Rapid and pervasive changes in genome-wide enhancer usage during mammalian development.

Enhancers are distal regulatory elements that can activate tissue-specific gene expression and are abundant throughout mammalian genomes. Although substantial progress has been made toward genome-wide annotation of mammalian enhancers, their temporal activity patterns and global contributions in the context of developmental in vivo processes remain poorly explored. Here we used epigenomic profiling for H3K27ac, a mark of active enhancers, coupled to transgenic mouse assays to examine the genome-wide utilization of enhancers in three different mouse tissues across seven developmental stages. The majority of the ∼90,000 enhancers identified exhibited tightly temporally restricted predicted activity windows and were associated with stage-specific biological functions and regulatory pathways in individual tissues. Comparative genomic analysis revealed that evolutionary conservation of enhancers decreases following midgestation across all tissues examined. The dynamic enhancer activities uncovered in this study illuminate rapid and pervasive temporal in vivo changes in enhancer usage that underlie processes central to development and disease.

A high-resolution enhancer atlas of the developing telencephalon.

The mammalian telencephalon plays critical roles in cognition, motor function, and emotion. Though many of the genes required for its development have been identified, the distant-acting regulatory sequences orchestrating their in vivo expression are mostly unknown. Here, we describe a digital atlas of in vivo enhancers active in subregions of the developing telencephalon. We identified more than 4,600 candidate embryonic forebrain enhancers and studied the in vivo activity of 329 of these sequences in transgenic mouse embryos. We generated serial sets of histological brain sections for 145 reproducible forebrain enhancers, resulting in a publicly accessible web-based data collection comprising more than 32,000 sections. We also used epigenomic analysis of human and mouse cortex tissue to directly compare the genome-wide enhancer architecture in these species. These data provide a primary resource for investigating gene regulatory mechanisms of telencephalon development and enable studies of the role of distant-acting enhancers in neurodevelopmental disorders.

Comparing per-pass performance of 2 types of needles for EUS-guided fine-needle biopsy sampling of pancreatobiliary masses in a randomized trial.

BACKGROUND AND AIMS: EUS-guided fine-needle biopsy sampling (EUS-FNB) has largely replaced FNA for tissue diagnosis of pancreatobiliary mass lesions. However, the optimal number of passes required for the diagnosis of malignancy is not clear. We aimed to compare the per-pass performance of 2 types of fine-needle biopsy (FNB) needles for the detection of malignancy. METHODS: One hundred fourteen patients referred for EUS evaluation of solid pancreatobiliary mass lesions underwent randomization between biopsy sampling with a Franseen needle and a 3-prong tip needle with an asymmetric cutting surfaces. Four passes of EUS-FNB were taken from each mass lesion. Two pathologists blinded to needle type analyzed the specimens. The final diagnosis of malignancy was made based on FNB specimen pathology, surgery, or a follow-up of at least 6 months after EUS-FNB. The sensitivity of EUS-FNB to diagnose malignancy was compared between the 2 groups. The cumulative sensitivity of detection of malignancy by EUS-FNB was calculated after each pass in each arm. Other characteristics of the specimens including cellularity and blood contents were also compared between the 2 groups. In the primary analysis, lesions categorized as suspicious on EUS-FNB were considered nondiagnostic for malignancy. RESULTS: Ninety-eight patients (86%) had a final diagnosis of malignancy, and 16 patients (14%) had benign disease. Four passes of EUS-FNB with the Franseen needle detected malignancy in 44 of 47 patients (sensitivity, 93.6%; 95% confidence interval [CI], 82.5-98.7) and with the 3-prong asymmetric-tip needle in 50 of 51 patients (sensitivity, 98%; 95% CI, 89.6-99.9; P = .35). Two passes of EUS-FNB detected malignancy with a sensitivity of 91.5% (95% CI, 79.6-97.6) with the Franseen needle and 90.2% (95% CI, 78.6-96.7) with the 3-prong asymmetric-tip needle. The cumulative sensitivities at pass 3 were 93.6% (95% CI, 82.5-98.6) and 96.1% (95% CI, 86.5-99.5), respectively. Samples collected with the Franseen needle had significantly higher cellularity than samples collected with the 3-prong asymmetric-tip needle (P < .01). However, no difference as found between the 2 types of needles in term of specimen bloodiness. CONCLUSIONS: No significant differences were found in the diagnostic performance of the Franseen needle versus the 3-prong asymmetric-tip needle in patients with suspected pancreatobiliary cancer. However, the Franseen needle yielded higher cellularity of the specimen. Two passes of EUS-FNB are required to detect malignancy with at least 90% sensitivity with either type of needle. (Clinical trial registration number: NCT04975620.).

Assisted conception as a potential prognostic factor predicting insulin therapy in pregnancies complicated by gestational diabetes mellitus.

BACKGROUND: Advanced maternal age, family history of diabetes, pre-gestational obesity, increased level of HbA1c, history of gestational diabetes mellitus (GDM), and poor pregnancy consequences are considered risk factors for antenatal insulin requirement in women with GDM. However, the role of assisted reproductive technology (ART) in increasing the risk of insulin therapy in pregnancies complicated with GDM remained elusive. The current study aimed to determine the role of ART in predicting insulin therapy in GDM women and investigate the clinical and biochemical factors predicting the need for insulin therapy in pregnancies complicated with GDM. METHODS: In this prospective cohort study, 236 Iranian women with GDM were diagnosed by one-step oral glucose tolerance test (OGTT) between October 2014 and June 2017. They were mainly assigned to two groups; the first group (n = 100) was designated as ART which was further subdivided into two subgroups as follows: 60 participants who received medical nutrition therapy (MNT) and 40 participants who received MNT plus insulin therapy (MNT-IT). The second group (n = 136) was labeled as the spontaneous conception (SC), consisting of 102 participants receiving MNT and 34 participants receiving MNT in combination with IT (MNT-IT). The demographic, clinical, and biochemical data were compared between groups. Multivariate logistic regression was performed to estimate prognostic factors for insulin therapy. RESULTS: A higher rate of insulin therapy was observed in the ART group as compared with the SC group (40% vs. 25%; P < 0.001). Multivariate logistic regression demonstrated that maternal age ≥ 35 years [OR: 2.91, 95% CI: (1.28-6.62)], high serum FBS [1.10: (1.04-1.16)], HbA1c [1.91 (1.09-3.34)], and ART treatment [2.94: (1.24-6.96)] were independent risk factors for insulin therapy in GDM women. CONCLUSIONS: Apart from risk factors mentioned earlier, ART may be a possible prognostic factor for insulin therapy in pregnancies complicated with GDM.

Obstetric and perinatal outcomes of singleton pregnancies conceived via assisted reproductive technology complicated by gestational diabetes mellitus: a prospective cohort study.

BACKGROUND: Growing evidence indicates that the risk of obstetric and perinatal outcomes is higher in women with assisted reproductive technology (ART). However, there is little known about pregnancy related complications and co-morbidity in gestational diabetes mellitus (GDM) following singleton pregnancies achieved by ART in comparison with spontaneous conception (SC). METHODS: Two hundred sixty singleton pregnant women conceived by ART and 314 pregnant women conceived by spontaneous conception (SC) were participated in this prospective cohort study. All participants were enrolled after GDM screening through one-step oral glucose tolerance test (OGTT) and then grouped into GDM and non-GDM groups. Women were followed for pregnancy outcomes including pregnancy-induced hypertension (PIH), preeclampsia, antepartum hemorrhage (APH), cesarean section (CS), preterm birth (PTB), intrauterine growth restriction (IUGR), being small or large for gestational age (SGA or LGA), macrosomia, low birth weight (LBW), respiratory distress, neonatal hypoglycemia, NICU admission and perinatal mortality from antenatal visits to delivery. Confounding factors were adjusted in logistic regression model in order to estimate adjusted odds ratios (aORs). RESULTS: Among 260 ART and 314 SC, 135 and 152 women were GDM women, respectively. Higher maternal age and pre-gravid BMI, shorter duration of gestation and lower gestational weight gain were observed in GDM groups (ART-GDM and SC-GDM) compared to those of the SC group. ART-GDM group had a higher risk (95% confidence interval) of obstetric complications including PIH [aOR:7.04 (2.24-22.15)], preeclampsia [aOR:7.78 (1.62-37.47)], APH [aOR:3.46 (1.28-9.33)], emergency CS [aOR:2.64 (1.43-4.88)], and perinatal outcomes such as PTB [aOR:3.89 (1.51-10.10)], LBW [aOR:3.11 (1.04-9.30)] and NICU admission [aOR:4.36 (1.82-10.45)], as well as neonatal hypoglycemia [aOR: 4.91 (1.50-16.07)], compared to SC group. SC-GDM group showed a higher risk of PIH [aOR: 4.12 (1.31-12.89)], emergency CS [aOR: 2.01 (1.09-3.73] and LGA [aOR: 5.20 (1.07-25.20)], compared to SC group. Additionally, ART group had a higher risk of PIH [aOR: 3.46(1.02-11.68), preeclampsia 5.29 (1.03-27.09), and NICU admission [aOR: 2.53 (1.05-6.09)] compared to SC. Insulin requirement (41.8% vs. 25.7%) was significantly higher in ART-GDM group compared to SC-GDM group. CONCLUSION: The findings of this study suggest that GDM occurring after ART conception increases the risk of adverse obstetric and perinatal outcomes.

The casual effect of lifestyle factors on outcomes of assisted reproductive techniques: a protocol study on Iranian infertile couples.

BACKGROUND: Attention to additional factors affecting the success of assisted reproduction techniques (ARTs) is very important and with appropriate interventions in some of these factors, success rate can be as high as improve a lot. There is a lot of evidence that lifestyle factors can influence on ARTs outcomes. Current knowledge of the effect of combined effect of several lifestyle factors on the outcomes of ARTs is low and contradictory. The importance of the causality of this phenomenon is felt by the pandemic of inappropriate lifestyle as well as the dramatic increase in infertility in the world. The aim of this cohort study is to scrutinize the casual effect of a specific range of contemporary lifestyle factors on ARTs outcomes. METHODS: A prospective cohort study will be conducted in Royan institute, Tehran, Iran. Each infertile couple will be monitored from the first visit to the end of treatment cycle. The data will be collected electronically and include the following: detailed interview about lifestyle and socioeconomic status, past medical history, general physical examination, assessment of menstrual and ovulatory status, assessment of tuboperitoneal, assessment of uterine, assessment of cervix, urogenital examination, semen analysis, anti-sperm antibodies, biochemical analysis, sperm-cervical mucus contact test, in vitro cervical mucus penetration test and sperm functional assays. To estimate the casual effect of lifestyle variables on clinical pregnancy and live birth, the obtained propensity score (PS) from generalized boosted models (GBM) will be matched between couple with and without live birth. DISCUSSION: This is the first study to prospectively obtain detailed information on causes of ARTs success. Determining the casual effect of lifestyle variables on ARTs success will be important to inform strategies most likely to increase the success rates in ARTs.

Predictive factors of gestational diabetes in pregnancies following assisted reproductive technology: a nested case-control study.

PURPOSE: To evaluate predictive factors for gestational diabetes mellitus (GDM) in singleton pregnancy following assisted reproductive technology (ART). METHODS: This nested case-control study was performed during October 2016-June 2017. Pregnant women who conceived following ART procedures referred to infertility clinic were selected and categorized into GDM and non-GDM based on ADA/IAPDSG criteria. The study variables including age, educational status, first-degree family history of chronic diseases, systolic and diastolic blood pressure, previous obstetric and perinatal outcomes, infertility history, and ART cycle characteristics were collected from medical records. Prediction model to develop GDM was employed by binary logistic regression analysis after adjustment for age and body mass index, family history of diabetes, and gravidity. RESULTS: In total, 270 women with singleton pregnancies (consisted of 135 GDM and 135 non-GDM women) conceived were studied. According to the final model, significant predictors of GDM were history of polycystic ovarian syndrome (PCOS), previous ovarian hyper-stimulation syndrome (OHSS) risk and progesterone injections. Administration of injectable progesterone during the first 10-12 weeks of pregnancy was associated with an approximately twofold increased risk of developing GDM [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.27-4.09)] compared to vaginal progesterone. In addition, the regression analysis revealed that previous OHSS risk (OR 2.40, 95% CI 1.34-4.31) and history of PCOS (OR 2.76, 95% CI 1.26-6.06) were other most important predictors of GDM. CONCLUSIONS: The route of progesterone administration, previous OHSS risk and history of PCOS seem to be putative risk factors for GDM in women conceived by ART.

Tissue-specific SMARCA4 binding at active and repressed regulatory elements during embryogenesis.

The SMARCA4 (also known as BRG1 in humans) chromatin remodeling factor is critical for establishing lineage-specific chromatin states during early mammalian development. However, the role of SMARCA4 in tissue-specific gene regulation during embryogenesis remains poorly defined. To investigate the genome-wide binding landscape of SMARCA4 in differentiating tissues, we engineered a Smarca4(FLAG) knock-in mouse line. Using ChIP-seq, we identified ∼51,000 SMARCA4-associated regions across six embryonic mouse tissues (forebrain, hindbrain, neural tube, heart, limb, and face) at mid-gestation (E11.5). The majority of these regions was distal from promoters and showed dynamic occupancy, with most distal SMARCA4 sites (73%) confined to a single or limited subset of tissues. To further characterize these regions, we profiled active and repressive histone marks in the same tissues and examined the intersection of informative chromatin states and SMARCA4 binding. This revealed distinct classes of distal SMARCA4-associated elements characterized by activating and repressive chromatin signatures that were associated with tissue-specific up- or down-regulation of gene expression and relevant active/repressed biological pathways. We further demonstrate the predicted active regulatory properties of SMARCA4-associated elements by retrospective analysis of tissue-specific enhancers and direct testing of SMARCA4-bound regions in transgenic mouse assays. Our results indicate a dual active/repressive function of SMARCA4 at distal regulatory sequences in vivo and support its role in tissue-specific gene regulation during embryonic development.

EMPathways2: Estimation of Enzyme Expression and Metabolic Pathway Activity Using RNA-Seq Reads.

In this chapter, we outline an approach to analyzing metatranscriptomic data, focusing on the assessment of differential enzyme expression and metabolic pathway activities using a novel bioinformatics software tool, EMPathways2. The analysis pipeline commences with raw data originating from a sequencer and concludes with an output of enzyme expressions and an estimate of metabolic pathway activities. The initial step involves aligning specific transcriptomes assembled from RNA-Seq data using Bowtie2 and acquiring gene expression data with IsoEM2. Subsequently, the pipeline proceeds to quality assessment and preprocessing of the input data, ensuring accurate estimates of enzymes and their differential regulation. Upon completion of the preprocessing stage, EMPathways2 is employed to decipher the intricate relationships between genes, enzymes, and pathways. An online repository containing sample data has been made available, alongside custom Python scripts designed to modify the output of the programs within the pipeline for diverse downstream analyses. This chapter highlights the technical aspects and practical applications of using EMPathways2, which facilitates the advancement of transcriptome data analysis and contributes to a deeper understanding of the complex regulatory mechanisms underlying living systems.

COVID-19-related fear and anxiety in a sample of patients with type 2 diabetes: a cross-sectional study in Iran after several peaks of the pandemic.

Purpose: The aim of this study was to assess COVID-19-related anxiety, and fear burden in diabetic patients, as a risk group for severe COVID-19. Methods: A cross-sectional online survey conducted on 111 type 2 diabetes mellitus (T2DM) patients referred to a Diabetes clinics of Royan institute, and 155 healthy controls recruited from normal population using a snowball sampling technique. Fear of COVID-19 Scale (FCV-19 S) and Coronavirus anxiety scale (CAS) were used. Results: The total score of coronavirus fear in T2DM patients was 15.79 (6.39) and in healthy controls 15.48 (5.97) (p = 0.696). The total score of coronavirus fear in T2DM patients was 15.79 (6.39) and in healthy controls 15.48 (5.97) (p = 0.696). Correlation matrix between coronavirus anxiety and fear scores in these samples confirmed that in T2DM participants CAS was significantly positively associated with FCV-19 (r = 0.407, p = 0.000). There was also statistically and positively significant correlation between CAS and FCV-19 in healthy subjects (r = 0.495, p = 0.000). Conclusion: The present study revealed that the level of fear and anxiety from COVID-19 was almost the same in a sample of Iranian T2DM patients and healthy controls. The pandemic with several peaks in the country cannot cause an increased anxiety and fear from COVID-19, especially in patients with diabetes. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01353-8.

Estimating Enzyme Expression and Metabolic Pathway Activity in Borreliella-Infected and Uninfected Mice.

Evaluating changes in metabolic pathway activity is essential for studying disease mechanisms and developing new treatments, with significant benefits extending to human health. Here, we propose EMPathways2, a maximum likelihood pipeline that is based on the expectation-maximization algorithm, which is capable of evaluating enzyme expression and metabolic pathway activity level. We first estimate enzyme expression from RNA-seq data that is used for simultaneous estimation of pathway activity levels using enzyme participation levels in each pathway. We implement the novel pipeline to RNA-seq data from several groups of mice, which provides a deeper look at the biochemical changes occurring as a result of bacterial infection, disease, and immune response. Our results show that estimated enzyme expression, pathway activity levels, and enzyme participation levels in each pathway are robust and stable across all samples. Estimated activity levels of a significant number of metabolic pathways strongly correlate with the infected and uninfected status of the respective rodent types.

A review of neurological side effects of COVID-19 vaccination.

Following the COVID-19 virus epidemic, extensive, coordinated international research has led to the rapid development of effective vaccines. Although vaccines are now considered the best way to achieve collective safety and control mortality, due to the critical situation, these vaccines have been issued the emergency use licenses and some of their potential subsequence side effects have been overlooked. At the same time, there are many reports of side effects after getting a COVID-19 vaccine. According to these reports, vaccination can have an adverse event, especially on nervous system. The most important and common complications are cerebrovascular disorders including cerebral venous sinus thrombosis, transient ischemic attack, intracerebral hemorrhage, ischemic stroke, and demyelinating disorders including transverse myelitis, first manifestation of MS, and neuromyelitis optica. These effects are often acute and transient, but they can be severe and even fatal in a few cases. Herein, we have provided a comprehensive review of documents reporting neurological side effects of COVID-19 vaccines in international databases from 2020 to 2022 and discussed neurological disorders possibly caused by vaccination.

Reconstruction of Viral Variants via Monte Carlo Clustering.

Identifying viral variants through clustering is essential for understanding the composition and structure of viral populations within and between hosts, which play a crucial role in disease progression and epidemic spread. This article proposes and validates novel Monte Carlo (MC) methods for clustering aligned viral sequences by minimizing either entropy or Hamming distance from consensuses. We validate these methods on four benchmarks: two SARS-CoV-2 interhost data sets and two HIV intrahost data sets. A parallelized version of our tool is scalable to very large data sets. We show that both entropy and Hamming distance-based MC clusterings discern the meaningful information from sequencing data. The proposed clustering methods consistently converge to similar clusterings across different runs. Finally, we show that MC clustering improves reconstruction of intrahost viral population from sequencing data.

Role of gender in explaining metabolic syndrome risk factors in an Iranian rural population using structural equation modelling.

Many factors can lead to an increase in the prevalence of metabolic syndrome (MetS) in different populations. Using an advanced structural equation model (SEM), this study is aimed to determine the most important risk factors of MetS, as a continuous latent variable, using a large number of males and females. We also aimed to evaluate the interrelations among the associated factors involved in the development of MetS. This study used data derived from the Fasa PERSIAN cohort study, a branch of the PERSIAN cohort study, for participants aged 35 to 70 years with 10,138 males and females. SEM was used to evaluate the direct and indirect effects, as well as gender effects of influencing factors. Results from the SEM showed that in females most changes in MetS are described by waist circumference (WC), followed by hypertension (HP) and triglyceride (TG), while in males most changes in MetS are described by WC, followed by TG then fasting blood glucose (FBG). Results from the SEM confirmed the gender effects of social status on MetS, mediated by sleep and controlled by age, BMI, ethnicity and physical activity. This study also shows that the integration of TG and WC within genders could be useful as a screening criterion for MetS in our study population.

Early Postpartum Glucose Intolerance, Metabolic Syndrome and Gestational Diabetes Mellitus Determinants after Assisted Conception: A Prospective Cohort Study.

BACKGROUND: This study aimed to determine the prevalence of postpartum metabolic syndrome (MetS), glucose intolerance,
and the determinants, 6-12 weeks postpartum in women with assisted reproduction technology conception
gestational diabetes mellitus diagnosis (ART-GDM) compared to women with spontaneous conception and GDM
diagnosis (SC-GDM).
Materials and Methods: In this prospective cohort study, two groups consisting of 62 ART-GDM and 64 SC-GDM
singleton pregnant women were followed 6-12 weeks after delivery for postpartum MetS. Fasting glucose, 75-g 2-h
OGTT, and lipid profile were assessed. Waist and hip circumference, and systolic and diastolic blood pressures (BP)
were measured at postpartum. Clinical, paraclinical, and obstetric data were recorded from registry offices. The prevalence
of MetS and glucose intolerance were determined. Predictors of MetS and glucose intolerance were evaluated
by logistic regression.
Results: The prevalence of postpartum MetS was 20.8% in ART-GDM women and 10.9% in SC-GDM (P=0.123).
Mean postpartum BMI and systolic BP were significantly higher in the ART-GDM group (P=0.016 and P=0.027
respectively). Adverse pregnancy outcomes were significantly higher in the ART-GDM group. Postpartum glucose
intolerance prevalence did not vary significantly between the groups. Family history of diabetes was a predictive factor
for postpartum MetS and glucose intolerance 6-12 weeks after delivery.
Conclusion: Early postpartum MetS and glucose intolerance prevalence after assisted conception did not vary significantly;
however, postpartum body mass index (BMI) and systolic BP were significantly higher in the ART-GDM group.
Lifestyle modification programs and long-term health care of ART women with GDM diagnosis can be recommended.
Further studies with larger sample size and longer follow-up are necessary to verify our findings.

Pipeline for Analyzing Activity of Metabolic Pathways in Planktonic Communities Using Metatranscriptomic Data.

In this article, we present our novel pipeline for analysis of metabolic activity using a microbial community's metatranscriptome sequence data set for validation. Our method is based on expectation-maximization (EM) algorithm and provides enzyme expression and pathway activity levels. Further expanding our analysis, we consider individual enzymatic activity and compute enzyme participation coefficients to approximate the metabolic pathway activity more accurately. We apply our EM pathways pipeline to a metatranscriptomic data set of a plankton community from surface waters of the Northern Gulf of Mexico. The data set consists of RNA-seq data and respective environmental parameters, which were sampled at two depths, six times a day over multiple 24-hour cycles. Furthermore, we discuss microbial dependence on day-night cycle within our findings based on a three-way correlation of the enzyme expression during antipodal times-midnight and noon. We show that the enzyme participation levels strongly affect the metabolic activity estimates: that is, marginal and multiple linear regression of enzymatic and metabolic pathway activity correlated significantly with the recorded environmental parameters. Our analysis statistically validates that EM-based methods produce meaningful results, as our method confirms statistically significant dependence of metabolic pathway activity on the environmental parameters, such as salinity, temperature, brightness, and a few others.

Gestational diabetes mellitus: Major risk factors and pregnancy-related outcomes: A cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) is a major pregnancy endocrine problem that has several confirmed risk factors and is associated with adverse pregnancy-related outcomes (PRO). OBJECTIVE: To evaluate the relationship between GDM diagnosis and the associated risk factors of PRO (maternal, intrapartum, perinatal, and neonatal) in accordance with International Association of Diabetes and Pregnancy Study Groups criteria. MATERIALS AND METHODS: This prospective cohort study was performed with 531 singleton parturient (265 GDM and 266 non-GDM). They were selected consecutively from referral hospitals, and the maternal, intrapartum, perinatal, and neonatal outcomes were assessed. RESULTS: The major risk factors influencing the GDM diagnosis were maternal age, obesity, family history of diabetes, previous history of GDM, and previous history of macrosomia. In the comparison of PRO between the groups, significant associations were detected for emergency cesarean delivery, preeclampsia, polyhydramnios, premature rupture of membrane, preterm delivery, and neonatal hyperbilirubinemia in the GDM group. In the multivariate logistic regression analysis, a previous history of stillbirth was significantly associated with maternal and perinatal outcomes. The odds ratios (CI 95%) of the PRO in the women with a GDM diagnosis were: maternal = 2.43 (1.51-3.90), intrapartum = 2.05 (1.35-3.11), perinatal = 2.00 (1.29-3.10), and neonatal = 1.68 (1.08-2.62). The PRO was significantly correlated with GDM diagnosis, but not with the risk factors. CONCLUSION: The adverse pregnancy outcomes were significantly correlated with GDM diagnosis, and the outcomes were not directly affected by the risk factors. Given the related adverse outcomes for mothers and offspring, early screening and management of GDM is necessary especially in Asians and in low-/middle-income countries.

From Alpha to Zeta: Identifying Variants and Subtypes of SARS-CoV-2 Via Clustering.

The availability of millions of SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) sequences in public databases such as GISAID (Global Initiative on Sharing All Influenza Data) and EMBL-EBI (European Molecular Biology Laboratory-European Bioinformatics Institute) (the United Kingdom) allows a detailed study of the evolution, genomic diversity, and dynamics of a virus such as never before. Here, we identify novel variants and subtypes of SARS-CoV-2 by clustering sequences in adapting methods originally designed for haplotyping intrahost viral populations. We asses our results using clustering entropy-the first time it has been used in this context. Our clustering approach reaches lower entropies compared with other methods, and we are able to boost this even further through gap filling and Monte Carlo-based entropy minimization. Moreover, our method clearly identifies the well-known Alpha variant in the U.K. and GISAID data sets, and is also able to detect the much less represented (<1% of the sequences) Beta (South Africa), Epsilon (California), and Gamma and Zeta (Brazil) variants in the GISAID data set. Finally, we show that each variant identified has high selective fitness, based on the growth rate of its cluster over time. This demonstrates that our clustering approach is a viable alternative for detecting even rare subtypes in very large data sets.

Potential Impact of Diabetes and Obesity on Alveolar Type 2 (AT2)-Lipofibroblast (LIF) Interactions After COVID-19 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new emerging respiratory virus, caused evolving pneumonia outbreak around the world. In SARS-Cov-2 infected patients, diabetes mellitus (DM) and obesity are two metabolic diseases associated with higher severity of SARS-CoV-2 related complications, characterized by acute lung injury requiring assisted ventilation as well as fibrosis development in surviving patients. Different factors are potentially responsible for this exacerbated response to SARS-CoV-2 infection. In patients with DM, base-line increase in inflammation and oxidative stress represent preexisting risk factors for virus-induced damages. Such factors are also likely to be found in obese patients. In addition, it has been proposed that massive injury to the alveolar epithelial type 2 (AT2) cells, which express the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2), leads to the activation of their stromal niches represented by the Lipofibroblasts (LIF). LIF are instrumental in maintaining the self-renewal of AT2 stem cells. LIF have been proposed to transdifferentiate into Myofibroblast (MYF) following injury to AT2 cells, thereby contributing to fibrosis. We hypothesized that LIF's activity could be impacted by DM or obesity in an age- and gender-dependent manner, rendering them more prone to transition toward the profibrotic MYF status in the context of severe COVID-19 pneumonia. Understanding the cumulative effects of DM and/or obesity in the context of SARS-CoV-2 infection at the cellular level will be crucial for efficient therapeutic solutions.

The Effect of Allograft Transplantation of Sertoli Cell on Expression of NF-кB, Bax Proteins, and Ischemic Tolerance in Rats with Focal Cerebral Ischemia.

One of the newest methods to reduce cerebral ischemia damages is cell therapy. The aim of this study is to evaluate the effect of Sertoli cell transplantation on ischemia-induced injuries in animal models of stroke. Rats were divided into four groups: transplant+ischemia, ischemia, sham, and control. Sertoli cells were separated from the other testis of rats and cultured. Unilateral Sertoli cell transplantation was performed in the right striatum by using stereotaxic surgery. For induction of brain ischemia, middle cerebral artery occlusion surgery was used 14 days after transplantation. By using western blotting method, expression of nuclear factor kappa (NF-кB) and Bax were evaluated. In this study, a remarkable decrease in neurological deficits, infection, blood-brain barrier permeability, and brain edema was observed in the cell transplant recipient group in comparison with the ischemia group. Probably, a reduction in inflammation (NF-кB factor) and apoptosis (Bax) following injection of Sertoli cells result in amelioration of ischemic damages induced by MCAO surgery.