Successful cancer immunotherapy requires a patient to mount an effective immune response against tumors; however, many cancers evade the body’s immune system. To investigate the basis for treatment failure, we examined spontaneous mouse models of hepatocellular carcinoma (HCC) with either an inflamed T cell–rich or a noninflamed T cell–deprived tumor microenvironment (TME). Our studies reveal that erythropoietin (EPO) secreted by tumor cells determines tumor immunotype. Tumor-derived EPO autonomously generates a noninflamed TME by interacting with its cognate receptor EPOR on tumor-associated macrophages (TAMs). EPO signaling prompts TAMs to become immunoregulatory through NRF2-mediated heme depletion. Removing either tumor-derived EPO or EPOR on TAMs leads to an inflamed TME and tumor regression independent of genotype, owing to augmented antitumor T cell immunity. Thus, the EPO/EPOR axis functions as an immunosuppressive switch for antitumor immunity.

Retinal degenerative diseases are frequently caused by the loss of retinal neural cells such as photoreceptors. Cell replacement is regarded as one of the most promising therapies. Multiple types of stem and somatic cells have been tested for photoreceptor conversion. However, current induction efficiencies are still low and the molecular mechanisms underlying reprogramming remain to be clarified. In this work, by combining treatment with small molecules, we directly reprogrammed human fetal retinal pigment epithelial (RPE) cells into chemically induced photoreceptor-like cells (CiPCs) in vitro. Bulk and single-cell RNA sequencing, as well as methylation sequencing, were performed to understand the transcriptional and epigenetic changes during CiPCs conversion. A multi-omics analysis showed that the direct reprogramming process partly resembled events of early retina development. We also found that the efficiency of CiPCs conversion from RPE is much better than that from human dermal fibroblasts (HDF). The small molecules effectively induced RPE cells into CiPCs via suppression of the epithelial-to-mesenchymal transition (EMT). Among the signaling pathways involved in CiPCs conversion, glutamate receptor activation is prominent. In summary, RPE cells can be efficiently reprogrammed into photoreceptor-like cells through defined pharmacological modulations, providing a useful cell source for photoreceptor generation in cell replacement therapy for retinal degenerative diseases.

To test the hypothesis that lung shunt fraction (LSF) in 90Y radioembolization of the liver can be modeled for clinical relevance and risk on the basis of cancer type, tumor size, and imaging modality. This was a retrospective analysis of 354 consecutive cases from a 34-month period at a single institution. Cancer type (HCC vs. non-HCC) and maximum tumor size were tracked. LSF was computed from planar imaging (LSF_planar) and three MAA-SPECT/CT methods with different corrections at the lung/liver boundary (LSF_Full, LSF_2cm, LSF_Left). Five tumor categories were analyzed: 1) HCC8 cm, 4) cases with TIPS/vascular invasion, 5) non-HCC. Median LSF was significantly different (all p5% and >10%, respectively, but only 7% and 2% using LSF_2cm. LSF was lower for HCC8 cm (p≤0.003). In the HCC20% or LSF_2cm>5%. Cases with TIPS/vascular invasion maintained the highest median LSF (LSF_planar: 9.0%, LSF_2cm: 2.8%) and the highest percentages of cases with LSF>10% and >20% across all methods. Despite significant variations with imaging modality and correction methods, consistent trends in LSF magnitude with cancer type and tumor size were still uncovered. The relative risk of observing clinically relevant LSF can be modeled for different liver tumor categories in 90Y radioembolization.

Background/Objectives: Systematic quality review of ultrasound exams is recommended to ensure accurate diagnosis. Our primary objectives were to develop a quantitative method for quality review of estimated fetal weight (EFW) and to assess the accuracy of EFW for an entire practice and for individual personnel. A secondary objective was to evaluate the accuracy of fetal sex determination. Methods: This is a retrospective cohort study. Eligible ultrasound exams included singleton pregnancies with live birth and known birth weight (BW). A published method was used to predict BW from EFW for exams with ultrasound-to-delivery intervals of up to 12 weeks. Mean error and median absolute error (AE) were compared between different personnel. Image audits were performed for exams with AE > 30% and exams with reported fetal sex different than newborn sex. Results: We analyzed 1938 exams from 890 patients. In the last exam before birth, the median AE was 5.9%, and the predicted BW was within ±20% of the actual BW in 97.2% of patients. AE was >30% in 28 exams (1.4%); image audit found correct caliper placement in all 28. Only two patients (0.2%) had AE > 30% on the last exam before birth. One sonographer systematically over-measured head and abdominal circumferences, leading to EFWs that were overestimated. Reported fetal sex differed from newborn sex in seven exams (0.4%) and five patients (0.6%). Images in four of these patients were annotated with the correct fetal sex, but a clerical error was made in the report. In one patient, an unclear image was labeled “probably female”, but the newborn was male. Conclusions: The accuracy of EFW in this practice was similar to literature reports. The quantitative analysis identified a sonographer with outlier measurements. Time-consuming image audits could be focused on a small number of exams with large errors. We suggest some enhancements to ultrasound reporting software that may help to reduce clerical errors. We provide tools to help other practices perform similar quality reviews.

Background/Objectives: Systematic quality review of ultrasound exams is recommended to assure accurate diagnosis. Our primary objectives were to develop a quantitative method for quality review of estimated fetal weight (EFW) and to assess accuracy of EFW for an entire practice and for individual personnel. A secondary objective was to evaluate accuracy of fetal sex determination. Methods: This is a retrospective cohort study. Eligible ultrasound exams included singleton pregnancies with live birth and known birth weight (BW). A published method was used to predict BW from EFW for exams with ultrasound-to-delivery intervals up to 12 weeks. Mean error and median absolute error (AE) were compared between different personnel. Image audits were performed for exams with AE>30% and exams with reported fetal sex different than newborn sex. Results: We analyzed 1,938 exams from 890 patients. In the last exam before birth, median AE was 5.9% and predicted BW was within ±20% of actual BW in 97.2% of patients. AE was >30% in 28 exams (1.4%); image audit found correct caliper placement in all 28. Only 2 patients (0.2%) had AE>30% on the last exam before birth. One sonographer systematically over-measured head and abdominal circumferences, leading to EFWs that were overestimated. Reported fetal sex differed from newborn sex in 7 exams (0.4%), 5 patients (0.6%). Images in 4 of these patients were annotated with correct fetal sex but a clerical error was made in the report. In 1 patient, the unclear image was labeled “probably female” but the newborn was male. Conclusions: Accuracy of EFW in this practice was similar to literature reports. Quantitative analysis identified a sonographer with outlier measurements. Time-consuming image audits could be focused on a small number of exams with large errors. We suggest some enhancements to ultrasound reporting software that may help to reduce clerical errors. We provide tools to help other practices perform similar quality reviews.