Trends and Correlates of Breakthrough Infections With SARS-CoV-2

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant has been hypothesized to decrease the efficacy of COVID-19 vaccines. Factors associated with infections with SARS-CoV-2 after vaccination are unknown. In this observational cohort study, we examined two groups in Harris County, Texas: (1) individuals with positive Nucleic Acid Amplification test between 12/14/2020 and 9/30/2021 and (2) the subset of individuals fully vaccinated in the same time period. Infected individuals were classified as a breakthrough if their infection occurred 14 days after their vaccination had been completed. Among fully vaccinated individuals, demographic and vaccine factors associated with breakthrough infections were assessed. Of 146,731 positive SARS-CoV-2 tests, 7.5% were breakthrough infections. Correlates of breakthrough infection included young adult age, female, White race, and receiving the Janssen vaccine, after adjustments including the amount of community spread at the time of infection. Vaccines remained effective in decreasing the probability of testing positive for SARS-CoV-2. The data indicate that increased vaccine booster uptake would help decrease new infections

Case Growth analysis to inform Local Response to Covid-19 Epidemic in a Diverse Us Community

Early detection of new outbreak waves is critical for effective and sustained response to the COVID-19 pandemic. We conducted a growth rate analysis using local community and inpatient records from seven hospital systems to characterize distinct phases in SARS-CoV-2 outbreak waves in the Greater Houston area. We determined the transition times from rapid spread of infection in the community to surge in the number of inpatients in local hospitals. We identified 193,237 residents who tested positive for SARS-CoV-2 via molecular testing from April 8, 2020 to June 30, 2021, and 30,031 residents admitted within local healthcare institutions with a positive SARS-CoV-2 test, including emergency cases. We detected two distinct COVID-19 waves: May 12, 2020-September 6, 2020 and September 27, 2020-May 15, 2021; each encompassed four growth phases: lagging, exponential/rapid growth, deceleration, and stationary/linear. Our findings showed that, during early stages of the pandemic, the surge in the number of daily cases in the community preceded that of inpatients admitted to local hospitals by 12-36 days. Rapid decline in hospitalized cases was an early indicator of transition to deceleration in the community. Our real-time analysis informed local pandemic response in one of the largest U.S. metropolitan areas, providing an operationalized framework to support robust real-world surveillance for outbreak preparedness

Inter-observer variability of radiologists for Cambridge classification of chronic pancreatitis using CT and MRCP: results from a large multi-center study

Purpose: Determine inter-observer variability among radiologists in assigning Cambridge Classification (CC) of chronic pancreatitis (CP) based on magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) and contrast-enhanced CT (CECT). Methods: Among 422 eligible subjects enrolled into the PROCEED study between 6/2017 and 8/2018, 39 were selected randomly for this study (chronic abdominal pain (n = 8; CC of 0), suspected CP (n = 22; CC of 0, 1 or 2) or definite CP (n = 9; CC of 3 or 4). Each imaging was scored by the local radiologist (LRs) and three of five central radiologists (CRs) at other consortium sites. The CRs were blinded to clinical data and site information of the participants. We compared the CC score assigned by the LR with the consensus CC score assigned by the CRs. The weighted kappa statistic (K) was used to estimate the inter-observer agreement. Results: For the majority of subjects (34/39), the group assignment by LR agreed with the consensus composite CT/MRCP score by the CRs (concordance ranging from 75 to 89% depending on cohort group). There was moderate agreement (63% and 67% agreed, respectively) between CRs and LRs in both the CT score (weighted Kappa [95% CI] = 0.56 [0.34, 0.78]; p-value = 0.57) and the MR score (weighted Kappa [95% CI] = 0.68 [0.49, 0.86]; p-value = 0.72). The composite CT/MR score showed moderate agreement (weighted Kappa [95% CI] = 0.62 [0.43, 0.81]; p-value = 0.80). Conclusion: There is a high degree of concordance among radiologists for assignment of CC using MRI and CT

Identification and Characterization of Nucleolin as a COUP-TFII Coactivator of Retinoic Acid Receptor β Transcription in Breast Cancer Cells

The orphan nuclear receptor COUP-TFII plays an undefined role in breast cancer. Previously we reported lower COUP-TFII expression in tamoxifen/endocrine-resistant versus sensitive breast cancer cell lines. The identification of COUP-TFII-interacting proteins will help to elucidate its mechanism of action as a transcriptional regulator in breast cancer.FLAG-affinity purification and multidimensional protein identification technology (MudPIT) identified nucleolin among the proteins interacting with COUP-TFII in MCF-7 tamoxifen-sensitive breast cancer cells. Interaction of COUP-TFII and nucleolin was confirmed by coimmunoprecipitation of endogenous proteins in MCF-7 and T47D breast cancer cells. In vitro studies revealed that COUP-TFII interacts with the C-terminal arginine-glycine repeat (RGG) domain of nucleolin. Functional interaction between COUP-TFII and nucleolin was indicated by studies showing that siRNA knockdown of nucleolin and an oligonucleotide aptamer that targets nucleolin, AS1411, inhibited endogenous COUP-TFII-stimulated RARB2 expression in MCF-7 and T47D cells. Chromatin immunoprecipitation revealed COUP-TFII occupancy of the RARB2 promoter was increased by all-trans retinoic acid (atRA). RARβ2 regulated gene RRIG1 was increased by atRA and COUP-TFII transfection and inhibited by siCOUP-TFII. Immunohistochemical staining of breast tumor microarrays showed nuclear COUP-TFII and nucleolin staining was correlated in invasive ductal carcinomas. COUP-TFII staining correlated with ERα, SRC-1, AIB1, Pea3, MMP2, and phospho-Src and was reduced with increased tumor grade.Our data indicate that nucleolin plays a coregulatory role in transcriptional regulation of the tumor suppressor RARB2 by COUP-TFII

Use of multiple time points to model parotid differentiation

AbstractIn order to understand the process of terminal differentiation in salivary acinar cells, mRNA and microRNA expression was measured across the month long process of differentiation in the parotid gland of the rat. Acinar cells were isolated at either nine time points (mRNA) or four time points (microRNA) in triplicate using laser capture microdissection (LCM). One of the values of this dataset comes from the high quality RNA (RIN>7) that was used in this study, which can be prohibitively difficult to obtain from such an RNaseI-rich tissue. Global mRNA expression was measured by rat genome microarray hybridization (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65586), and expression of microRNAs by qPCR array (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65324). Comparing expression at different ages, 2656 mRNAs and 64 microRNAs were identified as differentially expressed. Because mRNA expression was sampled at many time points, clustering and regression analysis were able to identify dynamic expression patterns that had not been implicated in acinar differentiation before. Integration of the two datasets allowed the identification of microRNA target genes, and a gene regulatory network. Bioinformatics R code and additional details of experimental methods and data analysis are provided

MicroRNA gene expression signatures in the developing neural tube

BACKGROUND: Neurulation requires precise, spatio-temporal expression of numerous genes and coordinated interaction of signal transduction and gene regulatory networks, disruption of which may contribute to the etiology of neural tube (NT) defects. MicroRNAs are key modulators of cell and tissue differentiation. In order to define potential roles of miRNAs in development of the murine NT, miRNA microarray analysis was conducted to establish expression profiles, and identify miRNA target genes and functional gene networks. METHODS: miRNA expression profiles in murine embryonic NTs derived from gestational days 8.5, 9.0 and 9.5 were defined and compared utilizing miRXplore(™) microarrays from Miltenyi Biotech GmbH. Gene expression changes were verified by TaqMan(™) quantitative Real-Time PCR. clValid R package and the UPGMA (hierarchical) clustering method were utilized for cluster analysis of the microarray data. Functional associations among selected miRNAs were examined via Ingenuity Pathway Analysis. RESULTS: miRXplore(™) chips enabled examination of 609 murine miRNAs. Expression of approximately 12% of these was detected in murine embryonic NTs. Clustering analysis revealed several developmentally regulated expression clusters among these expressed genes. Target analysis of differentially expressed miRNAs enabled identification of numerous target genes associated with cellular processes essential for normal NT development. Utilization of Ingenuity Pathway Analysis revealed interactive biological networks which connected differentially expressed miRNAs with their target genes, and highlighted functional relationships. CONCLUSIONS: The present study defined unique gene expression signatures of a range of miRNAs in the developing NT during the critical period of NT morphogenesis. Analysis of miRNA target genes and gene interaction pathways revealed that specific miRNAs may direct expression of numerous genes encoding proteins which have been shown to be indispensable for normal neurulation. This study is the first to identify miRNA expression profiles and their potential regulatory networks in the developing mammalian NT

Supplementary Material for: Cx43-Delivered miR-181b Negatively Regulates Sirt1/FOXO3a Signalling Pathway-Mediated Apoptosis on Intestinal Injury in Sepsis

Introduction: Gap junctions can transmit signals between cells, including miRNAs, leading to the amplification of adjacent cell damage. No previous study has addressed gap junctions and miRNAs in sepsis because the internal mechanism of sepsis-induced intestinal injury is complex. Therefore, we studied the relationship between connexin43 (Cx43) and miR-181b and provided a research direction for further study of sepsis. Methods: A mouse caecal ligation and puncture method was used to construct a mouse sepsis model. Firstly, damage to intestinal tissues at different time points was analysed. The levels of Cx43, miR-181b, Sirt1, and FOXO3a in intestinal tissues and the transcription and translation of the apoptosis-related genes Bim and puma, which are downstream of FOXO3a were analysed. Secondly, the effect of Cx43 levels on miR-181b and Sirt1/FOXO3a signalling pathway activity was explored by using the Cx43 inhibitor heptanol. Finally, luciferase assays were used to determine miR-181b binding to the predicted target sequence. Results: The results show that during sepsis, intestinal injury becomes increasingly worse with time, and the expression of Cx43 and miR-181b increase. In addition, we found that heptanol could significantly reduce intestinal injury. This finding indicates that inhibiting Cx43 regulates the transfer of miR-181b between adjacent cells, thereby reducing the activity of the Sirt1/FOXO3a signalling pathway and reducing the degree of intestinal injury during sepsis. Conclusions: In sepsis, the enhancement of Cx43 gap junctions leads to an increase in miR-181b intercellular transfer, affects the downstream SIRT1/FOXO3a signalling pathway and causes cell and tissue damage