TAT-beclin1 treatment accelerates the development of atherosclerotic lesions in ApoE-deficient mice.

The importance of autophagy in atherosclerosis has garnered significant attention regarding the potential applications of autophagy inducers. However, the impact of TAT-Beclin1, a peptide inducer of autophagy, on the development of atherosclerotic plaques remains unclear. Single-cell omics analysis indicates a notable reduction in GAPR1 levels within fibroblasts, stromal cells, and macrophages during atherosclerosis. Tat-beclin1 (T-B), an autophagy-inducing peptide derived from Beclin1, could selectively bind to GAPR1, relieving its inhibition on Beclin1 and thereby augmenting autophagosome formation. To investigate its impact on atherosclerosic plaque progression, we established the ApoE-/- mouse model of carotid atherosclerotic plaques. Surprisingly, intravenous administration of Tat-beclin1 dramatically accelerated the development of carotid artery plaques. Immunofluorescence analysis suggested that macrophage aggregation and autophagosome formation within atherosclerotic plaques were significantly increased upon T-B treatment. However, immunofluorescence and transmission electron microscopy (TEM) analysis revealed a reduction in autophagy flux through lysosomes. In vitro, the interaction between T-B and GAPR1 was confirmed in RAW264.7 cells, resulting in the increased accumulation of p62/SQSTM1 and LC3-II in the presence of ox-LDL. Additionally, T-B treatment elevated the protein levels of p62/SQSTM1, LC3-II, and cleaved caspase 1, along with the secretion of IL-1ß in response to ox-LDL exposure. In summary, our study underscores that T-B treatment amplifies abnormal autophagy and inflammation, consequently exacerbating atherosclerotic plaque development in ApoE-/- mice.

Who is at risk of lung nodules on low-dose CT in a Western country? A population-based approach.

BACKGROUND: This population-based study aimed to identify the risk factors for lung nodules in a Western European general population. METHODS: We quantified the presence or absence of lung nodules among 12 055 participants of the Dutch population-based ImaLife (Imaging in Lifelines) study (age ≥45 years) who underwent low-dose chest computed tomography. Outcomes included the presence of 1) at least one solid lung nodule (volume ≥30 mm3) and 2) a clinically relevant lung nodule (volume ≥100 mm3). Fully adjusted multivariable logistic regression models were applied overall and stratified by smoking status to identify independent risk factors for the presence of nodules. RESULTS: Among the 12 055 participants (44.1% male; median age 60 years; 39.9% never-smokers; 98.7% White), we found lung nodules in 41.8% (5045 out of 12 055) and clinically relevant nodules in 11.4% (1377 out of 12 055); the corresponding figures among never-smokers were 38.8% and 9.5%, respectively. Factors independently associated with increased odds of having any lung nodule included male sex, older age, low educational level, former smoking, asbestos exposure and COPD. Among never-smokers, a family history of lung cancer increased the odds of both lung nodules and clinically relevant nodules. Among former and current smokers, low educational level was positively associated with lung nodules, whereas being overweight was negatively associated. Among current smokers, asbestos exposure and low physical activity were associated with clinically relevant nodules. CONCLUSIONS: The study provides a large-scale evaluation of lung nodules and associated risk factors in a Western European general population: lung nodules and clinically relevant nodules were prevalent, and never-smokers with a family history of lung cancer were a non-negligible group.

Pretreatment prediction for IVF outcomes: generalized applicable model or centre-specific model?

STUDY QUESTION: What was the performance of different pretreatment prediction models for IVF, which were developed based on UK/US population (McLernon 2016 model, Luke model, Dhillon model, and McLernon 2022 model), in wider populations? SUMMARY ANSWER: For a patient in China, the published pretreatment prediction models based on the UK/US population provide similar discriminatory power with reasonable AUCs and underestimated predictions. WHAT IS KNOWN ALREADY: Several pretreatment prediction models for IVF allow patients and clinicians to estimate the cumulative probability of live birth in a cycle before the treatment, but they are mostly based on the population of Europe or the USA, and their performance and applicability in the countries and regions beyond these regions are largely unknown. STUDY DESIGN, SIZE, DURATION: A total of 26 382 Chinese patients underwent oocyte pick-up cycles between January 2013 and December 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: UK/US model performance was externally validated according to the coefficients and intercepts they provided. Centre-specific models were established with XGboost, Lasso, and generalized linear model algorithms. Discriminatory power and calibration of the models were compared as the forms of the AUC of the Receiver Operator Characteristic and calibration curves. MAIN RESULTS AND THE ROLE OF CHANCE: The AUCs for McLernon 2016 model, Luke model, Dhillon model, and McLernon 2022 model were 0.69 (95% CI 0.68-0.69), 0.67 (95% CI 0.67-0.68), 0.69 (95% CI 0.68-0.69), and 0.67 (95% CI 0.67-0.68), respectively. The centre-specific yielded an AUC of 0.71 (95% CI 0.71-0.72) with key predictors including age, duration of infertility, and endocrine parameters. All external models suggested underestimation. Among the external models, the rescaled McLernon 2022 model demonstrated the best calibration (Slope 1.12, intercept 0.06). LIMITATIONS, REASONS FOR CAUTION: The study is limited by its single-centre design and may not be representative elsewhere. Only per-complete cycle validation was carried out to provide a similar framework to compare different models in the sample population. Newer predictors, such as AMH, were not used. WIDER IMPLICATIONS OF THE FINDINGS: Existing pretreatment prediction models for IVF may be used to provide useful discriminatory power in populations different from those on which they were developed. However, models based on newer more relevant datasets may provide better calibrations. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China [grant number 22176159], the Xiamen Medical Advantage Subspecialty Construction Project [grant number 2018296], and the Special Fund for Clinical and Scientific Research of Chinese Medical Association [grant number 18010360765]. TRIAL REGISTRATION NUMBER: N/A.

Performance of Lung-RADS in different target populations: a systematic review and meta-analysis.

OBJECTIVES: Multiple lung cancer screening studies reported the performance of Lung CT Screening Reporting and Data System (Lung-RADS), but none systematically evaluated its performance across different populations. This systematic review and meta-analysis aimed to evaluate the performance of Lung-RADS (versions 1.0 and 1.1) for detecting lung cancer in different populations. METHODS: We performed literature searches in PubMed, Web of Science, Cochrane Library, and Embase databases on October 21, 2022, for studies that evaluated the accuracy of Lung-RADS in lung cancer screening. A bivariate random-effects model was used to estimate pooled sensitivity and specificity, and heterogeneity was explored in stratified and meta-regression analyses. RESULTS: A total of 31 studies with 104,224 participants were included. For version 1.0 (27 studies, 95,413 individuals), pooled sensitivity was 0.96 (95% confidence interval [CI]: 0.90-0.99) and pooled specificity was 0.90 (95% CI: 0.87-0.92). Studies in high-risk populations showed higher sensitivity (0.98 [95% CI: 0.92-0.99] vs. 0.84 [95% CI: 0.50-0.96]) and lower specificity (0.87 [95% CI: 0.85-0.88] vs. 0.95 (95% CI: 0.92-0.97]) than studies in general populations. Non-Asian studies tended toward higher sensitivity (0.97 [95% CI: 0.91-0.99] vs. 0.91 [95% CI: 0.67-0.98]) and lower specificity (0.88 [95% CI: 0.85-0.90] vs. 0.93 [95% CI: 0.88-0.96]) than Asian studies. For version 1.1 (4 studies, 8811 individuals), pooled sensitivity was 0.91 (95% CI: 0.83-0.96) and specificity was 0.81 (95% CI: 0.67-0.90). CONCLUSION: Among studies using Lung-RADS version 1.0, considerable heterogeneity in sensitivity and specificity was noted, explained by population type (high risk vs. general), population area (Asia vs. non-Asia), and cancer prevalence. CLINICAL RELEVANCE STATEMENT: Meta-regression of lung cancer screening studies using Lung-RADS version 1.0 showed considerable heterogeneity in sensitivity and specificity, explained by the different target populations, including high-risk versus general populations, Asian versus non-Asian populations, and populations with different lung cancer prevalence. KEY POINTS: • High-risk population studies showed higher sensitivity and lower specificity compared with studies performed in general populations by using Lung-RADS version 1.0. • In non-Asian studies, the diagnostic performance of Lung-RADS version 1.0 tended to be better than in Asian studies. • There are limited studies on the performance of Lung-RADS version 1.1, and evidence is lacking for Asian populations.

Trade-off between double cleavage-stage embryos transfer and single blastocyst-stage embryo transfer in patients with few good quality embryos in antagonist cycles: a retrospective study using a propensity score matching analysis.

OBJECTIVE: This study aimed to compare the per OPU clinical outcomes for transfer of Day 3 double cleavage-stage embryos (DET) and Day 5 single blastocyst-stage (SBT) in patients with five or fewer good quality embryos on day 3 per occyte pick-up cycle (OPU) in antagonist cycles with consideration of blastocyst formation failure. METHODS: This was a retrospective, observational cohort study of 2,116 cases of OPU treated with antagonist protocol in the affiliated Chenggong Hospital of Xiamen University between January 2013 and December 2020. DET was performed in 1,811cycles and SBT was performed in 305 cycles. The DET group was matched to the SBT group by propensity score (PS) matching according to multiple maternal baseline covariates. After PS matching, there were 303 ET cycles in each group. The primary outcomes were the cumulative live birth rate (CLBR), cumulative multiple pregnancy rate(CMPR)per OPU and the number of ET to achieve live birth per OPU. Secondary outcomes were the percentage of clinical pregnancy(CPR), live birth rate(LBR), multiple pregnancy rate(MPR). RESULTS: Following PS mating, the CLBR was slightly higher (48.8% versus 40.3% ; P = 0.041) and the CMPR was significantly higher in the DET group compared to SBT group(44.2% versus 7.9%, P < 0.001). The CPR, LBR and MPR per fresh transfer were higher in DET group compared to SBT group(50.2% versus 28.7%; 41.3% versus 21.5%;29.6% versus 0%, P < 0.001). The number of ET to achieve live birth per OPU in SBT group was obiviously more than in DET group(1.48 ± 0.578 versus 1.22 ± 0.557 ,P < 0.001). CONCLUSION: With a marginal difference cumulative live birth rate, the lower live birth rate per fresh transfer and higher number of ET per OPU in the SBT group suggested that it might take longer time to achieve a live birth with single blastocyst strategy. A trade-off decision should be made between efficiency and safety.

Indications affect neonatal outcomes following early rescue ICSI: a retrospective study.

PURPOSE: To investigate the impact of heterogeneity in patient indications or insemination protocols on neonatal outcomes of singletons following early rescue ICSI (rICSI) treatments. METHODS: A retrospective study was conducted. Propensity score matching and multivariable logistic regression were used to adjust for confounders and biases. RESULTS: A total of 9095 IVF patients, 2063 ICSI patients, and 642 early rICSI patients were included in the study. No differences were detected in neonatal outcomes except small for gestational age (SGA) which increased in early rICSI patients compared with both unmatched and matched IVF groups with the risk ratio (RR) of 1.31 (95% CI: 1.05, 1.64) and 1.49 (95% CI: 1.05, 2.12). Further analysis showed that SGA increased significantly in partial fertilization failure (PFF) cycles with RRs of 1.56 (95% CI: 1.08, 2.27) and 1.78 (95% CI: 1.22, 2.59) compared with both unmatched and matched IVF patients but not in TFF patients. A positive association between fertilization rate via IVF and birth weight z-score was revealed in the PFF patients. CONCLUSION: Early rICSI in patients with total fertilization failure (TFF) appeared to be safe in terms of neonatal outcomes. However, when expanding the indications of rICSI to PFF patients, the SGA in the offspring increased, suggesting a potential effect on long-term health. Since other treatment options, such as using only the IVF-origin embryos still exist for these patients, further studies were needed to confirm the optimal decision for these patients.

Does cleavage stage morphology increase the discriminatory power of prediction in blastocyst transfer outcome?

PURPOSE: To evaluate the contribution of the cleavage stage morphological parameters to the prediction of blastocyst transfer outcomes. METHODS: A retrospective study was conducted on 8383 single-blastocyst transfer cycles including 2246 fresh and 6137 vitrified-warmed cycles. XGboost, LASSO, and GLM algorithms were employed to establish models for assessing the predictive value of the cleavage stage morphological parameters in transfer outcomes. Four models were developed using each algorithm: all-in model with or without day 3 morphology and embryo quality-only model with or without day 3 morphology. RESULTS: The live birth rate was 48.04% in the overall cohort. The AUCs of the models with the algorithm of XGboost were 0.83, 0.82, 0.63, and 0.60; with LASSO were 0.66, 0.66, 0.61, and 0.60; and with GLM were 0.66, 0.66, 0.61, and 0.60 respectively. In models 1 and 2, female age, basal FSH, peak E2, endometrial thickness, and female BMI were the top five critical features for predicting live birth; In models 3 and 4, the most crucial factor was blastocyst formation on D5 rather than D6. In model 3, incorporating cleavage stage morphology, including early cleavage, D3 cell number, and fragmentation, was significantly associated with successful live birth. Additionally, the live birth rates for blastocysts derived from on-time, slow, and fast D3 embryos were 49.7%, 39.5%, and 52%, respectively. CONCLUSIONS: The value of cleavage stage morphological parameters in predicting the live birth outcome of single blastocyst transfer is limited.

Study on network pharmacology of Ginkgo biloba extract against ischaemic stroke mechanism and establishment of UPLC-MS/MS methods for simultaneous determination of 19 main active components.

INTRODUCTION: Ginkgo biloba extract (GBE) is an effective substance from traditional Chinese medicine (TCM) G. biloba for treating ischaemic stroke (IS). However, its active ingredients and mechanism of action remain unclear. OBJECTIVES: This study aimed to reveal the potential active component group and possible anti-IS mechanism of GBE. MATERIALS AND METHODS: The network pharmacology method was used to reveal the possible anti-IS mechanism of these active ingredients in GBE. An ultra-high-performance liquid chromatography triple quadrupole electrospray tandem mass spectrometry (UPLC-MS/MS) method was established for the simultaneous detection of the active ingredients of GBE. RESULTS: The active components of GBE anti-IS were screened by literature integration. Network pharmacology results showed that the anti-IS effect of GBE is achieved through key active components such as protocatechuic acid, bilobalide, ginkgolide A, and so on. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the possible anti-IS mechanism of GBE is regulating the PI3K-Akt signalling pathway and other signal pathways closely related to inflammatory response and apoptosis regulation combined with AKT1, MAPK, TNF, ALB, CASP3, and other protein targets. Nineteen main constituents in seven batches of GBE were successfully analysed using the established UPLC-MS/MS method, and the results showed that the content of protocatechuic acid, gallic acid, ginkgolide A, and so forth was relatively high, which was consistent with network pharmacology results, indicating that these ingredients may be the key active anti-IS ingredients of GBE. CONCLUSION: This study revealed the key active components and the anti-IS mechanism of GBE. It also provided a simple and sensitive method for the quality control of related preparations.

Association between ambient air pollutants and birthweight of singletons following assisted reproductive technologies.

OBJECTIVE: To investigate the associations between exposure to ambient air pollutants and birthweight following ART treatment. DESIGN: Retrospective cohort study. METHODS: We included 11,599 singletons derived from fresh cycles or frozen-thawed embryo transfer (FET) cycles between Jan 2013 and Dec 2019. Exposure to six air pollutants (SO2, NO2, CO, O3, PM2.5, and PM10) at patients` residences and the clinic site were estimated using the inverse distance weighting interpolation method based on data obtained from monitor sites. The daily mean levels of pollutants were estimated in potential exposure windows (the period from three months before treatment to oocyte retrieval, the period of ovarian stimulation, the period of in vitro culture, the period from embryo transfer to hCG test, the period of entire pregnancy, the 1st, 2nd, and 3rd trimester) were calculated. Generalized additive models adjusted for confounders including maternal age, BMI, and parity were used to evaluate the association between exposures and birthweight. Interaction of exposures and ART-associated factors, such as supraphysiologic estradiol and frozen-thawed, were explored in an XGboost model. MAIN OUTCOME MEASURES: Birthweight and z-score of singletons. RESULTS: In fresh cycles, O3 exposure during the period from three months before treatment to oocyte retrieval and SO2 exposure during in vitro culture at the ART clinic showed a linear association with birthweight (7.24, 95% CI: 1.18-13.31 g per 10 µg/m3 increase in O3; 25.92, 95% CI: 8.26-43.58 g per 10 µg/m3 increase in SO2, respectively). For patients receiving single blastocyst transfer with exposures below the China standard of 20 µg/m3, an increase of 10 µg/m3 in SO2 was associated with a 61.52 (95% CI: 1.13-121.91) g increase in birthweight. In FET cycles, no significant association was found between air pollution and birthweight. XGboost model did not reveal a strong interaction between the exposures and ART-related factors, except for the interactions between O3 exposure and BMI. However, none of the interactions reached a higher rank of importance. CONCLUSIONS: Air pollution exposure during ART treatment may affect the birthweight of the offspring.

Comprehensive Analysis of CircRNA Expression Profiles in Multiple Tissues of Pigs.

Circular RNAs (circRNAs) are a class of non-coding RNAs with diverse functions, and previous studies have reported that circRNAs are involved in the growth and development of pigs. However, studies about porcine circRNAs over the past few years have focused on a limited number of tissues. Based on 215 publicly available RNA sequencing (RNA-seq) samples, we conducted a comprehensive analysis of circRNAs in nine pig tissues, namely, the gallbladder, heart, liver, longissimus dorsi, lung, ovary, pituitary, skeletal muscle, and spleen. Here, we identified a total of 82,528 circRNAs and discovered 3818 novel circRNAs that were not reported in the CircAtlas database. Moreover, we obtained 492 housekeeping circRNAs and 3489 tissue-specific circRNAs. The housekeeping circRNAs were enriched in signaling pathways regulating basic biological tissue activities, such as chromatin remodeling, nuclear-transcribed mRNA catabolic process, and protein methylation. The tissue-specific circRNAs were enriched in signaling pathways related to tissue-specific functions, such as muscle system process in skeletal muscle, cilium organization in pituitary, and cortical cytoskeleton in ovary. Through weighted gene co-expression network analysis, we identified 14 modules comprising 1377 hub circRNAs. Additionally, we explored circRNA-miRNA-mRNA networks to elucidate the interaction relationships between tissue-specific circRNAs and tissue-specific genes. Furthermore, our conservation analysis revealed that 19.29% of circRNAs in pigs shared homologous positions with their counterparts in humans. In summary, this extensive profiling of housekeeping, tissue-specific, and co-expressed circRNAs provides valuable insights into understanding the molecular mechanisms of pig transcriptional expression, ultimately deepening our understanding of genetic and biological processes.

Study on detection of CNVs using human whole genome bisulfite sequencing data.

It has been reported that the aberrant DNA methylation may result in copy number variations (CNVs), and the CNVs may alter the levels of DNA methylation. Whole genome bisulfite sequencing (WGBS) is able to generate the sequencing data of DNAs, and shows the potential ability to detect CNVs. However, the evaluations and performances on the detections of CNVs using WGBS data is still unclear. In this study, five software with different strategies for CNV detections, e.g., BreakDancer, cn.mops, CNVnator, DELLY and Pindel, were selected to explore and benchmark the performances of CNV detections with WGBS data. Based on the real (2.62 billion reads) and simulated (12.35 billion reads) WGBS data of humans, we calculated the number, precision, recall, relative ability, memory usage, and running time of CNV detections by 150 times, and tried to figure out the optimal strategy for CNV detections with WGBS data. Based on the real WGBS data, Pindel detected the most deletions and duplications, CNVnator detected the deletions with the highest precision, cn.mops detected the duplications with the highest precision, Pindel detected the deletions with the highest recall, and cn.mops detected the duplications with the highest recall. Based on the simulated WGBS data, BreakDancer detected the most deletions, and cn.mops detected the most duplications. The CNVnator showed the highest precision and recall for both deletions and duplications. In real and simulated WGBS data, the ability of CNVnator to detect CNVs was likely to overtake that in the whole genome sequencing data. Additionally, DELLY and BreakDancer displayed the lowest peak of memory usage and the lest CPU runtime, while CNVnator expressed the highest peak of memory usage and the most CPU runtime. Taken together, CNVnator and cn.mops showed the excellent performances of CNV detections with WGBS data. These results suggested that it was feasible to detect CNVs using WGBS data, and provided the useful information to further investigate both CNVs and DNA methylation using WGBS data alone.

Mechanistic study of cobalt(I)-catalyzed asymmetric coupling of ethylene and enynes to functionalized cyclobutanes.

Density functional theory (DFT) calculations have been performed to gain insight into the reaction mechanism of the Co(I)-catalyzed asymmetric [2 + 2] cycloaddition reaction of enyne 1a with ethylene 2 to give the functionalized cyclobutene E-4a possessing a chiral, all-carbon quaternary center in the ring framework (Science, 361, 68-72). This study reveals that the whole catalysis can be characterized via three stages: (i) oxidative dimerization followed by reductive elimination gives the intermediate IM3, (ii) the alkenyl-Co(III) metallacycloheptene IM6 formation with the addition of another equivalent ethylene via an oxidative dimerization process, (iii) ß-Hydrogen elimination and reductive elimination from IM6 to result in the final product E-4a and regenerate the active speices IM1 for the next catalytic cycle. Each stage is kinetically and thermodynamically feasible for experimental realization under mild conditions, and the formation of the alkenyl-Co(III) metallacycloheptene IM6, with a barrier of 27.2 kcal mol-1 (i.e., IM2 → TS4), should be the rate-determining step (RDS) during the whole catalysis. In addition, the origins of enantioselectivity and regioselectivity of the product are discussed.

Does conventional morphological evaluation still play a role in predicting blastocyst formation?

BACKGROUND: Advanced models including time-lapse imaging and artificial intelligence technologies have been used to predict blastocyst formation. However, the conventional morphological evaluation of embryos is still widely used. The purpose of the present study was to evaluate the predictive power of conventional morphological evaluation regarding blastocyst formation. METHODS: Retrospective evaluation of data from 15,613 patients receiving blastocyst culture from January 2013 through December 2020 in our institution were reviewed. Generalized estimating equations (GEE) were used to establish the morphology-based model. To estimate whether including more features regarding patient characteristics and cycle parameters improve the predicting power, we also establish models including 27 more features with either LASSO regression or XGbosst. The predicted number of blastocyst were associated with the observed number of the blastocyst and were used to predict the blastocyst transfer cancellation either in fresh or frozen cycles. RESULTS: Based on early cleavage and routine observed morphological parameters (cell number, fragmentation, and symmetry), the GEE model predicted blastocyst formation with an AUC of 0.779(95%CI: 0.77-0.787) and an accuracy of 74.7%(95%CI: 73.9%-75.5%) in the validation set. LASSO regression model and XGboost model based on the combination of cycle characteristics and embryo morphology yielded similar predicting power with AUCs of 0.78(95%CI: 0.771-0.789) and 0.754(95%CI: 0.745-0.763), respectively. For per-cycle blastocyst yield, the predicted number of blastocysts using morphological parameters alone strongly correlated with observed blastocyst number (r = 0.897, P < 0.0001) and predicted blastocyst transfer cancel with an AUC of 0.926((95%CI: 0.911-0.94). CONCLUSION: The data suggested that routine morphology observation remained a feasible tool to support an informed decision regarding the day of transfer. However, models based on the combination of cycle characteristics and embryo morphology do not increase the predicting power significantly.

Low BMI is associated with poor IUI outcomes: a retrospective study in 13,745 cycles.

PURPOSE: To evaluate the association between body mass index (BMI) and pregnancy outcomes in women receiving intrauterine insemination (IUI) treatment. METHODS: The study included 6407 women undergoing 13,745 IUI cycles stratified by BMI. Cox regression was used to analyze the association between BMI and cumulative live births across multiple IUI cycles. A generalized estimating equation (GEE) was used to analyze the live birth rate per cycle. RESULTS: Compared with normal-weight women (n = 4563), underweight women (n = 990) had a lower cumulative pregnancy and live birth rate (20.71% vs 25.93% and17.17% vs 21.61%, respectively), while overweight women (n = 854) had a higher cumulative pregnancy and live birth rate (31.97%, 26.58%). Adjusted for confounders, the hazard ratio (HR) for achieving live birth following up to a maximum of four IUI cycles was 0.80 (95% CI: 0.67-0.95), comparing underweight with normal weight. In the GEE analyses, low BMI was also associated with a lower per-cycle birth rate (OR 0.79, 95% CI: 0.66-0.95), with adjustment for cycle-specific parameters, including ovarian stimulation, endometrial thickness, and follicular diameter. CONCLUSION: Low BMI is associated with poor IUI outcomes.

The effect of epididymal sperm cryopreservation on neonatal birthweight following PESA-ICSI.

PURPOSE: To compare the neonatal birthweight of singletons derived from ICSI cycles with fresh or frozen-thawed epididymal sperm in patients with obstructive azoospermia. METHODS: A total of 436 singletons derived from ICSI cycles with fresh (n = 220) or frozen-thawed (n = 216) epididymal sperm in obstructive azoospermia evaluated from 2012 to 2018 in the retrospective study. Multivariate generalized linear model was used to analyze the association between epididymal sperm cryopreservation and neonatal birthweight. RESULTS: The crude birthweight and z-score in neonates derived from frozen-thawed epididymal sperm were significantly lower than those from fresh epididymal sperm (3186.57 g vs 3303.61 g and - 0.18 vs 0.08, respectively), with a mean difference of 117.04 (95% CI 32.36-201.72) g and 0.25 (95% CI 0.06-0.45). Adjusted for confounders including parental age and BMI, maternal ovarian reserve, paternal FSH and T levels, peak E2 during OPU cycles, frozen-thawed embryo transfer, embryo development stage, gestational age, maternal parity and child gender, the multivariate model suggested that singletons conceived from ICSI with fresh epididymal sperm was on average 91.21 g heavier than those conceived from ICSI with frozen-thawed epdidiymal sperm (95% CI 12.72 to 166.7, P = 0.016). CONCLUSION: Cryopreservation of epididymal sperm may negatively affect birthweight.

AI-Driven Model for Automatic Emphysema Detection in Low-Dose Computed Tomography Using Disease-Specific Augmentation.

The objective of this study is to evaluate the feasibility of a disease-specific deep learning (DL) model based on minimum intensity projection (minIP) for automated emphysema detection in low-dose computed tomography (LDCT) scans. LDCT scans of 240 individuals from a population-based cohort in the Netherlands (ImaLife study, mean age ± SD = 57 ± 6 years) were retrospectively chosen for training and internal validation of the DL model. For independent testing, LDCT scans of 125 individuals from a lung cancer screening cohort in the USA (NLST study, mean age ± SD = 64 ± 5 years) were used. Dichotomous emphysema diagnosis based on radiologists' annotation was used to develop the model. The automated model included minIP processing (slab thickness range: 1 mm to 11 mm), classification, and detection maps generation. The data-split for the pipeline evaluation involved class-balanced and imbalanced settings. The proposed DL pipeline showed the highest performance (area under receiver operating characteristics curve) for 11 mm slab thickness in both the balanced (ImaLife = 0.90 ± 0.05) and the imbalanced dataset (NLST = 0.77 ± 0.06). For ImaLife subcohort, the variation in minIP slab thickness from 1 to 11 mm increased the DL model's sensitivity from 75 to 88% and decreased the number of false-negative predictions from 10 to 5. The minIP-based DL model can automatically detect emphysema in LDCTs. The performance of thicker minIP slabs was better than that of thinner slabs. LDCT can be leveraged for emphysema detection by applying disease specific augmentation.

Prostaglandin E1 attenuates AngII-induced cardiac hypertrophy via EP3 receptor activation and Netrin-1upregulation.

AIMS: Pathological cardiac hypertrophy induced by activation of the renin-angiotensin-aldosterone system (RAAS) is one of the leading causes of heart failure. However, in current clinical practice, the strategy for targeting the RAAS is not sufficient to reverse hypertrophy. Here, we investigated the effect of prostaglandin E1 (PGE1) on angiotensin II (AngII)-induced cardiac hypertrophy and potential molecular mechanisms underlying the effect. METHODS AND RESULTS: Adult male C57 mice were continuously infused with AngII or saline and treated daily with PGE1 or vehicle for two weeks. Neonatal rat cardiomyocytes were cultured to detect AngII-induced hypertrophic responses. We found that PGE1 ameliorated AngII-induced cardiac hypertrophy both in vivo and in vitro. The RNA sequencing (RNA-seq) and expression pattern analysis results suggest that Netrin-1 (Ntn1) is the specific target gene of PGE1. The protective effect of PGE1 was eliminated after knockdown of Ntn1. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the PGE1-mediated signaling pathway changes are associated with the mitogen-activated protein kinase (MAPK) pathway. PGE1 suppressed AngII-induced activation of the MAPK signaling pathway, and such an effect was attenuated by Ntn1 knockdown. Blockade of MAPK signaling rescued the phenotype of cardiomyocytes caused by Ntn1 knockdown, indicating that MAPK signaling may act as the downstream effector of Ntn1. Furthermore, inhibition of the E-prostanoid (EP) 3 receptor, as opposed to the EP1, EP2, or EP4 receptor, in cardiomyocytes reversed the effect of PGE1, and activation of EP3 by sulprostone, a specific agonist, mimicked the effect of PGE1. CONCLUSION: In conclusion, PGE1 ameliorates AngII-induced cardiac hypertrophy through activation of the EP3 receptor and upregulation of Ntn1, which inhibits the downstream MAPK signaling pathway. Thus, targeting EP3, as well as the Ntn1-MAPK axis, may represent a novel approach for treating pathological cardiac hypertrophy.

Donor-Stabilized Antimony(I) and Bismuth(I) Ions: Heavier Valence Isoelectronic Analogues of Carbones.

Isolation of two-coordinate compounds of heavier Group 15 elements in low oxidation state is challenging due to the preferential formation of dimers or oligomers. Herein, we report the first examples of donor-stabilized two-coordinate Sb(I) and Bi(I) ions. The reduction of antimony and bismuth trihalides with KC8 in the presence of cyclic alkyl(amino) carbene (cAAC) afforded Sb(I) and Bi(I) cations in the form of triflate salts [(cAAC)2Sb][OTf] (1) and [(cAAC)2Bi][OTf] (2). Compounds 1 and 2 belong to a new class of acyclic cations of Group 15 with eight valence electrons and are heavier valence isoelectronic analogues of carbones. Both compounds are isolated and well-characterized by NMR spectroscopy, cyclic voltammetry, single-crystal X-ray diffraction, and computational studies.

Does the transfer of a poor quality embryo with a good quality embryo benefit poor prognosis patients?

BACKGROUND: While single embryo transfer (SET) is widely advocated, double embryo transfer (DET) remains preferable in clinical practice to improve IVF success rate, especially in poor prognosis patients with only poor quality embryos (PQEs) available in addition to one or no good quality embryos (GQEs). Furthermore, previous studies suggest PQE might adversely affect the implantation of a GQE when transferred together. This study aims to evaluate the effect of transferring an additional PQE with a GQE on the outcomes in poor prognosis patients. METHODS: A total of 5037 frozen-thawed blastocyst transfer (FBT) cycles between January 2012 and May 2019 were included. Propensity score matching was applied to control for potential confounders, and we used generalized estimating equations (GEE) models to identify the association between the effect of an additional PQE and the outcomes. RESULTS: Overall, transferring a PQE with GQE (Group GP) achieved significantly higher pregnancy rate (PR), live birth rate (LBR) and multiple pregnancy rate (MPR) than GQE only (group G). The addition of a PQE increased LBR in patients aged 35 and over and in patients who received over 3 cycles of embryo transfer (ET) (48.1% vs 27.2%, OR:2.56, 95% CI: 1.3-5.03 and 46.6% vs 35.4%, OR:1.6, 95% CI: 1.09-2.35), but not in women under 35 and in women who received less than 3 cycles of ET (48.7% vs 43.9%, OR:1.22, 95% CI: 0.93-1.59 and 48.3% vs 41.4%, OR:1.33, 95% CI: 0.96-1.85). Group GP resulted in significantly higher MPR than group G irrespective of age and the number of previous IVF cycles. CONCLUSIONS: An additional PQE does not negatively affect the implantation potential of the co-transferred GQE. Nevertheless, the addition of a PQE contributes to both live birth and multiple birth in poor prognosis patients. Physicians should still balance the benefits and risks of DET.

Roles of estradiol levels on the day of human chorionic gonadotrophin administration in the live birth of patients with frozen embryo transfer.

BACKGROUND: Estradiol (E2 ) is an important hormone in women. Changes of serum E2 levels may affect the endometrial receptivity for embryo implantation and thus affect pregnancy outcomes. This study was to assess the association between serum E2 levels on the day of human chorionic gonadotrophin (HCG) administration and live-birth rates in patients with frozen embryo transfer (FET). METHODS: Totally 2071 women receiving long protocols of long-acting gonadotropin-releasing hormone (GnRH) agonists were enrolled. According to the E2 levels on the day of HCG administration, these patients were divided into four groups: 676 cases of E2  ≤ 3051 pg/mL in Q1 group, 676 cases of 3051 pg/mL < E2  ≤ 4558 pg/mL in Q2 group, 675 cases of 4558 pg/mL < E2  ≤ 6718 pg/mL in Q3 group, and 674 cases of E2  > 6718 pg/mL in Q4 group. The clinical indicators including female age, body mass index (BMI), duration of infertility, infertility styles, treatment protocols, hormone levels, total antral follicle count, endometrial thickness, top-level embryos, and live-birth rates were analyzed, and multivariable logistic model was conducted to select significant variables. RESULTS: Significant differences were observed for the female age (OR = 0.965, 95% CI: 0.946-0.985, P < .001), total antral follicle counts (OR = 1.025, 95% CI: 1.008-1.043, P = .004), transferring what day of embryos (OR = 1.242, 95% CI: 1.137-1.356, P < .001), endometrial thickness (OR = 1.058, 95% CI: 1.004-1.115, P = .035), top-level embryos (OR = 1.416, 95% CI: 1.157-1.731, P = .001), and E2 levels on HCG day >6781 pg/mL (OR = 1.344, 95% CI: 1.069-1.690, P = .011) between live-birth and non-live-birth groups. The area under the curve (AUC) for E2 levels on HCG day was 0.558, the sensitivity was 54.75%, and the specificity was 55.10%. CONCLUSION: Serum E2 level on HCG day was an independent predictor of live-birth achievement in patients with FET.