Sperm are transcriptionally and translationally quiescent and, therefore, rely on the seminal plasma microenvironment for function, survival and fertilization of the oocyte in the oviduct. The male ...reproductive system influences sperm function via the binding and fusion of secreted epididymal (epididymosomes) and prostatic (prostasomes) small extracellular vesicles (S-EVs) that facilitate the transfer of proteins, lipids and nucleic acids to sperm. Seminal plasma S-EVs have important roles in sperm maturation, immune and oxidative stress protection, capacitation, fertilization and endometrial implantation and receptivity. Supplementing asthenozoospermic samples with normospermic-derived S-EVs can improve sperm motility and S-EV microRNAs can be used to predict non-obstructive azoospermia. Thus, S-EV influence on sperm physiology might have both therapeutic and diagnostic potential; however, the isolation of pure populations of S-EVs from bodily fluids with current conventional methods presents a substantial hurdle. Many conventional techniques lack accuracy, effectiveness, and practicality; yet microfluidic technology has the potential to simplify and improve S-EV isolation and detection.
Can artificial intelligence (AI) improve the efficiency and efficacy of sperm searches in azoospermic samples?
This two-phase proof-of-concept study began with a training phase using eight ...azoospermic patients (>10,000 sperm images) to provide a variety of surgically collected samples for sperm morphology and debris variation to train a convolutional neural network to identify spermatozoa. Second, side-by-side testing was undertaken on two cohorts of non-obstructive azoospermia patient samples: an embryologist versus the AI identifying all the spermatozoa in the still images (cohort 1, n = 4), and a side-by-side test with a simulated clinical deployment of the AI model with an intracytoplasmic sperm injection microscope and the embryologist performing a search with and without the aid of the AI (cohort 2, n = 4).
In cohort 1, the AI model showed an improvement in the time taken to identify all the spermatozoa per field of view (0.02 ± 0.30 × 10–5s versus 36.10 ± 1.18s, P < 0.0001) and improved recall (91.95 ± 0.81% versus 86.52 ± 1.34%, P < 0.001) compared with an embryologist. From a total of 2660 spermatozoa to find in all the samples combined, 1937 were found by an embryologist and 1997 were found by the AI in less than 1000th of the time. In cohort 2, the AI-aided embryologist took significantly less time per droplet (98.90 ± 3.19 s versus 168.7 ± 7.84 s, P < 0.0001) and found 1396 spermatozoa, while 1274 were found without AI, although no significant difference was observed.
AI-powered image analysis has the potential for seamless integration into laboratory workflows, to reduce the time to identify and isolate spermatozoa from surgical sperm samples from hours to minutes, thus increasing success rates from these treatments.
Increasing age has a major detrimental impact on female fertility, which, with an ageing population, has major sociological implications. This impact is primarily mediated through deteriorating ...quality of the oocyte. Deteriorating oocyte quality with biological age is the greatest rate-limiting factor to female fertility. Here we have used label-free, non-invasive multi-spectral imaging to identify unique autofluorescence profiles of oocytes from young and aged animals. Discriminant analysis demonstrated that young oocytes have a distinct autofluorescent profile which accurately distinguishes them from aged oocytes. We recently showed that treatment with the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) restored oocyte quality and fertility in aged animals, and when our analysis was applied to oocytes from aged animals treated with NMN, 85% of these oocytes were classified as having the autofluorescent signature of young animals. Spectral unmixing using the Robust Dependent Component Analysis (RoDECA) algorithm demonstrated that NMN treatment altered the metabolic profile of oocytes, increasing free NAD(P)H, protein bound NAD(P)H, redox ratio and the ratio of bound to free NAD(P)H. The frequency of oocytes with simultaneously high NAD(P)H and flavin content was also significantly increased in mice treated with NMN. Young and Aged + NMN oocytes had a smoother spectral distribution, with the distribution of NAD(P)H in young oocytes specifically differing from that of aged oocytes. Identifying the multispectral profile of oocyte autofluorescence during aging could have utility as a non-invasive and sensitive measure of oocyte quality.
OBJECTIVE:The purpose of this study was to understand nurses’ perceptions of a newly adopted electronic health record (EHR).
BACKGROUND:As use of EHRs in hospital settings increases, leaders prepare ...staff members for change. There is limited information about impacts of EHR adoption on RNs using EHRs at the point of care.
METHODS:Clinical RNs were surveyed about 3 domains (ease of use, usefulness, and attitude) before and after implementation of an EHR. A small subset of nurses was interviewed for a deeper understanding of perceptions associated with this change.
RESULTS:One year after adoption, nurses believed that the EHR did not improve patient care, the learning curve was steep, and they had lower confidence using the EHR than anticipated. Nurses commented on both their frustration and optimism about EHRs.
CONCLUSIONS:This study provides insight into RNs’ perceptions of an EHR, providing important information for nursing administrators.
The purpose of this study is to develop a deep radiomic signature based on an artificial intelligence (AI) model. This radiomic signature identifies oocyte morphological changes corresponding to ...reproductive aging in bright field images captured by optical light microscopy. Oocytes were collected from three mice groups: young (4- to 5-week-old) C57BL/6J female mice, aged (12-month-old) mice, and aged mice treated with the NAD+ precursor nicotinamide mononucleotide (NMN), a treatment recently shown to rejuvenate aspects of fertility in aged mice. We applied deep learning, swarm intelligence, and discriminative analysis to images of mouse oocytes taken by bright field microscopy to identify a highly informative deep radiomic signature (DRS) of oocyte morphology. Predictive DRS accuracy was determined by evaluating sensitivity, specificity, and cross-validation, and was visualized using scatter plots of the data associated with three groups: Young, old and Old + NMN. DRS could successfully distinguish morphological changes in oocytes associated with maternal age with 92% accuracy (AUC~1), reflecting this decline in oocyte quality. We then employed the DRS to evaluate the impact of the treatment of reproductively aged mice with NMN. The DRS signature classified 60% of oocytes from NMN-treated aged mice as having a ‘young’ morphology. In conclusion, the DRS signature developed in this study was successfully able to detect aging-related oocyte morphological changes. The significance of our approach is that DRS applied to bright field oocyte images will allow us to distinguish and select oocytes originally affected by reproductive aging and whose quality has been successfully restored by the NMN therapy.
The coronavirus disease 2019 (COVID-19) pandemic substantially impacted different age groups, with children and young people not exempted. Many have experienced enduring health consequences. ...Presently, there is no consensus on the health outcomes to assess in children and young people with post-COVID-19 condition. Furthermore, it is unclear which measurement instruments are appropriate for use in research and clinical management of children and young people with post-COVID-19. To address these unmet needs, we conducted a consensus study, aiming to develop a core outcome set (COS) and an associated core outcome measurement set (COMS) for evaluating post-COVID-19 condition in children and young people. Our methodology comprised of two phases. In phase 1 (to create a COS), we performed an extensive literature review and categorisation of outcomes, and prioritised those outcomes in a two-round online modified Delphi process followed by a consensus meeting. In phase 2 (to create the COMS), we performed another modified Delphi consensus process to evaluate measurement instruments for previously defined core outcomes from phase 1, followed by an online consensus workshop to finalise recommendations regarding the most appropriate instruments for each core outcome. In phase 1, 214 participants from 37 countries participated, with 154 (72%) contributing to both Delphi rounds. The subsequent online consensus meeting resulted in a final COS which encompassed seven critical outcomes: fatigue; post-exertion symptoms; work/occupational and study changes; as well as functional changes, symptoms, and conditions relating to cardiovascular, neuro-cognitive, gastrointestinal and physical outcomes. In phase 2, 11 international experts were involved in a modified Delphi process, selecting measurement instruments for a subsequent online consensus workshop where 30 voting participants discussed and independently scored the selected instruments. As a result of this consensus process, four instruments met
consensus criteria for inclusion: PedsQL multidimensional fatigue scale for "fatigue"; PedsQL gastrointestinal symptom scales for "gastrointestinal"; PedsQL cognitive functioning scale for "neurocognitive" and EQ-5D for "physical functioning". Despite proposing outcome measurement instruments for the remaining three core outcomes ("cardiovascular", "post-exertional malaise", "work/occupational and study changes"), a consensus was not achieved. Our international, consensus-based initiative presents a robust framework for evaluating post-COVID-19 condition in children and young people in research and clinical practice
a rigorously defined COS and associated COMS. It will aid in the uniform measurement and reporting of relevant health outcomes worldwide.
Background: Technologies such as in vitro fertilization (IVF) are increasingly used to compensate for the loss of fertility associated with increasing maternal age and decline in oocyte quality. ...During IVF, superovulation yields more oocytes than are required, and the selection of oocytes for fertilization and implantation is based on poorly defined morphological features which are subject to user bias.
Aim: We aim to develop a deep radiomic signature based on an artificial intelligence (AI) model in order to identify oocyte morphological changes corresponding to reproductive ageing in bright field images captured by optical light microscopy. This approach has potential for application in assessment of human oocytes.
Method: Oocytes were collected from three groups of C57BL/6J female mice: young (4- to 5-week-old), aged (12-month-old) mice and aged mice treated with the NAD+ precursor nicotinamide mononucleotide (NMN), a treatment recently shown to rejuvenate aspects of fertility in aged mice. Deep learning, swarm intelligence and discriminative analysis were applied to images of mouse oocytes taken by bright field microscopy to identify a highly informative deep radiomic signature (DRS) of oocyte morphology. Approximately 25 oocyte images were derived from each group.
Results: This signature distinguished morphological changes in oocytes associated with maternal ageing, which are imperceptible to an experienced embryologist, with 92% accuracy (AUC
∼
1), reflecting the age-induced decline in oocyte quality. We then employed the DRS to evaluate the impact of the NMN treatment. The DRS signature classified 60% of oocytes from NMN-treated aged mice as having a ‘young’ morphology, demonstrating the signature’s sensitivity to improvements in quality and reinforcing its applicability for oocyte selection.
Conclusion: Our data illustrate the power of DRS for recognizing morphological features of cellular ageing, which outperforms current subjective methods relying on visual grading for the recognition and classification of oocytes based on maternal age.
Diamond samples containing silicon and nitrogen are shown to be heavily photochromic, with the dominant visible changes due to simultaneous change in total SiV0/− concentration. The photochromism ...treatment is not capable of creating or destroying SiV defects, and thus we infer the presence of the optically inactive SiV2− . We measure spectroscopic signatures we attribute to substitutional silicon in diamond, and identify a silicon-vacancy complex decorated with a nearest-neighbor nitrogen SiVN, supported by theoretical calculations.
Background and Aims: Chemotherapy induced ovarian failure and infertility is an important concern in female cancer patients of reproductive age or younger, and non-invasive, pharmacological ...approaches to prevent chemotherapy induced infertility are urgently needed. Here we investigate whether pharmacological elevation of nicotinamide adenine dinucleotide (NAD+) ameliorates chemotherapy induced female infertility in mice. Method: 8-week-old C57BL6 female mice were treated +/- chemotherapy (doxorubicin, Dox; 10 mg/kg) and +/- nicotinamide mononucleotide (NMN; 200 mg/kg i.p. once and 2 g/L in drinking water on-going), an orally bioavailable metabolic precursor to NAD+. Effects on fertility were measured by impact on ovarian reserve and folliculogenesis, ovulation rates and breeding performance. Effects on the ovarian NAD+ metabolome were assessed by mass spectrometry. A potential adverse effect of NMN on the efficiency of chemotherapy was assessed using a xenograft model of mammary cancer. Results: NMN treatment did not prevent a decline in the ovarian reserve caused by chemotherapy but did maintain the health of the remaining primordial follicle and total follicle populations, leading to a restoration in oocyte yield in chemo-treated mice (Dox vs Dox+NMN; P<0.007), culminating in an increase in pups born/mating in chemo+NMN treated mice (P<0.05). Chemo caused ovarian NMN, NADP+ and NADPH depletion, and NADPH was restored by NMN, which likely contributes to Dox detoxification. Importantly, treatment of the breast cancer mouse model with NMN reduced tumour growth and did not impair the efficacy of chemotherapy drugs in vivo or in diverse cancer cell lines. Conclusion: Overall, these findings raise the possibility that NAD+ precursors could be a non-invasive strategy for maintaining ovarian function and fertility in cancer patients, with potential benefits in cancer therapy.
Reproductive aging in female mammals is an irreversible process associated with declining oocyte quality, which is the rate-limiting factor to fertility. Here, we show that this loss of oocyte ...quality with age accompanies declining levels of the prominent metabolic cofactor nicotinamide adenine dinucleotide (NAD+). Treatment with the NAD+ metabolic precursor nicotinamide mononucleotide (NMN) rejuvenates oocyte quality in aged animals, leading to restoration in fertility, and this can be recapitulated by transgenic overexpression of the NAD+-dependent deacylase SIRT2, though deletion of this enzyme does not impair oocyte quality. These benefits of NMN extend to the developing embryo, where supplementation reverses the adverse effect of maternal age on developmental milestones. These findings suggest that late-life restoration of NAD+ levels represents an opportunity to rescue female reproductive function in mammals.
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•Declining NAD(P)H is associated with oocyte dysfunction during reproductive aging•Oocyte quality and fertility can be restored by NMN treatment in aged mice•Supplementation of embryo media with NMN improves developmental milestones•SIRT2 overexpression mimics benefits of NMN but is unlikely to mediate its effects
Declining oocyte quality is considered an irreversible feature of aging and is rate limiting for human fertility. Bertoldo et al. show that reversing an age-dependent decline in NAD(P)H restores oocyte quality, embryo development, and functional fertility in aged mice. These findings may be relevant to reproductive medicine.
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