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Abstract This retrospective study applied machine-learning models to predict treatment outcomes of women undergoing elective fertility preservation. Two-hundred-fifty women who underwent elective fertility preservation at a tertiary center, 2019–2022 were included. Primary outcome was the number of metaphase II oocytes retrieved. Outcome class was based on oocyte count (OC): Low (≤ 8), Medium (9–15) or High (≥ 16). Machine-learning models and statistical regression were used to predict outcome class, first based on pre-treatment parameters, and then using post-treatment data from ovulation-triggering day. OC was 136 Low, 80 Medium, and 34 High. Random Forest Classifier (RFC) was the most accurate model (pre-treatment receiver operating characteristic (ROC) area under the curve (AUC) was 77%, and post-treatment ROC AUC was 87%), followed by XGBoost Classifier (pre-treatment ROC AUC 74%, post-treatment ROC AUC 86%). The most important pre-treatment parameters for RFC were basal FSH (22.6%), basal LH (19.1%), AFC (18.2%), and basal estradiol (15.6%). Post-treatment parameters were estradiol levels on trigger-day (17.7%), basal FSH (11%), basal LH (9%), and AFC (8%). Machine-learning models trained with clinical data appear to predict fertility preservation treatment outcomes with relatively high accuracy.

Well-designed, dialogic, and interdisciplinary learning opportunities in science related disciplines can promote many educational goals. The difficulty lies in providing these opportunities in schools. Can out-of-school focus days fill the void? Here, we performed a mixed methods study to discover how middle school learners perceive focus days that included dialogic, interdisciplinary activities in mathematics, science, and philosophy, all around socio-scientific dilemmas. We also sought to understand the experiences’ impact on learners’ self-perceived dialogic engagement in the school classroom. We focused on (1) learners’ perceptions and recollections of the dialogic climate during the focus days; (2) the perceived contribution of the three disciplines (mathematics, science and philosophy) to the interdisciplinary focus days; and (3) the focus days’ effects on the dialogic climate in the everyday school environment. Our findings suggest that (1) learners generally considered the focus days as enjoyable and different than their everyday school experience; (2) students did not consider each discipline equally relevant to the focus days’ main topics; and (3) the effects of the focus days were localized, that is, no impact was found on the dialogic climate at school. We discuss implications for promoting interdisciplinary, dialogic science related learning in secondary schools.

Background/Objectives: Although high live birth rates are associated with oocyte donation (OD), these pregnancies are associated with increased obstetric and perinatal risks. This study evaluated maternal and neonatal risks after OD compared to in vitro fertilization (IVF) with autologous oocytes, and to spontaneous pregnancies (SPs), among singletons, twins and triplets. Methods: A retrospective, large, population-based cohort study was conducted based on electronic data from Maccabi Healthcare Services. A total of 469,134 pregnancies were grouped according to the mode of conception. The main outcome measures were preterm birth (PTB), small for gestational age (SGA) and pregnancy-induced hypertension (PIH). The data were analyzed separately for singletons, twins and triplets. Results: The mean maternal age was older in the OD group compared with the IVF and SP groups (singletons: 39.7 ± 4.1 vs. 34.5 ± 4.8 and 31.7 ± 5.3 years; twins: 39 ± 4.6 vs. 32.6 ± 4.4 and 31.2 ± 5.1 years; and triplets: 35.6 ± 2.5 vs. 32 ± 3.9 and 29.7 ± 5 years). The mean gestational age was younger among the OD group compared to the SP group (singletons: 37.5 ± 3 vs. 39 ± 2 p = 0.001, and twins: 35 ± 3 vs. 36 ± 2.5 p = 0.001). Higher rates of PTB < 37, PTB < 34 and PTB < 28 weeks were found among OD singletons. Multivariable logistic regressions for PTB < 37 weeks and SGA in singletons demonstrated that OD and IVF are significant risk factors (OR = 4.1, 95%CI = 3.3–5.2; OR = 4.3, 95%CI = 4.1–4.6; OR = 1.9, 95%CI = 1.3–2.6; OR = 2.2, 95%CI = 2–2.4, respectively). Significantly higher rates of PIH were demonstrated among the OD vs. IVF and SP groups in singleton (4.3% vs. 1.7% and 0.7%) and in twin pregnancies (7.5% vs. 4.3% and 3.4%). Conclusions: OD pregnancies are at increased risk for PTB, SGA and PIH.

Background: To compare the predictive value of the circadian syndrome (CircS) and Metabolic syndrome (MetS) for cardiovascular disease. Method: We used the data of 9360 Chinese adults aged ≥40 years from the 2011 China Health and Retirement Longitudinal Study (CHARLS). Of the participants, 8253 people were followed in the 2015 survey. MetS was defined using the harmonized criteria. CircS was based on the components of the International Diabetes Federation (IDF) MetS plus short sleep and depression. The cut‐off for CircS was set as ≥4. Multivariable logistic regression analysis was used to examine the associations. Results: The prevalence of CircS and MetS was 39.0% and 44.7%. Both MetS and CircS were directly associated with prevalent CVD. The odds ratios for prevalent CVD comparing CircS with MetS, respectively, were 2.83 (95%CI 2.33–3.43) and 2.34 (1.93–2.83) in men, and 2.33 (1.98–2.73) and 1.79 (1.53–2.10) in women. Similar associations were found for incident CVD. The five‐year incidence of CVD was 15.1% in CircS and 14.0% in MetS. The number of CircS components has a better predictive power for both prevalent and incident CVD than those of Mets components as indicated by the area under the ROC (AUC). AUC values for CVD in 2011 were higher for CircS than MetS in both men (0.659 (95%CI 0.634–0.684) vs 0.635 (95%CI 0.610–0.661)) and women (0.652 (95%CI 0.632–0.672) vs 0.619 (95%CI 0.599–0.640)). Conclusion: The circadian syndrome is a strong and better predictor for CVD than the metabolic syndrome in Chinese adults. [ABSTRACT FROM AUTHOR]

Abstract General anesthesia is frequently administered during oocyte retrieval. Its effects on the outcomes of IVF cycles are uncertain. This study investigated whether administration of general anesthesia (specifically propofol) during oocyte retrieval affects IVF outcomes. A total of 245 women undergoing IVF cycles were included in this retrospective cohort study. IVF outcomes of 129 women who underwent oocyte retrieval under propofol anesthesia and 116 without anesthesia were compared. Data were adjusted for age, BMI, estradiol on triggering day and total gonadotropin dose. The primary outcomes were fertilization, pregnancy and live birth rates. A secondary outcome was the efficiency of follicle retrieval associated with the use of anesthesia. Fertilization rate was lower in retrievals under anesthesia compared to without (53.4% ± 34.8 vs. 63.7% ± 33.6, respectively; p = 0.02). There was no significant difference in the ratio of expected to retrieved oocytes between retrievals with and without anesthesia (0.8 ± 0.4 vs. 0.8 ± 0.8, respectively, p = 0.96). The differences in pregnancy and live birth rates between the groups were not statistically significant. General anesthesia administered during oocyte retrieval may have adverse effects on the fertilization potential of oocytes. This impact on the developmental potential of oocytes may lead to negative IVF outcomes and should be investigated further.

Abstract Background This study investigated whether high physical activity affects ovarian reserve in normo-ovulatory, reproductive-age women. Methods This prospective, observational study compared 31 professional female athletes, with 31 women who did not engage in physical activity. It was conducted 2017–2020 in a tertiary medical center. Normo-ovulatory, professional athletes, ages 20–35 years were recruited from The Wingate Institute—the Israeli National Institute for Sport Excellence. They had high International Physical Activity Questionnaire (IPAQ) scores. Non-physically active women, matched by age and body mass index, were recruited from hospital staff. Women were evaluated for ovarian reserve markers on day 2–5 of the menstrual cycle, including follicular stimulating hormone, antral follicle count, anti-Mullerian hormone and Inhibin B. Results The average age of the high physical activity group was 29.9 ± 4.2 years and the nonactive group 31.6 ± 4.2 years (p = 0.062). Body mass index of both groups were similar (22.5 ± 5.0 vs. 21.4 ± 2.5, respectively; p = 0.1). No differences were observed with respect to follicle stimulating hormone (p = 0.12) and anti-Mullerian hormone (p = 0.16). A trend towards higher total antral follicle count in the high physical activity group vs. the non-active group (34.5 ± 12.9 vs. 28.1 ± 15.2, p = 0.08) and lower Inhibin B (68.1 ± 36.8 vs. 89.4 ± 46.1, p = 0.05). Menarche age correlated with anti-Mullerian hormone (r = 0.387, p = 0.003), as did total antral follicle count (r = 0.368, p = 0.004). IPAQ scores and basal follicle stimulating hormone levels were negatively correlated (r = − 0.292, p = 0.005). Conclusions Athletic, normo-ovulatory women have ovarian reserves that are at least as good as those of the general population. As this is the first study examining this issue, it could cautiously reassure women engaged in high physical activity regarding ovarian reserve.

Abstract This study evaluates the effect of GnRH agonist (GnRHa) trigger for ovulation induction among women with advanced maternal age (AMA). This is a retrospective study performed at a single assisted reproductive technology centre, 2012 to 2020. A total of 306 patients with 515 IVF cycles who were triggered with GnRHa for Ovum Pick Up (OPU), were divided into two groups according to maternal age: age ≥ 40 and age

Abstract Color vision tests use estimative of threshold color discrimination or number of correct responses to evaluate performance in chromatic discrimination tasks. Both approaches have advantages and disadvantages. In the present investigation, we compared the number of errors during color discrimination task in normal trichromats and participants with color vision deficiency (CVD) using pseudoisochromatic stimuli at fixed saturation levels. We recruited 28 normal trichromats and eight participants with CVD. Cambridge Color Test was used to categorize their color vision phenotype, and those with a phenotype suggestive of color vision deficiency had their L- and M-opsin genes genotyped. Pseudoisochromatic stimuli were shown with target chromaticity in 20 vectors radiating from the background chromaticity and saturation of 0.06, 0.04, 0.03, 0.02, 0.01, and 0.005 u’v' units. Each stimulus condition appeared in four trials. The number of errors for each stimulus condition was considered an indicator of the participant's performance. At high chromatic saturation, there were fewer errors from both phenotypes. The errors of the normal trichromats had no systematic variation for high saturated stimuli, but below 0.02 u’v' units, there was a discrete prevalence of tritan errors. For participants with CVD, the errors happened mainly in red-green chromatic vectors. A three-way ANOVA showed that all factors (color vision phenotype, stimulus saturation, and chromatic vector) had statistically significant effects on the number of errors and that stimulus saturation was the most important main effect. ROC analysis indicated that the performance of the fixed saturation levels to identify CVD was better between 0.02 and 0.06 u’v’ units reaching 100%, while saturation of 0.01 and 0.005 u’v’ units decreased the accuracy of the screening of the test. We concluded that the color discrimination task using high saturated stimuli separated normal trichromats and participants with red-green color vision deficiencies with high performance, which can be considered a promising method for new color vision tests based in frequency of errors.

Abstract Introduction Analyses of miscarriage products indicate that the majority of aneuploidies in early developing embryos derive from errors occurring during maternal meiosis and the paternal contribution is less than 10%. Our aim was to assess the aneuploidy (mainly monosmies) frequencies at the earliest stages of embryo development, 3 days following fertilization during In vitro fertilization (IVF) treatments and to elucidate their parental origin. Later, we compared monosomies rates of day 3 to those of day 5 as demonstrated from Preimplantation Genetic Testing for Structural chromosomal Rearrangement (PGT-SR) results. Methods For a retrospective study, we collected data of 210 Preimplantation Genetic Testing for Monogenic Disorder (PGT-M) cycles performed between years 2008 and 2019.This study includes 2083 embryos, of 113 couples. It also included 432 embryos from 90 PGT-SR cycles of other 45 patients, carriers of balanced translocations. Defining the parental origin of aneuploidy in cleavage stage embryos was based on haplotypes analysis of at least six informative markers flanking the analyzed gene. For comprehensive chromosomal screening (CCS), chromosomal microarray (CMA) and next generation sequencing (NGS) was used. Results We inspected haplotype data of 40 genomic regions, flanking analyzed genes located on 9 different chromosomes.151 (7.2%) embryos presented numerical alterations in the tested chromosomes. We found similar paternal and maternal contribution to monosomy at cleavage stage. We demonstrated paternal origin in 51.5% of the monosomy, and maternal origin in 48.5% of the monosomies cases. Conclusion In our study, we found equal parental contribution to monosomies in cleavage-stage embryos. Comparison to CCS analyses of PGT-SR patients revealed a lower rate of monosomy per chromosome in embryos at day 5 of development. This is in contrast to the maternal dominancy described in studies of early miscarriage. Mitotic errors and paternal involvement in chemical pregnancies and IVF failure should be re-evaluated. Our results show monosomies are relatively common and may play a role in early development of ART embryos.

This multi-center study evaluated a novel microscope system capable of quantitative phase microscopy (QPM) for label-free sperm-cell selection for intracytoplasmic sperm injection (ICSI). Seventy-three patients were enrolled in four in vitro fertilization (IVF) units, where senior embryologists were asked to select 11 apparently normal and 11 overtly abnormal sperm cells, in accordance with current clinical practice, using a micromanipulator and 60× bright field microscopy. Following sperm selection and imaging via QPM, the individual sperm cell was chemically stained per World Health Organization (WHO) 2021 protocols and imaged via bright field microscopy for subsequent manual measurements by embryologists who were blinded to the QPM measurements. A comparison of the two modalities resulted in mean differences of 0.18 µm (CI −0.442–0.808 µm, 95%, STD—0.32 µm) for head length, −0.26 µm (CI −0.86–0.33 µm, 95%, STD—0.29 µm) for head width, 0.17 (CI −0.12–0.478, 95%, STD—0.15) for length–width ratio and 5.7 for acrosome–head area ratio (CI −12.81–24.33, 95%, STD—9.6). The repeatability of the measurements was significantly higher in the QPM modality. Surprisingly, only 19% of the subjectively pre-selected normal cells were found to be normal according to the WHO2021 criteria. The measurements of cells imaged stain-free through QPM were found to be in good agreement with the measurements performed on the reference method of stained cells imaged through bright field microscopy. QPM is non-toxic and non-invasive and can improve the clinical effectiveness of ICSI by choosing sperm cells that meet the strict criteria of the WHO2021.

Summary: Microbial adaptation to changing environmental conditions is frequently mediated by hypermutable sequences. Here we demonstrate that such a hypermutable hotspot within a gene encoding a flagellar unit of Paenibacillus glucanolyticus generated spontaneous non-swarming mutants with increased stress resistance. These mutants, which survived conditions that eliminated wild-type cultures, could be carried by their swarming siblings when the colony spread, consequently increasing their numbers at the spreading edge. Of interest, the hypermutable nature of the aforementioned sequence enabled the non-swarming mutants to serve as “seeds” for a new generation of wild-type cells through reversion of the mutation.Using a mathematical model, we examined the survival dynamics of P. glucanolyticus colonies under fluctuating environments. Our experimental and theoretical results suggest that the non-swarming, stress-resistant mutants can save the colony from extinction. Notably, we identified this hypermutable sequence in flagellar genes of additional Paenibacillus species, suggesting that this phenomenon could be wide-spread and ecologically important.

Melanopsin is a photopigment found in a subset of retinal ganglion cells that is responsible for generating a series of responses to light in organisms, such as circadian rhythm regulation, pupillary light reflex, and body temperature control. The role of each melanopsin gene in the vertebrate retina is still not fully elucidated and a diversity of expression patterns of this photopigment can be observed in retinas of different vertebrate species. Owls are an excellent model for studying the role of melanopsin due to the diversity of species, which may present diurnal, nocturnal, or cathemeral habits. The purpose of this study was to characterize the expression of melanopsin genes in the retina of four different owl species from the Strigidae family (Athene cunicularia, Asio clamator, Glaucidium brasilianum, and Megascops choliba) through genetic and phylogenetic analysis. The specimens were euthanized, and the retinas were collected for RNA extraction and cDNA transcription. cDNA was used in the polymerase chain reaction (PCR) with subsequent sequencing to identify melanopsin genes expressed in the retina of owls. For the quantitative analysis of gene expression, real-time PCR was performed. The phylogenetic reconstruction was obtained by the maximum likelihood. The results showed that owls express both melanopsin genes, Opn4x and Opn4m, with different patterns of expression among the species. The expression of the Opn4x gene was two times higher in Asio clamator (nocturnal) compared to A. cunicularia (cathemeral), Glaucidium brasilianum (diurnal), and Megascops choliba (nocturnal). On the other hand, the expression of Opn4m was about two times lower in the cathemeral, A. cunicularia compared to the other three species. These results might indicate functional differences of the Opn4x and Opn4m genes among species, related to circadian rhythm regulation. Further investigation in owls at other times of the day will bring light to the circadian pattern of melanopsin expression in these species and its correlation with the different patterns of daily activity.

The visual processing of vertebrates initiates in the retina upon the absorbance of photons by the photoreceptors. These neurons contain the photopigments that are formed by a membrane protein, opsin or rhodopsin, covalently bound to a chromophore. The peak spectral sensitivity (λmax) of the photopigment is determined by the protein structure and the type of chromophore associated, 11-cis-retinal (A1-based chromophore) or 3,4-dehydroretinal (A2-based chromophore). The red-eared turtle, Trachemys scripta elegans, has five A2-based photopigments, SWS1, SWS2, RH1, RH2, and LWS, with known λmax at 372, 458, 518, 518, and 617 nm, respectively. We took advantage of this valuable model to investigate the applicability of computational modeling to estimate the λmax of A2-based opsins. First, we sequenced the five opsin genes expressed in the retina of T. s. elegans and estimated the opsins λmax based on known spectral tuning sites. The predictions were consistent with the values described in the literature: 373, 457, 518, 518, and 617 nm, for the SWS1, SWS2, RH1, RH2, and LWS, respectively. Then, we calculated the λmax using Comparative Modeling for the RH1, RH2, SWS1, and SWS2 opsins and using Threading Modeling for the LWS opsin. The absorption spectrum was analyzed using semiempirical Quantum Mechanical simulations, according to the TD-DFT method, applying the functional B3LYP and 6–31 G basis set. For each model, molecular docking was carried out to find the best positioning of the chromophore. The estimated λmax of the SWS1, RH1, and RH2 were consistent with known peaks (380, 524, and 520 nm, respectively), while the opsins SWS2 and LWS had considerable shifts compared to known values (478 and 636 nm, respectively). Although the calculated λmax of the cone opsins had some inconsistencies, the in silico analyses revealed promising results and opened a new methodologic approach for further investigations of vertebrate spectral sensitivity.

Abstract DNA polymerase template switching between short, non-identical inverted repeats (IRs) is a genetic mechanism that leads to the homogenization of IR arms and to IR spacer inversion, which cause multinucleotide mutations (MNMs). It is unknown if and how template switching affects gene evolution. In this study, we performed a phylogenetic analysis to determine the effect of template switching between IR arms on coding DNA of Saccharomyces cerevisiae. To achieve this, perfect IRs that co-occurred with MNMs between a strain and its parental node were identified in S. cerevisiae strains. We determined that template switching introduced MNMs into 39 protein-coding genes through S. cerevisiae evolution, resulting in both arm homogenization and inversion of the IR spacer. These events in turn resulted in nonsynonymous substitutions and up to five neighboring amino acid replacements in a single gene. The study demonstrates that template switching is a powerful generator of multiple substitutions within codons. Additionally, some template switching events occurred more than once during S. cerevisiae evolution. Our findings suggest that template switching constitutes a general mutagenic mechanism that results in both nonsynonymous substitutions and parallel evolution, which are traditionally considered as evidence for positive selection, without the need for adaptive explanations.