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Objective: To determine the diagnostic accuracy of Umbilical Artery and Middle Cerebral Artery Doppler in detection of intrauterine growth restriction among pregnant women. Study Design: Descriptive Cross-Sectional Study. Place and Duration of Study: The Department of Gynecology and Obstetrics, Fauji Foundation Hospital, Rawalpindi, over a period of six months from May 2019 to October 2019. Materials and Methods: Study participants were 159 pregnant women presented to antenatal clinics. The inclusion criteria were gestational age more than 30 weeks with singleton pregnancies, sure last menstrual period, period of gestation confirmed by dating ultrasonography, small for dates or clinical suspicious of intrauterine growth restriction, and women who provided informed consent. Doppler scan was performed in all those women. Results: Mean age of all the enrolled women was 26.8 (± 6.6) years. Out of 159 women, 32 (20 percent) were nulliparous. On Doppler scan, 29 (18.2 percent) women had intrauterine growth restriction. The mean gestational age at the time of delivery was 35.3 (± 0.95) weeks. Caesarean section was performed in 131 (82.5 percent) of the deliveries. At birth, 24 (15.1 percent) had intrauterine growth restriction. The sensitivity, specificity, positive and negative predictive values of Doppler scan to detect intrauterine growth restriction were 83.3 percent, 93.3 percent, 69.0 percent, and 96.9 percent respectively. The diagnostic accuracy of Doppler scan was 91.8 percent. Conclusions: Our study shows a high sensitivity and specificity of Doppler scan in detecting intrauterine growth restriction.

BackgroundApproximately 70% of all patients with myelodysplastic syndrome (MDS) present with lower-risk disease. Some of these patients will initially respond to treatment with growth factors to improve anemia but will eventually cease to respond, while others will be resistant to growth factor therapy. Eventually, all lower-risk MDS patients require multiple transfusions and long-term therapy. While some patients may respond briefly to hypomethylating agents or lenalidomide, the majority will not, and new therapeutic options are needed for these lower-risk patients. Our previous clinical trials with ezatiostat (ezatiostat hydrochloride, Telentra®, TLK199), a glutathione S-transferase P1-1 inhibitor in clinical development for the treatment of low- to intermediate-risk MDS, have shown significant clinical activity, including multilineage responses as well as durable red-blood-cell transfusion independence. It would be of significant clinical benefit to be able to identify patients most likely to respond to ezatiostat before therapy is initiated. We have previously shown that by using gene expression profiling and grouping by response, it is possible to construct a predictive score that indicates the likelihood that patients without deletion 5q will respond to lenalidomide. The success of that study was based in part on the fact that the profile for response was linked to the biology of the disease.MethodsRNA was available on 30 patients enrolled in the trial and analyzed for gene expression on the Illumina HT12v4 whole genome array according to the manufacturer's protocol. Gene marker analysis was performed. The selection of genes associated with the responders (R) vs. non-responders (NR) phenotype was obtained using a normalized and rescaled mutual information score (NMI).ConclusionsWe have shown that an ezatiostat response profile contains two miRNAs that regulate expression of genes known to be implicated in MDS disease pathology. Remarkably, pathway analysis of the response profile revealed that the genes comprising the jun-N-terminal kinase/c-Jun molecular pathway, which is known to be activated by ezatiostat, are under-expressed in patients who respond and over-expressed in patients who were non-responders to the drug, suggesting that both the biology of the disease and the molecular mechanism of action of the drug are positively correlated.

Simple Summary: This study explored a potentially significant player in the spread of metastatic cancer: "hybrid cells" (HCs) combining features of both epithelial (common in tissues) and immune cells (such as macrophages). HCs were found in more than one type of tumor (THC) and showed a unique transcriptional profile including the activation of functional pathways, potentially explaining their mobility, dissemination into circulation, and metastatic progression. Normal healthy tissue also showed hybrid cells (NHC), but they were rare and could be easily distinguished from THCs based on their gene expression profile. The study also developed a way to identify HCs in large datasets generated at the single-cell level, paving the way for further research on their function and as potential therapeutic targets. Metastatic cancer is a leading cause of death in cancer patients worldwide. While circulating hybrid cells (CHCs) are implicated in metastatic spread, studies documenting their tissue origin remain sparse, with limited candidate approaches using one–two markers. Utilizing high-throughput single-cell and spatial transcriptomics, we identified tumor hybrid cells (THCs) co-expressing epithelial and macrophage markers and expressing a distinct transcriptome. Rarely, normal tissue showed these cells (NHCs), but their transcriptome was easily distinguishable from THCs. THCs with unique transcriptomes were observed in breast and colon cancers, suggesting this to be a generalizable phenomenon across cancer types. This study establishes a framework for HC identification in large datasets, providing compelling evidence for their tissue residence and offering comprehensive transcriptomic characterization. Furthermore, it sheds light on their differential function and identifies pathways that could explain their newly acquired invasive capabilities. THCs should be considered as potential therapeutic targets. [ABSTRACT FROM AUTHOR]