Araştırma Çıktıları

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Author: search.filters.author.Dincer, AlpHas files: Yes

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    The Essential Role of Centrosomal NDE1 in Human Cerebral Cortex Neurogenesis
    (CELL PRESS, 2011-01-01) Bakircioglu, Mehmet; Carvalho, Ofelia P.; Khurshid, Maryam; Cox, James J.; Tuysuz, Beyhan; Barak, Tanyeri; Yilmaz, Saliha; Caglayan, Okay; Dincer, Alp; Nicholas, Adeline K.; Quarrell, Oliver; Springell, Kelly; Karbani, Gulshan; Malik, Saghira; Gannon, Caroline; Sheridan, Eamonn; Crosier, Moira; Lisgo, Steve N.; Lindsay, Susan; Bilguvar, Kaya; Gergely, Fanni; Gunel, Murat; Woods, C. Geoffrey
    We investigated three families whose offspring had extreme microcephaly at birth and profound mental retardation. Brain scans and postmortem data showed that affected individuals had brains less than 10\% of expected size (<= 10 standard deviation) and that in addition to a massive reduction in neuron production they displayed partially deficient cortical lamination tinicrolissencephaly). Other body systems were apparently unaffected and overall growth was normal. We found two distinct homozygous mutations of NDE1, c.83+1G>T (p.Ala29GlnfsX114) in a Turkish family and c.684\_685del (p.Pro229TrpfsX85) in two families of Pakistani origin. Using patient cells, we found that c.83+1G>T led to the use of a novel splice site and to a frameshift after NDE1 exon 2. Transfection of tagged NDE1 constructs showed that the c.684\_685del mutation resulted in a NDE1 that was unable to localize to the centrosome. By staining a patient-derived cell line that carried the c.83+1G>T mutation, we found that this endogeneously expressed mutated protein equally failed to localize to the centrosome. By examining human and mouse embryonic brains, we determined that NDE1 is highly expressed in neuroepithelial cells of the developing cerebral cortex, particularly at the centrosome. We show that NDE1 accumulates on the mitotic spindle of apical neural precursors in early neurogenesis. Thus, NDE1 deficiency causes both a severe failure of neurogenesis and a deficiency in cortical lamination. Our data further highlight the importance of the centrosome in multiple aspects of neurodevelopment.
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    Recessive LAMC3 mutations cause malformations of occipital cortical development
    (NATURE PUBLISHING GROUP, 2011-01-01) Barak, Tanyeri; Kwan, Kenneth Y.; Louvi, Angeliki; Demirbilek, Veysi; Saygi, Serap; Tuysuz, Beyhan; Choi, Murim; Boyaci, Huseyin; Doerschner, Katja; Zhu, Ying; Kaymakcalan, Hande; Yilmaz, Saliha; Bakircioglu, Mehmet; Caglayan, Ahmet Okay; Oeztuerk, Ali Kemal; Yasuno, Katsuhito; Brunken, William J.; Atalar, Ergin; Yalcinkaya, Cengiz; Dincer, Alp; Bronen, Richard A.; Mane, Shrikant; Ozcelik, Tayfun; Lifton, Richard P.; Sestan, Nenad; Bilguevar, Kaya; Guenel, Murat
    The biological basis for regional and inter-species differences in cerebral cortical morphology is poorly understood. We focused on consanguineous Turkish families with a single affected member with complex bilateral occipital cortical gyration abnormalities. By using whole-exome sequencing, we initially identified a homozygous 2-bp deletion in LAMC3, the laminin. 3 gene, leading to an immediate premature termination codon. In two other affected individuals with nearly identical phenotypes, we identified a homozygous nonsense mutation and a compound heterozygous mutation. In human but not mouse fetal brain, LAMC3 is enriched in postmitotic cortical plate neurons, localizing primarily to the somatodendritic compartment. LAMC3 expression peaks between late gestation and late infancy, paralleling the expression of molecules that are important in dendritogenesis and synapse formation. The discovery of the molecular basis of this unusual occipital malformation furthers our understanding of the complex biology underlying the formation of cortical gyrations.
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    In Vivo Renal Lipid Quantification by Accelerated Magnetic Resonance Spectroscopic Imaging at 3T: Feasibility and Reliability Study
    (MDPI, 2022-01-01) Alhulail, Ahmad A.; Servati, Mahsa; Ooms, Nathan; Akin, Oguz; Dincer, Alp; Thomas, M. Albert; Dydak, Ulrike; Emir, Uzay E.
    A reliable and practical renal-lipid quantification and imaging method is needed. Here, the feasibility of an accelerated MRSI method to map renal fat fractions (FF) at 3T and its repeatability were investigated. A 2D density-weighted concentric-ring-trajectory MRSI was used for accelerating the acquisition of 48 x 48 voxels (each of 0.25 mL spatial resolution) without respiratory navigation implementations. The data were collected over 512 complex-FID timepoints with a 1250 Hz spectral bandwidth. The MRSI sequence was designed with a metabolite-cycling technique for lipid-water separation. The in vivo repeatability performance of the sequence was assessed by conducting a test-reposition-retest study within healthy subjects. The coefficient of variation (CV) in the estimated FF from the test-retest measurements showed a high degree of repeatability of MRSI-FF (CV = 4.3 +/- 2.5\%). Additionally, the matching level of the spectral signature within the same anatomical region was also investigated, and their intrasubject repeatability was also high, with a small standard deviation (8.1 +/- 6.4\%). The MRSI acquisition duration was similar to 3 min only. The proposed MRSI technique can be a reliable technique to quantify and map renal metabolites within a clinically acceptable scan time at 3T that supports the future application of this technique for the non-invasive characterization of heterogeneous renal diseases and tumors.
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    Brain MRI Findings in Patients in the Intensive Care Unit with COVID-19 Infection
    (RADIOLOGICAL SOC NORTH AMERICA, 2020-01-01) Kandemirli, Sedat G.; Dogan, Lerzan; Sarikaya, Zeynep T.; Kara, Simay; Akinci, Canan; Kaya, Dilaver; Kaya, Yildiz; Yildirim, Duzgun; Tuzuner, Filiz; Yildirim, Mustafa S.; Ozluk, Enes; Gucyetmez, Bulent; Karaarslan, Ercan; Koyluoglu, Isil; Kaya, Hande S. Demirel; Mammadov, Orkhan; Ozdemir, Ilkay Kisa; Afsar, Nazire; Yalcinkaya, Beyza Citci; Rasimoglu, Sevdinaz; Guduk, Duygu E.; Jima, Ararso Kedir; Ilksoz, Aylin; Ersoz, Vildan; Eren, Meltem Yonca; Celtik, Nilufer; Arslan, Serdar; Korkmazer, Bora; Dincer, Saban S.; Gulek, Elif; Dikmen, Ibrahim; Yazici, Murathan; Unsal, Serkan; Ljama, Taner; Demirel, Ismail; Ayyildiz, Aykut; Kesimci, Isil; Deveci, Sahika Bolsoy; Tutuncu, Melih; Kizilkilic, Osman; Telci, Lutfi; Zengin, Rehile; Dincer, Alp; Akinci, Ibrahim O.; Kocer, Naci
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    The effect of tumor shape irregularity on Gamma Knife treatment plan quality and treatment outcome: an analysis of 234 vestibular schwannomas
    (NATURE PORTFOLIO, 2022-01-01) Sumer, Esra; Tek, Ece; Ture, O. Artunc; Sengoz, Meric; Dincer, Alp; Ozcan, Alpay; Pamir, M. Necmettin; Ozduman, Koray; Ozturk-Isik, Esin
    The primary aim of Gamma Knife (GK) radiosurgery is to deliver high-dose radiation precisely to a target while conforming to the target shape. In this study, the effects of tumor shape irregularity (TSI) on GK dose-plan quality and treatment outcomes were analyzed in 234 vestibular schwannomas. TSI was quantified using seven different metrics including volumetric index of sphericity (VioS). GK treatment plans were created on a single GK-Perfexion/ICON platform. The plan quality was measured using selectivity index (SI), gradient index (GI), Paddick's conformity index (PCI), and efficiency index (EI). Correlation and linear regression analyses were conducted between shape irregularity features and dose plan indices. Machine learning was employed to identify the shape feature that predicted dose plan quality most effectively. The treatment outcome analysis including tumor growth control and serviceable hearing preservation at 2 years, were conducted using Cox regression analyses. All TSI features correlated significantly with the dose plan indices (P < 0.0012). With increasing tumor volume, vestibular schwannomas became more spherical (P < 0.05) and the dose plan indices varied significantly between tumor volume subgroups (P < 0.001 and P < 0.01). VioS was the most effective predictor of GK indices (P < 0.001) and we obtained 89.36\% accuracy (79.17\% sensitivity and 100\% specificity) for predicting PCI. Our results indicated that TSI had significant effects on the plan quality however did not adversely affect treatment outcomes.
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    Plasmapheresis treatment in COVID-19-related autoimmune meningoencephalitis: Case series
    (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2020-01-01) Dogan, Lerzan; Kaya, Dilaver; Sarikaya, Tugce; Zengin, Rehile; Dincer, Alp; Akinci, Ibrahim Ozkan; Afsar, Nazire
    Severe SARS-CoV-2 (COVID-19) infection has the potential for a high mortality rate. In this paper, we report the results of plasmapheresis treatment in a series of severely ill patients with COVID-19-related autoimmune meningoencephalitis in the Intensive Care Unit (ICU).
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    Increased Prostate Imaging-Reporting and Data System Scores in Multiparametric Magnetic Resonance Imaging May Predict More Extensive Disease in Radical Prostatectomy Specimens
    (GALENOS YAYINCILIK, 2021-01-01) Karsiyakali, Nejdet; Ozgen, Mahir Bulent; Ozveren, Bora; Akbal, Cem; Dincer, Alp; Durak, Haydar; Turkeri, Levent
    Objective: This study aimed to investigate the correlation between index lesion prostate imaging-reporting and data system (PI-RADS) version-2 score and histopathological outcomes of prostatectomy specimens. Materials and Methods: A total of 78 male patients with prostate cancer (PCa) treated with robot-assisted radical prostatectomy between August 2015 and June 2020 were included in this study. In this cohort, suspicious lesions on multiparametric magnetic resonance imaging (mpMRI) were scored according to PI-RADS version-2 criteria. MpMRI-targeted prostate biopsy was performed for all suspicious lesions with a PI-RADS score of >= 3 followed by systematic prostate biopsy. The relationship between index lesion PI-RADS score and histopathological outcomes of prostatectomy specimens were evaluated statistically. Results: The mean age of the patients was 65.0 +/- 7.0 years. The distribution of PI-RADS scores of 3, 4, and 5 of the index lesions were 6 (7.7\%), 29 (37.2\%), and 43 (55.1\%), respectively. Lower tumor volume and tumor volume ratio were observed in patients with a PI-RADS score of 3 when they were compared with patients with PI-RADS scores of 4 and PI-RADS-5 (p<0.001, for each). No significant correlation was found between index lesion PI-RADS score in mpMRI and clinically significant PCa in prostatectomy specimens (r<0.200, p>0.05). However, a significant correlation was observed between index lesion PI-RADS score and extracapsular extension (ECE), as well as seminal vesicle invasion (SVI) and pT stage (r=0.327, p=0.004