Group SCAD Regression Analysis for Microarray Time Course Gene Expression Data

Since many important biological systems or processes are dynamic systems, it is important to study the gene expression patterns over time in a genomic scale in order to capture the dynamic behavior of gene expression. Microarray technologies have made it possible to measure the gene expression levels of essentially all the genes during a given biological process. In order to determine the transcriptional factors involved in gene regulation during a given biological process, we propose to develop a functional response model with varying coefficients in order to model the transcriptional effects on gene expression levels and to develop a group smoothly clipped absolute deviation (SCAD) regression procedure for selecting the transcriptional factors with varying coefficients that are involved in gene regulation during a biological process. Simulation studies indicated that such a procedure is quite effective in selecting the relevant variables with time-varying coefficients and in estimating the coefficients. Application to the yeast cell cycle microarray time course gene expression data set identified 19 of the 21 known transcriptional factors related to the cell cycle process. In addition, we have identified another 52 TFs that also have periodic transcriptional effects on gene expression during the cell cycle process. Compared to simple linear regression analysis at each time point, our procedure identified more known cell cycle related transcriptional factors. The proposed group SCAD regression procedure is very effective for identifying variables with time-varying coefficients, in particular, for identifying the transcriptional factors that are related to gene expression over time. By identifying the transcriptional factors that are related to gene expression variations over time, the procedure can potentially provide more insight into the gene regulatory networks

Microbial Population Changes and Their Relationship with Human Health and Disease

Specific microbial profiles and changes in intestinal microbiota have been widely demonstrated to be associated with the pathogenesis of a number of extra-intestinal (obesity and metabolic syndrome) and intestinal (inflammatory bowel disease) diseases as well as other metabolic disorders, such as non-alcoholic fatty liver disease and type 2 diabetes. Thus, maintaining a healthy gut ecosystem could aid in avoiding the early onset and development of these diseases. Furthermore, it is mandatory to evaluate the alterations in the microbiota associated with pathophysiological conditions and how to counteract them to restore intestinal homeostasis. This review highlights and critically discusses recent literature focused on identifying changes in and developing gut microbiota-targeted interventions (probiotics, prebiotics, diet, and fecal microbiota transplantation, among others) for the above-mentioned pathologies. We also discuss future directions and promising approaches to counteract unhealthy alterations in the gut microbiota. Altogether, we conclude that research in this field is currently in its infancy, which may be due to the large number of factors that can elicit such alterations, the variety of related pathologies, and the heterogeneity of the population involved. Further research on the effects of probiotics, prebiotics, or fecal transplantations on the composition of the human gut microbiome is necessary.Ongoing research is funded by grant PI-0538-2017, Junta de Andalucía, Spain (to L.F.)

Optimal Blood Pressure Control Target for Older Patients with Hypertension: A Systematic Review and Meta-Analysis

Objective: This study evaluated the optimal systolic blood pressure (SBP) target for older patients with hypertension.Method: A Bayesian network meta-analysis was conducted. The risk of bias of the included studies was assessed by using a modified version of the Cochrane risk of bias. The trial outcomes comprised the following clinical events: major adverse cardiovascular events (MACE), cardiovascular mortality, all-cause mortality, myocardial infarction, heart failure and stroke.Results: A total of six trials were included. We reclassified all treatment therapies into three conditions according to the final achieved SBP after intervention (<130 mmHg, 130–139 mmHg and ≥140 mmHg). Our results demonstrated that anti-hypertensive treatment with an SBP target <130 mmHg, compared with treatment with an SBP target ≥140 mmHg, significantly decreased the incidence of MACE (OR 0.43, 95%CI 0.19–0.76), but no statistical difference was found in other comparisons. Although the results showed a trend toward more intensive anti-hypertension therapy having better effects on preventing cardiovascular mortality, all-cause mortality, myocardial infarction, heart failure, and stroke, no significant differences were found among groups.Conclusions: Our meta-analysis suggested that SBP <130 mmHg might be the optimal BP control target for patients ≥60 years of age; however, further evidence is required to support our findings

Prediction of 1p/19q Codeletion in Diffuse Glioma Patients Using Pre-operative Multiparametric Magnetic Resonance Imaging

Kim D, Wang N, Ravikumar V, Raghuram DR, Li J, Patel A, Wendt RE III, Rao G and Rao A (2019) Prediction of 1p/19q Codeletion in Diffuse Glioma Patients Using Pre-operative Multiparametric Magnetic Resonance Imaging. Front. Comput. Neurosci. 13:52. doi: 10.3389/fncom.2019.00052https://openworks.mdanderson.org/mdacc_imgphys_pubs/1005/thumbnail.jp

Cerebral Blood Volume Changes During Radiotherapy May Predict Pseudoprogression versus Disease Progression for Patients with High Grade Glioma

https://openworks.mdanderson.org/sumexp21/1040/thumbnail.jp

Cell-free circulating mitochondrial DNA content and risk of hepatocellular carcinoma in patients with chronic HBV infection.

Recent studies have demonstrated a potential link between circulating cell-free mitochondrial DNA (mtDNA) content and cancers. However, there is no study evaluating the association between circulating mtDNA as a non-invasive marker of hepatocellular carcinoma (HCC) risk. We conducted a nested case-control study to determine circulating mtDNA content in serum samples from 116 HBV-related HCC cases and 232 frequency-matched cancer-free HBV controls, and evaluate the retrospective association between mtDNA content and HCC risk using logistic regression and their temporal relationship using a mixed effects model. HCC cases had significantly lower circulating mtDNA content than controls (1.06 versus 2.47, P = 1.7 × 10(-5)). Compared to HBV patients with higher mtDNA content, those with lower mtDNA content had a significantly increased risk of HCC with an odds ratio (OR) of 2.19 (95% confidence interval [CI] 1.28-3.72, P = 0.004). Quartile analyses revealed a significant dose-dependent effect (Ptrend = 0.001) for this association. In a pilot longitudinal sub-cohort of 14 matched cases-control pairs, we observed a trend of dramatically decreased mtDNA content in cases and slightly decreased mtDNA content in controls, with a significant interaction of case-control status with time (Pinteraction = 0.049). Our findings suggest that circulating mtDNA is a potential novel non-invasive biomarker of HCC risk in HBV patients

Incidence and Impact of Takotsubo Syndrome in Hospitalized Patients With COVID-19

Background Takotsubo syndrome has been reported in patients with COVID-19, although minimal data are available. This investigation assessed the incidence and impact of takotsubo syndrome on patients hospitalized with COVID-19. Methods A retrospective cohort study was conducted using International Statistical Classification of Diseases, Tenth Revision, codes to identify patients with a primary diagnosis of COVID-19 with or without takotsubo syndrome in the National Inpatient Sample 2020 database. Outcomes between groups were compared after propensity score matching for patient and hospital demographics and comorbidities. Results A total of 211,448 patients with a primary diagnosis of COVID-19 were identified. Of these, 171 (0.08%) had a secondary diagnosis of takotsubo syndrome. Before matching, patients with COVID-19 and takotsubo syndrome, compared with patients without takotsubo syndrome, were older (68.95 vs 64.26 years; P < .001); more likely to be female (64.3% vs 47.2%; P < .001); and more likely to have anxiety (24.6% vs 12.8%; P < .001), depression (17.5% vs 11.4%; P = .02), and chronic obstructive pulmonary disease (24.6% vs 14.7%; P < .001). The takotsubo syndrome group had worse outcomes than the non–takotsubo syndrome group for death (30.4% vs 11.1%), cardiac arrest (7.6% vs 2.1%), cardiogenic shock (12.9% vs 0.4%), length of hospital stay (10.7 vs 7.5 days), and total charges ($152,685 vs$78,468) (all P < .001). After matching and compared with the non–takotsubo syndrome group (n = 508), the takotsubo syndrome group (n = 170) had a higher incidence of inpatient mortality (30% vs 14%; P < .001), cardiac arrest (7.6% vs 2.8%; P = .009), and cardiogenic shock (12.4% vs 0.4%; P < .001); a longer hospital stay (10.7 vs 7.6 days; P < .001); and higher total charges ($152,943 vs$79,523; P < .001). Conclusion Takotsubo syndrome is a rare but severe in-hospital complication in patients with COVID-19

Decreased Cerebral Flow Velocities from General Anesthesia are Not Associated with Cerebral Hyperperfusion Syndrome

Objective: General anesthesia (GA) can decrease cerebral flow velocities and predispose patients to cerebral hyperperfusion syndrome (CHS) and other perioperative adverse events after carotid endarterectomy (CEA). The aim of this study was to investigate whether decreased pre-operative flow velocity is associated with an increased risk of CHS and perioperative cerebral infarct, and to further identify risk factors if there is any. Methods: We retrospectively evaluated 920 consecutive patients who received CEA from 2010 to 2020 at a major academic hospital in China. Middle cerebral artery (MCA) blood flow velocities were measured before and after induction of the GA by transcranial Doppler (TCD). Patients were classified into two groups: the NORMAL group if flow velocity decreased&lt;30% and the LOW group if flow velocity decreased ≥30%. The ultrasonographic diagnostic criterion of CHS was defined as the 100% increase in flow velocity by TCD from the baseline to post-CEA. The occurrence of CHS, perioperative cerebral infarction was compared between the two groups. Results: 399 (43.4%) were classified as LOW measurement, and 521 (56.6%) patients were classified as NORMAL measurement. In the LOW group, there were more patients with diabetes, fewer patients with ipsilateral ICA severe stenosis and the opening of anterior/posterior communicating artery. Although the occurrence of CHS per ultrasonography criteria was higher in the LOW group (21.3% vs 15.7%, P = 0.03), the occurrence of CHS per clinical criteria (3.2%, vs 2.1%, P = 0.28) or the perioperative cerebral infarct between the two groups (5.8% vs 5.0%, P = 0.60) is equivalent. Conclusion: Patients with decreased flow velocities post-GA were more likely to meet the ultrasonography criteria for CHS, but they are not at risk of developing clinical CHS or perioperative cerebral infarct

Targeting immunosuppressive classical monocytes prevents immunotherapy resistance

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