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Infertility affects 1-in-6 couples, with repeated intensive cycles of assisted reproductive technology (ART) required by many to achieve a desired live birth. In ART, typically, clinicians and laboratory staff consider patient characteristics, previous treatment responses, and ongoing monitoring to determine treatment decisions. However, the reproducibility, weighting, and interpretation of these characteristics are contentious, and highly operator-dependent, resulting in considerable reliance on clinical experience. Artificial intelligence (AI) is ideally suited to handle, process, and analyze large, dynamic, temporal datasets with multiple intermediary outcomes that are generated during an ART cycle. Here, we review how AI has demonstrated potential for optimization and personalization of key steps in a reproducible manner, including: drug selection and dosing, cycle monitoring, induction of oocyte maturation, and selection of the most competent gametes and embryos, to improve the overall efficacy and safety of ART., (© 2024. The Author(s).)

Objective: To quantify how representative a single measure of reproductive hormone level is of the daily hormonal profile using data from detailed hormonal sampling in the saline placebo-treated arm conducted over several hours., Design: Retrospective analysis of data from previous interventional research studies evaluating reproductive hormones., Setting: Clinical Research Facility at a tertiary reproductive endocrinology centre at Imperial College Hospital NHS Foundation Trust., Patients: Overall, 266 individuals, including healthy men and women (n = 142) and those with reproductive disorders and states (n = 124 [11 with functional hypothalamic amenorrhoea, 6 with polycystic ovary syndrome, 62 women and 32 men with hypoactive sexual desire disorder, and 13 postmenopausal women]), were included in the analysis., Interventions: Data from 266 individuals who had undergone detailed hormonal sampling in the saline placebo-treated arms of previous research studies was used to quantify the variability in reproductive hormones because of pulsatile secretion, diurnal variation, and feeding using coefficient of variation (CV) and entropy., Main Outcome Measures: The ability of a single measure of reproductive hormone level to quantify the variability in reproductive hormone levels because of pulsatile secretion, diurnal variation, and nutrient intake., Results: The initial morning value of reproductive hormone levels was typically higher than the mean value throughout the day (percentage decrease from initial morning measure to daily mean: luteinizing hormone level 18.4%, follicle-stimulating hormone level 9.7%, testosterone level 9.2%, and estradiol level 2.1%). Luteinizing hormone level was the most variable (CV 28%), followed by sex-steroid hormone levels (testosterone level 12% and estradiol level 13%), whereas follicle-stimulating hormone level was the least variable reproductive hormone (CV 8%). In healthy men, testosterone levels fell between 9:00 am and 5:00 pm by 14.9% (95% confidence interval 4.2, 25.5%), although morning levels correlated with (and could be predicted from) late afternoon levels in the same individual (r 2 = 0.53, P<.0001). Testosterone levels were reduced more after a mixed meal (by 34.3%) than during ad libitum feeding (9.5%), after an oral glucose load (6.0%), or an intravenous glucose load (7.4%)., Conclusion: Quantification of the variability of a single measure of reproductive hormone levels informs the reliability of reproductive hormone assessment., Competing Interests: Declaration of interests A.A. was supported by NIHR Clinician Scientist Award CS-2018-18-ST2-002. S.A. has nothing to disclose. M.P. was supported by an NIHR Academic Clinical Lectureship Award. C.I.E. was supported by an Imperial-BRC IPPRF Award (P79696). E.G.M. was supported by an NIHR Academic Clinical Lectureship Award. L.T. has nothing to disclose. K.K. was supported by NIHR Academic Clinical Fellowship Award ACF-2021-21-001. S.H. was supported by the UKRI CDT in AI for Healthcare http://ai4health.io (Grant number EP/S023283/1). T.H. has nothing to disclose. T.M.-M.T. was supported by the NIHR, Diabetes UK, and the JP Moulton Charitable Trust. K.T.A. was supported by the EPSRC via grant EP/T017856/1. A.N.C. was supported by the NHS. M.V. has nothing to disclose. W.S.D. was supported by an NIHR Senior Investigator Award., (Copyright © 2024. Published by Elsevier Inc.)

Understanding the human hypothalamic-pituitary-gonadal (HPG) axis presents a major challenge for medical science. Dysregulation of the HPG axis is linked to infertility and a thorough understanding of its dynamic behaviour is necessary to both aid diagnosis and to identify the most appropriate hormonal interventions. Here, we review how quantitative models are being used in the context of clinical reproductive endocrinology to: 1. analyse the secretory patterns of reproductive hormones; 2. evaluate the effect of drugs in fertility treatment; 3. aid in the personalization of assisted reproductive technology (ART). In this review, we demonstrate that quantitative models are indispensable tools enabling us to describe the complex dynamic behaviour of the reproductive axis, refine the treatment of fertility disorders, and predict clinical intervention outcomes., Competing Interests: Nothing declared., (© 2022 The Author(s).)

We present a first-draft digital reconstruction of the microcircuitry of somatosensory cortex of juvenile rat. The reconstruction uses cellular and synaptic organizing principles to algorithmically reconstruct detailed anatomy and physiology from sparse experimental data. An objective anatomical method defines a neocortical volume of 0.29 ± 0.01 mm(3) containing ~31,000 neurons, and patch-clamp studies identify 55 layer-specific morphological and 207 morpho-electrical neuron subtypes. When digitally reconstructed neurons are positioned in the volume and synapse formation is restricted to biological bouton densities and numbers of synapses per connection, their overlapping arbors form ~8 million connections with ~37 million synapses. Simulations reproduce an array of in vitro and in vivo experiments without parameter tuning. Additionally, we find a spectrum of network states with a sharp transition from synchronous to asynchronous activity, modulated by physiological mechanisms. The spectrum of network states, dynamically reconfigured around this transition, supports diverse information processing strategies., Paperclip: VIDEO ABSTRACT., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A series of novel types of 7-(4,6-dimethoxypyrimidin-2-yl)oxy- and -thio-3-methyl-1 (3H)-isobenzofuranones were discovered at Dr R Maag AG. From the thio-isobenzofuranyl series, CGA 279 233--BSI-proposed common name pyriftalid--was chosen for further development as a grass herbicide for use in rice. General synthetic approaches to these new phthalic acid-derived compounds are given, with emphasis on the synthesis of pyriftalid and its physico-chemical behaviour.