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We report on the identification of extracellular miRNA (ex-miRNA) biomarkers for early diagnosis and prognosis of preeclampsia (PE). Small RNA sequencing of maternal serum prospectively collected from participants undergoing evaluation for suspected PE revealed distinct patterns of ex-miRNA expression among different categories of hypertensive disorders in pregnancy. Applying an iterative machine learning method identified three bivariate miRNA biomarkers (miR-522-3p/miR-4732-5p, miR-516a-5p/miR-144-3p, and miR-27b-3p/let-7b-5p) that, when applied serially, distinguished between PE cases of different severity and differentiated cases from controls with a sensitivity of 93%, specificity of 79%, positive predictive value (PPV) of 55%, and negative predictive value (NPV) of 89%. In a small independent validation cohort, these ex-miRNA biomarkers had a sensitivity of 91% and specificity of 57%. Combining these ex-miRNA biomarkers with the established sFlt1:PlGF protein biomarker ratio performed better than either set of biomarkers alone (sensitivity of 89.4%, specificity of 91.3%, PPV of 95.5%, and NPV of 80.8%).

IntroductionMortality from preeclampsia (PE) and PE-associated morbidities are 3-to 5-fold higher in persons of African ancestry than in those of Asian and European ancestries.MethodsTo elucidate placental contribution to worse PE outcomes in African ancestry pregnancies, we performed bulk RNA sequencing on 50 placentas from persons with severe PE (sPE) of African (n = 9), Asian (n = 18) and European (n = 23) ancestries and 73 normotensive controls of African (n = 10), Asian (n = 15) and European (n = 48) ancestries.ResultsPreviously described canonical preeclampsia genes, involved in metabolism and hypoxia/angiogenesis including: LEP, HK2, FSTL3, FLT1, ENG, TMEM45A, ARHGEF4 and HTRA1 were upregulated sPE versus normotensive placentas across ancestries. LTF, NPR3 and PHYHIP were higher in African vs. Asian ancestry sPE placentas. Allograft rejection/adaptive immune response genes were upregulated in placentas from African but not in Asian or European ancestry sPE patients; IL3RA was of particular interest because the patient with the highest placental IL3RA expression, a person of African ancestry with sPE, developed postpartum cardiomyopathy, and was the only patient out of 123, that developed this condition. Interestingly, the sPE patients with the highest IL3RA expression among persons of Asian and European ancestries developed unexplained tachycardia peripartum, necessitating echocardiography in the European ancestry patient. The association between elevated placental IL3RA levels and unexplained tachycardia or peripartum cardiomyopathy was found to be significant in the 50 sPE patients (p = .0005).DiscussionHigh placental upregulation of both canonical preeclampsia and allograft rejection/adaptive immune response genes may contribute to worse PE outcomes in African ancestry sPE patients.

Purpose: This exploratory study developed a process for reinterpreting previously published research studies in the bilingual literature. Three previously published studies on bilingual phonological acquisition were revisited due to the following characteristics: (a) they applied a theoretical framework for bilingual speech production developed by white bilingual researchers, the "dual-systems hypothesis," and (b) project data were interpreted without the input and perspective of researchers representative of the community being studied. This study aims to provide a guide for the readership to reinterpret developmental speech and language studies on bilingual children through (a) the theoretical framework of "translanguaging," which was developed by minoritized bilingual scholars and members of the community being studied, and (b) community "Insider" lenses, or the perspectives of research team members whose lived linguistic experiences match those of the target population studied. Method: Original interpretations of data were reexamined and reinterpreted incorporating (a) a research team member from the target community and (b) a novel theoretical lens developed by members of the target community called "translanguaging." Results: Original findings were extended through the application of translanguaging as a theoretical lens. New interpretations of original data were uncovered when a researcher from the Latinx community was involved in the data interpretation process. New insights were gained on phonological acquisition in bilingual Spanish-English-speaking preschoolers by applying a reinterpretation framework. Conclusions: Differences in data interpretation reveal that translanguaging may improve understanding of languaging in bilingual/multilingual communities. Implications for development of representative research teams when examining minoritized pediatric populations are also discussed.

Preeclampsia (PE) is a heterogeneous disease for which the current clinical classification system is based on the presence or absence of specific clinical features. PE-associated placentas also show heterogeneous findings on pathologic examination, suggesting that further subclassification is possible. We combined clinical, pathologic, immunohistochemical, and transcriptomic profiling of placentas to develop integrated signatures for multiple subclasses of PE. In total, 303 PE and 1388 nonhypertensive control placentas were included. We found that maternal vascular malperfusion (MVM) in the placenta was associated with preterm PE with severe features and with small-for-gestational-age neonates. Interestingly, PE placentas with either MVM or no histologic pattern of injury showed a linear decrease in proliferative (p63+) cytotrophoblast per villous area with increasing gestational age, similar to placentas obtained from the nonhypertensive patient cohort; however, PE placentas with fetal vascular malperfusion or villitis of unknown etiology lost this phenotype. This is mainly because of cases of fetal vascular malperfusion in placentas of patients with preterm PE and villitis of unknown etiology in placentas of patients with term PE, which are associated with a decrease or increase, respectively, in the cytotrophoblast per villous area. Finally, a transcriptomic analysis identified pathways associated with hypoxia, inflammation, and reduced cell proliferation in PE-MVM placentas and further subclassified this group into extravillous trophoblast-high and extravillous trophoblast-low PE, confirmed using an immunohistochemical analysis of trophoblast lineage-specific markers. Our findings suggest that within specific histopathologic patterns of placental injury, PE can be subclassified based on specific cellular and molecular defects, allowing the identification of pathways that may be targeted for diagnostic and therapeutic purposes.

Evocations is a video work made from photographs taken at the conservation-zoned Turtle Swamp Wetlands on Canaipa (Russell Island) in southern Moreton Bay, Quandamooka Country, Queensland, Australia. The accompanying poem is a written response to the images, and evokes their sense of movement and energy.

Purpose: The purpose of this study was to examine the diagnostic accuracy of traditional measures of phonological ability developed for monolingual English-speaking children with their bilingual peers in both English and Spanish. We predicted that a composite measure, derived from a combination of English and Spanish phonological measures, would result in higher diagnostic accuracy than examining the individual phonological measures of bilingual children separately by language. Method: Sixty-six children, ages 3;3-6;3 (years; months), participated in this study: 29 typically developing bilingual Spanish-English-speaking children (x = 5;3), five bilingual Spanish-English-speaking children with speech sound disorders (x = 4;6), 26 typically developing monolingual English-speaking children (x = 4;8), and six monolingual English-speaking children with speech sound disorders (x = 4;9). Children were recorded producing single words using the Assessments of English and Spanish Phonology, and productions were phonetically transcribed and analyzed using the Logical International Phonetics Program. Overall consonants correct-revised; accuracy of early-, middle-, and late-developing sounds; and percent occurrence of phonological error patterns in both English and Spanish were calculated. Receiver operating characteristic curves and support vector machine models were applied to observe diagnostic accuracy, separately and combined, for each speaker group and each language. Results: Findings indicated the combination of measures improved diagnostic accuracy within both the English and Spanish of bilingual children and significantly increased accuracy when measures from both languages of bilingual children were combined. Combining measures for the productions of monolingual English-speaking children did not increase diagnostic accuracy. Conclusion: To prevent misdiagnosis of speech sound disorders in bilingual preschoolers, the composite phonological abilities of bilingual children need to be assessed across both gross and discrete measures of phonological ability.

Residence at high altitude (> 2500 m) has been associated with an increased frequency of preeclampsia. Pappalysin-2 (PAPP-A2) is an insulin-like growth factor binding protein-5 (IGFBP-5) protease that is elevated in preeclampsia, and up-regulated by hypoxia in placental explants. The relationships between PAPP-A2, altitude, and indices of uteroplacental ischemia are unknown. We aimed to evaluate the association of altitude, preeclampsia, and uterine artery flow or vascular resistance with PAPP-A2 levels. PAPP-A2, uterine artery diameter, volumetric blood flow, and pulsatility indices were measured longitudinally in normotensive Andean women residing at low or high altitudes in Bolivia and in a separate Andean high-altitude cohort with or without preeclampsia. PAPP-A2 levels increased with advancing gestation, with the rise tending to be greater at high compared to low altitude, and higher in early-onset preeclamptic compared to normotensive women at high altitude. Uterine artery blood flow was markedly lower and pulsatility index higher in early-onset preeclamptic normotensive women compared to normotensive women. PAPP-A2 was unrelated to uterine artery pulsatility index in normotensive women but positively correlated in the early-onset preeclampsia cases. We concluded that PAPP-A2 is elevated at high altitude and especially in cases of early-onset preeclampsia with Doppler indices of uteroplacental ischemia.

This study evaluates the impact of extended cardiac views on examination time, repeat imaging, and anomaly detection before and after implementation of 76811 guidelines (American Institute of Ultrasound in Medicine Consensus 2014). It is a retrospective study of singleton pregnancies undergoing detailed ultrasound imaging at 18 weeks' gestation or greater before and after the protocol change in an academic, tertiary care fetal center. Views required prior to 2014: 4-chamber, left outflow tract, right outflow tract. Additional views required after 2014: bicaval, aortic arch, 3-vessel, and 3-vessel trachea. Fetuses with known anomalies were excluded. Rates of detection of congenital heart disease (CHD), examination completion, repeat examination recommendation, fetal echocardiogram recommendation, completion by body mass index, and cardiac examination time were determined. Six hundred twenty-four subjects were included, 217 before and 407 after protocol change. Views obtained were as stated in the American Institute of Ultrasound in Medicine/Society for Maternal-Fetal Medicine consensus. Detection of CHD was not improved. Examination times increased by 20% (6.4 vs 7.7 minutes, P < 0.05). Number of incomplete studies increased by 130% (11% to 26%, P < 0.05). Twice as many patients were referred for repeat examination (6% vs 13%, P < 0.05). Completion rates were negatively correlated with body mass index. Recommendations for fetal echocardiogram were unchanged (5% vs 6%, P = 0.6). Additional imaging did not increase detection rate of CHD (3% vs 2%, P = 0.3). Extended cardiac views resulted in increased examination time, more incomplete examinations, and more repeat examinations without changing detection rates of CHD.

Emojis are being increasingly used in different types of communications, including in advertising campaigns. One emoji, the smiley face, has been an important part of consumers' informal communications. Interestingly, smiley faces now also appear in marketing communications, advertisements, and brand logos. The present research examines the role of smiley faces in restaurant logos as a form of marketing communication. A set of five studies—conducted in a lab and at a middle school—demonstrates that communication associated with restaurant logos including smileys is perceived as lower in healthfulness, which in turn leads to lower price expectations. These effects are caused by a visual association with a fast-food restaurant category, whereby consumers link the presence of smiley faces with fast-food restaurants. The authors conclude that including a smiley face logo in a restaurant's marketing communication can have unintended consequences on consumers' perceptions. [ABSTRACT FROM AUTHOR]

Pyramidal training may offer an efficient approach for disseminating behavior analytic teaching practices into public schools serving students with autism. In this study, we evaluated 16 teachers' use of behavioral skills training (BST) while they trained paraprofessionals to use discrete-trial teaching (DTT). All paraprofessionals demonstrated high levels of procedural integrity following the training, although six of the 16 teachers received experimenter feedback to increase the integrity of the paraprofessional's performance. A descriptive assessment of the training indicated that the majority of teachers used vocal instructions, modeling, and role play while training their paraprofessionals to implement DTT but only half of the teachers collected procedural integrity data to monitor the paraprofessionals' performance. Although all teachers provided feedback to their paraprofessionals during the in situ portion of the training, the teachers were more likely to deliver feedback for errors than for correctly implemented components. These findings suggest that training teachers to implement BST with their paraprofessionals is an effective and socially valid approach to dissemination.

Whole exome sequencing (WES) was used to determine the etiology of recurrent hydrops fetalis in this case of Hennekam lymphangiectasia-lymphedema syndrome-1. WES is a useful approach for diagnosing rare single-gene conditions with nonspecific phenotypes and should be considered early in the diagnostic process of investigating fetal abnormalities.

Margalefidinium polykrikoides is a mixotrophic dinoflagellate harmful algal bloom (HAB) species that blooms annually in the lower Chesapeake Bay. M. polykrikoides undertakes a diel vertical migration (DVM) which may give it a competitive advantage over purely phototrophic organisms who cannot access deeper nutrient pools and allow it to form large toxic blooms. Laboratory-based estimates of M. polykrikoides' DVM rates suggest that it is one of the fastest known dinoflagellate swimmers and understanding this behavior is likely important for modeling and predicting M. polykrikoides blooms. However, to date, no field-derived estimates of M. polykrikoides' DVM rates have been made in the Chesapeake Bay. In this study, we conducted four targeted field experiments to investigate the DVM of M. polykrikoides in the Lafayette River, a sub-tributary of the Chesapeake Bay. Vertical profiles of chlorophyll a fluorescence collected at least every 2 h over diel periods were used to track the DVM of M. polykrikoides during blooms. The maximum observed DVM rate for M. polykrikoides was 2.5 m h−1, with mean DVM rates around 1.3 m h−1 for both ascents and descents. As in studies from other regions, our results show that M. polykrikoides' ascent to/descent from the surface initiates before sunrise/sunset, suggesting phototaxis is not the primary trigger of their DVM. However, unlike in other studies where M. polykrikoides was observed to modulate its DVM to avoid excessively warm temperatures (≥30°C), we do not observe active thermotaxic avoidance, despite ambient temperatures exceeding their optimal threshold. [ABSTRACT FROM AUTHOR]

The article discusses evidence regarding both the decriminalization of sex work or consenting adults who are buying or selling sex are not committing a crime, and the legalization of sex work, which creates an affirmative regulatory scheme that creates rules governing the sale of sex between consenting adults. Topics include global context of sex work criminalization, violence, and HIV; violence as a key driver of HIV infection; and criminalization of sex work in the U.S.