or recent bleeding during emergency endoscopy. Methods: observational, analytical and prospective study. All patients were included, 188, assisted in the emergency unit at Dr. Luis Díaz Soto Central Military Hospital, from January 1 to December 31, 2012. An estimate risk for each scale components was performed. The predictive value using ROC curve was calculated. The sensitivity and specificity of cut off 1 was determined. Results: 61 (32.4 percent) out of the patients studied had scars of active or recent bleeding. Stigmas are more likely found in cases with systolic blood pressure ≤ 90 mmHg (RR 7.53; 95 percent CI 2.31 to 24.48; p= 0.001), heart rate ≥ 100 beats min (RR 5.49; 95 percent CI 2.78 to 10.83; p= 0.001) and hemoglobin ≤ 10 g/dL (RR 4.39; 95 percent CI 2.17 to 8.89; p = 0.001). The predictive capacity of Blatchford scale was good (c= 0.729; 95 percent CI: 0.652 to 0.807; p= .001). The cut point 1 showed a sensitivity of 11.81 percent and a specificity of 98.36 percent. Conclusions: the value of the Blatchford scale is confirmed abbreviated to predict the presence of stigmata of active or recent bleeding during endoscopic study in patients with non-variceal upper gastrointestinal bleeding(AU)