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The feature selection (FS) is an important step for data analysis. FS is used to reduce the dimension of data by selecting the relevant features; while removing the redundant, noisy and irrelevant features that lead to degradation of the performance. Several swarm techniques are used to solve the FS problem and these methods provide results better than classical approaches. However, most of these techniques have limitations such as slow convergence and time complexity. These limitations occur due that all the agents update their position according to the best one. However, this best agent may be not the optimal global solution for FS, therefore, the swarm getting stuck in a local solution. This paper proposes an improved Runner-Root Algorithm (RRA). The RRA is combined with chaotic Singer map and opposition-based learning to increase its accuracy. The experiments are performed in eight datasets and the performance of the proposed method is compared against swarm algorithms.

Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.

Background WW domain containing oxidoreductase (WWOX) gene was cloned in 2000; alteration has been seen in many cancer cells. It acts as a tumor suppresser by blocking cell growth and causing apoptosis. WWOX protein showed different expression of mice brain and spinal cord, for which deletion causes seizure and early death. Case presentation Clinical and molecular characteristics of a consanguineous family show a homozygous mutation of WWOX gene at specific bases, causing a debilitating syndrome characterized by growth retardation, intractable epilepsy, intellectual disability, and early death. Using Whole Exome Sequencing (WES), a novel homozygous mutation in the WWOX gene is identified in a consanguineous Arab family from Qatar with two daughters who presented with intractable seizure and developmental delay. Conclusion The study presents the importance of human WWOX gene for brain development and the association between gene mutation and epileptic encephalopathy. It also highlights the power of WES particularly in clinically challenging cases.

Newborn screening is a precondition for early diagnosis and successful treatment of remethylation disorders and classical homocystinuria (cystathionine-ß-synthase deficiency). Newborn screening for classical homocystinuria using total homocysteine measurement in dried blood spots has been very successfully performed for many years for newborns from Qatar.A new optimized newborn screening strategy for remethylation disorders and homocystinuria was developed and evaluated for newborns from Qatar using total homocysteine measurement as first-tier and methionine, methionine-phenylalanine-ratio and propionylcarnitine as second-tiers. Proposed cut-offs were also retrospectively evaluated in newborn screening samples of 12 patients with remethylation disorders and vitamin BOver a 12 months period, the proposed strategy led to a decrease in the recall rate in homocysteine screening for Qatar from 1.09% to 0.68%, while allowing for additional systematic inclusion of remethylation disorders and vitamin BThe proposed strategy for samples from Qatar allows inclusion of remethylation disorders and vitamin B

Intellectual disability (ID) is a measurable phenotypic consequence of genetic and environmental factors. In this study, we prospectively assessed the diagnostic yield of genomic tools (molecular karyotyping, multi-gene panel and exome sequencing) in a cohort of 337 ID subjects as a first-tier test and compared it with a standard clinical evaluation performed in parallel. Standard clinical evaluation suggested a diagnosis in 16% of cases (54/337) but only 70% of these (38/54) were subsequently confirmed. On the other hand, the genomic approach revealed a likely diagnosis in 58% (n=196). These included copy number variants in 14% (n=54, 15% are novel), and point mutations revealed by multi-gene panel and exome sequencing in the remaining 43% (1% were found to have Fragile-X). The identified point mutations were mostly recessive (n=117, 81%), consistent with the high consanguinity of the study cohort, but also X-linked (n=8, 6%) and de novo dominant (n=19, 13%). When applied directly on all cases with negative molecular karyotyping, the diagnostic yield of exome sequencing was 60% (77/129). Exome sequencing also identified likely pathogenic variants in three novel candidate genes (DENND5A, NEMF and DNHD1) each of which harbored independent homozygous mutations in patients with overlapping phenotypes. In addition, exome sequencing revealed de novo and recessive variants in 32 genes (MAMDC2, TUBAL3, CPNE6, KLHL24, USP2, PIP5K1A, UBE4A, TP53TG5, ATOH1, C16ORF90, SLC39A14, TRERF1, RGL1, CDH11, SYDE2, HIRA, FEZF2, PROCA1, PIANP, PLK2, QRFPR, AP3B2, NUDT2, UFC1, BTN3A2, TADA1, ARFGEF3, FAM160B1, ZMYM5, SLC45A1, ARHGAP33 and CAPS2), which we highlight as potential candidates on the basis of several lines of evidence, and one of these genes (SLC39A14) was biallelically inactivated in a potentially treatable form of hypermanganesemia and neurodegeneration. Finally, likely causal variants in previously published candidate genes were identified (ASTN1, HELZ, THOC6, WDR45B, ADRA2B and CLIP1), thus supporting their involvement in ID pathogenesis. Our results expand the morbid genome of ID and support the adoption of genomics as a first-tier test for individuals with ID.

denoising problem can be addressed as an inverse problem. One of the most recent approaches to solve an inverse problem is a sparse decomposition over overcomplete dictionaries. In sparse representation, images are represented as a linear combination of dictionary atoms. In this paper, we propose an algorithm for image denoising based on Orthogonal Matching Pursuit (OMP) for determining sparse representation over Gabor Wavelet adaptive dictionary by K- SVD algorithm. The results of this algorithm have more efficiency of image recovery than using DCT dictionary.

The reaction of the tetrahydrobenzo[b]thiophene derivatives 1a,b with benzoylisothiocyanate (2) afforded the thiourea derivatives 3a,b. Cyclization of the latter products gave the annulated products 4a,b. Compounds 3a,b reacted with either hydrazine hydrate (5a) or phenyl hydrazine (5b) afforded compounds 7a-d which underwent cyclization for compounds 7a,c afforded compound 9. On the other hand compounds 4a,b reacted with either hydrazine hydrate (5a) or phenyl hydrazine (5b) afforded compounds 6a-d a second pathway was applied to synthesize compound 6c which underwent cyclization afforded compound 9. Also compounds 4a,b reacted with either phenacyl bromide (10) afforded compounds 11a,b or ethylchloroacetae (12) compounds 13a,b were produced. The latter products reacted with each hydrazine hydrate (5a) and phenyl hydrazine (5b) afforded compounds 14a-d. Their antitumor activities were tested using three different cell lines.

Galaxy classification has an important role in understanding the formation of galaxies and the evaluation of our universe. Most of the machine learning methods were used to improve galaxy image classification. However, these methods suffer from some limitations, such as getting stuck in local point and slow convergence. Therefore, an alternative method to enhance the performance of galaxy images classification and avoid the limitations of other methods is proposed. The proposed method for galaxy classification (called BSOMFOG) is based on an improvement in the brain storm optimization (BSO) through combining it with the moth flame optimization (MFO). In this modified version of BSO (called BSOMFO), the MFO algorithm works as a local search operator to enhance the exploitation ability of BSO. The performance of the BSOMFO algorithm is compared against other algorithms through two experiments. In the first one, a set of 15 global optimization problems is used to evaluate the ability of the BSOMFO algorithm to find the solution for these problems. Meanwhile, in the second experiment, the BSOMFO is included in the BSOMFOG framework to improve the classification of the galaxy images into three classes, namely, spiral, lenticular, and elliptical. BSOMFOG consists of three phases: the first phase is to extract the shape, color, and texture features from the galaxy images, while the second phase used the BSOMFO algorithm to select the relevant features from the extracted features. The last phase is to evaluate the selected features through classification using the k -nearest neighbor classifier. The experimental results show that the BSOMFO algorithm provides better results than the traditional BSO algorithm and other metaheuristic algorithms to solve the optimization problem. Moreover, it makes the proposed BSOMFOG framework improves the classification accuracy (∼97 % ) for galaxy images, and its general purpose makes it suitable for automatic classification of galaxies.

Nonsense-mediated decay (NMD) is an important process that is best known for degrading transcripts that contain premature stop codons (PTCs) to mitigate their potentially harmful consequences, although its regulatory role encompasses other classes of transcripts as well. Despite the critical role of NMD at the cellular level, our knowledge about the consequences of deficiency of its components at the organismal level is largely limited to model organisms. In this study, we report two consanguineous families in which a similar pattern of congenital anomalies was found to be most likely caused by homozygous loss-of-function mutations in SMG9, encoding an essential component of the SURF complex that generates phospho-UPF1, the single most important step in NMD. By knocking out Smg9 in mice via CRISPR/Cas9, we were able to recapitulate the major features of the SMG9-related multiple congenital anomaly syndrome we observed in humans. Surprisingly, human cells devoid of SMG9 do not appear to have reduction of PTC-containing transcripts but do display global transcriptional dysregulation. We conclude that SMG9 is required for normal human and murine development, most likely through a transcriptional regulatory role, the precise nature of which remains to be determined.

Clinical exome sequencing (CES) has become an increasingly popular diagnostic tool in patients with heterogeneous genetic disorders, especially in those with neurocognitive phenotypes. Utility of CES in consanguineous populations has not yet been determined on a large scale. A clinical cohort of 149 probands from Qatar with suspected Mendelian, mainly neurocognitive phenotypes, underwent CES from July 2012 to June 2014. Intellectual disability and global developmental delay were the most common clinical presentations but our cohort displayed other phenotypes, such as epilepsy, dysmorphism, microcephaly and other structural brain anomalies and autism. A pathogenic or likely pathogenic mutation, including pathogenic CNVs, was identified in 89 probands for a diagnostic yield of 60%. Consanguinity and positive family history predicted a higher diagnostic yield. In 5% (7/149) of cases, CES implicated novel candidate disease genes (MANF, GJA9, GLG1, COL15A1, SLC35F5, MAGE4, NEUROG1). CES uncovered two coexisting genetic disorders in 4% (6/149) and actionable incidental findings in 2% (3/149) of cases. Average time to diagnosis was reduced from 27 to 5 months. CES, which already has the highest diagnostic yield among all available diagnostic tools in the setting of Mendelian disorders, appears to be particularly helpful diagnostically in the highly consanguineous Middle Eastern population.

iBoswellia carterii/i(BC) Birdwood oleogum resin is an ancient remedy of inflammation processes known since Ancient Egyptian time. Of boswellic acids, 3-acetyl-11-keto-β-boswellic acid (AKBA) is the most potent anti-inflammatory active principle. Liquisolid systems of the biologically active fraction of BC oleogum resin were prepared for improving dissolution properties using low dose oral delivery to achieve enhanced anti-inflammatory activity, in comparison with the standard oral anti-inflammatory; Indomethacin. AKBA was assayed, employing an accurate and sensitive HPLC method. Detection was carried out at 210 nm using UV/Vis detector. A solubility study for the bioactive fraction was conducted. Microcrystalline cellulose and Aeroperl®300 Pharma were used as carrier and coating materials. Angle of slide, liquid load factor and Carr's flow index were estimated. Six systems were prepared using polyethylene glycol 400, solvent and two drug loading concentrations; 20 and 40 %. For each concentration, three carrier: coat ratios were dispensed; 20:1, 10:1, and 5:1. Dissolution study was performed and two systems were selected for characterization and in vivo evaluation by investigating upper GIT ulcerogenic effect and anti-inflammatory efficacy in rats. Results indicate absence of ulcers and significantly higher and prolonged anti-inflammatory efficacy for formulations F1 and F2, with carrier: coat ratio, 5:1 and drug loads of 20 and 40 %, respectively, compared with standard oral indomethacin. We conclude higher efficacy of BC bioactive fraction liquisolids compared with Indomethacin with greater safety on GIT, longer duration of action and hence better patient compliance.

Background A consanguineous Arab family is affected by an apparently novel autosomal recessive disorder characterized by cognitive impairment, failure-to-thrive, hypotonia and dysmorphic features including bilateral ptosis and epicanthic folds, synophrys, midface hypoplasia, downturned mouth corners, thin upper vermillion border and prominent ears, bilateral 5th finger camptodactyly, bilateral short 4th metatarsal bones, and limited knee mobility bilaterally. Methods The family was studied by homozygosity mapping, candidate gene mutation screening and whole Exome Next Generation Sequencing of a single affected member to identify the offending gene and mutation. The mutated gene product was studied by structural bioinformatics methods. Results A damaging c.C5054G mutation affecting an evolutionary highly conserved amino acid p.S1685W was identified in the ZNF407 gene at 18q23. The Serine to Tryptophane mutation affects two of the three ZNF407 isoforms and is located in the last third of the protein, in a linker peptide adjoining two zinc-finger domains. Structural analyses of this mutation shows disruption of an H-bond that locks the relative spatial position of the two fingers, leading to a higher flexibility of the linker and thus to a decreased probability of binding to the target DNA sequence essentially eliminating the functionality of downstream domains and interfering with the expression of various genes under ZNF407 control during fetal brain development. Conclusions ZNF407 is a transcription factor with an essential role in brain development. When specific and limited in number homozygosity intervals exist that harbor the offending gene in consanguineous families, Whole Exome Sequencing of a single affected individual is an efficient approach to gene mapping and mutation identification.

We report on a consanguineous Arab family in which three sibs had an unusual skeletal dysplasia characterized by anterior defects of the spine leading to severe lumbar kyphosis and marked brachydactyly with cone epiphyses. The clinical phenotype also included dysmorphic facial features, epilepsy, and developmental delay. This constellation likely represents a previously undescribed skeletal dysplasia, most probably inherited in an autosomal recessive pattern. A homozygosity mapping approach has thus far failed to unearth the responsible gene as the region shared by these three sibs is 27.7 Mb in size and contains over 200 genes with no obvious candidate. © 2014 Wiley Periodicals, Inc.

This work has been carried out to investigate the utility of arylidene acetoacetanilides 3a, b in heterocyclic synthesis. Thus the synthesis of pyridine derivatives 6a, b, 8a-d, 12a, b were done by the reaction of arylidine derivatives 3a,b with activated methylene groups 4a, b , also synthesis of compounds 15, 21a, b, 22a, b were carried out via the reaction of compound 12a with benzaldehyde (2a) and reaction of arylidine derivatives 3a,b with ethylcyanoacetate (4b) in addition to reaction of compound 21a with either benzaldehyde (2a) or salicylaldehyde (2c) respectively. Isoquinoline derivative 14 was afforded via the reaction of compound 12a with malononitrile (4a). Thieno[3,4-c]pyridine derivatives 10, 19 were afforded via the reaction of 2-pyridone derivatives either 8a or 12a with elemental sulphur respectively, pyrazolo[3,4-b]pyridine drivatives 18a, b were synthesized through the reaction of compound 12a with either hydrazine hydrate or phenylhydrazine 16a, b. Finally pyrido[3,4-d]pyridazine derivatives 25a, b. were produced via the reaction between compound 21a and aryldiazonium chlorides 23a, b. The biological potentialities of the prepared compounds has been examined and evaluated as antitumor agents. All compounds showed significant growth inhibitory effect., European Chemical Bulletin, Vol 2, No 8 (2013): European Chemical Bulletin

A non-consanguineous Arabic family affected by a putative novel seemingly X-linked disease characterized by mental retardation and abnormal head shape was studied by gene mapping, candidate gene mutation screening and whole X chromosome Exome sequencing of a single affected member to identify the responsible gene defect. Clinical presentation includes mental retardation, hyperactivity, hypotonia, turricephaly (in one affected), dolichocephaly (in the other affected), narrow face, downward slanted palberal fissures, large ears, open mouth appearance, long and slender fingers. Neurologic and metabolic evaluations including urine organic acid, lysosomal enzyme analysis, gaunidinocompound, CDG and Fragile-X syndrome were negative. SNP genotyping with the HumanOmniExpress bead chip [Illumina, USA], analyzed with the GeneMapper software mapped the responsible gene to four possible X-chromosome intervals [p22.33-22.2, p22.2-21.1, p31.1-q22.3, q26.3-28] as the family structure did not allow identification of a single interval with a significant LOD score. Based on the clinical presentation one candidate gene (FGF16) was screened but no pathogenic mutations were identified. Whole Exome target enrichment Next Generation Sequencing for the X chromosome was performed on the ABI SOLiD4 platform for a single affected individual. Three variants were identified within the linkage intervals: AMMECR1 [c.C208T/p.L70F] was excluded as it did not co-segregate with the disease phenotype. A second variant (c.C11T/p.P4L) in the Rab40 GTP-binding protein gene (RAB40AL). Pathogenic mutations within this gene have been associated with Martin-Probst X-linked mental retardation syndrome (MRXSMP) which presents with a different phenotype characterized by hearing loss. The last variant (c.G227A/p.C76Y) at the H2BFWT histone family gene has damaging effects according to PolyPhen and SIFT protein-modeling software, co-segregates to the disease phenotype and is absent in 752 ethnically matched control chromosomes. No known diseases have been associated with mutations in H2BFWT apart from male infertility. Tissue specific H2BFWT expression studies show expression in human fetal brain, making this mutation the likely developmental defect. At present, mutation analyses in additional healthy normal maternal male relatives are underway for the possible exclusion of H2BFWT as the offending gene.

Consanguinity and endogamy is common in the Middle East resulting in higher frequency of autosomal recessive genetic disorders, in particular private or rare genetic conditions. Most of these diseases are due to homoallelic state of pathogenic variants, a direct consequence of founder effect and increased co-efficient of inbreeding. Advanced molecular genetic technologies such as next-generation sequencing (NGS) are playing an important role in identifying the genetic basis of rare genetic conditions, specifically when a consanguineous couple has more than one affected child with a rare genetic condition suggestive of autosomal recessive inheritance. The NGS technology is used to sequence the whole genome or whole exome with high accuracy in limited time at a very low cost. There are many platforms available for this technology with slightly different chemistry and variable calling rates. In general, the Qatari population is a highly endogamous population and largely made up of tribal communities with high prevalence of autosomal recessive disorders. The NGS technology will facilitate a promising outcome for unraveling the genetic aetiology of such inherited conditions. However, this technology requires highly trained laboratory geneticists along with bioinformatics support to develop pipelines for data analysis and interpretation, requiring considerable local and international collaborative interactions. In this paper, we will share our experience with collaborative research projects funded by Qatar National Research Fund (QNRF) to transfer and develop these genetic technologies in the State of Qatar, for the investigation of inherited monogenic disorders.

Van Den Ende-Gupta syndrome (VDEGS) is an infrequently described disorder characterized by arachnodactyly, camptodactyly, blepharophimosis, malar hypoplasia, narrow nasal bridge, convex nasal ridge, and everted lower lip. Patients show normal growth and cognition. We report on three male and three female cases from four consanguineous families, of which three belong to the same highly inbred tribe from Qatar. The phenotype in the patients is remarkably homogeneous. VDEGS has been suggested both to follow an autosomal recessive and autosomal dominant pattern of inheritance, but our observations suggest an autosomal recessive pattern of inheritance, although genetic heterogeneity cannot be excluded.

Hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome (also known as Woodhouse-Sakati syndrome) is a rare autosomal recessive neuroendocrine and ectodermal disorder. The syndrome was first described by Woodhouse and Sakati in 1983, and 47 patients from 23 families have been reported so far. We report on an additional seven patients (four males and three females) from two highly consanguineous Arab families from Qatar, presenting with a milder phenotype of Woodhouse-Sakati syndrome. These patients show the spectrum of clinical features previously found in Woodhouse-Sakati syndrome, but lack evidence of diabetes mellitus and extrapyramidal symptoms. These two new families further illustrate the natural course and the interfamilial phenotypic variability of Woodhouse-Sakati syndrome that may lead to challenges in making the diagnosis. In addition, our study suggests that Woodhouse-Sakati syndrome may not be as infrequent in the Arab world as previously thought.

Background: Vitamin B12 (vit B12) deficiency is one of the major causes of megaloblastic anaemia and should be avoided as early as possible since a supplementation of mother and child can prevent neurological symptoms of the baby. Furthermore, the neurological symptoms of affected children are (partially) reversible. Elevated methylmalonic acid in urine and homocysteine (Hcy) in plasma are sensitive indicators. In the State of Qatar, extended newborn screening of classical homocystinuria was realized for all 73,994 neonates in last 4.5 years. Newborns with slightly elevated Hcy levels in dried blood spots (DBS) were followed up with regard to possible vit B12 deficiency. In addition, the propionylcarnitine (C3) levels were analysed. Methods: Determination of Hcy in DBS was performed using liquid chromatography electrospray tandem mass spectrometry. C3 levels were obtained from general newborn screening. The vit B12 levels in plasma were analysed spectrophotometrically. Results: In all, 117 cases with mildly elevated Hcy levels were found. 65 were diagnosed with vit B12 deficiency. Only 9 of these 65 newborns had abnormal C3 levels. No correlation was found in this group between Hcy and C3 levels. Conclusion: Extended neonatal screening of Hcy is a useful tool for early diagnosis and treatment of vit B12 deficiency.