Developing a Deep Neural Network model for COVID-19 diagnosis based on CT scan images.

COVID-19 is most commonly diagnosed using a testing kit but chest X-rays and computed tomography (CT) scan images have a potential role in COVID-19 diagnosis. Currently, CT diagnosis systems based on Artificial intelligence (AI) models have been used in some countries. Previous research studies used complex neural networks, which led to difficulty in network training and high computation rates. Hence, in this study, we developed the 6-layer Deep Neural Network (DNN) model for COVID-19 diagnosis based on CT scan images. The proposed DNN model is generated to improve accurate diagnostics for classifying sick and healthy persons. Also, other classification models, such as decision trees, random forests and standard neural networks, have been investigated. One of the main contributions of this study is the use of the global feature extractor operator for feature extraction from the images. Furthermore, the 10-fold cross-validation technique is utilized for partitioning the data into training, testing and validation. During the DNN training, the model is generated without dropping out of neurons in the layers. The experimental results of the lightweight DNN model demonstrated that this model has the best accuracy of 96.71% compared to the previous classification models for COVID-19 diagnosis.

Detecting and analyzing topics of massive COVID-19 related tweets for various countries.

With the flare-up of the COVID-19 infection since 2020, COVID-19 has been one of the hottest topics on Twitter. Topic modeling is one of the most popular analyses, which extracts the topics from the text. This paper proposes a method to extract the most-discussed topics for 32 countries of the world. In this regard, more than five million related tweets have been studied, and a method based on content analysis is proposed to identify the exact location of each tweet. Then, by using the statistical algorithm of Latent Dirichlet Allocation, the main topics of the tweets are identified. By leveraging sentiment analysis, the topics are afterward divided into positive and negative groups, and their trends in a quarterly period are investigated for the countries under study. The outcome of the analysis of time trends shows that for most countries, the trend of negative topics is highly correlated with the number of confirmed cases of COVID-19.

A review of methods for preserving male fertility.

Male infertility is responsible for 50% of men's health problems and has always been a concern for personal and social issues. A survey of global statistics suggests an increase in infertility rate as one of the critical issues documented in studies. There are different ways of maintaining fertility in men, depending on their age. In this paper, we review the preservation methods used for fertility treatment in Iran and other countries. Available data were reviewed from Google Scholar, PubMed, Scopus, Web of Science, IranMedex, MEDLIB, IranDoc and Scientific Information Database and searched for articles published up to 2018, using the medical subject heading (MeSH) terms for cryopreservation, sperm, testicular, spermatogonia stem cell, male infertility and/or Iranian and in the world, to provide evidence from evaluation of fertility preservation the methods. Based the search strategy, 274 manuscripts were found. After reviewing the titles, abstracts and manuscripts in their entirety, 119 articles were obtained and selected according to the eligibility criteria. The 85 studies mentioned above were divided into three categories (sperm, testis, and spermatogonia stem cells (SSCs)), and methods of fertility preservation were investigated. Ways to maintain male fertility were different depending on age, and included sperm, testicular, and SSC freezing. The number of studies on testicular tissue and SSCs was low for human samples, and more studies are still needed. Sperm freezing at infertility centres is the top for male fertility preservation.

Cancer driver gene and non-coding RNA alterations as biomarkers of brain metastasis in lung cancer: A review of the literature.

Brain metastasis (BM) is the most common event in patients with lung cancer. Despite multimodal treatments and advances in systemic therapies, development of BM remains one of the main factors associated with poor prognosis and mortality in patients with lung cancer. Therefore, better understanding of mechanisms involved in lung cancer brain metastasis (LCBM) is of great importance to suppress cancer cells and to improve the overall survival of patients. Several cancer-related genes such as EGFR and KRAS have been proposed as potential predictors of LCBM. In addition, there is ample evidence supporting crucial roles of non-coding RNAs (ncRNAs) in mediating LCBM. In this review, we provide comprehensive information on risk assessment, predictive, and prognostic panels for early detection of BM in patients with lung cancer. Moreover, we present an overview of LCBM molecular mechanisms, cancer driver genes, and ncRNAs which may predict the risk of BM in lung cancer patients. Recent clinical studies have focused on determining mechanisms involved in LCBM and their association with diagnosis, prognosis, and treatment outcomes. These studies have shown that alterations in EGFR, KRAS, BRAF, and ALK, as the most frequent coding gene alterations, and dysregulation of ncRNAs such as miR-423, miR-330-3p, miR-145, piR-651, and MALAT1 can be considered as potential biomarkers of LCBM.

A survey on infertility in men and its relation to risk factors in selected provinces of Iran.

OBJECTIVE: Infertility in men cause significant morbidity and mortality, unfortunately there is not enough information about it due to the lack of a registry in the country. The purpose of this study was to determine the frequency of infertility in men and its association with risk factors. METHODS: This cross-sectional study used data from a nation-wide project on reproductive morbidities among males in Iran in 2007. 2,293 men aged 25-60 years were selected from four provinces across the country including, Golestan Province in the North, Hormozgan Province in the South, Kermanshah Province in the West, and Isfahan Province by cluster sampling scheme. Then, we determined the frequency of infertility in married men, and related risk factors such as smoking, infection, trauma, etc. RESULTS: Of the 2,293 men interviewed, 2,076 were married, 78 were infertile; current primary and secondary infertility was estimated at 3.75%. The incidence of infertility in urban areas was significantly higher than in rural areas (p value<0.003), and finally the clinically male infertility was estimated at 2%. CONCLUSIONS: We need to explain that this project was a cross-sectional study. Therefore, it is recommended that more studies be conducted for accurate estimates of infertility in Iranian men.

Coding and Non-Coding RNAs, as Male Fertility and Infertility Biomarkers.

Semen analysis is usually the first step in the assessment of male fertility. Although analyzes provide valuable information about male fertility, success of cytoplasmic sperm injection using this method is not predictable. In the recent years, studies have shown that sperm quality assessment helps clinicians predict male fertility status based on the expression of biomarkers. To write this article, a comprehensive study was conducted on several RNA transcripts by searching related words on medical information databases by 2018. According to the literature, spermatogenesis based disorders in male infertility have a significant relationship with the expression level of some RNA molecules (like DAZ and PRM1/PRM2 ratio) in semen and testicular tissue. Thus, they might be used as predictor biomarkersto evaluate success rate of testicular sperm extraction (TESE) procedure, but confirmation of this hypothesis requires more extensive research. By comparing the number of RNAs attributed to each fertility disorder in men, it is possible to trace the causes of disease or return fertility to some infertile patients by regulating the mentioned molecules. Further researches can provide a better understanding of the use of RNA expression profiles in the diagnosis and treatment of male infertility.

GSVMA: A Genetic Support Vector Machine ANOVA Method for CAD Diagnosis.

BACKGROUND: Coronary artery disease (CAD) is one of the crucial reasons for cardiovascular mortality in middle-aged people worldwide. The most typical tool is angiography for diagnosing CAD. The challenges of CAD diagnosis using angiography are costly and have side effects. One of the alternative solutions is the use of machine learning-based patterns for CAD diagnosis. METHODS: Hence, this paper provides a new hybrid machine learning model called genetic support vector machine and analysis of variance (GSVMA). The analysis of variance (ANOVA) is known as the kernel function for the SVM algorithm. The proposed model is performed based on the Z-Alizadeh Sani dataset so that a genetic optimization algorithm is used to select crucial features. In addition, SVM with ANOVA, linear SVM (LSVM), and library for support vector machine (LIBSVM) with radial basis function (RBF) methods were applied to classify the dataset. RESULTS: As a result, the GSVMA hybrid method performs better than other methods. This proposed method has the highest accuracy of 89.45% through a 10-fold crossvalidation technique with 31 selected features on the Z-Alizadeh Sani dataset. CONCLUSION: We demonstrated that SVM combined with genetic optimization algorithm could be lead to more accuracy. Therefore, our study confirms that the GSVMA method outperforms other methods so that it can facilitate CAD diagnosis.

Association of the MTHFR 677C>T and 1298A>C polymorphisms and male infertility risk: a meta-analysis.

BACKGROUND AND OBJECTIVES: One of the possible male sterility risk factors are polymorphisms of Methylenetetrahydrofolate reductase (MTHFR). However, the epidemiologic investigations described inconsistent results regarding MTHFR polymorphism and the risk of male infertility. For that reason, we carried out a meta-analysis of published case-control studies to re-examine the controversy. METHODS: Electronic searches of Cochrane, EMBASE, Google Scholar, and PubMed were conducted to select eligible studies for this meta-analysis (updated to May 2019). According to our exclusion and inclusion criteria, only high-quality studies that remarked the association between MTHFR polymorphisms and male infertility risk were included. The Crude odds ratio (OR) with a confidence interval of 95% (CI) was used to assess the relationship between MTHFR polymorphism and male infertility risk. RESULTS: Thirty-four case-control studies with 9662 cases and 9154 controls concerning 677C/T polymorphism and 22 case-control studies with 5893 cases and 6303 controls concerning 1298A/C polymorphism were recruited. Both MTHFR polymorphisms had significant associations with male infertility risk (CT + TT vs. CC: OR = 1.37, 95% CI: 1.21-1.55, P = 0.00, I2 = 41.9%); (CC vs. CA + AA: OR = 0.82, 95% CI: 0.52-1.30, P = 0.04, I2 = 50.1%). Further, when stratified by ethnicity, the significant association results were observed in Asians and Caucasians for 677C/T and just Asians for 1298A/C. CONCLUSIONS: Some of MTHFR polymorphisms like MTHFR 677C > T are associated with an elevated male infertility risk. To confirm our conclusion and to provide more accurate and complete gene-environment communication with male infertility risk, more analytical studies are needed.

Association of Increased Levels of lncRNA H19 in PBMCs with Risk of Coronary Artery Disease.

OBJECTIVE: Considerable research shows that long non-coding RNAs, those longer than 200 nucleotides, are involved in several human diseases such as various cancers and cardiovascular diseases. Their significant role in regulating the function of endothelial cells, smooth muscle cells, macrophages, vascular inflammation, and metabolism indicates the possible effects of lncRNAs on the progression of atherosclerosis which is the most common underlying pathological process responsible for coronary artery disease (CAD). The aim of present study was to assess whether the expression of the lnc RNA H19 was associated with a susceptibility to CAD by evaluating the expression level of H19 in the peripheral blood. MATERIALS AND METHODS: A case-control study of 50 CAD patients and 50 age and sex-matched healthy controls was undertaken to investigate whether the H19 lncRNA expression level is associated with a CAD using Taqman Real-Time polymerase chain reaction (PCR). RESULTS: The subsequent result indicated that the H19 lncRNA was over-expressed in CAD patients in comparison with the controls. However, it was not statistically significant. This overexpression may be involved in coronary artery disease progression. CONCLUSION: We report here, the up-regulation of H19 lncRNA in the whole blood of CAD patients and suggest a possible role for H19 in the atherosclerosis process and its consideration as novel biomarker for CAD.

Altered methylation and expression patterns of genes regulating placental nitric oxide pathway in patients with severe preeclampsia.

Pre-eclampsia is a common pregnancy disorder syndrome whose molecular mechanism is not clear. Nitric oxide (NO) is a key regulator of placentation. Reduction of NO has previously been associated with endothelial dysfunction in pre-eclamptic women. Therefore, we measured expression and methylation of some placental genes that were involved in NO pathway like named ARG II, PRMT1 and DDAH2 in pre-eclampsia and normal pregnancies in order to determine whether impairment of expression of these genes in the pre-eclamptic placenta could contribute to development of disease. ARG II, PRMT1 expressions as well as DDAH2 expression and methylation, in placentas collected from 59 patients with preeclampsia and 40 normotensive pregnancies were measured using real-time PCR and methylation specific PCR, respectively. The relationship among ARG II, PRMT1 and DDAH2 expressions was analyzed statistically. ARG II expression was increased, PRMT1 expression was not significantly changed. DDAH2 expression was decreased and qualitative methylation patterns were 32/59 and 21/40 in placentas from patients with pre-eclampsia compared with control group, respectively. The alterations in ARG II and DDAH2 expressions in pre-eclampsia patients maybe correlated with decreased eNOS expression. These findings indicate that ARG II and DDAH2 may be involved in pre-eclampsia pathogenesis and could be potential therapeutic targets for this disease.

The combined effects of three-dimensional cell culture and natural tissue extract on neural differentiation of P19 embryonal carcinoma stem cells.

Tissue engineering, as a novel transplantation therapy, aims to create biomaterial scaffolds resembling the extracellular matrix in order to regenerate the damaged tissues. Adding bioactive factors to the scaffold would improve cell-tissue interactions. In this study, the effect of chitosan polyvinyl alcohol nanofibres containing carbon nanotube scaffold with or without active bioglass (BG+ /BG- ), in combination with neonatal rat brain extract on cell viability, proliferation, and neural differentiation of P19 embryonic carcinoma stem cells was investigated. To induce differentiation, the cells were cultured in α-MEM supplemented with neonatal rat brain extract on the scaffolds. The expression of undifferentiated stem cell markers as well as neuroepithelial and neural-specific markers was evaluated and confirmed by real-time Reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence procedures. Finally, the three-dimensional (3D) cultured cells were implanted into the damaged neural tubes of chick embryos, and their fates were followed in ovo. Based on the histological and immunofluorescence observations, the transplanted cells were able to survive, migrate, and penetrate into the host embryonic tissues. Gene network analysis suggested the possible involvement of neurotransmitters as a downstream target of synaptophysin and tyrosine hydroxylase. Overall, the results of this study indicated that combining the effects of 3D cell culture and natural brain tissue extract can accelerate the differentiation of P19 embryonic carcinoma cells into neuronal phenotype cells.

Evaluation of Placental mir-155-5p and Long Non-coding RNA sONE Expression in Patients with Severe Pre-eclampsia.

It has been well documented that preeclampsia (PE) has a common etiological background, but little is known about its linkage at the molecular level.Non- coding RNAs are critical posttranscriptional regulators ofgene expression. This study was performed to determine whether PE is associated with alterations in placental non-coding RNAs expression. MicroRNA (miR)-155-5p and long non-coding RNA (lnc)sONE expression, in placentas collected sequentially from 59 patients with PE and 40 normotensive pregnancies were measured using real-time PCR.The relationship between miR-155-5p and lncsONE expressions was analyzed statistically. miR-155-5p expression was increased (fold change =1.6, P=0.04), while lncsONE expression was not significantly changed (fold change =1.1, P=0.68), in placentas from patients compared with control group.miR-155-5p was upregulated in placentas from patients with PE and may have influenced eNOS expression. These findings indicate that miRNA-155-5p may be involved in PE pathogenesis and could be a potential biomarker for this disease.

A Case with late onset of ambiguous genitalia.

BACKGROUND: Ambiguous genitalia is an uncommon situation that happens between 1 and 2 per every 1000 live births and falls under the umbrella diagnosis of disorders of sexual development. CASE: In this article, we report a case of male pseudohermaphroditism with ambiguous genitalia. The proband was a 12 yr old girl without any uterus or ovarian tissues. Karyotype of the case is 46, XY. Genes involved in sexual differentiation such as AR, SRD5A2, LH, LHR, FSH, 17 B HSD and SRY genes were sequenced in both directions. No mutations were found in these genes either. CONCLUSION: It seems advisable to be cautious in similar cases, and revise protocol for tracing the genes involved in the patients.

Outer Dense Fiber Proteins: Bridging between Male Infertility and Cancer.

BACKGROUND: The similarities between gametogenic and carcinogenesis processes have been noted for more than decades. Among prominent similarities between these two processes is expression of a group of antigens, namely cancer-testis antigens in both the testes and various cancer tissues. Outer dense fiber (ODF) proteins are testis-specific proteins localized to sperm tails and involved in sperm motility. METHODS: We performed a computerized search of the MEDLINE/PUBMED databases with keywords "outer dense fiber, ODF, cancer, testis, gametogenesis and infertility". RESULTS: The results of animal and human studies show ODF contribution to male fertility. In addition, ODFs are expressed in some cancers, including prostate adenocarcinoma, breast cancer, chronic myeloid leukemia and basal cell carcinoma. CONCLUSION: ODF expression analysis in cancer may pave the way for identification of cancer biomarkers or therapeutic targets.

Hyperostosis-hyperphosphatemia syndrome (HHS): report of two cases with a recurrent mutation and review of the literature.

Hyperostosis-hyperphosphatemia syndrome (HHS) is a rare autosomal recessive metabolic disorder caused by mutations in the GALNT3 and FGF23 genes. The main features of this disorder include painful swelling of long bones, increased renal reabsorption of phosphate but normal renal function and vitamin D and parathormone levels. Previously, we reported a novel missense mutation in the FGF23 gene in a patient suffering from HHS. In the present report, we demonstrated the same mutation (c.471C>A) in two other cases of HHS with similar clinical manifestations. As this nucleotide change has not been reported previously, it can be a population specific mutation in Iran that can facilitate carrier testing and prenatal diagnosis of HHS.

Segregation of a novel homozygous 6 nucleotide deletion in GLUT2 gene in a Fanconi-Bickel syndrome family.

Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, impaired utilization of glucose and galactose, rickets, and severe short stature. It has been shown to be caused by mutations in GLUT2 gene, a member of the facilitative glucose transporter family. Here, we report an Iranian family with 2 affected siblings. The clinical findings in the patients include developmental delay, failure to thrive, hepatomegaly, enlarged kidneys and rickets. A novel 6 nucleotide deletion (c.1061_1066del6, p.V355_S356del2) is shown to be segregated with the disease in this family.

Can we rely on the multiplex ligation-dependent probe amplification method (MLPA) for prenatal diagnosis?

BACKGROUND: The major aneuploidies that are diagnosed prenatally involve the autosomal chromosomes 13, 18, and 21, as well as sex chromosomes, X and Y. Because multiplex ligation-dependent probe amplification (MLPA) is rapid and non-invasive, it has replaced traditional culture methods for the screening and diagnosis of common aneuploidies in some countries. OBJECTIVE: To evaluate the sensitivity and specificity of MLPA in a cross-sectional descriptive study for the detection of chromosomal aneuploidies in comparison to other methods. MATERIALS AND METHODS: Genomic DNA was extracted from the peripheral blood samples of 10 normal controls and the amniotic fluid of 55 patients. Aneuploidies screening of chromosomes 13, 18, 21, X and Y were carried out using specific MLPA probe mixes (P095-A2). For comparison purposes, samples were also tested by Quantitative Fluorescent-PCR (QF-PCR) and routine chromosomal culture method. RESULTS: Using this specific MLPA technique and data-analyzing software (Genemarker v1.85), one case was diagnosed with 45, X (e.g. Monosomy X or Turner's Syndrome), and the remaining 54 cases revealed normal karyotypes. These results were concordant with routine chromosomal culture and QF-PCR findings. CONCLUSION: The experiment demonstrates that MLPA can provide a rapid and accurate clinical method for prenatal identification of common chromosomal aneuploidies with 100% sensitivity and 100% specificity.

Complex translocation among chromosomes 2, 3, 9, 15, 18, 20 in a patient with 3p-syndrome.

A 3-month old girl with monosomy for distal part of the short arm of chromosome 3 is described. Physical examination showed growth retardation, microcephaly, ptosis, micrognathia, low set ears, broad nasal bridge, Simian crease, long philtrum, thin lips and hypertelorism. The patient's clinical phenotype largely resembled that of 3p- syndrome but her karyotype was more complicated than just losing the telomeric portion (3p-25.3) of the short arm of one of her chromosomes 3. Her karyotype was 46, XX, t(2;18) (p12;q12.1), del(3) (p23p26), t(3;9;15; 20) (q13;p23;q12; p12). Her parents showed a normal karyotype pattern.

A de novo Reciprocal X; 9 Translocation in A Patient with Premature Ovarian Failure.

Premature ovarian failure (POF) causes hypergonadotrophic amenorrhea in 1-3% of females, occurring before the age of 40 among women with chromosomal rearrangements in the long arm of the X chromosome 'critical region'. In this article, we report a case of POF and primary amenorrheain a girl with a de novo reciprocal translocation between chromosomes X and 9. The proband was a 17 years old girl with a history of irregular menstruation and high level of follicle-stimulating hormone (FSH) (151 mlU/mL) and luteinizing hormone (LH) (56 mlU/mL). In ultrasound examination, left ovarian gonad was atrophic without any follicles. Right ovarian gonad was not seen. Cytogenetical analysis was performed on the patient and her parents. Her karyotype results was 46, X, rcp (X; 9) (q24; q13) dn. Her parents had normal karyotype. This reciprocal translocation between chromosome X and 9 and observed POF in the patient suggest either the disruption of a critical gene expression due to 'position effect' or deletion of one or more POF-related genes in the disrupted long arm of the affected X chromosome.

The association of TGF-ß1 codon 10 polymorphism with suicide behavior.

Many risk factors have been identified for suicide behavior and although a role for cytokines has been suggested in specific psychiatric conditions and suicide behavior, this role is not well-defined. Since some polymorphisms can alter the expression of cytokines, in this study we attempted to assess the role of TGF-ß1 codon 10 (T/C) polymorphisms (rs1982073) in suicide behavior. A total of 145 individuals with suicide behavior as well as 200 control participants (without any history of suicide behavior) were included in the study. TGF-ß1 codon 10 polymorphism was determined using allele-specific oligonucleotide polymerase chain reaction. Our results demonstrated that the TGF-ß1 codon 10 T/T genotype was significantly more prevalent in individuals with suicide behavior (41.7%), in comparison with the controls (27%). The findings of this study demonstrated an association between TGF-ß1 (codon 10) T/C polymorphisms and suicide behavior.