Follicular reconstruction and neo-oogenesis in xenotransplantation of human ovarian isolated cells derived from chemotherapy-induced POF patients.

BACKGROUND: Developing new strategies to restore fertility in patients with chemotherapy-induced Premature Ovarian Failure (Chemo-POF) is important. We aimed to construct an Artificial Ovary (AO) by seeding Human Ovarian Cortical Cells (HOCCs) into Human ovarian Decellularized Cortical Tissue (DCT). We assessed the AO's ability to produce new ovarian follicles following xenotransplantation to NMRI mice. MATERIAL AND METHODS: The DCTs were prepared, and cell removal was confirmed through DNA content, MTT assay, DAPI and H&E staining. Next, HOCCs were isolated from both Chemo-POF and Trans (as a control group) ovarian patients. The HOCCs were characterized using immunostaining (FRAGILIS, Vimentin, and Inhibin α) and real time PCR (DDX4, STELLA, FRAGILIS, Vimentin, FSH-R, KI67) assays. The HOCCs were then seeded into the DCTs and cultured for one week to construct an AO, which was subsequently xenotransplanted into the mice. The existence of active follicles within the AO was studied with H&E and immunofluorescence (GDF9) staining, Real-time PCR (GDF9, ZP3) and hormone analysis (Estradiol, FSH and AMH). RESULTS: The results of gene expression and immunostaining showed that 85-86% of the isolated cells from both Trans and Chemo-POF groups were positive for vimentin, while 2-5% were granulosa cells and OSCs were less than 3%. After xenotransplantation, histological study confirmed the presence of morphologically healthy reconstructed human ovarian follicles. Additionally, immunofluorescence staining of GDF9 and hormonal assay confirmed the presence of secretory-active follicles on the AO. CONCLUSION: Our findings demonstrate that an artificial ovary produced by seeding HOCCs on DCT can support HOCCs proliferation as well as neo-oogenesis, and enable sex hormone secretion following xenotransplantation.

Epidemiological trend of suicide in north of Iran from 2011 to 2018 with a focus on joinpoint regression.

Background: Deaths due to potential suicide are preventable and this phenomenon is costly for the health care system and contradicts the values and cultural standards of an Islamic country. Methods: This study is a retrospective study. The research population includes all cases of suicide during the years 2011-2018 who were referred to the emergency department of Babol hospitals. The results were analyzed using SPSS v.23 and Joinpoint Trend Analysis software 4.9.0.0 to identify significant changes in the temporal trends of the outbreak. Results: The highest percentage of suicides occurred in summer (27.8%), on Saturdays (13%) and at night (53%). A total of 1.9% of the cases were commit suicides (leading to death). The highest frequency of suicide was shown in 1397 (21.2%) and the lowest in 1392 (5.1%) and was more common in women (68.2% vs. 31.8%). Suicide-related deaths was higher in the second four years (63.5%), but suicide rate was significantly higher in the first four years (2011-2014) and the mortality rate due to suicide was higher in men than women. Conclusion: Suicide attempts were higher in women than men but the death rate was higher in men which means that men attempt suicide more seriously than women. The model also predicted that suicide rates would rise in the coming years. For this reason, this important issue, along with a detailed analysis of the roots of suicidal ideation and preventive measures, should be considered by health officials and social institutions.

Development of a Machine Learning-Based Screening Method for Thyroid Nodules Classification by Solving the Imbalance Challenge in Thyroid Nodules Data.

BACKGROUND: This study aims to show the impact of imbalanced data and the typical evaluation methods in developing and misleading assessments of machine learning-based models for preoperative thyroid nodules screening. STUDY DESIGN: A retrospective study. METHODS: The ultrasonography features for 431 thyroid nodules cases were extracted from medical records of 313 patients in Babol, Iran. Since thyroid nodules are commonly benign, the relevant data are usually unbalanced in classes. It can lead to the bias of learning models toward the majority class. To solve it, a hybrid resampling method called the Smote-was used to creating balance data. Following that, the support vector classification (SVC) algorithm was trained by balance and unbalanced datasets as Models 2 and 3, respectively, in Python language programming. Their performance was then compared with the logistic regression model as Model 1 that fitted traditionally. RESULTS: The prevalence of malignant nodules was obtained at 14% (n = 61). In addition, 87% of the patients in this study were women. However, there was no difference in the prevalence of malignancy for gender. Furthermore, the accuracy, area under the curve, and geometric mean values were estimated at 92.1%, 93.2%, and 76.8% for Model 1, 91.3%, 93%, and 77.6% for Model 2, and finally, 91%, 92.6% and 84.2% for Model 3, respectively. Similarly, the results identified Micro calcification, Taller than wide shape, as well as lack of ISO and hyperechogenicity features as the most effective malignant variables. CONCLUSION: Paying attention to data challenges, such as data imbalances, and using proper criteria measures can improve the performance of machine learning models for preoperative thyroid nodules screening.

Developing machine learning-based models to predict intrauterine insemination (IUI) success by address modeling challenges in imbalanced data and providing modification solutions for them.

BACKGROUND: This study sought to provide machine learning-based classification models to predict the success of intrauterine insemination (IUI) therapy. Additionally, we sought to illustrate the effect of models fitting with balanced data vs original data with imbalanced data labels using two different types of resampling methods. Finally, we fit models with all features against optimized feature sets using various feature selection techniques. METHODS: The data for the cross-sectional study were collected from 546 infertile couples with IUI at the Fatemehzahra Infertility Research Center, Babol, North of Iran. Logistic regression (LR), support vector classification, random forest, Extreme Gradient Boosting (XGBoost) and, Stacking generalization (Stack) as the machine learning classifiers were used to predict IUI success by Python v3.7. We employed the Smote-Tomek (Stomek) and Smote-ENN (SENN) resampling methods to address the imbalance problem in the original dataset. Furthermore, to increase the performance of the models, mutual information classification (MIC-FS), genetic algorithm (GA-FS), and random forest (RF-FS) were used to select the ideal feature sets for model development. RESULTS: In this study, 28% of patients undergoing IUI treatment obtained a successful pregnancy. Also, the average age of women and men was 24.98 and 29.85 years, respectively. The calibration plot in this study for IUI success prediction by machine learning models showed that between feature selection methods, the RF-FS, and among the datasets used to fit the models, the balanced dataset with the Stomek method had well-calibrating predictions than other methods. Finally, the brier scores for the LR, SVC, RF, XGBoost, and Stack models that were fitted utilizing the Stomek dataset and the chosen feature set using the Random Forest technique obtained equal to 0.202, 0.183, 0.158, 0.129, and 0.134, respectively. It showed duration of infertility, male and female age, sperm concentration, and sperm motility grading score as the most predictable factors in IUI success. CONCLUSION: The results of this study with the XGBoost prediction model can be used to foretell the individual success of IUI for each couple before initiating therapy.

Incidence and investigation of Covid-19 trend in Babol, northern Iran: A Joinpoint regression analysis.

Background: In December 2019, China released the first report of the coronavirus (COVID-19). On March 11, 2020 the World Health Organization (WHO) characterized the COVID-19 as "pandemic". The rapid occurrence of positive cases motivated this study to examine the trend of incidence cases. Methods: We used the data from the database of the Deputy of Health of Babol City and in Iran, the country report of definite cases of the disease that was reported to the World Health Organization had been used. This study was a cross-sectional study and the data from period of 56 weeks (from February 24, 2020 to March 20, 2021) were gathered. Descriptive analysis with SPSS20 and data classification with EXCEL2016 and Joinpoint regression with Joinpoint trend analysis software 4.9.0.0 identify the significant changes in the temporal trends of the outbreak. Results: In this study, 11341 patients with a mean age of 53.56 years, of whom 5865(51.5%) were males, were studied. Three waves of Covid19 were created. AWPC (average weekly percentage change) incidence rate with a slope of 2.7 was estimated for Babol and 6.2 for Iran. The incidence was higher in men in the first wave of 1887(55.6%) and so is the third 2373(50.1%), the average age in the third wave (50.92) was lower than the other waves as well. Conclusion: The incidence of coronavirus in men was higher in three waves and also the incidence was increasing in younger age groups. Also, due to the observance of health protocols and quarantine during the peak in Iran and Babol, we witnessed a decrease in incidence.

Two-Decade Experience of Royan Institute in Obtaining Mature Oocyte from Cryopreserved Ovarian Tissue: In Vitro and In Vivo Approaches.

Ovarian tissue cryopreservation (OTC) holds promise for preservation of fertility among women who have lost their fertility due to diseases such as cancer. OTC has significantly assisted such cases by helping them maintain normal hormonal levels and menstrual cycles. Appropriate strategies to develop and extract mature oocytes from OTC could overcome a range of complications that are associated with ovarian dysfunction, caused by aging, and primary or secondary ovarian insufficiency. Scientists from different departments at The Royan Institute (Tehran, Iran) have been conducting studies to find the best way to extract mature oocytes from animal and human cryopreserved ovarian tissues. The various studies conducted in this area in the past 20 years, by researchers of the Royan Institute, are collated and provided in this review, in order to provide an idea of where we are now in the area of fertility preservation.

Small Non-coding RNAs in Embryonic Pre-implantation.

Failure of embryo implantation has been introduced as an important limiting parameter in early assisted reproduction and pregnancy. The embryo-maternal interactions, endometrial receptivity, and detections of implantation consist of the embryo viability. For regulating the implantation, multiple molecules may be consistent; however, their specific regulatory mechanisms still stand unclear. MicroRNAs (miRNAs) have attracted a lot of attention due to their important effect on human embryo implantation. MicroRNA (miRNA), which acts as the transcriptional regulator of gene expression, is consisted of embryo implantation. Recent studies indicated that miRNAs not only act inside the cells but also can be secreted by cells into the extracellular environment via multiple packaging forms, facilitating intercellular communication and providing indicative information related to various conditions. The detection of extracellular miRNAs provided new information in cases of implantation studies. For embryo-maternal communication, MiRNAs offered novel approaches. In addition, in assisted reproduction, for embryo choice and prediction of endometrial receptivity, they can act as non-invasive biomarkers and can enhance the accuracy in the process of reducing the mechanical damage for the tissue.

Ethyl acetate fraction of Allium hirtifolium improves functional parameters of isolated hearts of diabetic rats.

OBJECTIVE: Allium hirtifolium (Persian shallot) has a hypoglycemic effect on diabetic animals. The aim of this study was to assess the effect of the ethyl acetate fraction of Allium hirtifolium on the function of isolated hearts of diabetic rats. METHODS: The control and diabetic animals were randomly divided into four groups: saline- or extract-treated controls (n=10 and n=6, respectively) and saline- or extract-treated diabetic rats (n=8 and n=9, respectively), which received normal saline or extract for four weeks by daily gavage. The hearts were perfused according to the Langendorff method. Cardiac function parameters, including left ventricular developed pressure (LVDP), heart rate (HR), rate pressure product (RPP; LVDP×HR), and dp/dt were measured. RESULTS: The findings of this study showed that in the extract-treated diabetic rats, LVDP (94.5±9.1 mm Hg, mean±SEM), HR (249±15 beats/min), RPP (22732±1246) and +dp/dt (2598±230) at the baseline were significantly higher than those in the saline-treated diabetic animals, (71.5±4.0), (189±6), (13923±984), and (1701±124), respectively. Furthermore, RPP and HR were also significantly higher than the corresponding values obtained in the saline-treated diabetic rats after ischemia. CONCLUSION: Besides blood glucose lowering action, oral administration of the ethyl acetate fraction of Allium hirtifolium significantly improved the baseline and post-ischemic cardiac function parameters in streptozotocin-induced diabetic rats.

The effect of Tribulus terrestris extract on motility and viability of human sperms after cryopreservation.

BACKGROUND: Semen cryopreservation produces significant amounts of reactive oxygen species (ROS), which may lead to impairment of sperm morphology, function, and ultimately, male fertility. Since Tribulus terrestris has antioxidant and free-radical-scavenging properties, this study aims to reveal the effect of the Tribulus terrestris extract on motility and vitality of human sperms after cryopreservation. MATERIALS AND METHODS: Semen specimens from 80 healthy volunteers were divided into eight groups: fresh control (group I), freeze control (group II), groups III, IV, and V, which had 20, 40, and 50 µg/mL doses of Tribulus terrestris extract added before cryopreservation, and groups VI, VII, and VIII, which were supplemented by these extract doses after the freeze-thaw process. To evaluate the effects of the Tribulus terrestris extract, the semen samples were incubated with the extract and evaluated with a light microscope for motility and viability. RESULTS: After cryopreservation, a significant improvement in spermatozoa viability was observed in group VII. In groups VII and VIII, motility, according to World Health Organization (WHO) criteria, increased considerably (p < 0.001). There was no significant difference among groups III, IV, and V. CONCLUSION: The present study demonstrated that the protective effects of Tribulus terrestris, which improves human sperm motility and viability, may be due to its antioxidant properties. On the basis of the results, the researchers concluded that Tribulus terrestris can be used as a safe therapeutic alternative to current modalities for the management of motility dysfunction in males.

Tribulus terrestris Extract Improves Human Sperm Parameters In Vitro.

OBJECTIVE: The object of present study was to investigate the effects of direct addition of Tribulus terrestris extract on human sperm parameters. DESIGN: Semen specimens from 40 healthy men volunteers were divided into 4 groups: one group received no treatment (control group) while the others were incubated with 20, 40, and 50 µg/mL of T terrestris extract (experimental groups). Motility, viability, and DNA fragmentation were assessed in all groups. RESULTS: The incubation of human semen with 40 and 50 µg/mL of T terrestris extract significantly enhanced total sperm motility, number of progressive motile spermatozoa, and curvilinear velocity over 60 to 120 minutes' holding time ( P < .05 or P < < .01). Furthermore, viability was significantly enhanced by using T terrestris extract ( P < .01). CONCLUSIONS: In vitro addition of the T terrestris extract to human sperm could affect male fertility capacity.