Association of basal serum testosterone levels with ovarian response and in vitro fertilization outcome

<p>Abstract</p> <p>Background</p> <p>To evaluate basal testosterone (T) levels during follicular phase of the menstrual cycle as a predictor for ovarian response and in vitro fertilization (IVF) outcome.</p> <p>Method</p> <p>We analyzed data retrospectively from hospital-based IVF center including one thousand two hundred and sixty Chinese Han women under their first IVF cycle reached the ovum pick-up stage, without polycystic ovary syndrome (PCOS) or endometriosis undergoing long IVF protocol. Patients were divided into 2 groups. Group 1: patients with diminished ovarian reserve (basal FSH >10 IU/L) (n = 187); Group 2: patients with normal ovarian reserve (basal FSH < = 10 IU/L) (n = 1073). We studied the association of basal T levels with ovarian response and IVF outcome in the two groups. Long luteal down-regulation protocol was used in all patients, that is, the gonadotropin releasing hormone agonist was administered in the midluteal phase of the previous cycle and use of recombinant FSH was started when satisfactory pituitary desensitization was achieved.</p> <p>Results</p> <p>Basal T levels were markly different between pregnant and non-pregnant women in Group 1; whereas not in Group 2. A testosterone level of 47.85 ng/dl was shown to predict pregnancy outcome with a sensitivity of 52.8% and specificity of 65.3%; and the basal T was correlated with the numbers of large follicles (> 14 mm) on HCG day in Group 1. Significantly negative correlations were observed between basal T, days of stimulation and total dose of gonadotropins after adjusting for confounding factors in both groups.</p> <p>Conclusion</p> <p>In women with diminished ovarian reserve, basal T level was a predictor for the number of large follicles on HCG day and pregnancy outcome; but could not in those with normal serum FSH. Basal T levels were associated with both days of stimulation and total dose of gonadotropins, indicating that lower level of T might relate with potential ovarian poor response.</p

Excellent energy storage performance in Bi0.5Na0.5TiO3-based lead-free high-entropy relaxor ferroelectrics via B-site modification

Next-generation advanced high/pulsed power capacitors urgently require dielectric materials with outstanding energy storage performance. Bi0.5Na0.5TiO3-based lead-free materials exhibit high polarization, but the high remanent polarization and large polarization hysteresis limit their applications in dielectric capacitors. Herein, high-entropy perovskite relaxor ferroelectrics (Na0.2Bi0.2Ba0.2Sr0.2Ca0.2)(Ti1−x%Zrx%)O3 are designed by adding multiple ions in the A-site and replacing the B-site Ti4+ with a certain amount of Zr4+. The newly designed system showed high relaxor feature and slim polarization–electric (P–E) loops. Especially, improved relaxor feature and obviously delayed polarization saturation were found with the increasing of Zr4+. Of particular importance is that both high recoverable energy storage density of 6.6 J/cm3 and energy efficiency of 93.5% were achieved under 550 kV/cm for the ceramics of x = 6, accompanying with excellent frequency stability, appreciable thermal stability, and prosperous discharge property. This work not only provides potential dielectric materials for energy storage applications, but also offers an effective strategy to obtain dielectric ceramics with ultrahigh comprehensive energy storage performance to meet the demanding requirements of advanced energy storage applications

Comparative genomic analysis of esophageal squamous cell carcinoma among different geographic regions

IntroductionEsophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence, survival, and risk factors. Although the genomic characteristics of ESCC have been extensively characterized, the genomic differences between different geographic regions remain unclear.MethodsIn this study, we sequenced 111 patients with ESCC from northern (NC) and southern (SC) China, combined their data with those of 1081 cases from previous reports, and performed a comparative analysis among different regions. In total, 644 ESCC cases were collected from six geographic regions (NC, SC, Xinjiang, China [XJC], Japan [JP], Vietnam [VN], and Europe &amp; America [EA]) as the discovery cohort. Validation cohort 1 included 437 patients with ESCC from the NC region. Validation cohort 2 included 54 and 57 patients from the NC and SC regions, respectively.ResultsPatients with ESCC in different regions had different genomic characteristics, including DNA signatures, tumor mutation burdens, significantly mutated genes (SMGs), altered signaling pathways, and genes associated with clinical features. Based on both the DNA mutation signature and the mutation profile of the most common genes, the NC and SC groups were clustered close together, followed by the JP, XJC, EA, and VN groups. Compared to patients with ESCC from SC, SMGs, including KMT2D, FAT1, and NOTCH1 were more frequently identified in patients with ESCC from NC. Furthermore, some genes (TDG and DNAH8) correlated with overall survival in completely opposite ways in patients with ESCC from different geographical regions.ConclusionsOur study provides insights into genomic differences in ESCC among different regions. These differences may be related to differences in environmental carcinogens, incidence, and survival

The identification of switch-like alternative splicing exons among multiple samples with RNA-Seq data.

Alternative splicing is an ubiquitous phenomenon in most human genes and has important functions. The switch-like exon is the type of exon that has a high level of usage in some tissues, but has a low level of usage in the other tissues. They usually undergo strong tissue-specific regulations. There is still a lack a systematic method to identify switch-like exons from multiple RNA-seq samples. We proposed a novel method called iterative Tertile Absolute Deviation around the mode (iTAD) to profile the distribution of exon relative usages among multiple samples and to identify switch-like exons and other types of exons using a robust statistic estimator. We validated the method with simulation data, and applied it on RNA-seq data of 16 human body tissues and detected 3,100 switch-like exons. We found that switch-like exons tend to be more associated with Alu elements in their flanking intron regions than other types of exons

The percentage of Alu elements present in the upstream flanking region, the exon body and the downstream flanking region of each type of exons.

<p>The percentage of Alu elements present in the upstream flanking region, the exon body and the downstream flanking region of each type of exons.</p

The settings of experiment 1 and the corresponding parameters calculated by iTAD.

<p>The settings of experiment 1 and the corresponding parameters calculated by iTAD.</p

The schematic diagram of iTAD.

<p>(A) The calculation of <i>PSI</i> as the measurement of exon relative usage. <i>n</i>_<i>UJC</i> and <i>n</i>_<i>DJC</i> are the counts of reads at the exon’s upstream splice junction and its downstream splice junction, respectively. <i>n</i>_<i>SJC</i> is the count of junction reads connecting its upstream and downstream exons but skipping this exon. (B) Calculating PSIs on multiple samples. (C) The histogram of the exon’s relative usage in multiple samples. The mode is identified as the center of a PSIS. (D) The Tertile Absolute Deviation around the mode (TAD) is calculated to describe the intensity of the PSIS. If there are sufficient samples within a narrow region around the mode, reflected by a threshold on the TAD, we identify the PSIS as a dominating PSIS. (E) The identification of the second PSIS after removing samples belonging to ±c region of the first PSIS. (F) The detection of the switch-like exon based on the two PSISs. (G) Four typical relative usage patterns of alternative splicing exons across multiple samples.</p

The settings of experiment 2 and the corresponding parameters calculated by iTAD.

<p>The settings of experiment 2 and the corresponding parameters calculated by iTAD.</p

The heatmap of TAD for the first and second PSISs for candidates of exons.

<p>The candidates of one exon type represents exons having the corresponding dominating or non-dominating PSISs but before being tested by the significance tests. Switch-like, solo-dominating and non-dominating exons are shown. Constitutive exons are not shown as they only have one PSIS. The “density” on the heatmap shown in colors is the number of exons whose TADs fall into the corresponding region.</p