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The study of microRNAs (miRNAs) has emerged in recent decades as a key approach to understanding the pathophysiology of many diseases, exploring their potential role as biomarkers, and testing their use as future treatments. Not only have neurological, cardiovascular diseases, or cancer benefited from this research but also infertility. Female infertility, as a disease, involves alterations at multiple levels, such as ovarian and uterine alterations. This review compiles the latest studies published in humans that link female disorders that affect fertility with altered miRNA profiles. Studies on ovarian alterations, including diminished ovarian reserve (DOR), poor ovarian response to stimulation (POR), premature ovarian insufficiency (POI), and polycystic ovary syndrome (PCOS), are summarized and classified based on the expression and type of sample analyzed. Regarding uterine disorders, this review highlights upregulated and downregulated miRNAs primarily identified as biomarkers for endometriosis, adenomyosis, decreased endometrial receptivity, and implantation failure. However, despite the large number of studies in this field, the same limitations that reduce reproducibility are often observed. Therefore, at the end of this review, the main limitations of this type of study are described, as well as specific precautions or safety measures that should be considered when handling miRNAs.

A hands-on introduction to advanced applications of power system transients with practical examples Transient Analysis of Power Systems: A Practical Approach offers an authoritative guide to the traditional capabilities and the new software and hardware approaches that can be used to carry out transient studies and make possible new and more complex research. The book explores a wide range of topics from an introduction to the subject to a review of the many advanced applications, involving the creation of custom-made models and tools and the application of multicore environments for advanced studies. The authors cover the general aspects of the transient analysis such as modelling guidelines, solution techniques and capabilities of a transient tool. The book also explores the usual application of a transient tool including over-voltages, power quality studies and simulation of power electronics devices. In addition, it contains an introduction to the transient analysis using the ATP. All the studies are supported by practical examples and simulation results. This important book: Summarises modelling guidelines and solution techniques used in transient analysis of power systems Provides a collection of practical examples with a detailed introduction and a discussion of results Includes a collection of case studies that illustrate how a simulation tool can be used for building environments that can be applied to both analysis and design of power systems Offers guidelines for building custom-made models and libraries of modules, supported by some practical examples Facilitates application of a transients tool to fields hardly covered with other time-domain simulation tools Includes a companion website with data (input) files of examples presented, case studies and power point presentations used to support cases studies Written for EMTP users, electrical engineers, Transient Analysis of Power Systems is a hands-on and practical guide to advanced applications of power system transients that includes a range of practical examples. 

<p>The simulation of electromagnetic transients is a mature field that plays an important role in the design of modern power systems. Since the first steps in this field to date, a significant effort has been dedicated to the development of new techniques and more powerful software tools. Sophisticated models, complex solution techniques and powerful simulation tools have been developed to perform studies that are of supreme importance in the design of modern power systems. The first developments of transients tools were mostly aimed at calculating over-voltages. Presently, these tools are applied to a myriad of studies (e.g. FACTS and Custom Power applications, protective relay performance, simulation of smart grids) for which detailed models and fast solution methods can be of paramount importance.</p> <p>This book provides a basic understanding of the main aspects to be considered when performing electromagnetic transients studies, detailing the main applications of present electromagnetic transients (EMT) tools, and discusses new developments for enhanced simulation capability.</p> <p><b>Key features:</b>&#160;</p> <ul> <li>Provides up-to-date information on solution techniques and software capabilities for simulation of electromagnetic transients.</li> <li>Covers key aspects that can expand the capabilities of a transient software tool (e.g. interfacing techniques) or speed up transients simulation (e.g. dynamic model averaging).</li> <li>Applies EMT-type tools to a wide spectrum of studies that range from fast electromagnetic transients to slow electromechanical transients, including power electronic applications, distributed energy resources and protection systems.</li> <li>Illustrates the application of EMT tools to the analysis and simulation of smart grids.</li> </ul>

Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I–IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling >4,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC. Models recapitulate many of the genetic and transcriptomic features of the donors, but defined less complex molecular sub-groups because of the loss of human stroma. Linking molecular profiles with drug sensitivity patterns identifies novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab. The heterogeneity of colorectal cancer has important clinical and therapeutic implications. Here the authors analysed the responses of a large biobank of organoids and xenografts derived from colorectal patients to a panel of clinically relevant therapeutic agents to identify genes signatures associated with drug response.

The diagnosis of endometriosis by laparoscopy is delayed until advanced stages. In recent years, microRNAs have emerged as novel biomarkers for different diseases. These molecules are small non-coding RNA sequences involved in the regulation of gene expression and can be detected in peripheral blood. Our aim was to identify candidate serum microRNAs associated with endometriosis and their role as minimally invasive biomarkers. Serum samples were obtained from 159 women, of whom 77 were diagnosed with endometriosis by laparoscopy and 82 were healthy women. First, a preliminary study identified 29 differentially expressed microRNAs between the two study groups. Next, nine of the differentially expressed microRNAs in the preliminary analysis were evaluated in a new cohort of 67 women with endometriosis and 72 healthy women. Upon validation by quantitative real-time PCR technique, the circulating level of miR-30c-5p was significantly higher in the endometriosis group compared with the healthy women group. The area under the curve value of miR-30c-5p was 0.8437, demonstrating its diagnostic potential even when serum samples registered an acceptable limit of hemolysis. Dysregulation of this microRNA was associated with molecular pathways related to cancer and neuronal processes. We concluded that miR-30c-5p is a potential minimally invasive biomarker of endometriosis, with higher expression in the group of women with endometriosis diagnosed by laparoscopy.

Background: A healthy pregnancy begins with an adequate endometrial state, even before the arrival of a blastocyst. Proper endometrial priming and the development of a tolerogenic decidua are key steps in creating the perfect environment for implantation and pregnancy. In these processes, the involvement of the maternal immune system seems to be of great relevance, modulating the different decidual immune populations to prepare the endometrium for a potential pregnancy. However, certain local pathologies of an inflammatory and autoimmune nature appear to have a direct impact on these phenomena, thus altering patients’ reproductive outcomes. Methods: This literature review analyzes original articles, reviews, systematic reviews, and meta-analyses published between 1990 and 2024, concerning the impact of different inflammatory and autoimmune conditions on endometrial status and fertility. The included papers were obtained from Medline (Pubmed) and the Cochrane library. Results: There is evidence that endometriosis, adenomyosis, and chronic endometritis, through the promotion of a chronic inflammatory environment, are capable of altering endometrial immune populations, and, thus, processes essential for early pregnancy. Among other effects, these conditions have been linked to impaired decidualization, alterations in progesterone responsiveness, and hindered placentation. Similarly, antiphospholipid syndrome (APS), thyroid dysfunction, diabetes, and other pathologies related to glucose and gluten metabolism, due to their autoimmune nature, also appear to have a local impact on the uterine environment, affecting reproductive success through different mechanisms, including altered hormonal response and, again, impaired decidualization. Conclusions: The management of inflammatory and autoimmune diseases in assisted reproduction patients is gaining importance due to their direct impact on the endometrium. It is necessary to follow current expert recommendations and established therapeutic approaches in order to improve patients’ prospects, ranging from antibiotic treatment in chronic endometritis to heparin and aspirin in APS, as well as hormonal treatments for endometriosis/adenomyosis or a gluten-free diet in celiac disease. All of them and the rest of the therapeutic perspectives, both current and under investigation, are presented throughout this work, assessing the possible improvements for reproductive outcomes.

Nowadays, recurrent pregnancy loss (RPL) is an undesirable condition suffered by many patients of reproductive age. In this scenario, certain immune cell populations and molecules, involved in maternal–fetal compatibility, have emerged as factors related with the pathogenesis of RPL. Among them, uterine Natural Killer cells (uNKs) appear to be of great relevance. These cells are involved in numerous processes during pregnancy, such as the remodeling of uterine spiral arteries or the control of trophoblast invasion. These functions are regulated by the interactions that these cells establish with the extravillous trophoblast, mainly through their Killer Immunoglobulin-like Receptors (KIRs) and the Human Leukocyte Antigen-C (HLA-C) molecules expressed by the embryo. A high level of polymorphism has been reported for both molecules involved in this interaction, with some of the possible KIR–HLA-C combinations being associated with an increased risk of RPL. However, the complexity of the maternal–fetal interface goes beyond this, as other HLA molecules also appear to be related to this reproductive pathology. In this review, we will discuss the role of uNKs in pregnancy, as well as the polymorphisms and clinical implications of KIR–HLA-C binding. We will also address the involvement of other, different HLA molecules in RPL, and the current advice on the appropriate management of patients with ‘immunological mismatch’, thus covering the main aspects regarding the involvement of maternal–fetal compatibility in RPL.

Current knowledge on ovarian physiology has challenged the traditional concept of folliculogenesis, creating the basis for novel ovarian stimulation protocols in assisted reproduction technology. The purpose of this review was to evaluate the efficacy of novel clinical interventions that could aid clinicians in individualizing their protocols to patients’ characteristics and personal situations. We conducted a literature review of the available evidence on new approaches for ovarian stimulation from both retrospective and prospective studies in the PubMed database. Here, we present some of the most important interventions, including follicle growth in the gonadotropin-independent and dependent stage, manipulation of estradiol production throughout ovarian stimulation, control of mid-cycle gonadotropin surges, and luteal phase support after different stimulation protocols and trigger agents. The latest research on IVF has moved physicians away from the classical physiology, allowing the development of new strategies to decouple organ functions from the female reproductive system and challenging the traditional concept of IVF.

Telomeres are the protective structures located at the ends of linear chromosomes. They were first described in the 1930s, but their biology remained unexplored until the early 70s, when Alexey M. Olovnikov, a theoretical biologist, suggested that telomeres cannot be fully copied during DNA replication. He proposed a theory that linked this phenomenon with the limit of cell proliferation capacity and the “duration of life” (theory of marginotomy), and suggested a potential of telomere lenghthening for the prevention of aging (anti-marginotomy). The impact of proliferative telomere shortening on life expectancy was later confirmed. In humans, telomere shortening is counteracted by telomerase, an enzyme that is undetectable in most adult somatic cells, but present in cancer cells and adult and embryonic stem and germ cells. Although telomere length dynamics are different in male and female gametes during gametogenesis, telomere lengths are reset at the blastocyst stage, setting the initial length of the species. The role of the telomere pathway in reproduction has been explored for years, mainly because of increased infertility resulting from delayed childbearing. Short telomere length in ovarian somatic cells is associated to decreased fertility and higher aneuploidy rates in embryos. Consequently, there is a growing interest in telomere lengthening strategies, aimed at improving fertility. It has also been observed that lifestyle factors can affect telomere length and improve fertility outcomes. In this review, we discuss the implications of telomere theory in fertility, especially in oocytes, spermatozoa, and embryos, as well as therapies to enhance reproductive success.

Endometriosis, despite only affecting 10-15% of women of fertile age, is still an enigmatic disease. Recent developments in assisted reproductive technology have contributed to a better understanding of where and how endometriosis could compromise fertility. In this mini-review we will show how the main point of damage in endometriosis is quantitative impairment of the ovaries, if the \"less is more\" mantra should be applied when considering ovarian surgery, and when fertility preservation prior to ovarian surgery could be considered. Endometrial receptivity, however, does not seem to be affected.