Interventions to increase colorectal cancer screening adherence in low-income settings within the United States: A systematic review and meta-analysis.

The USPS Task Force recommends screening for colorectal cancer (CRC) in adults aged 45-75. Screening rates are low in underserved populations. We conducted a systematic review of interventions to increase CRC screening adherence in low-income settings in US. We included randomized control trials of CRC screening interventions conducted in low-income settings in the US. Outcome was CRC screening adherence. Random-effects meta-analysis of relative risks was conducted for the effectiveness of CRC screening interventions. We identified 46 studies that met inclusion criteria. Interventions were grouped into four categories: mailed outreach, patient navigation, patient education, and types of reminders. Mailed outreach with enclosed fecal immunohistochemical test (FIT) (RR 2.20, 95% CI 1.74, 2.78), guaiac based fecal occult blood test (gFOBT) (RR 4.34, 95% CI 1.29, 14.67), and without FIT/gFOBT (RR 1.80, 95% CI 1.15, 2.82) all significantly increased CRC screening, as did non-individualized education (RR 1.44, 95% CI 1.07, 1.94) and patient navigation (RR 1.62, 95% CI 1.29, 2.02). Mailed outreach with an incentive (RR 0.97, 95% CI 0.81, 1.16) and individualized education (RR 1.07, 95% CI 0.83, 1.38) did not significantly improve screening adherence. Telephone reminders are slightly more effective than reminder letters (RR 1.16, 95% CI 1.02, 1.33), but there is no difference between personal or automated phone calls (RR 1.17, 95% CI 0.74, 1.84). Mailed outreach and patient navigation are the most effective strategies to improve colorectal cancer screening in low-income populations. There was significant heterogeneity between studies, likely due to differences in intervention design, screening tests, and follow-up.

Functional human gastrointestinal organoids can be engineered from three primary germ layers derived separately from pluripotent stem cells.

Human organoid model systems lack important cell types that, in the embryo, are incorporated into organ tissues during development. We developed an organoid assembly approach starting with cells from the three primary germ layers-enteric neuroglial, mesenchymal, and epithelial precursors-that were derived separately from human pluripotent stem cells (PSCs). From these three cell types, we generated human antral and fundic gastric tissue containing differentiated glands surrounded by layers of smooth muscle containing functional enteric neurons that controlled contractions of the engineered antral tissue. Using this experimental system, we show that human enteric neural crest cells (ENCCs) promote mesenchyme development and glandular morphogenesis of antral stomach organoids. Moreover, ENCCs can act directly on the foregut to promote a posterior fate, resulting in organoids with a Brunner's gland phenotype. Thus, germ layer components that are derived separately from PSCs can be used for tissue engineering to generate complex human organoids.

Accuracy of Signs, Symptoms, and Hematologic Parameters for the Diagnosis of Infectious Mononucleosis: A Systematic Review and Meta-Analysis.

BACKGROUND: The accuracy of individual symptoms, signs, and several easily obtainable hematologic parameters for diagnosing infectious mononucleosis (IM) still needs to be confirmed. Improving the diagnosis of IM based on the clinical findings could prompt physicians to identify better which patients need a diagnostic test for IM. This study performed a systematic review to determine the accuracy of symptoms, signs, and hematologic parameters in patients with suspected IM that used heterophile antibody test or viral capsid antigen tests as the reference standard. METHODS: The PubMed database was searched for all relevant articles. Two reviewers reviewed all studies in parallel and assessed the quality of the selected studies using the quality assessment of diagnostic accuracy studies 2 (QUADAS-2) criteria. The pooled measures of diagnostic performance were calculated by bivariate meta-analysis for each clinical finding, which included sensitivity, specificity, likelihood ratios, the diagnostic odds ratios, and the area under the receiver operating characteristic curve. RESULTS: Seventeen studies were included in our final analysis. The prevalence of IM ranged from 2.1% to 80% among prospective cohort studies. The presence of splenomegaly (positive likelihood ratio [LR+], 2.39; 95% confidence interval [CI], 1.11-5.51), palatal petechiae (LR+, 1.32-11.40), posterior cervical lymphadenopathy (LR+, 3.16; 95% CI, 1.45-5.20), and axillary or inguinal cervical lymphadenopathy (LR+, 3.05; 95 CI, 1.85-4.70) were moderately useful for ruling in IM. The most helpful hematologic parameters for ruling in IM include lymphocytes greater than 4 × 109/L and greater than 40% to 50%, or atypical lymphocytes greater than 40%. A combination of lymphocytes greater than 50% and atypical lymphocytes greater than 10% (LR+, 50.40; 95% CI, 8.43-162) was also found to be helpful to rule in disease. Most of the clinical findings have limited diagnostic value in ruling out the disease when absent. CONCLUSIONS: Although most symptoms and signs were unhelpful, the likelihood of IM is appreciably increased by several examination findings. Hematologic parameters were more accurate than symptoms and signs. Since most clinical findings have limited diagnostic value in ruling out the disease, physicians should not rely on the absence of any individual symptom or clinical sign for ruling out IM.

Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis.

Visceral organs, such as the lungs, stomach and liver, are derived from the fetal foregut through a series of inductive interactions between the definitive endoderm (DE) and the surrounding splanchnic mesoderm (SM). While DE patterning is fairly well studied, the paracrine signaling controlling SM regionalization and how this is coordinated with epithelial identity is obscure. Here, we use single cell transcriptomics to generate a high-resolution cell state map of the embryonic mouse foregut. This identifies a diversity of SM cell types that develop in close register with the organ-specific epithelium. We infer a spatiotemporal signaling network of endoderm-mesoderm interactions that orchestrate foregut organogenesis. We validate key predictions with mouse genetics, showing the importance of endoderm-derived signals in mesoderm patterning. Finally, leveraging these signaling interactions, we generate different SM subtypes from human pluripotent stem cells (hPSCs), which previously have been elusive. The single cell data can be explored at: https://research.cchmc.org/ZornLab-singlecell .