bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence of weak itinerant ferromagnetism and Griffiths like phase in MnFeGe
Authors: Dara Hanuma Kumar , Patra Debashish , Moharana Gyanti Prakash , Sarangi S N , Samal D
Published: June 2023

Realizing the itinerant type of magnetic exchange in Mn-based alloys is quite unusual because of the weak hybridization between Mn-moments and conduction electrons. However, in the current study, we found MnFeGe to exhibit weak itinerant type magnetic character possibly arising due to the hybridization between Mn, Fe atoms with Ge atoms. Here, we present a comprehensive structural and magnetic study on polycrystalline MnFeGe. Rietveld refinement of the XRD pattern confirms that Mn and Fe atoms randomly (atomic disorder) occupy the 2a and 2d sites in MnFeGe. From the magnetic measurements, Curie temperature and saturation moment values are found to be 162 K and 1.58

μ

B

/

f
.
u
.

at 2 K, respectively. The relative low values of Curie temperature, saturation magnetic moment, and a large value of Rhodes–Wohlfarth ratio (∼3.4) indicate the weak itinerant ferromagnetic character of the system. The Takahashi spin fluctuation theory analysis further supports the weak itinerant ferromagnetism in MnFeGe. Besides, we also observed Griffiths phase (GP) like behavior above the Curie temperature, which is attributed to the presence of atomic disorder in the system. The presence of GP is further confirmed by the zero spontaneous magnetization. Our findings demonstrate that MnFeGe is one of the very few Mn-based systems with weak itinerant magnetic behavior.
A deep neural network architecture for reliable 3D position and size determination for Lagrangian particle tracking using a single camera
Authors: Ratz M , Sachs S , König J , Cierpka C
Published: June 2023

Microfluidic flows feature typically fully three-dimensional velocity fields. However, often the optical access for measurements is limited. Astigmatism or defocus particle tracking velocimetry is a technique that enables the 3D position determination of individual particles by the analysis of astigmatic/defocused particle images. The classification and position determination of particles is a task well suited to deep neural networks (DNNs). In this work, two DNNs are used to extract the class and in-plane position (object detection) as well as the depth position (regression). The performance of both DNNs is assessed by the position uncertainties as well as the precision of the size classes and the amount of recalled particles. The DNNs are evaluated on a synthetic dataset and establish a new benchmark of DNNs in defocus tracking applications. The recall is higher than compared to classic methods and the in-plane errors are always subpixel accurate. The relative uncertainty in the depth position is below 1% for all examined particle seeding concentrations. Additionally, the performance on experimental images, using four different particle sizes, ranging from 1.14

μ

m

to 5.03

μ

m

is analyzed. The particle images are systematically rearranged to produce comprehensive datasets of varying particle seeding concentrations. The distinction between particles of similar size is more challenging but the DNNs still show very good results. A precision above 96% is reached with a high recall above 95%. The error in the depth position remains below 1% and the in-plane errors are subpixel accurate with respect to the labels. The work shows that first, DNNs can be trained with artificially rearranged data sets based on individual experimental images and are therefore easily adaptable to various experimental setups and applicable by non-experts. Second, the DNNs can be successfully adapted to determine additional variables as in this case the size of the suspended particles.
An alternately optimized generative adversarial network with texture and content constraints for deformable registration of 3D ultrasound images
Authors: Zhang Jiaju , Fu Tianyu , Wang Yuanyuan , Li Jingshu , Xiao Deqiang , Fan Jingfan , Lin Yucong , Song Hong , Ji Fei , Yang Meng , Yang Jian
Published: June 2023

Objective. 3D ultrasound non-rigid registration is significant for intraoperative motion compensation. Nevertheless, distorted textures in the registered image due to the poor image quality and low signal-to-noise ratio of ultrasound images reduce the accuracy and efficiency of the existing methods. Approach. A novel 3D ultrasound non-rigid registration objective function with texture and content constraints in both image space and multiscale feature space based on an unsupervised generative adversarial network based registration framework is proposed to eliminate distorted textures. A similarity metric in the image space is formulated based on combining self-structural constraint with intensity to strengthen the robustness to abnormal intensity change compared with common intensity-based metrics. The proposed framework takes two discriminators as feature extractors to formulate the texture and content similarity between the registered image and the fixed image in the multiscale feature space respectively. A distinctive alternating training strategy is established to jointly optimize the combination of various similarity loss functions to overcome the difficulty and instability of training convergence and balance the training of generator and discriminators. Main results. Compared with five registration methods, the proposed method is evaluated both with small and large deformations, and achieves the best registration accuracy with average target registration error of 1.089 mm and 2.139 mm in cases of small and large deformations, respectively. The performance on peak signal to noise ratio (PSNR) and structural similarity (SSIM) also proves the effective constraints on distorted textures of the proposed method (PSNR is 31.693 dB and SSIM is 0.9 in the case of small deformation; PSNR is 28.177 dB and SSIM is 0.853 in the case of large deformation). Significance. The proposed 3D ultrasound non-rigid registration method based on texture and content constraints with the distinctive alternating training strategy can eliminate the distorted textures with improving the registration accuracy.
A semantic segmentation of the lung nodules using a shape attention-guided contextual residual network
Authors: Zhang Xugang , Fei Liangyan , Gong Qingshan
Published: June 2023

Objective. The early diagnosis of lung cancer depends on the precise segmentation of lung nodules. However, the variable size, uneven intensity, and blurred borders of lung nodules bring many challenges to the precise segmentation of lung nodules. Approach. We propose a shape attention-guided contextual residual network to address the difficult problem in lung nodule segmentation. Firstly, we establish a selective kernel convolution residual module to replace the original encoder and decoder. This module incorporates selective kernel convolution, which automatically selects convolutions with different receptive fields to acquire multi-scale spatial features. Secondly, we construct a multi-scale contextual attention module to assist the network in extracting multi-scale contextual features of local feature maps. Finally, we develop a shape attention-guided module to assist the network to restore details such as the boundary and shape of lung nodules during the upsampling phase. Main results. The proposed network is comprehensively analyzed using the publicly available LUNA16 data set, and an ablation experiment is designed to validate the effectiveness of each individual component. Ultimately, the dice similarity coefficient of the experimental results reaches 87.39% on the test set. Compared to other state-of-the-art segmentation methods, the proposed network achieves superior performance in lung nodule segmentation. Significance. Our proposed network improves the accuracy of lung nodule segmentation, which provides an important support for physicians to subsequently develop treatment plans.
Standard-based personalized healthcare delivery for kidney illness using deep learning
Authors: Sachdeva Shelly
Published: June 2023

Motivation and objective. Predictive analytics is an active area of research in healthcare. It aims to provide better services to the patient and helps the medical practitioners to know what particular treatment would be suitable for a patient based on their past data. Deep learning is an emerging branch of machine learning in which deep artificial neural networks are used to learn a specific pattern for mapping input to output. It has revolutionized predictive analytics by achieving far better accuracy than conventional learning models. This paper aims to analyze the effect of deep learning on a standardized electronic health records dataset by diagnosing kidney-related diseases. Approach. The current study uses a general modularized deep learning architecture called encoder-combiner-decoder (ECD), which offers a robust framework. The model’s performance is enhanced by the availability of variations and extensions to the basic ECD architecture, corresponding to respective input and output feature types. The openEHR benchmark dataset (ORBDA) is used to train the model. It is a real-world dataset that has been provided by the Brazilian Public Health System through the SUS (DATASUS) Database Department of Informatics. Results. In the current research, the model trained using deep learning on the part of this benchmark dataset can help in diagnosing kidney-related illnesses. The evaluation metrics show high precision, recall, and F1 score for kidney-related diseases, meaning that they can be identified almost every time. Significance. The model is a novel attempt to analyze a standardized healthcare dataset that can be deployed in medical institutions in order for its performance to be evaluated by a medical professional.
UV activated single aligned TiO2 nanofiber embedded silver nanoparticles as room temperature ammonia gas sensor
Authors: Khalafi M , Nikfarjam A , Hajghassem H , Bidmeshkipour S
Published: June 2023

In this work, by using an electro-spinning process and a secondary electrostatic field on rectangular electrodes, a single-aligned nanofiber of silver nanoparticle (SNP)-TiO2 fabricated for NH3 gas sensing with UV irradiation at room temperature. XRD, FE-SEM and UV spectroscopy adopted for characterization of the single nanofiber. The response of SNP-TiO2 single nanofiber sensor evaluated for 70 ppb to 12 ppm ammonia gas at room temperature up to the optimum temperature of 150 °C. The response of this sensor for 5 ppm ammonia gas is 46.1 at the optimum temperature of 150 °C. However, the response is also evaluated at room temperature under 365 nm UV illumination. The response improved up to 4 times from 11 at dark condition to 45.1 under UV illumination for the ammonia gas concentration of 5 ppm. In addition, UV light exposure led to a considerable reduction in both the response and recovery times. Moreover, the results for detecting other gases such as methanol, ethanol, propanol and water vapor compare to ammonia shows that for SNP-TiO2 sensor the best response is for ammonia gas, whereas its sensitivity to humidity is considerably low (about 9%). This shows the sensor can be used in related applications like breath analysis.
Understanding the role of oxygen-vacancy defects in Cu2O(111) from first-principle calculations
Authors: Dongfang Nanchen , Al-Hamdani Yasmine S , Iannuzzi Marcella
Published: June 2023

The presence of defects, such as copper and oxygen vacancies, in cuprous oxide films determines their characteristic carrier conductivity and consequently their application as semiconducting systems. There are still open questions on the induced electronic re-distribution, including the formation of polarons. Indeed, to accurately reproduce the structural and electronic properties at the cuprous oxide surface, very large slab models and theoretical approaches that go beyond the standard generalized gradient corrected density functional theory are needed. In this work we investigate oxygen vacancies formed in proximity of a reconstructed Cu2O(111) surface, where the outermost unsaturated copper atoms are removed, thus forming non-stoichiometric surface layers with copper vacancies. We address simultaneously surface and bulk properties by modelling a thick and symmetric slab, to find that hybrid exchange-correlation functionals are needed to describe the oxygen vacancy in this system. Our simulations show that the formation of oxygen vacancies is favoured in the sub-surface layer. Moreover, the oxygen vacancy leads to a splitting and left-shift of the shallow hole states in the gap, which are associated with the deficiency of copper at the surface. These findings suggest that surface electronic structure and reactivity are sensitive to the presence of oxygen vacancies, also when the latter are formed deeper within the film.
Improving inpatient discharge workflows through pharmacist pending discharge medication orders
Authors: Lee Kasheng , Nixon Grace , Niemi Kristin , Rose Anne
Published: June 2023

Purpose

Hospital discharge represents a difficult care transition for patients, with the potential for medication-related problems (MRPs) and adverse events. Medication reconciliation is widely accepted as a best practice to minimize MRPs at the time of discharge. Pharmacists can play a key role in identification and resolution of MRPs, although pharmacist reconciliation usually occurs after provider medication reconciliation. This workflow is often inefficient and results in duplication of work within the care team. A prospective pharmacist-led pilot program with preparation of discharge medication orders for provider review, also known as pended medication orders, was investigated to determine its impact on MRPs and discharge processing time.

Patient discharges from February through April 2022 were compared for 2 hospital medicine services at a large academic medical center. One group participated in the pilot workflow, while the other used standard discharge workflows. The pilot group had a significant decrease in the average number of clinical interventions made by a pharmacist after provider orders were placed (52.4% decrease; P = 0.03) and a nonsignificant reduction in the time from provider order entry to completion of the final pharmacist medication reconciliation (47.6% reduction; P = 0.18) compared to the group using standard workflows.

Conclusion

Pharmacist-led, prospective discharge medication reconciliation with pending of medication orders for provider review increases overall discharge efficiency. Data from this project and previous studies support an expanded pharmacist role in the discharge process and continued high-level collaboration between pharmacists and providers.
Reclaiming Broken Bodies (or, This Is Gonna Hurt Some): Pain, Healing, and the Opioid Crisis
Authors: Shuman Joel James
Published: June 2023

I argue here that the ways we experience, think about, and treat pain are bound up with sociocultural and technological phenomena that shape our desires and expectations. I propose a way of imagining caring for and offering healing to those who suffer pain informed by the Christian theological tradition. This way does not aspire to replace the care and healing made possible by modern medicine, but rather to place it within the common life of a community of mutual love, hospitality, and reciprocal care.
O-011 Cardiovascular morbidity and mortality in women with PCOS: a cohort study of 75142 participants from the UK biobank
Authors: Doulgeraki T , Wright A , Frederick H , Celis-Morales C A , Pell J P , Sattar N , Iliodromiti S
Published: June 2023

Study question

Are women with PCOS at an increased risk of cardiovascular mortality and morbidity?

Summary answer

Although PCOS is strongly associated with cardiovascular risk factors, it does not increase the risk of cardiovascular morbidity and mortality in women aged 40-60 years.

What is known already

PCOS is one the commonest endocrinopathies in women of reproductive age characterised by anovulation, hyperandrogenism and polycystic ovaries in ultrasound surveillance. The prevalence of PCOS has been quoted 8 to13% of women in the UK, however, up to 70% of the cases may be undiagnosed. Women with PCOS are at increased risk of developing adverse cardiometabolic outcomes including insulin resistance, type 2 diabetes (T2DM), metabolic syndrome, hypertension and dyslipidaemia. Those unfavourable risk factors would place women with PCOS at an increased risk for cardiovascular mortality and morbidity, however, the evidence from epidemiological studies are so far heterogenous with conflicting results.

Study design, size, duration

We conducted a cohort study including a total of 75142 participants from the UK biobank, of whom 15747 had PCOS. Women were followed up for 11.1 years in average.

Participants/materials, setting, methods

The primary outcome was morbidity and mortality from ischemic heart disease and stroke. We constructed Cox regression analysis adjusted for confounders and risk factors to quantify the risk of cardiovascular morbidity and mortality in women with PCOS.

Main results and the role of chance

The incidence rate of cardiovascular events was 1.92/1000 person years in the PCOS population and 1.90/1000 person years in women without PCOS. PCOS was associated with a higher risk of obesity (OR 1.63, 95% CI 1.56-1.70), hypertension (OR 1.18, 95% CI 1.13-1.23) and type 2 diabetes (OR 1.44, 95% CI 1.31-1.58). In the adjusted cox regression model, PCOS doesn’t increase the risk of CVD morbidity and mortality (HR 0.89, 95% CI 0.78-1.01), however, the cumulative hazard risk in women over 60 years old with a history of PCOS was greater compared to women without PCOS.

Limitations, reasons for caution

The low response rate (5.5%) to the UK biobank recruitment introduces a healthy responder bias which may limit the representation of the population. PCOS was both self-reported and assessed by clinical and biochemical features and other variables were also self-reported, hence reporting bias cannot be excluded.

Wider implications of the findings

The strong association of PCOS with cardiometabolic risk factors and that the CVD morbidity/mortality risk becomes comparable with that of women without PCOS after correcting for these factors, highlights the need to strengthen public health strategies for surveillance, lifestyle interventions and prompt treatment of those co-morbidities in women with PCOS.

Trial registration number

Not applicable
O-028 Genital tract infection and pelvic surgery contribute to the development of endometriosis
Authors: Han A R , Lee S K , Park J C , Han J
Published: June 2023

Study question

Was the incidence of endometriosis in women with a recent history of genital infection, pelvic surgery, or both increased?

Summary answer

The pelvic inflammation resulting from genital infection and pelvic surgical injury may play a role in developing endometriosis.

What is known already

Endometriosis is a multifactorial disease, and inflammation is considered a core pathology. Inflammation occurs due to pathogenic infection and tissue injury, and genital tract infection and surgical injury can be inducers for pelvic inflammation in endometriosis.

Study design, size, duration

A retrospective cohort study using the Korean National Health Insurance Service -National Sample Cohort I (KNHIS-SC I) from 2002-2013 (N = 1,025,340) was performed.

Participants/materials, setting, methods

20- to 49-year-old women diagnosed with genital tract infections (GTI) or who underwent pelvic surgeries between 2002 and 2008 were collected and followed up for five years. A total of 30,336 women were diagnosed with GTI, 2,894 women underwent pelvic surgery, and 788 women with GTI and pelvic surgery were enrolled in each study. The comparison groups matched sociodemographic factors for each group were collected. The incidence of endometriosis in each group was analyzed.

Main results and the role of chance

The incidence of endometriosis per 1,000 person-year was 5.37, 5.17, and 20.81 in each case group and was significantly higher than in each comparison group. A recent history of GTI increased an adjusted hazard ratio (aHR) of 2.29 (1.99-2.63, 95% confidence interval) for the development of endometriosis. The aHRs of pelvic surgery history and the history of both GTI and pelvic surgery were 2.10 and 7.82, respectively.

Limitations, reasons for caution

The diagnosis and treatment codes registered on the NHIS data are used to claim HIRA NHI benefits, which may differ from the diagnosis or treatment performed in practice and it does not contain the used diagnostic method, disease severity, and the disease led to pelvic surgery were not specified.

Wider implications of the findings

Active treatment of genital infections and careful surgical procedures to minimize tissue injury may reduce the incidence of pelvic endometriosis.

Trial registration number

Not Applicable
O-044 The future of contraception
Authors: Thomas M A
Published: June 2023

In 1960, the first hormonal contraceptive agent, Enovid approved by the Food and Drug Administration in the United States. The pill contained mestranol 150 mcg and norethynodrel 10 mg. High dose pills containing >50 mcg of estrogen were discontinued in 1988 due to a higher risk of myocardial infraction and stroke secondary to thrombosis. Until recently, the only estrogens used in combination OCPs were mestranol and ethinyl estradiol (EE). Estetrol (E4) and 17-beta estradiol have been added to newer pill and intravaginal ring (IVR) formulations in order to reduce the risk of thrombosis. Progestins confer the primary contraceptive effect in combination agents and can be used without estrogens. First generation progestins include norethynodrel, ethynodiol diacetate, norethindrone and norethindrone acetate (estranes). Second generation progestins include norgestrel and levonorgestrel (gonanes). Third generation include gestoden, desogrestrel and norgestimate, which are less androgen versions of the second generation progestins. Fourth generation progestins have no androgenicity include drospirenone. The fourth generation progestin is a 17 carbon compound which separates it from the other progestins that are primarily 19 carbon derivatives of androgens. Segesterone acetate (SA) is a newer progestin that is less potent and has no androgenic properties. SA, combined with EE, is currently being used in an IVR. However, clinical trials are ongoing using SA with 17-beta estradiol in an IVR and another with EE as a contraceptive gel. Other new methods of hormonal contraception include progestins in a biodegradable implant, longer acting injectables that can last 6-12 months, transdermal patches that are imbedded with an array of microneedles where either the contraceptive agent is in a reservoir or in the needles themselves. Microchip technology is being developed by the Gates Foundation that would allow levonorgestrel to be released systemically at will over a 16-year period using a remote device. Multipurpose technologies are being developed utilizing contraceptive pills, injectables and IVRs containing hormonal agents as well as medications to prevent STI/HIV acquisition.
O-046 Nutritional habits might improve your fertility
Authors: Dupont C , Sermondade N , Bachelot G , Lévy R
Published: June 2023

Many lifestyle factors have been identified as risk factors for male infertility. For example, an unbalanced diet leading to overweight, obesity, metabolic disorders, and micronutrient deficiencies can have consequences for male reproductive functions. Obese men present more often altered semen parameters and a reduced chance of pregnancy naturally or after medically assisted procreation. In some cases, weight loss can reverse the adverse effects of obesity. However, few interventional studies have demonstrated the effectiveness of a preconceptional intervention in men.

In contrast, more and more studies are highlighting the importance of a balanced diet and physical activity to improve fertility. A qualitatively adequate and balanced diet and appropriate daily intake of micronutrients are fundamental for male reproductive functions. Some teams have highlighted the benefits of the Mediterranean diet on sperm production, whereas the Western diet, including reconstituted meats, fried foods, and sweet foods and drinks, was associated with altered semen parameters. However, few interventional studies have confirmed the impact of men's diets on the chances of natural or medically assisted pregnancy and live birth, and their results are controversial.

Therefore, robust randomised controlled studies are needed. Practical advice and education can be recommended to men who wish to conceive to help them maintain or achieve the public health recommendations that encourage a balanced diet, such as the Mediterranean diet.
O-058 Metabolism, histone modification and early embryo development
Authors: Li J
Published: June 2023

Cellular metabolism provides fundamental components for chromatin dynamics and epigenetics. However, metabolic features, and their impact on epigenetic remodeling during mammalian pre-implantation development, remain poorly understood. In this study, we established the metabolic landscape of mouse pre-implantation embryos from zygote to blastocyst, and quantified their absolute carbohydrate metabolites. We found that amino acid/carbohydrate/lipid metabolism increased during pre-implantation development, whereas nucleotide metabolism increased at the 4- and 8-cell stages. We further demonstrated that oxidized nicotinamide adenine dinucleotide (NAD+) is indispensable for mouse pre-implantation development. Mechanistically, NAD+ avoids excessive minor zygotic gene activation (ZGA) by cooperating with deacylase SIRT1 to remove zygotic H3K27ac. In human, NAD+ supplement can promote the removal of zygotic H3K27ac and benefit preimplantation development. Our findings demonstrate that precise and timely regulation of minor ZGA is controlled by metabolic dynamics, and enhance our understanding of the metabolism of mammalian early embryos.
O-073 Delta-9-THC acts on the calcium channel CatSper and alters human sperm function
Authors: Wehrli L , Zufferey F , Rossier M , Nef S , Rahban R
Published: June 2023

Study question

Do the main psychoactive phytocannabinoid delta-9-tetrahydrocannabinol (THC) and its non-psychoactive analog cannabidiol (CBD) affect human sperm function?

Summary answer

THC reduces the ligand-dependent activation of sperm-specific Ca2+ channel CatSper and affects human sperm functions in vitro.

What is known already

Marijuana (Cannabis sativa) is one of the most commonly used recreational drugs worldwide. Although the impact of phytocannabinoids on reproductive health has been investigated, there is no evidence of a direct effect of THC on CatSper function.

Study design, size, duration

We studied the effects of the main psychoactive phytocannabinoid, THC, its non-psychoactive analog, CBD, as well as their major metabolites on Ca2+ influx via CatSper in human spermatozoa. THC and CBD were selected to further evaluate their action on progesterone-, prostaglandin-, and pH-induced activation of human CatSper. The effects of THC and CBD on hyperactivation, progressive motility in viscous media, and acrosomal exocytosis were also assessed.

Participants/materials, setting, methods

The impact of phytocannabinoids on CatSper activity was investigated on sperm samples from healthy volunteers using kinetic Ca2+ fluorimetry. Motility assessment was performed using Computer-Assisted Sperm Analysis (CASA). Sperm penetration into viscous media was assessed using a modified Kremer test. Acrosomal exocytosis was evaluated by flow cytometry using Pisum sativum agglutinin-stained spermatozoa.

Main results and the role of chance

Both THC and CBD suppress natural ligand-induced calcium influx via CatSper. In particular, THC inhibits progesterone-induced Ca2+ influx via CatSper at pharmacologically relevant concentrations in a non-competitive manner and reduces the pH-induced activation of CatSper. In addition, THC impaired sperm hyperactivation and penetration into viscous media and induced spontaneous acrosomal exocytosis in vitro.

Limitations, reasons for caution

This is an in vitro study. Future studies are needed to test the physiological relevance in vivo and whether THC can disrupt human sperm function.

Wider implications of the findings

The action of THC on CatSper in human sperm might impair the fertilization process. Healthcare providers, especially fertility clinicians, should be aware of the potentially negative effects of cannabis consumption on sperm physiology

Trial registration number

not applicable
P-685 Extracellular vesicles of human follicular fluid as biomarkers of ovarian disease
Authors: Chiechio R , Moulin G , Neyroud A S , Ducarre S , Ouzaid Y , Dupont A , Even-Hernandez P , Le Cornu Q , Marchi V , Ravel C
Published: June 2023

Study question

Our aim is to analyze the morphology of follicular fluid extracellular vesicles (EVs) according to ovarian pathology by labeling the vesicles with luminescent gold nanoclusters.

Summary answer

Cryo-TEM analysis reveals that EVs from the follicular fluid of patients presenting with polycystic ovary syndrome have a particularly complex morphology compared to normo-ovulatory women.

What is known already

EVs are particles enclosed by a lipid membrane and secreted by cells. Previously considered as cellular debris, they are in fact involved in a multitude of biological functions and are potential biomarkers. Development of an optical biosensor based on luminescent nanoparticles would make it possible to analyze them in biological fluids.

Study design, size, duration

Samples were provided by GERMETHEQUE, Biobank dedicated to human fertility. Samples from 32 patients presenting with ovarian pathology (ovarian failure, polycystic ovary syndrome) and 32 normo-ovulatory patients were analyzed.

Participants/materials, setting, methods

Luminescent gold nanoclusters (1 to 2 nm in diameter) have been synthesized and functionalized in order to interact with extracellular vesicles. Analysis of the morphology of EVs was carried out by cryoTEM. Qualitative results were analyzed by Chi2 or Fisher tests. The quantitative results were analyzed by the Kruskal Wallis test.

Main results and the role of chance

The interactions between luminescent gold nanoclusters and lipid membranes show that it is possible to induce electrostatically and in a controlled manner either significant structural changes in the membranes or membrane labeling. Patients presenting with ovarian pathology have more oval vesicles (p = 0.0014). Differences are especially significant in polycystic ovary syndrome showing that simple vesicles are less abundant than controls (p < 0.0001) and large tubules more frequent (p = 0.0023).

Limitations, reasons for caution

The first results concerning the interactions between luminescent nanoclusters and vesicles demonstrate their potential for labeling these membrane structures

Wider implications of the findings

The characterization of these anomalies could allow a better understanding of ovarian pathology and open up new therapeutic fields. An efficient method of encapsulation in liposomes of gold nanoclusters has been developed.

Trial registration number

GERM 20220705
P-686 Long photoperiod exposure results in glycometabolism disorder in the cumulus-oocyte complex in SD rats
Authors: Ying Y , Yao S , Chen X , Zhang D
Published: June 2023

Study question

Does long photoperiod exposure cause glycometabolism changes in the cumulus-oocyte complex?

Summary answer

The levels of key enzymes and substrates involved in glycometabolism have changed in the cumulus-oocyte complex in SD rats due to circadian rhythm changes.

What is known already

Circadian rhythm is essential for maintaining the required reproductive activities in mammalians. In our previous research, long photoperiod exposure results in the reduction of ovulation number and the increase of ROS level in oocytes. In the process of oocyte maturation, the tricarboxylic acid cycle and energy metabolism gradually increase, while the ability of the oocyte to absorb glucose is low. It is mainly metabolized by cumulus granulosa cells into pyruvate and then transported to oocytes for subsequent metabolism. Metabolomics is a comprehensive analysis of small molecules, which provides key information about cellular metabolic states.

Study design, size, duration

Female SD rats, 6-8 weeks old, were randomized into two groups. The rats (n = 20) were exposed to the control photoperiod (12 hours light/12 hours dark) or long photoperiod (16 hours light/8 hours dark) for 12 weeks.

Participants/materials, setting, methods

Cumulus-oocyte complexes were collected after ovarian stimulation and numbers were counted. The parameters compared include MII rate, fertilization rate, and ovarian follicle number. We used mass spectrometry-based metabolomics to directly measure metabolite abundance. The glycometabolism pathway and its regulatory signaling molecules were analyzed by qPCR and/or Western blots.

Main results and the role of chance

Long photoperiod exposure significantly reduced the ovulation rate, MII rate and fertilization rate. Interestingly, we find secondary follicle and antral follicle were decreased (p < 0.01), while primordial follicle and primary follicle were increased (p < 0.01). We identified a total of 318 metabolites in COC. Among them, 59 metabolite levels have significant differences between the two groups (FDR < 0.05). The metabolical function analysis suggested that the phosphatidylinositol phosphate metabolism, pyruvate metabolism, phosphatidylcholine biosynthesis, and glycolysis pathways were influenced by circadian interference. In addition, hexokinase, glucose-6-phosphate isomerase, phosphofructokinase glyceraldehyde 3-phosphate expression level were down regulated.

Limitations, reasons for caution

More studies are required to address how clock gene regulating glycometabolism process. And Translating results in rat model to the human setting is a limitation of this study.

Wider implications of the findings

Our study findings are first to demonstrate that glycolmetabolism is regulated by long photoperiod exposure in follicle development. This knowledge could help to develop strategies to modulate specific recovery strategies based on metabolic regulator to improve human IVF.

Trial registration number

Not applicable
P-688 The relationship between higher levels of serum AMH and in vitro fertilization outcomes
Authors: Albu A , Iancu E M , Albu D
Published: June 2023

Study question

What is the relationship between increased serum anti-mullerian hormone (AMH) levels and in vitro fertilization (IVF) outcomes in women with infertility?

Summary answer

High levels of AMH are associated with higher oocytes and embryo number, but a lower proportion of GQE from the transferred and the total number.

What is known already

Although serum AMH level is considered a predictor of ovarian response to controlled ovarian stimulation, the predictive value of higher AMH levels is not clearly established due to contradictory reports, with both positive and negative associations with IVF outcomes.

Study design, size, duration

We performed a retrospective study in the Department of Reproductive Medicine of a private hospital. The medical records of all consecutive patients who underwent IVF between January 2014 and December 2021 with all causes of infertility were reviewed. The study group included 1401 patients with a median age [interquartile range] of 35 [6] years and median AMH of 1.99 [2.79] ng/mL.

Participants/materials, setting, methods

Patients with various causes of infertility undergoing IVF-ICSI and normal ovarian reserve (defined as a serum level of AMH above 1.1 ng/mL) were included in the study. Only patients with serum levels of AMH and age available for analysis were included in the study. The outcomes included were oocytes and obtained embryos number, the proportion of good-quality embryos from the total number of embryos obtained (GQE/T) and from the transferred number of embryos (GQE/Tr).

Main results and the role of chance

Patients were divided according to their serum AMH level into 3 groups: group 1 with AMH between 1.1 ng/ml and 5 ng/mL, group 2 with AMH between 5 and 8 ng/mL and group 3 with AMH more than 8 ng/mL. After adjustment for age, patients in groups 2 and 3 had a higher number of oocytes (beta 0.231, p < 0.0001 and beta 0.206, p < 0.0001) and embryos (beta 0.143, p < 0.0001 and beta 0.158, p < 0.0001). After adjustment for age, patients in group 2 had a lower proportion of GQE/T in comparison with patients in group 1 (beta -0.077, p 0.037) and patients in both groups 2 (beta -0.119, p 0.001) and 3 (beta -0.103, p 0.004) had a lower proportion of GQE/Tr in comparison with group 1. Being in groups with higher AMH (2 and 3) was not associated with the number of GQE.

Limitations, reasons for caution

Patients included in this study are infertile patients with an indication for IVF treatment. Therefore, the results of this study should be used with caution in other populations

Wider implications of the findings

Our study suggests that having higher levels of serum AMH (above 5 ng/mL) is not associated with better IVF outcomes in terms of the number of good-quality embryos. Moreover, obtaining a higher number of embryos is not associated with a proportional increase in good-quality embryo availability.

Trial registration number

NA
P-690 RESEarch on ovarian reseRVE among Neurologic patients: the RESERVEN study
Authors: Di Girolamo R , Carbone L , Conforti A , Iorio G G , Cariati F , Alviggi C
Published: June 2023

Study question

Could Multiple Sclerosis (MS) reduce the levels of main ovarian reserve markers, measured through automated systems?

Summary answer

There is no statistically significant difference in ovarian reserve markers between women affected by Multiple Sclerosis and healthy controls.

What is known already

Few studies evaluated the issue of ovarian reserve in women affected by MS, so far. The majority of them observed no differences in ovarian reserve markers between women affected by MS and healthy controls. However, interestingly, women with MS in case of a more active disease were observed to have lower levels of ovarian reserve markers. In fact, evidence suggests that an inflammatory status may reduce the ovarian reserve, where autoimmune-related diseases are considered a possible cause of Premature Ovarian Insufficiency (POI).

Study design, size, duration

This is a single-center multidisciplinary prospective case-control (44 cases and 72 controls) study performed from September 2019 to September 2022.

Participants/materials, setting, methods

Cases were reproductive-age women affected by MS recruited at our MS unit, controls were age- and body mass index (BMI) - matched healthy women recruited at our assisted reproductive technology (ART) unit. During the early follicular phase, a transvaginal ultrasound was performed with sonoAVC software (GE medical systems) for 3D antral follicle count and a blood sample taken for hormonal assays (Anti-Müllerian hormone levels was measured using the Roche Elecsys AMH Plus).

Main results and the role of chance

There are no differences in age (p = 0.11), BMI (p = 0.96) as per protocol. Moreover, differences in FSH (p = 0.14), LH (p = 0.13), estradiol (p = 0.92), and AMH (p = 0.99) levels were not statistically significant. The 3D antral follicle count showed a statistically significant difference (p = 0.03), but following a re-evaluation of pictures in post-processing, removing the small antral follicles (2-4 mm) the difference was not statistically significant (p = 0.14).

Limitations, reasons for caution

We could not assess women before they started on medication for MS. Therefore, we could not exclude that medication have an impact in these results, also because the sample is small and patients were not treated with the same drug. Moreover, all patients were in disease remission at enrollment.

Wider implications of the findings

This is the first study to evaluate ovarian reserve markers with automated systems. Our results confirmed the ones previously published. However, the interesting data on 3D antral follicle count increased in MS women should be confirmed and studied in order to evaluate if follicular dynamics are altered in Multiple Sclerosis.

Trial registration number

Not applicable
P-705 Homozygous missense variant in MEIOSIN causes premature ovarian insufficiency
Authors: Guo T , Zhang Q , Zhang W , Zhao S , Qin Y
Published: June 2023

Study question

Are the gene variants involved in meiosis initiation responsible for premature ovarian insufficiency (POI)?

Summary answer

MEIOSIN variant participates in the pathogenesis of human POI by impairing meiosis due to insufficient transcriptional activation of essential meiotic genes.

What is known already

Meiosis is the key event for the establishment of the ovarian reserve, and several gene defects impairing meiotic homologous recombination have been found to contribute to the pathogenesis of POI. However, the genes involved in meiosis initiation have not been associated with POI.

Study design, size, duration

Retrospective genetic study. An in-house whole exome sequencing (WES) database of 1,030 idiopathic POI patients was screened for variations of meiosis initiation genes.

Participants/materials, setting, methods

Gene variations involved in meiosis initiation were screened in the in-house WES database of 1,030 POI cases. The pathogenicity of the variation was verified by in vitro experiments, including protein structure prediction and dual-luciferase reporter assay. The effect of the variant on ovarian function and meiosis was demonstrated through histological analyses in a point mutation mouse model.

Main results and the role of chance

A homozygous variant of MEIOSIN that initiates meiosis via the retinoic acid dependent pathway was identified in a patient with idiopathic POI. The dual-luciferase reporter assay revealed that the variant adversely affected the transcriptional function of MEIOSIN in upregulating meiotic genes. Further knock-in mice with the homologous mutation confirmed that the variation impacted the meiotic prophase I program and accelerated oocyte depletion.

Limitations, reasons for caution

Further studies are needed to explore the role of other meiosis initiation genes in the pathogenesis of POI.

Wider implications of the findings

The present study firstly identified pathogenic MEIOSIN variants in patients with POI. Although the causative variation in meiotic initiation genes is rare in POI, our study expanded the spectrum of causative genes and elucidated the different mechanisms in human infertility.

Trial registration number

Not available
P-735 Are there any differences in preimplantation blastocyst chromosomal abnormalities between polycystic ovary syndrome patients and controls? A multi-center retrospective cohort study
Authors: Luo L , Wenjun W , Yan X , Limei Z , Fei G , Qiong W
Published: June 2023

Study question

Are there possible differences in the preimplantation blastocyst chromosome aberrations between polycystic ovary syndrome (PCOS) patients and controls?

Summary answer

PCOS lowers aneuploidy risk but increases mosaicism risk in preimplantation embryos, and PCOS-related insulin resistance should be investigated as a potential cause.

What is known already

PCOS is thought to alter granulosa cell functions and effects on oocyte development, potentially leading to chromosomal abnormalities and increasing the risk of pregnancy loss. However, few studies have compared the chromosomal status of preimplantation embryos from PCOS patients to those from healthy controls.

Study design, size, duration

This was a multi-center retrospective cohort study conducted at 3 IVF centers. A total of 707 blastocysts from 147 PCOS patients and 3006 blastocysts from 821 control women receiving preimplantation genetic testing (PGT) between 2015 and 2021.

Participants/materials, setting, methods

PGT was performed using next-generation sequencing (NGS). Differences in the chromosome aberrations were compared. Multivariate and subgroup analyses were conducted to control for confounders. Influences of insulin resistance and PCOS phenotype on the risks of specific chromosomal abnormalities were also examined.

Main results and the role of chance

Compared to controls, blastocysts from PCOS patients demonstrated lower aneuploidy rate (14.7% vs. 25.4%, P < 0.001) but greater mosaicism rate (16.5% vs. 8.7%, P < 0.001). Multivariable analysis adjusting for age, IVF center, body mass index (BMI), total gonadotropin (Gn) dose, and peak serum estradiol (E2) on trigger day, identified PCOS as an independent protective factor against embryonic aneuploidy (adjusted OR = 0.56, 95% CI, 0.42–0.76, P<0.001) but a risk factor for embryonic mosaicism (adjusted OR = 2.05, 95% CI 1.48–2.85, P<0.001). These differences in chromosomal spectrum were also observed in subgroups stratified by age, IVF center and BMI. Further multivariate analysis suggested that insulin resistance could be responsible for the increased risk of embryonic mosaicism among PCOS patients (OR = 1.89, 95% CI, 1.06–3.34, P=0.03).

Limitations, reasons for caution

The main limitation is the retrospective design. Besides, methodological uncertainties still exist in detecting mosaicism in current reproductive medicine. A longer-term, multiple-center prospective study with greater methodological standardization is warranted to confirm the present results.

Wider implications of the findings

These results suggest that PCOS pathology may increase the risk of mitosis errors but not the risk of meiosis errors during oocyte development, and PCOS-related insulin resistance should be investigated as a potential cause.

Trial registration number

2020[325]
P-749 Increased accuracy in infertility workup by the additional use of new modern diagnostic methods (“diagnostic TRIO”): results from a large retrospective analysis
Authors: Török P , Boldogh B Z , Lipták M G , Herman T , Lampé R , Di Donna M C , Laganà A S
Published: June 2023

Study question

Is there any positive effect of adding new modalities to the traditional infertility work-up, like 3D sonography, office hysteroscopy and endometrial biopsy?

Summary answer

During infertility workup conventional diagnostic tests should be combined with new approaches (3D-TVS, OHSC and endometrial biopsy) to achieve more accurate and less invasive diagnostics.

What is known already

Female infertility can be explained by functional or organic abnormalities affecting the reproductive system. The most common organic causes include abnormalities within the uterine cavity (e.g. endometrial polyp, submucosal fibroid, intrauterine adhesion), morphological disorders (e.g. dysmorphic uterus, uterine septum) and abnormalities of the endometrium (e.g. chronic endometritis).

Study design, size, duration

In our retrospective study, we examined patients with primary and secondary infertility. All the patients were assessed by 3D-TVS and OHSC to detect morphological and intrauterine disorders, and in special cases (repeated implantation failure – RIF), endometrial biopsies were carried out to detect endometrial disorders.

Participants/materials, setting, methods

Data of 606 patients examined between 2018 and 2022 were analyzed retrospectively.

Main results and the role of chance

In 606 cases 3D-TVS and OHSC were performed in patients (65.51 % primary, 34.49 % secondary infertility), who had unknown reason to infertility. By the combination of 3D-TVS and OHSC we could verify uterine disorders in 39.93 % of cases. Together these two diagnostic methods found the probable infertility causing lesion almost 40 % of our patients. In the subgroup of 40 repeated implantation failure (RIF) patients, the “diagnostic TRIO” confirmed a disorder in 57.50 % of the cases.

Limitations, reasons for caution

Number of patients should be more to conclude more accurate data.

Wider implications of the findings

The proper condition of the uterine milieu, through correction of uterine cavity if necessary, endometrial receptivity are of paramount importance for the success of the treatment; as a result, intrauterine surgery as a new subspecialty has been developing.

Trial registration number

DE RKEB/IKEB: H.0250-2020