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Objectives The objective of this study was to evaluate SOX17, a transcription factor from the Sry high-mobility group–related box superfamily, as a diagnostic marker to determine site of origin using both whole-tissue sections and tissue microarrays (TMAs). Methods SOX17 immunohistochemistry was performed on gynecologic and nongynecologic tissues (N = 1004) using whole-tissue sections and both internally constructed and commercially available TMAs. SOX17 nuclear reactivity was scored as positive or negative on the whole-tissue sections and using the semiquantitative H score method on TMAs. Results Using both whole-tissue sections and TMAs, SOX17 was positive in 94% (n = 155) of endometrial tumors and 96% (n = 242) of ovarian tumors. All breast cases (n = 241) and vulvar/cervical squamous cell carcinomas (n = 150) were negative. Among 1004 tumors from 20 sites, the only organs with positive tumors were ovary, uterus, and testis. Conclusions SOX17 is a sensitive and specific marker for gynecologic origin in the tissues tested and may be a valuable adjunct to PAX8 and other commonly used markers to confirm endometrial or ovarian origin. SOX17 expression is lower in mucinous tumors, endocervical adenocarcinoma, high-grade neuroendocrine tumors, and undifferentiated/dedifferentiated endometrial carcinoma. [ABSTRACT FROM AUTHOR]

Introduction: Non‐Invasive Prenatal Screening (NIPS) is a useful screening method for common aneuploidies that can occur in pregnancies. It yields high sensitivities and specificities for the targeted conditions it tests for. Most commonly, these include Trisomies in chromosomes 21, 18, and 13, as well as aneuploidies in chromosomes X and Y. It does not, however, replace diagnostic testing. We review four cases seen by our institutions of patients who had NIPS performed with low‐risk results and subsequently had fetuses affected with trisomy 18. Methods: All fetal samples were evaluated by level II anatomic ultrasound and tested on amniocytes or products of conception through karyotype or chromosomal microarray following low‐risk NIPS. Results: None of the fetuses showed evidence of mosaicism and had features (both on ultrasound and postnatally) consistent with Trisomy 18. Postnatal fluorescence in situ hybridization performed on Formalin‐Fixed Paraffin‐Embedded tissue from 3 of the affected pregnancies' placentas identified mosaicism of trisomy 18. Discussion: We discuss the possible explanations for the discrepancy between NIPS results and fetal karyotype, including, but not limited to placental mosaicism, placental size, and limitations of NIPS as a screening test. Key points: What is already known about this topic? Cell‐free DNA is a screening test for common aneuploidiesScreening tests can generate false positive and false negative resultsThere are more cases of false positive cases than false negative cases following cell‐free DNA screening What does this study add? Demonstrates four cases of full fetal Trisomy 18 after low‐risk cell‐free DNA screening, adding to the literature surrounding false negative casesPlacental fluorescence in situ hybridization (FISH) was obtained in 3 cases showing mosaicism not seen in the affected fetus/neonate [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is defined by a rapid decline in renal function. Regardless of the initial cause of injury, the influx of immune cells is a common theme during AKI. While an inflammatory response is critical for the initial control of injury, a prolonged response can negatively affect tissue repair. In this review, we focus on the role of macrophages, from early inflammation to resolution, during AKI. These cells serve as the innate defense system by phagocytosing cellular debris and pathogenic molecules and bridge communication with the adaptive immune system by acting as antigen-presenting cells and secreting cytokines. While many immune cells function to initiate inflammation, macrophages play a complex role throughout AKI. This complexity is driven by their functional plasticity: the ability to polarize from a "pro-inflammatory" phenotype to a "pro-reparative" phenotype. Importantly, experimental and translational studies indicate that macrophage polarization opens the possibility to generate novel therapeutics to promote repair during AKI. A thorough understanding of the biological roles these phagocytes play during both injury and repair is necessary to understand the limitations while furthering the therapeutic application. [ABSTRACT FROM AUTHOR]

Rift Valley fever virus (RVFV) infection causes abortions in ruminant livestock and is associated with an increased likelihood of miscarriages in women. Using sheep and human placenta explant cultures, we sought to identify tissues at the maternal–fetal interface targeted by RVFV. Sheep villi and fetal membranes were highly permissive to RVFV infection resulting in markedly higher virus titers than human cultures. Sheep cultures were most permissive to wild-type RVFV and ΔNSm infection, while live-attenuated RVFV vaccines (LAVs; MP-12, ΔNSs, and ΔNSs/ΔNSm) exhibited reduced replication. The human fetal membrane restricted wild-type and LAV replication, and when infection occurred, it was prominent on the maternal-facing side. Type I and type III interferons were induced in human villi exposed to LAVs lacking the NSs protein. This study supports the use of sheep and human placenta explants to understand vertical transmission of RVFV in mammals and whether LAVs are attenuated at the maternal–fetal interface. IMPORTANCE A direct comparison of replication of Rift Valley fever virus (RVFV) in sheep and human placental explants reveals comparative efficiencies and permissivity to infection and replication. Vaccine strains of RVFV demonstrated reduced infection and replication capacity in the mammalian placenta. This study represents the first direct cross-host comparison of the vertical transmission capacity of this high-priority emerging mosquito-transmitted virus. [ABSTRACT FROM AUTHOR]