Morphology Score Research Articles

Preoperative CT-based morphological heterogeneity for predicting survival in patients with colorectal cancer liver metastases after surgical resection: a retrospective study

ObjectiveTo explore the value of preoperative CT-based morphological heterogeneity (MH) for predicting local tumor disease-free survival (LTDFS) and progression-free survival (PFS) in patients with colorectal cancer liver metastases (CRLM).MethodsThe latest CT data of 102 CRLM patients were retrospectively analyzed. The morphological score of each liver metastasis was obtained, and the morphological heterogeneity difference (MHD) was calculated. The receiver operating characteristic (ROC) curve was drawn, and the cutoff value was found. The Kaplan-Meier method was used to draw survival curves of patients with or without MH. The Cox regression analysis was used to build the model with MH and clinical characteristics for predicting PFS.ResultsIn 78 patients without MH, median PFS was 9.0 months (95% CI:6.5–11.5), while in 24 patients with MH, median PFS was 6.0 months (95% CI:4.0-8.1), indicating that MH significantly affected PFS (p = 0.001). MH affected PFS in both the chemotherapy group and the chemotherapy combined with targeted therapy group (p = 0.005, p = 0.043). MH, preoperative carcinoembryonic antigen (CEA) and chemotherapy after surgery were independent predictors for postoperative PFS in patients with CRLM.ConclusionPreoperative CT-based MH had good efficacy for predicting LTDFS and PFS of CRLM patients after surgical resection, regardless of preoperative treatment. MH is one of the independent predictors of PFS.

Preimplantation genetic testing for a Chinese pedigree affected with Primary carnitine deficiency

To investigate the results of preimplantation genetic testing for monogenic diseases (PGT-M) in a Chinese pedigree affected with Primary carnitine deficiency (PCD). A pedigree affected with PCD who visited Hainan Women and Children's Medical Center in April 2023 due to "SLC22A5 gene mutation found in offspring genetic testing and preparing for a second child" was selected as the study subject. Pathogenicity of the proband's variant sites was determined by referring to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG). Sanger sequencing was used to verify the variant sites of SLC22A5 gene in the proband and her parents, and the single nucleotide polymorphism (SNP) haplotype of the family was constructed by SNP microarray (SNP array) method to determine the carrier status of pathogenic genes. After fertilization via assisted reproductive technology, whole genome amplification (WGA) was performed on the biopsied trophoblastic cells. Sanger sequencing, next-generation sequencing (NGS), and SNP array techniques were then used to detect the variants in the SLC22A5 gene and chromosome copy number variation (CNV) in the embryos. Embryos without the variants were selected for transferring. After the successful pregnancy of the proband's mother, amniocentesis was not performed for prenatal diagnosis due to repeated vaginal bleeding. After delivery, neonatal peripheral blood sample was collected to verify the results of PGT-M, and follow-up was conducted. This study was reviewed and approved by the Medical Ethics Committee of Hainan Women and Children's Medical Center (Ethics No. HNWCMC-2022-178). In this study, the c.338G>A and c.760C>T variants in SLC22A5 gene were evaluated as pathogenic variants. Sanger sequencing results of this family showed that the c.338G>A and c.760C>T variants of the proband were inherited from his father and mother, respectively. Haplotypes of c.338G>A and c.760C>T variants of SLC22A5 gene were successfully constructed. PGT-M results showed that 2 of the 8 blastulas biopsied failed WGA, and the CNV detection results of the remaining 6 blastocysts were all euploid: 2 had no mutations in the SLC22A5 gene, 3 were single heterozygous carriers of paternal or maternal origin, and 1 was compound heterozygous carriers of paternal and maternal origin. Combined with the embryo morphology score, an intrauterine singleton pregnancy was achieved after the successful transfer of an optimal embryo with no CNV abnormalities and no paternal or maternal SLC22A5 gene mutations, resulting in the birth of a healthy female baby at 38+3 weeks of gestation. The results of peripheral blood chromosomal karyotyping analysis, CNV detection and SLC22A5 gene c.338G>A and c.760C>T site variant detection of the infant were consistent with those of PGT-M, and no abnormality was found. PGT-M had helped the couple carrying SLC22A5 gene variant to have a healthy offspring and effectively blocked the transmission of PCD in this family.

Physiological Characterization of Pigeon Pea Genotypes [Cajanus cajan (L) Mill sp.] for Water Logging Tolerance

Background: Water- logging stress is one of the important abiotic stress in pigeon pea crop especially in low lying areas in pigeon pea growing states. Being a rainy season crop, pigeon pea is invariably exposed to intermittent water-logging conditions for different durations from germination to early vegetative growth stages, which damage the crop partially and sometime eliminate the entire crop depending on intensity and duration of water stagnation. The present experiment was conducted to study the morphological characters and yield performance of water logging tolerant and susceptible pigeon pea genotypes so that large number of pigeon pea genotypes for water logging tolerance based on morphological and Physiological parameters standardized might be screened. Methods: As per approved technical programme, the experiment was conducted with 30 pigeon pea genotypes including checks, these were IPAC-79, ICPL-7035, ICPL-20241, ICPL-87051, ICPL-87091, ICP-2376, ICP-5028, ICPL-149, MA-3, MA-6, NDA-1, IPA-15F, Bahar, IPA-203, IPAC-211, IPAC-202, RCM/DD-17, WB-2019/25, WB-2019/26, WB-2019/27, IPAC-212, IPAWL-22-1, IPAWL-22.2, IPAWL-22-3, IPAWL-22-4, IPAWL- 22-5, IPAWL-22-6, IPAWL-22-7, IPAWL -22-8, IPAWL -22-9. Water logging stress was imposed for 24 h-48h-72h having minimum depth of water 12 inches at 30 DAS with 03 replications and a set of all these genotypes were also sown under normal control condition. Morphological Scoring (0-3) at the end of water logging stress was done. and at harvesting yield attributes and yields were recorded. Result: Morphological Scoring (0-3) at the end of water logging stress showed highest score (0) in genotypes including IPAC-79 (Check for Tolerant) followed by ICPL-87091, ICP-2376, ICPL-20241, IPAC-212, IPAWL-22-7 and IPAWL-22-8 and may be considered as water logging tolerant. Pigeon pea genotypes like ICP-5028, MA-6 and IPAC-202 showed the score of (01) and may be considered as moderately tolerant to water logging stress. Pigeon pea genotypes namely MA-3, NDA-1, IPA-15F, Bahar, IPAC-211, IPA-203, IPAWL-22-6 and IPAWL-22-9 showed moderate score (02) and may be considered as moderately susceptible. The lowest score (03) was recorded in ICPL-87051, ICP-149, RCM/DD-17, WB-2019/25, WB-2019/26, WB-2019/27, IPAWL-22-1, IPAWL-22-2, IPAWL-22-3, IPAWL-22-4 and IPAWL-22-5 and these were at par with ICPL-7035 (Check for susceptibility) and considered susceptible to water logging stress. Development of adventitious roots was observed under water logged condition only and it was recorded highest in genotypes which are water logging tolerant group. In susceptible genotypes no/negligible adventitious roots were found. In yield attributes and yield the reduction % due to water logging stress over normal control was minimum in tolerant/moderately tolerant genotypes whereas, it was found maximum in Susceptible/moderately susceptible group of genotypes.

Development and validation of a clinical prediction model for blastocyst formation during IVF/ICSI-ET

PurposeThis study aims to create and validate a clinical model that predict the probability of blastocyst formation in IVF/ICSI-ET cycles.MethodsThis study employed a retrospective methodology, gathering data from 4961 cleavage-stage embryos that cultured in the reproductive center’s of the Fourth Hospital of Hebei Medical University between June 2020 and March 2024. 3472 were in the training set and 1489 were in the validation set when it was randomly split into the training set and validation set in a 7:3 ratio. The study employed both univariate and multivariate logistic regression analysis to determine the factors those influence in the process of blastocyst formation. Based on the multiple regression model, a predictive model of blastocyst formation during IVF was created. The calibration and decision curves were used to assess the effectiveness and therapeutic usefulness of this model.ResultsThe following factors independently predicted the probability of blastocyst formation: the method of insemination, number of oocytes retrieved, pronuclear morphological score, the number of cleavage ball, cleavage embryo symmetry, fragmentation rate and morphological score and basal P levels of female. The receiver operating characteristic curve’s area under the curve (AUC) in the training set is 0.742 (95% CI: 0.724,0.759), while the validation set’s AUC is 0.729 (95% CI: 0.703,0.755), indicating a rather high clinical prediction capacity.ConclusionOur generated nomogram has the ability to forecast the probability of blastocyst formation in IVF, hence can assist clinical staff in making informed decisions.

Study on the embryotoxic effects and potential mechanisms of Aconitum diterpenoid alkaloids in rat whole embryo culture through morphological and transcriptomic analysis

Ethnopharmacological relevanceThe lateral root of Aconitum carmichaelii Debeaux, or Fuzi, is recognized in Asia for its anti-inflammatory, analgesic, and cardiotonic effects. Its main active compounds are diester diterpenoid alkaloids (DDAs) such as aconitine (AC), mesoacitine (MA), and hypoaconitine (HA), which are also toxic and have a narrow therapeutic window, limiting their clinical use. Although Aconitum DDAs are known for cardiotoxic and neurotoxic effects, their impact on embryonic development remains unclear. Aim of the studyThe embryotoxicity of three representative Aconitum DDAs (AC, MA, and HA) and their metabolites were systematically assessed, and the mechanisms underlying AC-induced embryotoxicity was explored. Materials and methodsThe embryotoxicity of these DDAs was assessed by indicators such as morphological scores in a whole embryo culture (WEC) system. Immunofluorescence analysis was conducted to detect DNA damage and apoptosis in embryos, and transcriptomic analysis and western blotting were performed to explore the underlying mechanisms. ResultsDDAs, particularly AC, induced dose-dependent developmental retardation and malformation in rat embryos. Notably, the embryotoxicity of AC metabolites such as benzoyltrypine (BAC) and aconine, was significantly reduced. AC treatment caused substantial DNA damage and apoptosis in embryos. Transcriptomic analysis indicate that AC treatment may impair DNA replication and histone synthesis by activating the p53/p21/CDK2/NPAT pathway, ultimately affecting embryonic development. ConclusionAmong these Aconitum DDAs, AC exhibited the strongest embryotoxicity, mainly through DNA damage and regulation of histone genes via the p53/p21/CDK2/NPAT pathway.

Application of the Morphological Uterine Scoring Assessment in Ultrasound for Abnormal Uterine Bleeding

Application of the Morphological Uterine Scoring Assessment in Ultrasound for Abnormal Uterine Bleeding

Effects of effluents from the Villa Victoria Reservoir (Mexico) on the development of Danio rerio at early life stages through apoptotic response and oxidative-induced state

As one of Mexico's most crucial water storage facilities, the Villa Victoria Reservoir (VVR) supplies water to over six million people residing in the Mexico City Metropolitan Area. In recent years, this water resource has been subjected to significant risks due to several factors, including human population growth, alterations in global climate patterns, excessive resource utilization, and insufficient protective regulations, thereby endangering not only the biocenosis itself, but also the water supply for numerous inhabitants. This study aimed to evaluate the current state of the reservoir through the determination of conventional and emerging pollutants present in the sampling points, as well as embryotoxicity and oxidative damage in Danio rerio embryos exposed to effluents from the VVR. Embryotoxicity was quantified using the General Morphology Score (GMS) and teratogenic index, whereas oxidative damage was assessed based on lipid peroxidation, hydroperoxide content, oxidized proteins, antioxidant enzyme activity, and gene expression. These results revealed the presence of heavy metals, diverse pharmaceutical compounds, and pesticides. In addition, elevated lipid, hydroperoxide, and protein oxidation accompanied by alterations in superoxide dismutase (SOD) and catalase (CAT) enzymatic activity were observed during exposure. GMS resulted in impaired embryo development and teratogenic effects, including pericardial, axial, and skeletal edema. Furthermore, the upregulation of genes associated with apoptotic processes and antioxidant defense reflects a comprehensive response to oxidative stress. The study concluded that pollutants in VVR water induced oxidative damage, modified antioxidant activity, elicited embryotoxicity, and upregulated oxidative damage-related genes. The findings underscore the necessity of undertaking restoration efforts for water sources, as pollution can potentially endanger aquatic organisms and human well-being.

Evaluation of the toxic potential of ethyl methanesulphonate (EMS) on Hydra vulgaris

The effect of EMS at final concentration of 0.09, 0.18, 0.27 and 0.37mM was studied on Hydra vulgaris using morphological, regeneration, oxidative stress markers and DNA damage as parameters. The morphological scores showed a significant dose dependent difference in the Hydra exposed to 0.18, 0.27, and 0.37mM of EMS for 24, 48, 72 and 96 hrs. The regeneration scores also showed a significant difference in the gastric region of Hydra exposed to 0.37mM of EMS for 48hr. A significant difference in the scores of regeneration was observed for the mid body portion exposed to 0.18, 0.27 and 0.37mM of EMS for 72 and 96hr of duration compared to control. A dose-dependent significant increase in the activities of glutathione-S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) was observed compared to control. The thiobarbituric acid reactive species (TBARS) levels were also significantly increased compared to control. The genotoxic damage was assessed in the cells of gastric region of the Hydra exposed to 0.09, 0.18, 0.27 and 0.37mM of EMS for 48hr by performing comet assay. A significant dose-dependent increase in the DNA damage was observed compared to control.

Microglia morphological response to mesenchymal stromal cell extracellular vesicles demonstrates EV therapeutic potential for modulating neuroinflammation

BackgroundMesenchymal stromal cell derived extracellular vesicles (MSC-EVs) are a promising therapeutic for neuroinflammation. MSC-EVs can interact with microglia, the resident immune cells of the brain, to exert their immunomodulatory effects. In response to inflammatory cues, such as cytokines, microglia undergo phenotypic changes indicative of their function e.g. morphology and secretion. However, these changes in response to MSC-EVs are not well understood. Additionally, no disease-relevant screening tools to assess MSC-EV bioactivity exist, which has further impeded clinical translation. Here, we developed a quantitative, high throughput morphological profiling approach to assess the response of microglia to neuroinflammation- relevant signals and whether this morphological response can be used to indicate the bioactivity of MSC-EVs.ResultsUsing an immortalized human microglia cell-line, we observed increased size (perimeter, major axis length) and complexity (form factor) upon stimulation with interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). Upon treatment with MSC-EVs, the overall morphological score (determined using principal component analysis) shifted towards the unstimulated morphology, indicating that MSC-EVs are bioactive and modulate microglia. The morphological effects of MSC-EVs in TNF-α /IFN-γ stimulated cells were concomitant with reduced secretion of 14 chemokines/cytokines (e.g. CXCL6, CXCL9) and increased secretion of 12 chemokines/cytokines (e.g. CXCL8, CXCL10). Proteomic analysis of cell lysates revealed significant increases in 192 proteins (e.g. HIBADH, MEAK7, LAMC1) and decreases in 257 proteins (e.g. PTEN, TOM1, MFF) with MSC-EV treatment. Of note, many of these proteins are involved in regulation of cell morphology and migration. Gene Set Variation Analysis revealed upregulation of pathways associated with immune response, such as regulation of cytokine production, immune cell infiltration (e.g. T cells, NK cells) and morphological changes (e.g. Semaphorin, RHO/Rac signaling). Additionally, changes in microglia mitochondrial morphology were measured suggesting that MSC-EV modulate mitochondrial metabolism.ConclusionThis study comprehensively demonstrates the effects of MSC-EVs on human microglial morphology, cytokine secretion, cellular proteome, and mitochondrial content. Our high-throughput, rapid, low-cost morphometric approach enables screening of MSC-EV batches and manufacturing conditions to enhance EV function and mitigate EV functional heterogeneity in a disease relevant manner. This approach is highly generalizable and can be further adapted and refined based on selection of the disease-relevant signal, target cell, and therapeutic product.

Steady morphokinetic progression is an independent predictor of live birth: a descriptive reference for euploid embryos.

Can modelling the longitudinal morphokinetic pattern of euploid embryos during time-lapse monitoring (TLM) be helpful for selecting embryos with the highest live birth potential? Longitudinal reference ranges of morphokinetic development of euploid embryos have been identified, and embryos with steadier progression during TLM are associated with higher chances of live birth. TLM imaging is increasingly adopted by fertility clinics as an attempt to improve the ability of selecting embryos with the highest potential for implantation. Many markers of embryonic morphokinetics have been incorporated into decision algorithms for embryo (de)selection. However, longitudinal changes during this temporal process, and the impact of such changes on embryonic competence remain unknown. Aiming to model the reference ranges of morphokinetic development of euploid embryos and using it as a single longitudinal trajectory might provide an additive value to the blastocyst morphological grade in identifying highly competent embryos. This observational, retrospective cohort study was performed in a single IVF clinic between October 2017 and June 2021 and included only autologous single euploid frozen embryo transfers (seFET). Reference ranges were developed from [hours post-insemination (hpi)] of the standard morphokinetic parameters of euploid embryos assessed as tPB2, tPNa, tPNf, t2-t9, tSC, tM, tSB, and tB. Variance in morphokinetic patterns was measured and reported as morphokinetic variance score (MVS). Nuclear errors (micronucleation, binucleation, and multinucleation) were annotated when present in at least one blastomere at the two- or four-cell stages. The blastocyst grade of expansion, trophectoderm (TE), and inner cell mass (ICM) were assessed immediately before biopsy using Gardner's criteria. Pre-implantation genetic diagnosis for aneuploidy (PGT-A) was performed by next-generation sequencing. All euploid embryos were singly transferred in a frozen transferred cycle and outcomes were assessed as live birth, pregnancy loss, or not pregnant. Association of MVS with live birth was investigated with regression analyses. TLM data from 340 seFET blastocysts were included in the study, of which 189 (55.6%) resulted in a live birth. The median time for euploid embryos to reach blastulation was 109.9 hpi (95% CI: 98.8-121.0 hpi). The MVS was calculated from the variance in time taken for the embryo to reach all morphokinetic points and reflects the total morphokinetic variability it exhibits during its development. Embryos with more erratic kinetics, i.e. higher morphokinetic variance, had higher rates of pregnancy loss (P = 0.004) and no pregnancy (P < 0.001) compared to embryos with steadier morphokinetic patterns. In the multivariable analysis adjusting for ICM, TE grade, presence of nuclear errors, and time of blastulation, MVS was independently associated with live birth (odds ratio [OR]: 0.62, 95% CI: 0.46-0.84, P = 0.002) along with ICM quality. Live birth rate of embryos with the same ICM grading but different morphokinetic variance patterns differed significantly. Live birth rates of embryos exhibiting low MVS with ICM grades A, B, and C were 85%, 76%, and 67%, respectively. However, ICM grades A, B, and C embryos with high MVS had live birth rates of 65%, 48%, and 21% (P < 0.001). The addition of the MVS to embryo morphology score (ICM and TE grading) significantly improved the model's AUC value (0.67 vs 0.62, P = 0.015) and this finding persisted through repeat cross-validation (0.64 ± 0.08 vs 0.60 ± 0.07, P < 0.001). The exclusion of IVF cases limits, for now, the utility of the model to only ICSI-derived embryos. The utility of these reference ranges and the association of MVS with various clinical outcomes should be further investigated. We have developed reference ranges for morphokinetic development of euploid embryos and a marker for measuring total morphokinetic variability exhibited by developed blastocysts. Longitudinal assessment of embryonic morphokinetics rather than static time points may provide more insight about which embryos have higher live birth potential. The developed reference ranges and MVS show an association with live birth that is independent of known morphological factors and could emerge as a valuable tool in prioritizing embryos for transfer. This study received no external funding. The authors declare no conflicting interests. N/A.

Clinical validation of the early embryo viability assessment system: Analysis for the blastocyst morphology and pregnancy outcomes

Objective: To determine the relationship between the early embryo viability assessment (EEVA) and blastocyst morphological parameters and pregnancy outcomes. Methods: This retrospective cohort study was conducted on 291 intracytoplasmic sperm injection cycles including 2 522 embryos with indications of prolonging embryo culture to the blastocyst stage in the Genea embryo review incubator, and 511 single vitrified- warmed blastocyst transfer cycles from January 2020 to June 2023. The EEVA system produced an EEVA score from E1 (best) to E5 (worse) for the potential of blastocyst formation. Blastocyst morphology was evaluated. The association between the EEVA score and each type of blastocyst morphology, implantation rate, clinical pregnancy, and ongoing pregnancy were assessed using generalized estimating equations. Results: The inner cell mass A (ICM A), trophectoderm A (TE A), blastocoele expansion degree of 3, 4, 5, 6, 7 rates were higher with lower the EEVA score. The adjusted odd ratio (aOR) (E5 vs E1) was 0.3 for ICM A, 0.174 for TE A and 0.210 for BL3, 4, 5, 6, 7 (all P&lt;0.001), suggesting a significant association between lower EEVA scores and improved embryo quality. The implantation, clinical pregnancy, and ongoing pregnancy rate were also higher with lower the EEVA score. The aOR of E5 vs E1 was 0.245 for implantation, 0.185 for clinical pregnancy and 0.200 for ongoing pregnancy rate (P&lt;0.001). Conclusions: There were associations between blastocyst morphology, pregnancy outcome and EEVA scores. The good blastocyst morphology and pregnancy outcomes are higher with lower the EEVA score.

Survival prediction of colorectal liver metastases underwent surgical resection after neoadjuvant chemotherapy: Tumor response combined with the genetic and morphological evaluation score

IntroductionNeoadjuvant chemotherapy is becoming routine for colorectal liver metastasis (CRLM) in patients with high risks of recurrence or in whom resection is difficult. This retrospective study aimed to establish a modified survival prediction model for patients with CRLM who underwent hepatectomy after neoadjuvant chemotherapy. Materials and methodsA total of 619 patients who received neoadjuvant chemotherapy followed by hepatectomy between 2006 and 2021 were included and divided into training and validation groups at a ratio of 2:1. The model was established in training group and validated in validation group. Chemotherapy response was integrated into the genetic and morphological evaluation (GAME) score as a new NeoGAME model, with assigned points based on the hazard ratio in the multivariate Cox regression. The NeoGAME score grouping cutoff was divided using X-tile, and the predictive power was compared with that of traditional models. ResultsThe 5-year overall survival were significantly different in the NeoGAME low-risk (0–2 points), medium-risk (3–4 points) and high-risk (≥5 points) groups (training group, P < 0.001; validation group, P = 0.0012). The area under the curve in predicting 5-year survival was 0.67 and 0.66 for the training and validation groups, respectively. Time-dependent receiver operating characteristic curve showed better discrimination ability of NeoGAME than the GAME score in predicting 5-year survival. ConclusionsThe newly established NeoGAME score can predict survival more precisely for patients with CRLM receiving neoadjuvant chemotherapy. Moreover, the model offers a useful tool for assessing tumor behavior and selecting a benefiting population for liver resection.

Utility of the morphological scoring of costal cartilage ossification in age estimation of adult Egyptians using multidetector computed tomography

Abstract Age estimation of adults is a challenging procedure in forensic practice. Inspired by the previous work by Chinese scholars, we established population specific age estimation models from the osseous and calcified projections (OCP) of costal cartilages, using three-dimensional volume-rendering technique. A total of 168 clinical CT scans (2 mm slice thickness) were used to develop the sex-specific age prediction models from a sample of Egyptians, comprising 70 females and 98 males, with documented ages between 12 and 85 years. The sample was also used for validating the Chinese model. We reported the differences between the predictive accuracy of the Egyptian (population specific) and Chinese (non population specific) models. The most accurate age estimation model was stepwise linear regression with standard error of estimates (SEE) of 10.9 and 11.8 years in males and females, respectively. For the simple linear regression models, the most accurate formula included OCP of the right second costal cartilage in males and OCP of the left third costal cartilage in females with SEE of 11.2 and 12.2 years, respectively and mean absolute error (MAE) of 8.8 and 9.6 years, respectively. By comparison, the best accuracy rates produced by the Chinese vs. the Egyptian models in males and females within 5 years were 30.61% and 32.86% vs. 35.71% and 32.86%, respectively, whereas within 10 years, the accuracy rates increased up to 57.14% and 58.57% vs. 72.45% and 64.29%, respectively. Although the accuracy rates from the Chinese models were lower than those obtained from the Egyptian models, the MAE and least error values were comparable in both sexes. Notable accurate age estimation rates in the advanced age group ≥40 years were reached being 81.25% to 97.92% in males and 69.77% to 93.02% in females. OCP of the right first costal cartilage was the most accurate in cross-population application for males and females with MAE values of 10.7 and 11.03 years, respectively with balanced accuracy rates of age estimation using the 10-year interval and 40-year cutoff.

Investigation of the potential teratogenic effects of fructose on the embryo using the rat whole embryo culture model

Excessive consumption of fructose-sweetened foods and beverages is a growing concern worldwide. Studies have demonstrated that fructose consumption before and during pregnancy can result in adverse outcomes such as decreased decidualization, increased fetal losses, and low birth weight. The study investigated the teratogenic effects of fructose on rat embryos during organogenesis using whole embryo culture. Within the scope of the study, 4 groups were formed as control, low, medium, and high-dose fructose (HDF) with 10 embryos in each group. The 9.5-day-old rat embryos were cultured with different concentrations of fructose (1, 5 and 10 mM) for 48 h and the possible effects of fructose were examined using morphological scoring, histochemistry, immunofluorescence, and TUNEL methods. According to the analyses, protein synthesis and proliferation were decreased, vascular formation was suppressed, and apoptosis was increased in embryos exposed to fructose, especially at concentrations of 5 mM and above. According to the morphological scoring results, it was determined that heart, hind limb, and somite development were retarded in all experimental groups compared to the control group, developmental retardation increased in direct proportion to fructose concentration, and also significant malformations were observed in all parameters examined in the HDF group. In addition, analysis of yolk sac diameter, head length, crown rump length and somite numbers showed that these parameters were significantly decreased in all experimental groups. End of the study, it was concluded that fructose at concentrations of 1 mM and above may induce embryonic development retardation and other anomalies by decreasing protein synthesis and cell proliferation, suppressing vascular formation, and increasing apoptosis in embryonic tissues.

Rate-Dependent Pacemap Matching in Scar-Related Ventricular Tachycardia: Impact of “TR Fusion” Phenomenon

BackgroundThe impact of varying rates of pacemapping (PM) rates on QRS morphology and PM score matching in patients with scar-related ventricular tachycardia (VT) has not been systematically assessed. ObjectivesIn this study, the authors sought to assess the variability in PM score matching at different pacing rates. MethodsDuring substrate mapping for VT ablation, PM was performed at cycle lengths (CLs) of 600 ms, 500 ms, 400 ms, 300 ms, and VT CL. PM scores were compared for the entire QRS, the first half (H1) of QRS, and the second half (H2) of QRS to examine the influence of the preceding T-wave superimposed into the onset of paced QRS complex (TR fusion). ResultsA total of 269 PMs in 40 patients undergoing scar-related VT ablation were systematically analyzed. The PM score improved at rates closer to VT with a median difference of 6% (Q1-Q3: 4%-10%; range: 0%-33%) between the lowest and the highest PM scores at a given site. Greater slurring of the QRS onset was observed at faster-paced CL, corresponding to a superimposition of the preceding T-wave into QRS onset, with significant differences in H1 but not H2 of the QRS complex. At faster PM rates, 32% of overall sites developed pseudo delta wave and 69% of endocardial pacing sites fulfilled epicardial criteria. ConclusionsThe rate of pacemapping can significantly alter morphologic score matching, with the most optimal match observed closest to VT CL. The onset of QRS complex morphology is influenced by superimposition of the preceding T-wave at faster rates, resulting in an underrecognized TR fusion phenomenon that may confound epicardial electrocardiographic criteria predicated upon the initial QRS slope and vector.

Longitudinal Magnetic Resonance Imaging of Changes in Lung Morphology and Perfusion in Children with Cystic Fibrosis From Infancy through Adolescence.

The progression of lung changes in cystic fibrosis (CF) from infancy through adolescence remains poorly understood due to limited longitudinal imaging data. To assess changes in lung morphology and perfusion in children with CF through the pediatric age range by longitudinal chest magnetic resonance imaging (MRI). 1112 annual chest MRI were performed in 226 patients with CF aged 0-18yr. MRI was assessed using a validated MRI scoring system. The MRI global score continuously increased from 5.5±4.6 at infancy (0yr) to 17.9±8.4 at adolescence (range 12-18yr), and the MRI morphology score from 5.0±3.9 to 12.4±6.0 (P<0.001). Bronchiectasis/wall thickening prevalence increased from 89.1% at infancy to approx. 100% from preschool age (1-5yr), and the subscore increased from 3.1±1.9 at infancy to 6.6±2.1 at adolescence (P<0.001). Mucus plugging prevalence increased from 55.4% at infancy to 83.5% at adolescence, and the subscore increased from 1.2±1.6 to 3.7±2.5 in the same period (P<0.001). Perfusion abnormalities were found in 44.4% at infancy, and increased to approx. 90% from preschool age (P<0.001). The MRI perfusion score increased from 1.1±1.6 at infancy to 5.6±3.0 at adolescence (P<0.001). Chronic Pseudomonas aeruginosa infection was associated with higher MRI scores from school age (6-11yr, P<0.05-0.001). This is the first study assessing longitudinal changes in lung morphology and perfusion in CF throughout the pediatric age range, providing percentiles as age-specific reference for lung disease severity. Our data may facilitate the use of MRI as an endpoint in clinical trials in children with CF.

Day 3 embryo assessment does not provide a reliable prediction for blastocyst formation and designation: a retrospective cohort study.

Although many Fertility Centers have adopted day 5 or 6 embryo transfer policy, yet, 30% of embryo transfers in the US are performed on day 3. This is mainly due to concerns related to longer embryo culture effect and higher rates of embryo transfer cancellation on day 5, with no effect on cumulative pregnancy rate. We conducted a retrospective cohort study comparing individual embryo transfer order rank, best embryo for fresh transfer and intention to freeze, of day-3 and day-5 embryos based on their morphology score. Day-3 embryos of each patient were ranked by embryologists for the order of transfer and intention to freeze, based on morphological score, blinded to actual blastulation outcome. The corresponding blastocysts were similarly ranked for the order of transfer and vitrification intention. Ranking was compared to test the predictive value of day-3 morphological assessment. Sixty patients with 784 day-3 embryos were included. There was only a moderate positive significant correlation between ranks on day-3 and ranks on day-5 [r = 0.662 95% CI (0.611-0.706, p < 0.001)]. Only 25% of the best embryos for transfer on day 3 (rank = 1) were chosen for fresh transfer on day 5. A total of 441 embryos were intended to be frozen on day 3. Of those, 201 were not transferred nor vitrified on day 5-6 (45%), 3.35 embryos per patient. No significant difference was found between average day-3 rank of embryos ranked 1, 2 (3.12 vs 4.12, p = 0.074) and 3 (3.12 vs 4.08, p = 0.082) on day-5-6. To conclude, this study brings a different perspective to the comparison of day 3 and day 5 by following each embryo's putative and actual designation. Day-3 ranking of embryo morphology did not provide a reliable prediction for blastocyst formation, transfer order and vitrification intention, and may support transfer or cryopreservation of blastocysts over cleavage stage embryos.

Breeding Value Estimation Based on Morphological Evaluation of the Maremmano Horse Population through Factor Analysis.

Morphological scoring is a common evaluation method for domestic animals. The National Association of Maremmano Breeders (ANAM) has provided a dataset containing the records of 600 horses, four metric measurements (cm) and 24 traits with a continuous evaluation scale, each one with 15 classes. Moreover, a body condition score (BCS) with five classes is included. In this study, factor analysis was conducted to create a small number of informative factors (3) obtained from these traits, and a new BLUP-AM-MT index was established. The New Estimated Breeding Value (NEBV1) of each horse was computed by adding the genetic indexes of the three factors, with each one multiplied using a coefficient indicated by ANAM. The practical feasibility of the NEBV1 was evaluated through Spearman correlations between the rankings of the NEBV1 and the rankings of the BLUP-AM-MT, estimated through the four biometric measures and the morphological score (MS) assigned to each horse by the ANAM judges. The factorial analysis was used to estimate three factors: the "Trunk Dimension", "Legs" and "Length". As the explained variance was only 32%, the model was rotated, and the heritability of the three factors were 0.51, 0.05 and 0.41, respectively. After rotation, the estimated correlations between the new NEBV1 and the biometric measures were improved. These results should encourage breeders to adopt a breeding value index that takes into consideration the factors derived from all the variables observed in the morphological evaluation of the Maremmano. In this way, breeders can use it to select the best animals for breeding.

Application of the blastomere count variations "skip value" in the embryo AI assessment

Objective: To explore the correlation between blastomere count variations "skip value" which extracted from by time-lapse technology (TLT) combined with artificial intelligence (AI) and morphological features of in vitro fertilization (IVF) embryo, and to test its feasibility in clinical applications. Methods: This study was a diagnostic experiment (AI reassessment of embryo transferred patients), a total of 6 545 embryos from 1 226 patients who underwent IVF at the Women and Children's Hospital of Chongqing Medical University from December 2020 to December 2021 were retrospectively analyzed, of which 2 869 embryos were attempted to cultured to blastocyst stage by TLT. The embryo dynamic map (EDM) was drawn by Embryo Viewer, a TLT recording software, based on embryo developmental kinetics. The self-developed AI embryo evaluation software identified and recorded the number of cleavages in real time during embryonic development, and compared with the EDM, the correlation between the skip value formed by the change of cleavage sphere counts and the outcomes of the embryos was analyzed. The correlation among skip value, morphological score of embryo, implantation rate and live birth rate were performed by Spearman and step-up logistic regression. The receiver operating characteristic (ROC) curve was selected for reporting there relationship of skip value and morphology. Finally, predicting power of skip value for implantation and live birth rate were performed by ROC analysis. Results: The total skip values extracted from the blastomere count of embryos (72 hours post-fertilization) were negatively correlated with abnormal cleavage, blastocyst formation rate, day 3 (D3)-cell score, uneven size and fragmentation (the β values were -0.268, -0.116, -0.213, -0.159 and -0.222, respectively; all P<0.001); positively correlated with D3-cell number (β=0.034; P<0.001); negatively correlated with blastocyst formation rate and implantation rate (OR=0.97, 95%CI: 0.93-0.99, P=0.034; OR=0.96, 95%CI: 0.93-0.98, P=0.044). The power of predicting implantation were similar between the order selection of skip values and traditional morphology criteria [area under curve (AUC): 0.679 vs 0.620]. Live birth rate were negatively correlated with female age (OR=0.91, 95%CI: 0.88-0.93; P<0.001), D3 general score (OR=0.77, 95%CI: 0.59-0.99; P=0.045) and order selection of skip values (OR=0.98, 95%CI: 0.96-0.99; P=0.038), while positively correlated with retrieved oocyte number and endometrial thickness in embryo transferred (OR=1.08, 95%CI:1.05-1.11, P<0.001; OR=1.09, 95%CI:1.06-0.12, P<0.001, respectively) from multivariate regression analysis, and the power of predicting live birth was 0.666 for AUC. Conclusions: The skip value and its order form is a systematic quantification of embryo development, correlated with embryo developmental quality and clinical outcome. It could be an addition parameter for embryo culture and selection.

Optimizing single blastocyst selection: the role of day 3 embryo morphology in vitrified-warmed blastocyst transfer cycles

Can day 3 embryo morphology serve as an independent criterion for optimal single blastocyst selection? This retrospective, single-centre cohort study included 1517 single vitrified-warmed blastocyst transfer (SVBT) cycles conducted between October 2019 and July 2022. The live birth rate (LBR) and other clinical outcomes of SVBT cycles were evaluated, considering both good-quality and non-good-quality day 3 embryos. The associations of day 3 morphological characteristics, encompassing number of blastomeres and embryo grade, were assessed. Multivariable analyses were undertaken using multiple models adjusted for day of blastocyst development and blastocyst grade. Blastocysts from good-quality day 3 embryos had significantly higher LBR compared with those from non-good-quality embryos for both day 5 (51.5% versus 42.9%; P = 0.013) and day 6 (25.1% versus 17.6%; P = 0.018) blastocysts. LBR did not differ significantly with number of blastomeres on day 3, regardless of day of blastocyst development (day 5/6) or blastocyst grade. LBR varied significantly by day 3 embryo grade for both day 5 (48.0%, 51.5%, 46.6% and 32.7% for grades I, II, III and IV-V; P = 0.005) and day 6 (41.5%, 23.6%, 15.9% and 16.1% for grades I, II, III and IV-V; P = 0.001) blastocysts. Multivariable logistic regression revealed that non-good-quality embryos and lower morphological grade (IV-V) on day 3 were significantly and negatively correlated with LBR, while the number of blastomeres on day 3 was not an independent factor. When selecting blastocysts of equal quality for SVBT cycles, those with higher day 3 morphological scores are preferred. Day 3 morphological evaluation is a valuable supplement to conventional selection methods.