Transcriptional control of gene expression by microRNAs.

MicroRNAs (miRNAs) control gene expression in animals and plants. Like another class of small RNAs, siRNAs, they affect gene expression posttranscriptionally. While siRNAs in addition act in transcriptional gene silencing, a role of miRNAs in transcriptional regulation has been less clear. We show here that in moss Physcomitrella patens mutants without a DICER-LIKE1b gene, maturation of miRNAs is normal but cleavage of target RNAs is abolished and levels of these transcripts are drastically reduced. These mutants accumulate miRNA:target-RNA duplexes and show hypermethylation of the genes encoding target RNAs, leading to gene silencing. This pathway occurs also in the wild-type upon hormone treatment. We propose that initiation of epigenetic silencing by DNA methylation depends on the ratio of the miRNA and its target RNA.

DICER-LIKE1a autoregulation based on intronic microRNA processing is required for stress adaptation in Physcomitrium patens.

The Physcomitrium patens DICER-LIKE1a (PpDCL1a) mRNA encoding the essential Dicer protein for microRNA (miRNA) biogenesis harbors an intronic miRNA (miR1047). An autoregulatory mechanism to control PpDCL1a abundance that is based on competitive processing of the intronic miRNA and proper PpDCL1a mRNA splicing has previously been proposed. If intron splicing occurs first the mRNA can be translated into the functional PpDCL1a protein, whereas the processing of the intronic miRNA catalyzed by PpDCL1a itself, prior to pre-mRNA splicing, generates a truncated transcript unable to produce a functional protein. This proposed autoregulation of DCL1 has not been functionally analyzed in any plant species, and the existence of this autoregulatory control is expected to have a general impact on the overall miRNA biogenesis pathway and the transcriptome that is under miRNA control. We abolished PpDCL1a autoregulatory feedback control by the precise deletion of the MIR1047-containing intron. The generated line displayed hypersensitivity to salt stress and hyposensitivity to the plant hormone ABA, accompanied by the disturbed expression of miRNAs and mRNAs, revealed by transcriptome analyses. The feedback control together with the phenotypic abnormalities and molecular changes in the intron-less line can be rescued by the re-insertion of a modified intron harboring a sequence-unrelated artificial miRNA. Our findings indicate the physiological importance of miR1047-based feedback control of PpDCL1a transcript abundance, which controls the expression of miRNAs, and their cognate target RNAs during salt stress adaptation, and suggests a key role for this autoregulation in the molecular adaptation of land plants to terrestrial habitats.

Dual-Modal Electrical Imaging of Two-Phase Flow-Experimental Evaluation of the State Estimation Approach.

Accurate measurement of two-phase flow quantities is essential for managing production in many industries. However, the inherent complexity of two-phase flow often makes estimating these quantities difficult, necessitating the development of reliable techniques for quantifying two-phase flow. In this paper, we investigated the feasibility of using state estimation for dynamic image reconstruction in dual-modal tomography of two-phase oil-water flow. We utilized electromagnetic flow tomography (EMFT) to estimate velocity fields and electrical tomography (ET) to determine phase fraction distributions. In state estimation, the contribution of the velocity field to the temporal evolution of the phase fraction distribution was accounted for by approximating the process with a convection-diffusion model. The extended Kalman filter (EKF) and fixed-interval Kalman smoother (FIKS) were used to reconstruct the temporally evolving velocity and phase fraction distributions, which were further used to estimate the volumetric flow rates of the phases. Experimental results on a laboratory setup showed that the FIKS approach outperformed the conventional stationary reconstructions, with the average relative errors of the volumetric flow rates of oil and water being less than 4%. The FIKS approach also provided feasible uncertainty estimates for the velocity, phase fraction, and volumetric flow rate of the phases, enhancing the reliability of the state estimation approach.

Enhanced resonances by waveguide wrapping of a bulbed microring resonator.

A high Q-factor novel bulb design, to the best of our knowledge, inspired by the well-studied pulley microring resonator (MRR), is demonstrated and compared with circle and racetrack MRRs at wavelengths of 1.45-1.65 µm. A wrapping of 60% around the ring showed a three times Q-factor increment (Q=828) compared to a standard circle MRR (Q=206) at a telecom wavelength of 1.55 µm with a fixed ring radius of 2 µm, while further increasing the wrapping at 80% shows a decrease in its Q-factor (Q=454). A comparison of the wavelength dependence of the bulb design with other typical MRR designs suggests that bulb designs are highly sensitive to wavelength and have very high Q-factors at lower wavelengths.

Correlation between blood pressure and lung function in Malaysian adult population.

INTRODUCTION: The correlation between pulmonary function and hypertension remains ambiguous. This study therefore determined the relationship between pulmonary function and hypertension among adult subgroup in Malaysia. MATERIALS AND METHODS: Data for this study were obtained from an ongoing Prospective Urban Rural Epidemiology- Rural Urban Study (PURE RUS) , which is a prospective cohort study done by MARA University of Technology (UiTM) Medical Faculty research team to track risk factors, changing lifestyles, and chronic diseases in rural and urban population. The inclusion criteria included: Malaysian citizen, age 18-80 years, not on any anti-hypertensive agents, and able to perform lung function test. 1640 participants satisfied the criteria and were recruited in this study. RESULTS: From the studied population, males comprised 43.5% of them and female comprised 56.5%. A significant inverse relationship was found between pulmonary function and systolic blood pressure in both sexes measured by forced vital capacity (FVC) and Forced Expiratory Volume in 1 second (FEV1). A substantial inverse relationship was also found between pulmonary function and age, and there was a profound positive association between blood pressure and age. No major disparities were significant in pulmonary function between hypertensive and age-matched normotensive participants. CONCLUSION: Even though a substantial inverse relationship was evident between systolic blood pressure and pulmonary function, its precise clinical importance needs to be further explored particularly when age can influence both pulmonary function and blood pressure. Clearly, the impact of age has to be removed before FVC can be used as a prognosticator of hypertension.

Identification of small non-coding RNAs responsive to GUN1 and GUN5 related retrograde signals in Arabidopsis thaliana.

Chloroplast perturbations activate retrograde signalling pathways, causing dynamic changes of gene expression. Besides transcriptional control of gene expression, different classes of small non-coding RNAs (sRNAs) act in gene expression control, but comprehensive analyses regarding their role in retrograde signalling are lacking. We performed sRNA profiling in response to norflurazon (NF), which provokes retrograde signals, in Arabidopsis thaliana wild type (WT) and the two retrograde signalling mutants gun1 and gun5. The RNA samples were also used for mRNA and long non-coding RNA profiling to link altered sRNA levels to changes in the expression of their cognate target RNAs. We identified 122 sRNAs from all known sRNA classes that were responsive to NF in the WT. Strikingly, 142 and 213 sRNAs were found to be differentially regulated in both mutants, indicating a retrograde control of these sRNAs. Concomitant with the changes in sRNA expression, we detected about 1500 differentially expressed mRNAs in the NF-treated WT and around 900 and 1400 mRNAs that were differentially regulated in the gun1 and gun5 mutants, with a high proportion (~30%) of genes encoding plastid proteins. Furthermore, around 20% of predicted miRNA targets code for plastid-localised proteins. Among the sRNA-target pairs, we identified pairs with an anticorrelated expression as well pairs showing other expressional relations, pointing to a role of sRNAs in balancing transcriptional changes upon retrograde signals. Based on the comprehensive changes in sRNA expression, we assume a considerable impact of sRNAs in retrograde-dependent transcriptional changes to adjust plastidic and nuclear gene expression.

PpGRAS12 acts as a positive regulator of meristem formation in Physcomitrium patens.

KEY MESSAGE: This study focused on the key regulatory function of Physcomitrium patens GRAS12 gene underlying an increasing plant complexity, an important step in plant terrestrialization and the evolutionary history of life. The miR171-GRAS module has been identified as a key player in meristem maintenance in angiosperms. PpGRAS12 is a member of the GRAS family and a validated target for miR171 in Physcomitrium (Physcomitrella) patens. Here we show a regulatory function of miR171 at the gametophytic vegetative growth stage and targeted deletion of the PpGRAS12 gene adversely affects sporophyte production since fewer sporophytes were produced in ΔPpGRAS12 knockout lines compared to wild type moss. Furthermore, highly specific and distinct growth arrests were observed in inducible PpGRAS12 overexpression lines at the protonema stage. Prominent phenotypic aberrations including the formation of multiple apical meristems at the gametophytic vegetative stage in response to elevated PpGRAS12 transcript levels were discovered via scanning electron microscopy. The production of multiple buds in the PpGRAS12 overexpression lines similar to ΔPpCLV1a/1b disruption mutants is accompanied by an upregulation of PpCLE and downregulation of PpCLV1, PpAPB, PpNOG1, PpDEK1, PpRPK2 suggesting that PpGRAS12 acts upstream of these genes and negatively regulates the proposed pathway to specify simplex meristem formation. As CLV signaling pathway components are not present in the chlorophytic or charophytic algae and arose with the earliest land plants, we identified a key regulatory function of PpGRAS12 underlying an increasing plant complexity, an important step in plant terrestrialization and the evolutionary history of life.

Improved multiplex TaqMan qPCR assay with universal internal control offers reliable and accurate detection of Clavibacter michiganensis.

AIM: Clavibacter michiganensis (Cm) is a seed-borne plant pathogen that significantly reduces tomato production worldwide. Due to repeated outbreaks and rapid spread of the disease, seeds/transplants need to be certified free of the pathogen before planting. To this end, we developed a multiplex TaqMan qPCR assay that can accurately detect Cm in infected samples. METHODS AND RESULTS: A specific region of Cm (clvG gene) was selected for primer design using comparative genomics approach. A fully synthetic universal internal control (UIC) was also designed to detect PCR inhibitors and false-negative results in qPCRs. The Cm primers can be used alone or in a triplex TaqMan qPCR assay with UIC and previously described Clavibacter primers. The assay was specific for Cm and detected up to 10 fg of Cm DNA in sensitivity and spiked assays. Addition of the UIC did not change the specificity or sensitivity of the multiplex TaqMan qPCR assay. CONCLUSION: The triplex TaqMan qPCR provides a specific and sensitive diagnostic assay for Cm. SIGNIFICANCE AND IMPACT OF THE STUDY: This assay can be used for biosecurity surveillance, routine diagnostics, estimating bacterial titres in infected material and for epidemiological studies. The UIC is fully synthetic, efficiently amplified and multiplex compatible with any other qPCR assay.

Performance assessment of gasification reactors for sustainable management of municipal solid waste.

The issue of waste management has received considerable critical attention due to the increase of waste generation worldwide. One of the solutions for waste disposal that has been widely implemented is through the use of the landfill due to its economic benefits. Landfill, however, results in many adverse impacts on the environment and human health. Recycling can extract some useful materials from waste, however not every waste can be recycled and a significant volume of waste, particularly the municipal solid waste (MSW) goes to landfill even though it has extractable energy potentials. Extraction of energy from MSW has been a key focus of research due to the scope of energy recovery, environmental and economic benefits. The principal concept of waste to energy is to convert waste into energy through thermal and/or biological processes. In addition, thermochemical processes such as gasification have been found as a promising technology offering several benefits. This paper presents a critical assessment of waste to energy gasification technology for MSW on processing, energy recovery, environmental performance and economic perspectives. These aspects have been analyzed for the landfill as well. The review also explored and identified suitable simulation tools for optimizing gasification. Subsequently, an assessment and comparison of different gasification reactors were carried out which indicate that the plasma gasification can be a feasible technology for MSW management due to higher energy efficiency (816 kWh/tonne) with minimum emission and lowest residue. Although plasma gasification is an energy intensive application which has relatively higher investment cost, it can be built as a large system (up to several 1000 MW system), which can make it economically competitive too. Other technologies such as; fluidized bed gasifier, fixed bed gasifier also have good energy efficiency (547-571 kWh/tonne) however, they contribute to higher CO2 emission. Considering overall waste management, it was found that gasification technology is beneficial to economy, environment and energy extraction compared to the landfill option. A number of tools and their relevant properties have been identified to develop appropriate gasifier model. It is expected that this study will advance further research and innovation that will be helpful to manage waste efficiently as well as to improve the environment.

Identification of small RNAs during cold acclimation in Arabidopsis thaliana.

BACKGROUND: Cold stress causes dynamic changes in gene expression that are partially caused by small non-coding RNAs since they regulate protein coding transcripts and act in epigenetic gene silencing pathways. Thus, a detailed analysis of transcriptional changes of small RNAs (sRNAs) belonging to all known sRNA classes such as microRNAs (miRNA) and small interfering RNA (siRNAs) in response to cold contributes to an understanding of cold-related transcriptome changes. RESULT: We subjected A. thaliana plants to cold acclimation conditions (4 °C) and analyzed the sRNA transcriptomes after 3 h, 6 h and 2 d. We found 93 cold responsive differentially expressed miRNAs and only 14 of these were previously shown to be cold responsive. We performed miRNA target prediction for all differentially expressed miRNAs and a GO analysis revealed the overrepresentation of miRNA-targeted transcripts that code for proteins acting in transcriptional regulation. We also identified a large number of differentially expressed cis- and trans-nat-siRNAs, as well as sRNAs that are derived from long non-coding RNAs. By combining the results of sRNA and mRNA profiling with miRNA target predictions and publicly available information on transcription factors, we reconstructed a cold-specific, miRNA and transcription factor dependent gene regulatory network. We verified the validity of links in the network by testing its ability to predict target gene expression under cold acclimation. CONCLUSION: In A. thaliana, miRNAs and sRNAs derived from cis- and trans-NAT gene pairs and sRNAs derived from lncRNAs play an important role in regulating gene expression in cold acclimation conditions. This study provides a fundamental database to deepen our knowledge and understanding of regulatory networks in cold acclimation.

Precision Measurement of the Neutron Scattering Length of

We report a 0.08% measurement of the bound neutron scattering length of ^{4}He using neutron interferometry. The result is b=(3.0982±0.0021[stat]±0.0014[syst]) fm. The corresponding free atomic scattering length is a=(2.4746±0.0017[stat]±0.0011[syst]) fm. With this result the world average becomes b=(3.0993±0.0025) fm, a 2% downward shift and a reduction in uncertainty by more than a factor of six. Our result is in disagreement with a previous neutron interferometric measurement but is in good agreement with earlier measurements using neutron transmission.

Comparative genomics reveals signature regions used to develop a robust and sensitive multiplex TaqMan real-time qPCR assay to detect the genus Dickeya and Dickeya dianthicola.

AIMS: Dickeya species are high consequence plant pathogenic bacteria; associated with potato disease outbreaks and subsequent economic losses worldwide. Early, accurate and reliable detection of Dickeya spp. is needed to prevent establishment and further dissemination of this pathogen. Therefore, a multiplex TaqMan qPCR was developed for sensitive detection of Dickeya spp. and specifically, Dickeya dianthicola. METHODS AND RESULTS: A signature genomic region for the genus Dickeya (mglA/mglC) and unique genomic region for D. dianthicola (alcohol dehydrogenase) were identified using a whole genome-based comparative genomics approach. The developed multiplex TaqMan qPCR was validated using extensive inclusivity and exclusivity panels, and naturally/artificially infected samples to confirm broad range detection capability and specificity. Both sensitivity and spiked assays showed a detection limit of 10 fg DNA. CONCLUSION: The developed multiplex assay is sensitive and reliable to detect Dickeya spp. and D. dianthicola with no false positives or false negatives. It was able to detect mixed infection from naturally and artificially infected plant materials. SIGNIFICANCE AND IMPACT OF THE STUDY: The developed assay will serve as a practical tool for screening of propagative material, monitoring the presence and distribution, and quantification of target pathogens in a breeding programme. The assay also has applications in routine diagnostics, biosecurity and microbial forensics.

Screening of vitamin D and calcium concentrations in neonates of mothers at high risk of vitamin D deficiency.

OBJECTIVE: The aim of this study was to determine, retrospectively, the serum 25OHD and calcium concentrations of screened neonates of mothers at high risk of 25OHD deficiency and examine whether their measurement contributes to the management of these neonates. METHODS: Serum 25OHD and calcium concentrations from 600 samples of umbilical cord blood or venous blood collected from neonates over a 12-month period were analysed. RESULTS: There was a high prevalence of vitamin D insufficiency (27.6%, 30-50 nmol/L) and deficiency (21.3%, < 30 nmol/L) in neonates from high-risk maternal groups. There was a statistically positive but weak correlation (ρ = 0.22, P < 0.0001) between 25OHD and serum calcium. Only 7 neonates out of 569 (1.2%) had calcium concentrations in the hypocalcaemic range; however, a significant number (47.6%) were reported to be in the hypercalcaemic range. Nearly all of these were venous samples collected in first 24 h after birth. CONCLUSION: Vitamin D deficiency is prevalent in neonates of high-risk mothers but the risk of hypocalcaemia due to vitamin D deficiency at birth is low. Screening neonates entails blood testing which can cause distress to neonates and their parents, substantial imposition on staff and financial burden on the health care system. Vitamin D supplementation of these neonates from birth without routine screening appears more reasonable. Also, the data from this study suggest that the paediatric reference range for corrected calcium concentrations in neonates should be re-evaluated.

COVID-19: Impact analysis and recommendations for power sector operation.

The demand of electricity has been reduced significantly due to the recent COVID-19 pandemic. Governments around the world were compelled to reduce the business activity in response to minimize the threat of coronavirus. This on-going situation due to COVID-19 has changed the lifestyle globally as people are mostly staying home and working from home if possible. Hence, there is a significant increase in residential load demand while there is a substantial decrease in commercial and industrial loads. This devastating situation creates new challenges in the technical and financial activities of the power sector and hence most of the utilities around the world initiated a disaster management plan to tackle this ongoing challenges/threats. Therefore, this study aims to investigate the global scenarios of power systems during COVID-19 along with the socio-economic and technical issues faced by the utilities. Then, this study further scrutinized the Indian power system as a case study and explored scenarios, issues and challenges currently being faced to manage the consumer load demand, including the actions taken by the utilities/power sector for the smooth operation of the power system. Finally, a set of recommendations are presented to support the government/policymakers/utilities around the world not only to overcome the current crisis but also to overcome future unforeseeable pandemic alike scenario.

Analysis of isolates from Bangladesh highlights multiple ways to carry resistance genes in Salmonella Typhi.

BACKGROUND: Typhoid fever, caused by Salmonella Typhi, follows a fecal-oral transmission route and is a major global public health concern, especially in developing countries like Bangladesh. Increasing emergence of antimicrobial resistance (AMR) is a serious issue; the list of treatments for typhoid fever is ever-decreasing. In addition to IncHI1-type plasmids, Salmonella genomic island (SGI) 11 has been reported to carry AMR genes. Although reports suggest a recent reduction in multidrug resistance (MDR) in the Indian subcontinent, the corresponding genomic changes in the background are unknown. RESULTS: Here, we assembled and annotated complete closed chromosomes and plasmids for 73 S. Typhi isolates using short-length Illumina reads. S. Typhi had an open pan-genome, and the core genome was smaller than previously reported. Considering AMR genes, we identified five variants of SGI11, including the previously reported reference sequence. Five plasmids were identified, including the new plasmids pK91 and pK43; pK43and pHCM2 were not related to AMR. The pHCM1, pPRJEB21992 and pK91 plasmids carried AMR genes and, along with the SGI11 variants, were responsible for resistance phenotypes. pK91 also contained qnr genes, conferred high ciprofloxacin resistance and was related to the H58-sublineage Bdq, which shows the same phenotype. The presence of plasmids (pHCM1 and pK91) and SGI11 were linked to two H58-lineages, Ia and Bd. Loss of plasmids and integration of resistance genes in genomic islands could contribute to the fitness advantage of lineage Ia isolates. CONCLUSIONS: Such events may explain why lineage Ia is globally widespread, while the Bd lineage is locally restricted. Further studies are required to understand how these S. Typhi AMR elements spread and generate new variants. Preventive measures such as vaccination programs should also be considered in endemic countries; such initiatives could potentially reduce the spread of AMR.

Development of a loop-mediated isothermal amplification assay for specific detection of all known subspecies of Clavibacter michiganensis.

AIMS: Clavibacter michiganensis is an important bacterial plant pathogen that causes vast destruction to agriculturally important crops worldwide. Early detection is critical to evaluate disease progression and to implement efficient control measures to avoid serious epidemics. In this study, we developed a sensitive, specific and robust loop-mediated isothermal amplification (LAMP) assay for detection of all known subspecies of C. michiganensis. METHODS AND RESULTS: Whole genome comparative genomics approach was taken to identify a unique and conserved region within all known subspecies of C. michiganensis. Primer specificity was evaluated in silico and with 64 bacterial strains included in inclusivity and exclusivity panels; no false positives or false negatives were detected. Both the sensitivity and spiked assay of the developed LAMP assay was 1 fg of the pathogen DNA per reaction. A 100% accuracy was observed when tested with infected plant samples. CONCLUSIONS: The developed LAMP assay is simple, sensitive, robust and easy to perform using different detection platforms and chemistries. SIGNIFICANCE AND IMPACT OF THE STUDY: The developed LAMP assay can detect all known subspecies of C. michiganensis. The LAMP process can be performed isothermally at 65°C and results can be visually assessed, which makes this technology a promising tool for monitoring the disease progression and for accurate pathogen detection at point-of-care.

Generation of a Lattice of Spin-Orbit Beams via Coherent Averaging.

We describe a highly robust method, applicable to both electromagnetic and matter-wave beams, that can produce a beam consisting of a lattice of orbital angular momentum (OAM) states coupled to a two-level system. We also define efficient protocols for controlling and manipulating the lattice characteristics. These protocols are applied in an experimental realization of a lattice of optical spin-orbit beams. The novel passive devices we demonstrate here are also a natural alternative to existing methods for producing single-axis OAM and spin-orbit beams. Our techniques provide new tools for investigations of chiral and topological materials with light and particle beams.

Three Phase-Grating Moiré Neutron Interferometer for Large Interferometer Area Applications.

We demonstrate a three phase-grating moiré neutron interferometer in a highly intense neutron beam as a robust candidate for large area interferometry applications and for the characterization of materials. This novel far-field moiré technique allows for broad wavelength acceptance and relaxed requirements related to fabrication and alignment, thus circumventing the main obstacles associated with perfect crystal neutron interferometry. We observed interference fringes with an interferometer length of 4 m and examined the effects of an aluminum 6061 alloy sample on the coherence of the system. Experiments to measure the autocorrelation length of samples and the universal gravitational constant are proposed and discussed.

Study of Insulin Resistance in Patients With ß Thalassemia Major and Validity of Triglyceride Glucose (TYG) Index.

Complications like impaired glucose tolerance and diabetes mellitus due to iron overload need early identification in thalassemia. We studied the proportion of insulin resistance in thalassemia major patients on chronic transfusion, identified insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride glucose (TYG) index, compared them and validated TYG index. In total, 73 thalassemia patients on regular transfusion for 3 years with serum ferritin >1500 ng/mL were studied. Serum ferritin, fasting blood glucose, triglycerides, and insulin levels were measured, HOMA-IR, and TYG index calculated and analyzed. Mean fasting glucose, triglyceride, and serum insulin values were 104 mg/dL, 164.18 mg/dL, and 19.6 m IU/mL, respectively. Mean serum ferritin was 5156 ng/mL. Insulin resistance was prevalent in one third of thalassemia patients and showed increase with age and serum ferritin. Insulin resistance by HOMA-IR was 32% as against 16% by TYG index with a cut-off value of 4.3. Using receiver operating charecteristic curve analysis, it was found that, by lowering the value of TYG index to 4.0215, sensitivity improved to 78.3% (from 39.13%) with specificity of 70%. Hence, we recommend a newer lower cut-off value of 4.0215 for TYG index for better sensitivity and specificity in identifying insulin resistance.

First and Second Trimester Serum sFlt-1/PlGF Ratio and Subsequent Preeclampsia: A Systematic Review.

OBJECTIVE: Angiogenic biomarkers may be predictive of preeclampsia before clinical symptoms. The objective of this review was to determine the relationship between first and second trimester soluble fms-like tyrosine kinase-1/ placental growth factor (sFlt-1/PlGF) ratio and preeclampsia. METHODS: A search algorithm using appropriate medical subject headings was developed. PubMed, EMBASE, and Cochrane were searched for publications from inception to July 4, 2017. Observational studies, including prospective and retrospective cohorts, that measured serum sFlt-1/PlGF ratio at ≤24 weeks' gestation were included. Study characteristics, study design, timing of blood samples, and outcome data were systematically extracted. Study cohorts were grouped into women with low-risk and high-risk factors for preeclampsia. RESULTS: Fifteen studies were included for analysis, including 11 779 pregnancies. In studies of women with low-risk features, four subgroups from seven studies demonstrated higher sFlt-1/PlGF ratios in women who developed preeclampsia versus those who did not. In studies of women with high-risk features, six subgroups from nine studies demonstrated a higher sFlt-1/PlGF ratio in women who later developed preeclampsia. Elevated sFlt-1/PlGF ratios were especially seen in women who had early-onset or severe preeclampsia. CONCLUSION: The serum sFlt-1/PlGF ratio measured at ≤24 weeks' gestation may be elevated in select women who later develop preeclampsia, but inconsistently so.