The transfer of fresh embryos is generally preferred over the transfer of frozen embryos for in vitro fertilization (IVF), but some evidence suggests that frozen-embryo transfer may improve the ...live-birth rate and lower the rates of the ovarian hyperstimulation syndrome and pregnancy complications in women with the polycystic ovary syndrome.
In this multicenter trial, we randomly assigned 1508 infertile women with the polycystic ovary syndrome who were undergoing their first IVF cycle to undergo either fresh-embryo transfer or embryo cryopreservation followed by frozen-embryo transfer. After 3 days of embryo development, women underwent the transfer of up to two fresh or frozen embryos. The primary outcome was a live birth after the first embryo transfer.
Frozen-embryo transfer resulted in a higher frequency of live birth after the first transfer than did fresh-embryo transfer (49.3% vs. 42.0%), for a rate ratio of 1.17 (95% confidence interval CI, 1.05 to 1.31; P=0.004). Women who underwent frozen-embryo transfer also had a lower frequency of pregnancy loss (22.0% vs. 32.7%), for a rate ratio of 0.67 (95% CI, 0.54 to 0.83; P<0.001), and of the ovarian hyperstimulation syndrome (1.3% vs. 7.1%), for a rate ratio of 0.19 (95% CI, 0.10 to 0.37; P<0.001), but a higher frequency of preeclampsia (4.4% vs. 1.4%), for a rate ratio of 3.12 (95% CI, 1.26 to 7.73; P=0.009). There were no significant between-group differences in rates of other pregnancy and neonatal complications. There were five neonatal deaths in the frozen-embryo group and none in the fresh-embryo group (P=0.06).
Among infertile women with the polycystic ovary syndrome, frozen-embryo transfer was associated with a higher rate of live birth, a lower risk of the ovarian hyperstimulation syndrome, and a higher risk of preeclampsia after the first transfer than was fresh-embryo transfer. (Funded by the National Basic Research Program of China and others; ClinicalTrials.gov number, NCT01841528.).
Increasing the density of sinks such as grain boundaries and interfaces for irradiation-induced defects and implanted ions has been demonstrated to be an effective way to improve the irradiation ...resistance of materials. To understand the effects of grain boundaries on the degradation mechanism of nanostructured materials, nanocrystalline tungsten was fabricated by high pressure torsion (HPT-W). Morphological changes of HPT-W and coarse grain tungsten (CG-W) during helium ion irradiation were evaluated in situ in a helium ion microscopy. It has been shown that the degradation mechanisms of CG-W and HPT-W are remarkably different. Blister occurs on the surface of CG-W when the irradiation dose increases up to 5.0 × 1021 m−2, and orientation dependence of blistering has been observed. However, no blister is formed on the surface of HPT-W even when the irradiation dose increases up to 1.0 × 1023 m−2. Instead, crack formation along grain boundaries is the major degradation mechanism during helium irradiation of HPT-W, supporting a different irradiation degradation mechanism. This explains the unprecedented irradiation tolerance of HPT-W in terms of blistering. Molecular dynamics results also show that grain boundaries and helium clusters play an important role during the propagation of a crack. The zigzag crack planes are attributed to the coalescence and growth of helium blister/bubble-induced crack. The results document that grain boundaries play decisive roles in the irradiation resistance of nanostructured materials, and provide a new perspective to the design of plasma facing materials with excellent irradiation resistance. It is thus suggested that excellent irradiation resistance can be achieved by a meticulous design of grain boundaries based on “interface engineering”.
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•Ca and P incorporated layers were prepared on Mg alloy by micro-arc oxidation (MAO).•Ca and P inside the MAO layer existed with amorphous phase.•Dicalcium phosphate dihydrate crystals were formed by ...hydrothermal treatment.•MAO and hydrothermal treatment enhanced the biocorrosion resistance of Mg alloy.•The pitting corrosion resistance of Mg alloy was improved greatly.
A layer containing dicalcium phosphate dihydrate (DCPD) and β-Ca3(PO4)2 was prepared on magnesium alloy by hydrothermal treatment of micro-arc oxide (MAO) layer. The biocorrosion resistance of the oxide layers before and after hydrothermal treatment was analyzed by anodic polarization and electrochemical impedance spectroscopy (EIS) in Hank’s solution. The prepared MAO layers consisted mainly of MgO and MgAl2O4, and Ca and P inside the oxide layers existed with amorphous phase. Hydrothermal treatments not only made the amorphous Ca and P change into DCPD and β-Ca3(PO4)2 crystals, but also improved the biocorrosion resistance of magnesium alloys, especially the pitting corrosion resistance.
Although alkaline sensation is critical for survival, alkali-activated receptors are yet to be identified in vertebrates. Here, we showed that the OTOP1 channel can be directly activated by ...extracellular alkali. Notably, OTOP1 biphasically mediated proton influx and efflux with extracellular acid and base stimulation, respectively. Mutations of K221 and R554 at the S5-S6 and S11-S12 linkers significantly reduced alkali affinity without affecting acid activation, suggesting that different domains are responsible for acid- and alkali-activation of OTOP1. The selectivity for H
was significantly higher in OTOP1 activated by alkali than that by acid, further suggesting that the two activations might be independent gating processes. Given that the alkali-activation of OTOP1 and the required key residues were conserved in the six representative vertebrates, we cautiously propose that OTOP1 participates in alkaline sensation in vertebrates. Thus, our study identified OTOP1 as an alkali-activated channel.
The present study investigated the effects of infertility on Chinese women’s life satisfaction. Infertile women (
n
= 466) who were seeking medical help completed a survey that included the ...Fertility Problem Inventory (FPI), the Dyadic Adjustment Questionnaire (DAS), the Connor-Davidson Resilience Scale (CD-RISC), the Satisfaction with Life Scale, and demographic variables. We used a moderated mediation model to test our hypotheses, with life satisfaction as the dependent variable, representations about the importance of parenthood as the independent variable, the impact of infertility on life domains as a mediator, and marital satisfaction and resilience as moderators. Results showed that representations about the importance of parenthood and the impact of infertility on life domains are two main types of infertility-related stress, which could play independent roles in predicting life satisfaction. Representations about the importance of parenthood had a negative indirect effect on life satisfaction through the impact of infertility on life domains, and the indirect effect of the impact of infertility on life domains was moderated by marital satisfaction and resilience. Specially, representations about the importance of parenthood had a weaker indirect effect (through the impact of infertility on life domains) on life satisfaction in individuals with higher marital satisfaction or resilience. Therefore, the type of infertility-related stress and both marital satisfaction and resilience should be addressed in psychological interventions for women coping with infertility in mainland China.
To facilitate the clinical implementation of genomic medicine by next-generation sequencing, it will be critically important to obtain accurate and consistent variant calls on personal genomes. ...Multiple software tools for variant calling are available, but it is unclear how comparable these tools are or what their relative merits in real-world scenarios might be.
We sequenced 15 exomes from four families using commercial kits (Illumina HiSeq 2000 platform and Agilent SureSelect version 2 capture kit), with approximately 120X mean coverage. We analyzed the raw data using near-default parameters with five different alignment and variant-calling pipelines (SOAP, BWA-GATK, BWA-SNVer, GNUMAP, and BWA-SAMtools). We additionally sequenced a single whole genome using the sequencing and analysis pipeline from Complete Genomics (CG), with 95% of the exome region being covered by 20 or more reads per base. Finally, we validated 919 single-nucleotide variations (SNVs) and 841 insertions and deletions (indels), including similar fractions of GATK-only, SOAP-only, and shared calls, on the MiSeq platform by amplicon sequencing with approximately 5000X mean coverage.
SNV concordance between five Illumina pipelines across all 15 exomes was 57.4%, while 0.5 to 5.1% of variants were called as unique to each pipeline. Indel concordance was only 26.8% between three indel-calling pipelines, even after left-normalizing and intervalizing genomic coordinates by 20 base pairs. There were 11% of CG variants falling within targeted regions in exome sequencing that were not called by any of the Illumina-based exome analysis pipelines. Based on targeted amplicon sequencing on the MiSeq platform, 97.1%, 60.2%, and 99.1% of the GATK-only, SOAP-only and shared SNVs could be validated, but only 54.0%, 44.6%, and 78.1% of the GATK-only, SOAP-only and shared indels could be validated. Additionally, our analysis of two families (one with four individuals and the other with seven), demonstrated additional accuracy gained in variant discovery by having access to genetic data from a multi-generational family.
Our results suggest that more caution should be exercised in genomic medicine settings when analyzing individual genomes, including interpreting positive and negative findings with scrutiny, especially for indels. We advocate for renewed collection and sequencing of multi-generational families to increase the overall accuracy of whole genomes.
Neuroblastoma is a paediatric malignancy that typically arises in early childhood, and is derived from the developing sympathetic nervous system. Clinical phenotypes range from localized tumours with ...excellent outcomes to widely metastatic disease in which long-term survival is approximately 40% despite intensive therapy. A previous genome-wide association study identified common polymorphisms at the LMO1 gene locus that are highly associated with neuroblastoma susceptibility and oncogenic addiction to LMO1 in the tumour cells. Here we investigate the causal DNA variant at this locus and the mechanism by which it leads to neuroblastoma tumorigenesis. We first imputed all possible genotypes across the LMO1 locus and then mapped highly associated single nucleotide polymorphism (SNPs) to areas of chromatin accessibility, evolutionary conservation and transcription factor binding sites. We show that SNP rs2168101 G>T is the most highly associated variant (combined P = 7.47 × 10(-29), odds ratio 0.65, 95% confidence interval 0.60-0.70), and resides in a super-enhancer defined by extensive acetylation of histone H3 lysine 27 within the first intron of LMO1. The ancestral G allele that is associated with tumour formation resides in a conserved GATA transcription factor binding motif. We show that the newly evolved protective TATA allele is associated with decreased total LMO1 expression (P = 0.028) in neuroblastoma primary tumours, and ablates GATA3 binding (P < 0.0001). We demonstrate allelic imbalance favouring the G-containing strand in tumours heterozygous for this SNP, as demonstrated both by RNA sequencing (P < 0.0001) and reporter assays (P = 0.002). These findings indicate that a recently evolved polymorphism within a super-enhancer element in the first intron of LMO1 influences neuroblastoma susceptibility through differential GATA transcription factor binding and direct modulation of LMO1 expression in cis, and this leads to an oncogenic dependency in tumour cells.
To evaluate the efficacy of the long-acting gonadotropin-releasing hormone agonist (GnRH-a) administration before hormone replacement treatment for frozen-thawed embryo transfer in women with ...different times of embryo implantation failures.
A retrospective cohort study was performed between January 2015 and December 2019. A total of 9263 women who underwent frozen-thawed embryo transfer were included in the study. The study is divided into three parts based on the times of embryo implantation failures. The sample sizes were 4611 for no implantation failure, 3565 for one failure and 1087 for multiple failures. Two endometrium preparation protocols, HRT and HRT with GnRH-a pretreatment (G-HRT), were compared. Confounding factors were treated by propensity score matching and generalized estimation equation.
For women with no failure of embryo implantation, the live birth rate was not statistically different when they underwent HRT and G-HRT (HRT: 42.75% 498/1165, G-HRT: 45.24% 527/1165, P=0.2261). Similar outcome also appeared in women with one failure of embryo implantation (HRT: 47.22% 535/1133, G-HRT: 50.31% 570/1131, P=0.1413). For women with multiple failures of embryo implantation, the live birth rate was significantly difference (HRT: 38.74% 117/302, G-HRT: 45.48% 357/785, P=0.0449). When stratified by age, the live birth rate is similar for women older than 37 years. Generalized estimation equation showed that GnRH agonist pretreatment was independently associated with the live birth rate for women with multiple failures (adjust OR: 1.5, 95%CI: 1.12-2.00).
For women with no/one failure of embryo implantation, the live birth rate is similar between HRT and G-HRT protocols. For women with multiple failure of embryo implantation, GnRH agonist pretreatment is beneficial to raise the live birth rate.
•Polycrystalline tungsten films with different sizes and crystalline phases were prepared using a magnetron sputtering deposition•The films were performed selective implantation and in-situ analysis ...using a helium ion microscope•After implantation, longitudinal cracks are formed which is different from that of a single crystal•β-W polycrystalline film with simple cubic has stronger resistance to implantation than α-W with body-centered cubic
Tungsten is regarded as a potential plasma facing material (PFM) in nuclear fusion reactors owing to its high melting point, good thermal conductivity, and low sputtering yield. However, various types of defects such as interstitial atoms, vacancies, dislocation rings, cavities, helium bubbles, and “fuzz” occur in W under helium irradiation. In this study, we obtained α- and β-phase W films with nanochannels and used a helium ion microscope to conduct helium ion implantation experiments on the films. The implantation dose and energy were 1.5 × 1022 ions/m2, and 30 keV, respectively. There was no helium bubble formation in the β-W film until the completion of the implantation. The uniformly distributed columnar crystals growing perpendicular to the substrate constitute remarkable nanochannels. These effectively inhibit the aggregation of helium atoms. For α-W films prepared at high temperatures, the escape efficiency of the implanted helium atoms was reduced owing to the chaotic and reduced number of nanochannels, and helium bubbles are eventually formed. Cross-sectional images revealed that helium atoms tended to gather near the grain boundaries and gradually followed the nanochannels formed by the grain boundaries. The expansion eventually formed numerous longitudinal fissures. The results show that grain boundaries play a decisive role in the radiation resistance of nanostructured materials. Furthermore, the preparation of regular nanochannels that reach the sample surface is an effective method to improve the helium escape capability.
Mental disorders present a global health concern, while the diagnosis of mental disorders can be challenging. The diagnosis is even harder for patients who have more than one type of mental disorder, ...especially for young toddlers who are not able to complete questionnaires or standardized rating scales for diagnosis. In the past decade, multiple genomic association signals have been reported for mental disorders, some of which present attractive drug targets. Concurrently, machine learning algorithms, especially deep learning algorithms, have been successful in the diagnosis and/or labeling of complex diseases, such as attention deficit hyperactivity disorder (ADHD) or cancer. In this study, we focused on eight common mental disorders, including ADHD, depression, anxiety, autism, intellectual disabilities, speech/language disorder, delays in developments, and oppositional defiant disorder in the ethnic minority of African Americans. Blood-derived whole genome sequencing data from 4179 individuals were generated, including 1384 patients with the diagnosis of at least one mental disorder. The burden of genomic variants in coding/non-coding regions was applied as feature vectors in the deep learning algorithm. Our model showed ~65% accuracy in differentiating patients from controls. Ability to label patients with multiple disorders was similarly successful, with a hamming loss score less than 0.3, while exact diagnostic matches are around 10%. Genes in genomic regions with the highest weights showed enrichment of biological pathways involved in immune responses, antigen/nucleic acid binding, chemokine signaling pathway, and G-protein receptor activities. A noticeable fact is that variants in non-coding regions (e.g., ncRNA, intronic, and intergenic) performed equally well as variants in coding regions; however, unlike coding region variants, variants in non-coding regions do not express genomic hotspots whereas they carry much more narrow standard deviations, indicating they probably serve as alternative markers.
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