Hemodynamic changes and perinatal outcome associated with umbilical artery thrombosis: a retrospective study.

OBJECTIVE: Poor fetal and perinatal outcomes in fetuses associated with umbilical artery thrombosis (UAT), such as severe intrauterine growth restriction (IUGR) and intrauterine asphyxia have been reported by some case series. Its hemodynamic impact remains unclear. The aim of this study was to evaluate the hemodynamic changes and perinatal outcome in UAT fetuses with a relatively large sample. METHODS: We included singleton fetuses diagnosed with UAT and with at least one available Doppler evaluation before the end of pregnancy in our center from 2016 to 2023. Fetuses with structural abnormalities and with no follow-up results were excluded. Doppler waveforms from the Umbilical artery (UA), middle cerebral artery (MCA), ductus venosus (DV) and uterine artery (UtA) were routinely evaluated according to ISUOG Practice Guidelines from diagnosis. The same sample of GA-matched normal fetuses with Doppler measurements during the same period were randomly selected as control group. RESULTS: Eighty-nine singleton fetuses with UAT with at least one Doppler evaluation before the end of pregnancy were identified, 13 fetuses with no follow-up results were excluded. After comprehensive prenatal counseling, 14 cases received urgent cesarean section, the remaining 55 cases received expectant management, the median day between GA at diagnosis and end of pregnancy was 13 (5-53) days (range, 2-159). 7 (7/76, 9.2%) cases occurred stillbirth, and the incidence of IUGR and Neonatal Intensive Care Unit (NICU) admission were 18.4% (14/76) and 13.2% (10/76) respectively. 49 fetuses (49/76, 64.5%) combined with Doppler abnormalities. UA abnormalities (35/76, 46.1%) and MCA abnormalities (34/76, 44.7%) were the most changes at presentation. Compared to control group, UA-EDV was significantly increased in UAT fetuses [21.84 (15.59-26.64) vs. 16.40 (12.43-20.70) cm/s, p < 0.001], UA-PI and UA-RI significantly decreased [0.68 (0.57-0.84) vs. 0.92 (0.79-1.11), p<0.001; 0.51 (0.44-0.59) vs. 0.62 (0.55-0.68), p < 0.001, respectively]. Both the MCA-PSV and MCA-EDV were significantly higher in UAT fetuses [54.60 (48.00-61.34) vs. 44.47 (29.66-57.60) cm/s, p < 0.001; 11.19 (7.84-17.60) vs. 8.22 (5.21-12.00) cm/s, p < 0.001, respectively], this led to a lower MCA-PI and MCA-RI. Meanwhile, DV-PIV was significantly higher in UAT fetuses [0.6 (0.47-0.87) vs. 0.45 (0.37-0.55), p < 0.001], CPR and UtA-PI were no significant difference between these two groups. Multivariate logistic regression analysis showed that DV-PIV was an independent risk factor for adverse pregnancy outcomes (OR 161.922, p<0.001), the area under the ROC curve (AUC) was 0.792 (95% CI 0.668-0.917; p < 0.001). CONCLUSION: Our data showed serious adverse pregnancy consequences are combined with UAT fetuses. Hemodynamic changes in UAT fetuses showed the remaining artery for compensation and brain perfusion derangement. With a comprehensive and standardized Doppler evaluation, progression of fetal deterioration may be detailed presented.

Prenatal Diagnosis and Postnatal Outcomes of Persistent Left Superior Vena Cava Associated With Mild Narrow Aorta: A Cohort Study.

PURPOSE: To explore prenatal ultrasonic features and prognosis of the persistent left superior vena cava (PLSVC) complicated with mild narrow aorta. MATERIALS AND METHODS: A retrospective study was conducted involving 1348 fetuses diagnosed with PLSVC prenatally between January 2016 and December 2019. Forty-five fetuses with PLSVC associated with mild narrow aorta were selected from the cohort as the study group and 79 fetuses with isolated PLSCV were recruited randomly as the control group. All clinical and ultrasound results, including images and parameters of cardiac structures, were reviewed retrospectively. General conditions, ultrasound (US) measurements, and fetal prognosis were compared between the groups. RESULTS: Aorta valve diameter (AOD), Z-score of aorta valve (AODz-score), aortic isthmus diameter (AOIsD), and pulmonary diameter (PAD)/AOD were significantly different in study group than control group no matter in the second or third trimester. Thirty-eight fetuses in study group were born with favorable outcomes after long-term follow-up. A total of 13.16% (5/38) remain mild narrow aorta and 3 of them showed smaller left ventricle after 3 years follow up. Prenatal AODz-score in infants remains mild narrow aorta after 2 years aged was higher than ones' aorta return to normal (P = .01), especially when AODz-score >1.725. Moreover, when prenatal ratio of AOIsD/left subclavian artery was <1.12, it was more likely that the aorta would remain mildly narrow at age 2. CONCLUSION: Fetuses diagnosed with PLSVC with mild narrow aorta had favorable prognosis. AODz-score and AOIsD/left subclavian artery may be two predictors that reveal the risk of a mildly narrowed aorta remaining after birth.

Single-cell transcriptomic analysis reveals the landscape of epithelial-mesenchymal transition molecular heterogeneity in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a prevalent and highly lethal malignant disease. The epithelial-mesenchymal transition (EMT) is crucial in promoting ESCC development. However, the molecular heterogeneity of ESCC and the potential inhibitory strategies targeting EMT remain poorly understood. In this study, we analyzed high-resolution single-cell transcriptome data encompassing 209,231 ESCC cells from 39 tumor samples and 16 adjacent samples obtained from 44 individuals. We identified distinct cell populations exhibiting heterogeneous EMT characteristics and identified 87 EMT-associated molecules. The expression profiles of these EMT-associated molecules showed heterogeneity across different stages of ESCC progression. Moreover, we observed that EMT primarily occurred in early-stage tumors, before lymph node metastasis, and significantly promoted the rapid deterioration of ESCC. Notably, we identified SERPINH1 as a potential novel marker for ESCC EMT. By classifying ESCC patients based on EMT gene sets, we found that those with high EMT exhibited poorer prognosis. Furthermore, we predicted and experimentally validated drugs targeting ESCC EMT, including dactolisib, docetaxel, and nutlin, which demonstrated efficacy in inhibiting EMT and metastasis in ESCC. Through the integration of scRNA-seq, RNA-seq, and TCGA data with experimental validation, our comprehensive analysis elucidated the landscape of EMT during the entire course of ESCC development and metastasis. These findings provide valuable insights and a reference for refining ESCC clinical treatment strategies.

Systematic identification of reference genes for qRT-PCR of Ardisia kteniophylla A. DC under different experimental conditions and for anthocyanin-related genes studies.

Ardisia kteniophylla A. DC, widely known as folk medicinal herb and ornamental plant, has been extensively investigated due to its unique leaf color, anti-cancer and other pharmacological activities. The quantitative real-time PCR (qRT-PCR) was an excellent tool for the analysis of gene expression with its high sensitivity and quantitative properties. Normalizing gene expression with stable reference genes was essential for qRT-PCR accuracy. In addition, no studies have yet been performed on the selection, verification and stability of internal reference genes suitable for A. kteniophylla, which has greatly hindered the biomolecular researches of this species. In this study, 29 candidate genes were successfully screened according to stable expression patterns of large-scale RNA seq data that from a variety of tissues and the roots of different growth stages in A. kteniophylla. The candidates were then further determined via qRT-PCR in various experimental samples, including MeJA, ABA, SA, NaCl, CuSO4, AgNO3, MnSO4, CoCl2, drought, low temperature, heat, waterlogging, wounding and oxidative stress. To assess the stability of the candidates, five commonly used strategies were employed: delta-CT, geNorm, BestKeeper, NormFinder, and the comprehensive tool RefFinder. In summary, UBC2 and UBA1 were found to be effective in accurately normalizing target gene expression in A. kteniophella regardless of experimental conditions, while PP2A-2 had the lowest stability. Additionally, to verify the reliability of the recommended reference genes under different colored leaf samples, we examined the expression patterns of six genes associated with anthocyanin synthesis and regulation. Our findings suggested that PAP1 and ANS3 may be involved in leaf color change in A. kteniphella. This study successfully identified the ideal reference gene for qRT-PCR analysis in A. kteniphella, providing a foundation for future research on gene function, particularly in the biosynthesis of anthocyanins.

Simulation of morphology for oil droplets in aqueous solution controlled by electric fields.

This study investigate the morphology of oil-in-water at high density ratio controlled by electric field. We incorporated the electric field into the Lattice Boltzmann method (LBM). The focus is on the modified lattice Boltzmann color gradient model simulate the evolution of the oil-in-water and analyze the relation between morphologies and electric field parameters. The results show that the stretching, merging and even breaking can be regulated by electric field strength, conductivity, dielectric constant, oil-water density ratio and droplet radius. Simulation results showed that the larger dielectric constant resulted in the smaller deformation, and the larger conductivity related to the greater deformation. Meanwhile, the larger radius droplet is easier to deform and break, and the higher density droplet is less likely to break. And this paper also gives the morphology of the stretching and destabilization of the droplets at each stage. These results are in good agreement with the relevant theoretical and experimental results.

Laser Linewidth Analysis and Filtering/Fitting Algorithms for Improved TDLAS-Based Optical Gas Sensor.

Tunable Diode Laser Absorption Spectroscopy (TDLAS) has been widely applied in in situ and real-time monitoring of trace gas concentrations. In this paper, an advanced TDLAS-based optical gas sensing system with laser linewidth analysis and filtering/fitting algorithms is proposed and experimentally demonstrated. The linewidth of the laser pulse spectrum is innovatively considered and analyzed in the harmonic detection of the TDLAS model. The adaptive Variational Mode Decomposition-Savitzky Golay (VMD-SG) filtering algorithm is developed to process the raw data and could significantly eliminate the background noise variance by about 31% and signal jitters by about 12.5%. Furthermore, the Radial Basis Function (RBF) neural network is also incorporated and applied to improve the fitting accuracy of the gas sensor. Compared with traditional linear fitting or least squares method (LSM), the RBF neural network brings along the enhanced fitting accuracy within a large dynamic range, achieving an absolute error of below 50 ppmv (about 0.6%) for the maximum 8000 ppmv methane. The proposed technique in this paper is universal and compatible with TDLAS-based gas sensors without hardware modification, allowing direct improvement and optimization for current optical gas sensors.

Hydrothermal deposition synthesis of dual-mode luminescent material GdVO4 :Eu3+ /carbon dots with optimal luminescence and its application in anti-counterfeiting.

To obtain optimal luminescence, 0.12 g of GdVO4 :3%Eu3+ nanocrystals (NCs) and different volumes of nitrogen-doped carbon dots (N-CDs) crude solution were used as precursors, and the composite synthesized using the hydrothermal deposition method showed optimal luminescence when 11 ml (2.45 mmol) crude solution was used. In addition, similar composites with the same molar ratio as GVE/cCDs(11) were also prepared with the hydrothermal and physical mixing processes. Based on the test results of XRD, XPS, and PL spectra, for the composite GVE/cCDs(11), the highest (lowest) peak intensity of the C-C/C=C (C=O/C=N) bond, which was 1.18 (0.75) times that of GVE/cCDs-m, indicated most N-CDs deposition and led to their highest emission intensity under 365 nm excitation, although nitrogen atoms in the composite were shed slightly during the deposition process. Finally, as can be seen from the patterns designed for security applications that the optimally luminescent composite is one of the most promising candidates in the anti-counterfeiting field.

Prenatal Diagnosis of Pierre Robin Sequence and Its Prognosis: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to explore the efficiency of ultrasound (US) in prenatal diagnosis and prognosis of Pierre Robin sequence (PRS) of 18 cases. STUDY DESIGN: A total of 79,305 women admitted for prenatal US examinations were recruited from January 2017 to December 2020. Eighteen cases of PRS fetuses were selected form the cohort and 40 cases of isolated micrognathia were recruited randomly as control group. All the clinical and imaging results were retrospectively reviewed. General condition, US measurements, and prognosis of fetuses were compared between groups. RESULTS: Cleft palate, glossoptosis, and micrognathia were found in all 18 fetuses with PRS by prenatal US. Compared with the isolated micrognathia group, there were no significant differences in the PRS group in examination of maternal age, gestational weeks at assessment, and gender of fetuses, but significant lower measures in inferior facial angle, jaw index, and frontal nasal-mental angle (each p < 0.05). Twelve fetuses were defined to have other associated malformations. Ear malformations were the most common associated malformations with a prevalence of 44.4% (8/18). All of the18 cases were confirmed with PRS after delivery or autopsy. Two delivered infants were found bucking easily, one baby was spitting up frequently but growth showed normal. CONCLUSION: Prenatal detection of PRS with US examination is highly efficient. Even with the triad of malformations, isolated PRS had good outcomes following initial stabilization and management in the neonatal period. Prenatal detection of Pierre Robin syndrome with targeted US examination is efficient in discerning characteristics of this rare syndrome. Even with the triad of malformations, isolated PRS had good outcomes following initial stabilization and management in the neonatal period. KEY POINTS: · Prenatal diagnosis of fetal PRS is of great clinical importance.. · Micrognathia has been identified as the primary feature of PRS.. · Posterior displacement of the tongue may cause acute neonatal respiratory distress.. · Even with triad malformation, isolated PRS seemed to have good outcomes..

The relationship between intolerance of uncertainty, coping style, resilience, and anxiety during the COVID-19 relapse in freshmen: A moderated mediation model.

Background: The repeated outbreaks of COVID-19 and the rapid increase in uncertainty have had many negative effects on the public's mental health, especially on emotional aspects such as anxiety and depression. However, in previous studies, there are few studies exploring the positive factors between uncertainty and anxiety. The innovation of this study is the first to explore the mechanism of coping style and resilience as people's psychological protective factors between uncertainty and anxiety caused by the COVID-19 pandemic. Methods: This study explored the relationship between intolerance of uncertainty and anxiety of freshmen with coping style as mediating variable and resilience as moderating variable. A total of 1049 freshmen participated in the study and completed the Intolerance of Uncertainty Scale (IUS-12), Self-rating Anxiety Scale (SAS), Simplified Coping Style Questionnaire (SCSQ), and Connor-Davidson Resilience Scale (CD-RISC). Results: SAS score of the surveyed students (39.56 ± 10.195) was significantly higher than that of the Normal Chinese score (29.78 ± 10.07, p < 0.001). Intolerance of uncertainty was significantly positively correlated with anxiety (ß = 0.493, p < 0.001). Positive coping style has a significant negative impact on anxiety (ß = -0.610, p < 0.001), negative coping style has a significant positive impact on anxiety (ß = 0.951, p < 0.001). Resilience moderates the second half of the influence of negative coping style on anxiety (ß = 0.011, t = 3.701, p < 0.01). Conclusion: The findings suggest that high levels of intolerance of uncertainty had negative effects mental burden during the COVID-19 pandemic. The knowledge of the mediating role of coping style and the moderating role of resilience may be used by health care workers when consulting freshmen with physical health complaints and psychosomatic disorders.

Association Between Urinary Stress Incontinence and Levator Avulsion Detected by 3D Transperineal Ultrasound.

PURPOSE: To determine the association between levator avulsion and urinary stress incontinence (USI) by 3/4D transperineal ultrasound. MATERIALS AND METHODS: 842 patients who were admitted to our hospital from 2016 to 2019 were recruited for our study. 3D/4D transperineal ultrasound was performed. After standard interview and clinical evaluation, general conditions and levator hiatus data were collected and measured to compare with each group. The odds ratio (OR) of USI symptoms or ultrasound features with levator avulsion were calculated. RESULTS: A total of 593 women were studied: 204 suffered from levator avulsion (96 cases of left-side avulsion, 80 cases of right-side avulsion and 28 cases of bilateral avulsion) and 389 women had no avulsion. The gravidity and episiotomy conditions of the avulsion groups were significantly different from the no-avulsion group. Significant differences were found in the transverse diameters and anteroposterior diameters between the levator avulsion group and the no-avulsion group, but there was no difference among the avulsion groups, regardless of whether the patient was at rest or performing the Valsalva maneuver. Interestingly, a significant difference was found in the presence of USI symptoms between the uni-avulsion group and the no-avulsion group. The odds ratio (OR) of USI symptoms in the uni-avulsion group is 2.786 (95 %CI, 1.663-4.669), but 0.939 (95 %CI, 0.276-3.199) for the bilateral avulsion and no-avulsion groups. CONCLUSION: Unilateral levator avulsion may be a risk factor for urinary stress incontinence.

The fate of Cd during the replacement of Cd-bearing calcite by calcium phosphate minerals.

Carbonate-bound speciation is a critical sink of potentially toxic elements (PTEs) like cadmium (Cd) in soil and sediment. In a phosphate-rich environment, carbonate minerals could be replaced by phosphate minerals such as dicalcium phosphate dihydrate (DCPD, also known as brushite), octacalcium phosphate (OCP), and hydroxylapatite (HAP). Currently, it is unclear the migration and fate of PTEs during the replacement of PTEs-bearing carbonates by HAP and related intermediate minerals. Therefore, we synthesized Cd-bearing calcite by the coprecipitation method and converted it to DCPD, OCP, and HAP to investigate the redistribution and fate of Cd. The results showed that Cd incorporation in calcite significantly inhibited their replacement by DCPD and OCP, respectively. 1.26% of Cd in calcite was released into the solution when DCPD replaced calcite, and subsequently, most of the released Cd was recaptured by OCP. Significantly, the released Cd was below 0.05‰ when all the solid converted to HAP. These results suggested that with the application of phosphate fertilizer in alkaline soil, the secondary calcium phosphate minerals could control the environmental behavior of Cd.

Small-volume highly-sensitive all-optical gas sensor using non-resonant photoacoustic spectroscopy with dual silicon cantilever optical microphones.

A small-volume highly-sensitive photoacoustic spectroscopy (PAS) methane detection system based on differential silicon cantilever optical microphones (SCOMs) is proposed and experimentally demonstrated. The system contains a compact non-resonant photoacoustic cell with a small volume of 1.2 mL and symmetrically-located dual SCOMs, as well as a distributed feedback laser at 1650.96 nm. The two identical SCOMs utilize the Fabry-Perot interferometric fiber-optic structure, with the differential Q-point demodulation algorithm to suppress the external vibration noise. Experimental results show that the SCOM has a high displacement sensitivity about 7.1 µm/Pa at 150 Hz and within 2.5 dB fluctuation between 5 Hz and 250 Hz. In the PAS gas sensing experiment, the normalized noise equivalent absorption coefficient of the PAS system is estimated to be 1.2 × 10-9 cm-1·W·Hz-1/2 and the minimum detection limit for methane is about 111.2 ppb with 1 s integration time. External disturbance is also applied to the dual SCOM system and results show excellent stability and noise resistance. The proposed PAS system exhibits superiorities of low gas consumption, high sensitivity and immunity to vibration and electromagnetic interference, which has an enormous potential in medicine, industry and environment.

Design of Environmentally Friendly Ca-Alginate Beads for Self-Healing Cement-Based Materials.

Ca-alginate beads have strong hygroscopicity, which have been used for the self-healing and internal curing of cement-based materials. However, ca-alginate beads in cement will chelate with calcium ions, which decreases the swelling rate of ca-alginate beads in the healing environment and is detrimental to the self-healing of cement-based materials. In this paper, the mechanism and steps for preparing ca-alginate beads with a lower ability to chelate with calcium ions were proposed based on protonation theory. In addition, the molecular structure and the swelling rates in cement filtrate and healing environment of ca-alginate beads prepared by the proposed method were characterized. The results showed that the ca-alginate beads prepared by the proposed method had higher molecular density and a lower ability to chelate with calcium ions. The swelling rate in the healing environment is not decreased. Furthermore, the equilibrium swelling rate in cement filtrate can satisfy the need for internal curing of cement-based materials.

Twin-Twin Transfusion Syndrome After Radiofrequency Ablation in Dizygotic Monochorionic Triamniotic Triplet Pregnancy With Sex Discordance: A Case Report.

Background: We report a case of dizygotic monochorionic triamniotic triplet pregnancy. Twin-twin transfusion syndrome was subsequently diagnosed combined with sex discordance in the two surviving fetuses after one fetus was reduced, which is extremely rare and has not been previously reported. Case Presentation: After reducing one fetus by radiofrequency ablation of a monochorionic triamniotic triplet pregnancy, twin-twin transfusion syndrome was subsequently diagnosed combined with sex discordance in the two surviving fetuses. Amniotic fluid for chromosome analysis showed normal karyotype 46, XY/46, XX of the donor and recipient fetus, and short tandem repeat (STR) analysis revealed dizygotic twins. Conclusions: Through this is an unusual case, we aim to emphasize the importance of accurate diagnosis of chorionicity and zygosity in sex discordant triplet pregnancy, which is the key to appropriate clinical management.

Fluxonium: An Alternative Qubit Platform for High-Fidelity Operations.

Superconducting qubits provide a promising path toward building large-scale quantum computers. The simple and robust transmon qubit has been the leading platform, achieving multiple milestones. However, fault-tolerant quantum computing calls for qubit operations at error rates significantly lower than those exhibited in the state of the art. Consequently, alternative superconducting qubits with better error protection have attracted increasing interest. Among them, fluxonium is a particularly promising candidate, featuring large anharmonicity and long coherence times. Here, we engineer a fluxonium-based quantum processor that integrates high qubit coherence, fast frequency tunability, and individual-qubit addressability for reset, readout, and gates. With simple and fast gate schemes, we achieve an average single-qubit gate fidelity of 99.97% and a two-qubit gate fidelity of up to 99.72%. This performance is comparable to the highest values reported in the literature of superconducting circuits. Thus our work, within the realm of superconducting qubits, reveals an alternative qubit platform that is competitive with the transmon system.

Metabacillus dongyingensis sp. nov. Is Represented by the Plant Growth-Promoting Bacterium BY2G20 Isolated from Saline-Alkaline Soil and Enhances the Growth of Zea mays L. under Salt Stress.

A novel plant growth-promoting rhizobacterium (PGPR), which was designated strain BY2G20, was isolated from saline-alkaline soil in Dongying, China. Strain BY2G20 can grow at a NaCl range from 0 to 7% and a pH range from 7 to 9 and can prevent the growth of the phytopathogen Ralstonia solanacearum. Based on its phenotypic and genomic characteristics and phylogenetic analysis, strain BY2G20 represents a novel species of the genus Metabacillus, for which the name Metabacillus dongyingensis sp. nov. is proposed. Comparative genomic analysis of strain BY2G20 with its closely related species exhibited a high level of evolutionary plasticity derived by horizontal gene transfer, which facilitated adaptative evolution. Different evolutionary constraints have operated on the diverse functions of BY2G20, with the gene adapted to saline-alkaline ecosystems experiencing functional constraints. We determined the genetic properties of saline-alkaline tolerance and plant growth promotion, such as cation-proton antiporters, cation transporters, osmoprotectant synthesis and transport, H+-transporting F1F0-ATPase, indole-3-acetic acid production, and secondary metabolite synthesis. We also evaluated the effects of strain BY2G20 on the growth of Zea mays L. (maize) under salt stress. The physiological parameters of maize such as plant height, stem diameter, dry biomass, and fresh biomass were significantly higher after inoculating strain BY2G20 under salt stress, indicating that inoculation with BY2G20 enhanced the growth of maize in saline areas. This study demonstrates that M. dongyingensis sp. nov. BY2G20 is a potential candidate for organic agriculture biofertilizers in saline-alkaline areas. IMPORTANCE Plant growth and yield are adversely affected by soil salinity. PGPRs can promote plant growth and enhance plant tolerance to salt stress. In this study, a saline-alkaline tolerant PGPR strain BY2G20 was isolated from the rhizosphere of Ulmus pumila in Dongying, China. Strain BY2G20 represents a novel species within the genus Metabacillus based on phenotypic, genomic, and phylogenetic analysis. Genomic components have undergone different functional constraints, and the disparity in the evolutionary rate may be associated with the adaptation to a specific niche. Genomic analysis revealed numerous adaptive features of strain BY2G20 to a saline-alkaline environment and rhizosphere, especially genes related to salt tolerance, pH adaptability, and plant growth promotion. Our work also exhibited that inoculation of strain BY2G20 enhanced the growth of maize under salt stress. This study demonstrates that PGPRs play an important role in stimulating salt tolerance in plants and can be used as biofertilizers to enhance the growth of crops in saline-alkaline areas.

Hypothesis Learning in Automated Experiment: Application to Combinatorial Materials Libraries.

Machine learning is rapidly becoming an integral part of experimental physical discovery via automated and high-throughput synthesis, and active experiments in scattering and electron/probe microscopy. This, in turn, necessitates the development of active learning methods capable of exploring relevant parameter spaces with the smallest number of steps. Here, an active learning approach based on conavigation of the hypothesis and experimental spaces is introduced. This is realized by combining the structured Gaussian processes containing probabilistic models of the possible system's behaviors (hypotheses) with reinforcement learning policy refinement (discovery). This approach closely resembles classical human-driven physical discovery, when several alternative hypotheses realized via models with adjustable parameters are tested during an experiment. This approach is demonstrated for exploring concentration-induced phase transitions in combinatorial libraries of Sm-doped BiFeO3 using piezoresponse force microscopy, but it is straightforward to extend it to higher-dimensional parameter spaces and more complex physical problems once the experimental workflow and hypothesis generation are available.

Diverse cardiac phenotypes among different carriers of the same MYH7 splicing variant allele (c.732+1G>A) from a family.

BACKGROUND: Left ventricular non-compaction cardiomyopathy (LVNC) is a rare congenital heart defect. Gene defections have been found in patients with LVNC and their family members; and MYH7 is the most frequent gene associated with LVNC. METHODS: We performed a complete prenatal ultrasound and echocardiographic examination on a fetus with cardiac abnormality and a parent-child trio whole-exome sequencing to identify the potential genetic causes. When the genetic abnormality in MYH7 was identified in the fetus, we performed echocardiography and genetic screening on its high-risk relatives. RESULTS: Second trimester ultrasound and echocardiography showed several malformations in the fetus: Ebstein's anomaly (EA), heart dilatation, perimembranous ventricle septal defects, mild seroperitoneum, and single umbilical artery. Heterozygous genotyping of a splicing variant allele (NM_00025.3: c.732+G>A) was identified in this fetus and her mother, not her father, indicating a maternal inheritance. Subsequently, direct sequencing confirmed the presence of this splicing variant among her grandmother (mother of mother), mother, older sister, and herself in a heterozygous manner. No PCR products were amplified by qRT-PCR for the RNA samples extracted from peripheral blood cells. In addition to this proband who was diagnosed with EA, her older sister and grandmother (mother of mother) were diagnosed with isolated asymptomatic LVCN, but her mother was just a carrier with no marked clinical manifestations after family screening. CONCLUSION: The presence of MYH7 splicing variant c.732+G>A can be inherited maternally, and its cardiac phenotypes are different from one carrier to another.