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1.  Red Cell Distribution Width and Coronary Artery Calcification 
Korean Circulation Journal  2016;46(2):270-272.
PMCID: PMC4805575  PMID: 27014361
2.  Assessment of expressions of Bcl-XL, b-FGF, Bmp-2, Caspase-3, PDGFR-α, Smad1 and TGF-β1 genes in a rat model of lung ischemia/reperfusion 
Ischemia is described as organs and tissues are destitute of oxygen due to decreased arterial or venous blood flow. Many mechanisms play role in cell death happened as a consequence of a new blood flow is needed for both cell regeneration and to clean toxic metabolites during ischemia and later. Lung damage induced by ischemia/reperfusion (I/R) is a frequent problem in lung transplantation. Apoptosis (programmed cell death) is known as cell suicide, and plays a key role in embryonic developmental and in maintain adult tissue’s life.
Materials and Methods:
It is investigated expressions of Smad1, Bmp-2, Bcl-XL, b-FGF, Caspase-3, TGF-β1, PDGFR-α genes for molecular changes in lung tissues, after I/R is formed, in this study. For this, we included 40 Wistar albino rats to this study and divided 4 groups (n=10). The Groups were determined as Control (C), Group 1= 1 hr ischemia (I), Group 2= 1 hr ischemia+2 hr reperfusion (I+2R), Group 3= 1 hr ischemia+4 hr reperfusion (I+4R). Besides, molecular analysis and histopathologic examinations of tissues were performed, and the results were evaluated by normalization and statistics analysis.
We have found a significant increase in expression of Bcl-XL (P=0.046) and Caspase-3 (P=0.026) genes of group 1, and it was not monitored any significant difference in Group 2 and Group 3. In all groups, the changes in b-FGF (P=0.087), Bmp-2 (P=0.457), TGF-β1 (P=0.201) and PDGFR-α (P=0.116) were not significant compared to control group. We did not see any mRNA expression of Smad1 gene in all groups include control.
These findings suggest that I/R injury may trigger apoptotic mechanism in lung.
PMCID: PMC4818370  PMID: 27081467
Apoptosis; Growth factors; Ischemia/reperfusion; Lung
4.  Germline Mutations in Shelterin Complex Genes Are Associated With Familial Glioma 
Gliomas are the most common brain tumor, with several histological subtypes of various malignancy grade. The genetic contribution to familial glioma is not well understood. Using whole exome sequencing of 90 individuals from 55 families, we identified two families with mutations in POT1 (p.G95C, p.E450X), a member of the telomere shelterin complex, shared by both affected individuals in each family and predicted to impact DNA binding and TPP1 binding, respectively. Validation in a separate cohort of 264 individuals from 246 families identified an additional mutation in POT1 (p.D617Efs), also predicted to disrupt TPP1 binding. All families with POT1 mutations had affected members with oligodendroglioma, a specific subtype of glioma more sensitive to irradiation. These findings are important for understanding the origin of glioma and could have importance for the future diagnostics and treatment of glioma.
PMCID: PMC4296199  PMID: 25482530
5.  The Effect of Intravitreal Azithromycin on the Albino Newborn Rabbit Retina 
To evaluate the effect of intravitreal azithromycin on the retina in a newborn rabbit model.
Twelve, two-week old New Zealand albino rabbits were divided into two groups (six in each). The right eyes of six rabbits received 0.75 mg (0.05 mL) azithromycin and the right eyes of the remaining six rabbits 1.5 mg (0.1 mL) azithromycin intravitreally. Left eyes were served as the control and received the same volume of saline. All eyes were enucleated at the third postinjection week. Retinal histology was examined by light microscopy. Apoptosis of the retinal cells was further evaluated by immunohistochemical staining for caspase-3 and in situ terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) of DNA fragments.
Light microscopy demonstrated no retinal abnormalities in all eyes. However, retinal nuclear DNA fragmentation was evident in both study groups (33.6% with 1.5 mg and 21.4% with 0.75 mg azithromycin) with the TUNEL method. TUNEL staining ratio was statistically higher only in the second group treated with 1.5 mg azithromycin when compared to the control group (p=0.01 Mann Whitney U test). The ratio of caspase-3 positive cells in the two study groups was 21.5% and 20.2%, respectively. Caspase-3 staining ratio was statistically higher in both study groups when compared to the control eyes (p=0.00, p=0.00 respectively). The difference of TUNEL staining ratio between the two study groups was statistically significant (p=0.028), but there were no statistically significant differences in the two study groups by caspase-3 staining (p=0.247).
In newborn rabbits, intravitreal azithromycin injection resulted in an apoptotic activity in the photoreceptor, bipolar and ganglion cells. Immunohistochemical analysis suggested that doses of 0.75 mg and 1.5 mg azithromycin, administered intravitreally might be toxic to the newborn rabbit retina.
PMCID: PMC4780483  PMID: 27014381
Azithromycin; apoptic cell death; bacteriostatic agent; retina
6.  Simultaneous Single Dexamethasone Implant and Ranibizumab Injection in a Case with Active Serpiginous Choroiditis and Choroidal Neovascular Membrane 
Case Reports in Ophthalmology  2015;6(3):408-414.
Intravitreal anti-vascular endothelial growth factor (VEGF) agents seem to be effective in choroidal neovascular membranes (CNV) in association with various entities of posterior uveitis. We herein report a 46-year-old woman who was treated with a simultaneous single intravitreal dexamethasone implant and ranibizumab administration for the treatment of unilateral extrafoveal CNV associated with an active serpiginous choroiditis. Simultaneously with the intravitreal therapy, oral mycophenolic acid (2 × 720 mg) was started, and oral cyclosporine (3 × 100 mg) was then added 2 months later. On the other hand, the fellow eye had been treated for subfoveal CNV but with an inactive disease 4 years previously and ended up with a final visual acuity of counting fingers despite treatment with a single session of photodynamic therapy and 3 subsequent intravitreal ranibizumab injections. Simultaneous administration of anti-VEGF agents and a dexamethasone implant can be a viable approach in eyes with CNV and active serpiginous choroiditis.
PMCID: PMC4777959  PMID: 26955341
Choroidal neovascular membrane; Dexamethasone implant; Ozurdex; Ranibizumab; Serpiginous choroiditis
7.  Grossesse sur utérus cloisonné menée à terme: à propos d'un cas avec revue de la literature 
L'utérus cloisonné est la malformation utérine la plus fréquente, comptant pour 30 à 50% des cas, suivie par les malformations utérines de type utérus bicorne et utérus unicorne. Nous rapportons un cas d'utérus cloisonné total suspecté lors de l'examen obstétrical d'une parturiente en travail, et confirmé à l'exploration au cours d'une césarienne réalisé pour le même motif. L'intérêt de ce cas est de montrer le pronostic obstétrical chez les femmes fertiles porteuses de cette malformation utérine.
PMCID: PMC4760728  PMID: 26955410
Utérus cloisonné; utérus bicorne; utérus unicorne; échographie 3D; hystérosonographie 3D; septate uterus; Bicornuate uterus; horned uterus; 3D ultrasound; 3D hysterosonography
8.  Genome sequence of Anoxybacillus ayderensis AB04T isolated from the Ayder hot spring in Turkey 
Species of Anoxybacillus are thermophiles and, therefore, their enzymes are suitable for many biotechnological applications. Anoxybacillus ayderensis AB04T (= NCIMB 13972T = NCCB 100050T) was isolated from the Ayder hot spring in Rize, Turkey, and is one of the earliest described Anoxybacillus type strains. The present work reports the cellular features of A. ayderensis AB04T, together with a high-quality draft genome sequence and its annotation. The genome is 2,832,347 bp long (74 contigs) and contains 2,895 protein-coding sequences and 103 RNA genes including 14 rRNAs, 88 tRNAs, and 1 tmRNA. Based on the genome annotation of strain AB04T, we identified genes encoding various glycoside hydrolases that are important for carbohydrate-related industries, which we compared with those of other, sequenced Anoxybacillus spp. Insights into under-explored industrially applicable enzymes and the possible applications of strain AB04T were also described.
PMCID: PMC4584021  PMID: 26413199
Anoxybacillus; Bacillaceae; Bacillus; Geobacillus; Glycoside hydrolase; Thermophile
9.  Intravitreal Aflibercept Injection and Photodynamic Treatment of a Patient with Unilateral Subretinal Neovascular Membrane Associated with Fundus Flavimaculatus 
We report the good outcome of combined intravitreal aflibercept injection and photodynamic treatment in a case with fundus flavimaculatus (FFM) and unilateral subretinal neovascular membrane (SRNM). A 57-year-old man with FFM and unilateral SRNM who was treated with two consecutive ranibizumab injections with no improvement at another institution was referred to us. He was treated successfully with three aflibercept injections three months apart and a single photodynamic treatment performed a week after the initial aflibercept injection. Six weeks after the last aflibercept injection visual acuity was improved and submacular exudation exhibited dramatic resolution with a moderate degree of residual scarring. SRNM formation is rarely observed in eyes with FFM and a satisfactory outcome can be achieved with a proper treatment.
PMCID: PMC4363630  PMID: 25821619
10.  Disulfiram is a direct and potent inhibitor of human O6-methylguanine-DNA methyltransferase (MGMT) in brain tumor cells and mouse brain and markedly increases the alkylating DNA damage 
Carcinogenesis  2013;35(3):692-702.
This study identified the MGMT direct reversal DNA repair protein as a target for disulfiram (an established drug for treatment of alcoholism) and support repurposing of disulfiram for enhancing the efficacy of anti-glioma alkylating agents.
The alcohol aversion drug disulfiram (DSF) reacts and conjugates with the protein-bound nucleophilic cysteines and is known to elicit anticancer effects alone or improve the efficacy of many cancer drugs. We investigated the effects of DSF on human O6-methylguanine-DNA methyltransferase (MGMT), a DNA repair protein and chemotherapy target that removes the mutagenic O6-akyl groups from guanines, and thus confers resistance to alkylating agents in brain tumors. We used DSF, copper-chelated DSF or CuCl2–DSF combination and found that all treatments inhibited the MGMT activity in two brain tumor cell lines in a rapid and dose-dependent manner. The drug treatments resulted in the loss of MGMT protein from tumor cells through the ubiquitin-proteasome pathway. Evidence showed that Cys145, a reactive cysteine, critical for DNA repair was the sole site of DSF modification in the MGMT protein. DSF was a weaker inhibitor of MGMT, compared with the established O6-benzylguanine; nevertheless, the 24–36h suppression of MGMT activity in cell cultures vastly increased the alkylation-induced DNA interstrand cross-linking, G2/M cell cycle blockade, cytotoxicity and the levels of apoptotic markers. Normal mice treated with DSF showed significantly attenuated levels of MGMT activity and protein in the liver and brain tissues. In nude mice bearing T98 glioblastoma xenografts, there was a preferential inhibition of tumor MGMT. Our studies demonstrate a strong and direct inhibition of MGMT by DSF and support the repurposing of this brain penetrating drug for glioma therapy. The findings also imply an increased risk for alkylation damage in alcoholic patients taking DSF.
PMCID: PMC3941740  PMID: 24193513
11.  Single Bilateral Dexamethasone Implant in Addition to Panretinal Photocoagulation and Oral Azathioprine Treatment in IRVAN Syndrome 
Case Reports in Ophthalmology  2015;6(1):56-62.
The idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN) syndrome is a disease characterized by multiple retinal macroaneurysms, neuroretinitis and peripheral capillary nonperfusion. Visual loss may result from either ischemia-related complications or macular involvement. Treatment is not always rewarding. We report a case with stage 2 IRVAN syndrome who was successfully treated with a single bilateral intravitreal dexamethasone implant in addition to panretinal photocoagulation and systemic azathioprine treatment.
PMCID: PMC4357687  PMID: 25802506
Azathioprine; Dexamethasone implant; IRVAN syndrome; Laser photocoagulation; Ozurdex
12.  Targeted Sequencing in Chromosome 17q Linkage Region Identifies Familial Glioma Candidates in the Gliogene Consortium 
Scientific Reports  2015;5:8278.
Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further investigation. We applied a filtering schema to narrow the original list of 4830 annotated variants down to 21 very rare (<0.1% frequency), non-synonymous variants. Our findings implicate the MYO19 and KIF18B genes and rare variants in SPAG9 and RUNDC1 as candidates worthy of further investigation. Burden testing and functional studies are planned.
PMCID: PMC4317686  PMID: 25652157
13.  A large primary dumbbell hydatid cyst causing neural foraminal widening of the thoracic spine: A case report and literature review 
Spinal hydatid cyst is a rare, but serious condition.
Presentation of the case
Herein, we present a 17-year-old male patient with back pain radiating to the legs and progressive weakness in the lower limbs. CT and MRI showed a spinal-paraspinal hydatid cyst with a dumbbell appearance that caused neural foraminal widening and spinal cord compression. The case was explored via right T3-T4 hemilaminectomy, and the hydatid cyst was completely removed.
The clinical presentation, diagnosis, and surgical treatment of this rare case of spinal hydatid disease are discussed, and all published cases of primary dumbbell hydatid cyst are reviewed.
Even if serological test results are negative, hydatid cysts should be considered in the differential diagnosis of cystic lesions of the spine.
PMCID: PMC4353951  PMID: 25625491
Echinococcosis; Hydatid cyst; Surgical treatment; Thoracic spine
14.  Spectral Domain Optical Coherence Tomographic Findings of Bietti Crystalline Dystrophy 
Journal of Ophthalmology  2014;2014:739271.
We analyzed the OCT features of 24 eyes of 12 patients with Bietti crystalline dystrophy (BCD) with the Heidelberg HRA2-OCT. Seventeen of 24 eyes were in intermediate stage of the disease and seven in advanced stage of the disease at the time of latest OCT examination performed in 2014. Outer retinal tubulations and retinal hyperreflective dots were present in 20 of 24 eyes. The remaining four eyes had advanced disease with very thin retina. Appearance of bright plaque on top of RPE-Bruch membrane was present in all eyes. Choroidal hyperreflective spots were noted in 19 of 24 eyes. The remaining five eyes had advanced disease stage with very thin choroid. Mean central macular thickness was 163.08 μm ± 62.52 for all eyes (170.35 μm ± 56.46 in eyes with intermediate disease and 145.42 μm ± 77.2 in eyes with advanced disease). Mean subfoveal choroidal thickness was 95.37 μm ± 55.93 for the study eyes (116.47 ± 46.92 μm in eyes with intermediate disease and 44.14 μm ± 42.43 in eyes with advanced disease). Choroidal hyperreflective spots were noted in 21 of 24 eyes (87.5%). SD-OCT shows the disease progression in retinal and choroidal layers delicately in eyes with BCD and expands our knowledge about the ongoing disease process.
PMCID: PMC4258374  PMID: 25505979
15.  Endothelial Colony Forming Cells (ECFCs) As a Model for Studying Effects of Low-Dose Ionizing Radiation: Growth Inhibition by a Single Dose 
Cancer investigation  2013;31(5):359-364.
Identification of measurable nontransient responses to low-dose radiation in human primary cell cultures remains a problem. To this end, circulating endothelial colony-forming (progenitor) cells (ECFCs) were examined as an experimental model. ECFCs were isolated from three cord blood donors. Cells were positive for endothelial cell markers and remained highly proliferative after long-term cryopreservation. A single dose of X-ray radiation (0.06–0.38 Gy) inhibited ECFC culture growth. This effect was evident at 48 hours and persisted up to 72 hr postirradiation. Such protracted cytostatic response of ECFCs to low-dose radiation suggests that ECFC primary cultures can be used to study low-dose radiation effects.
PMCID: PMC3754852  PMID: 23621632
Cancer biomarkers; Cancer prevention; Carcinogenesis
16.  Carbon monoxide poisoning increases Tpeak–Tend dispersion and QTc dispersion 
Cardiovascular Journal of Africa  2014;25(3):106-109.
Carbon monoxide (CO) poisoning leads to cardiac dysrhythmia. Increased heterogeneity in ventricular repolarisation on electrocardiogram (ECG) shows an increased risk of arrhythmia. A number of parameters are used to evaluate ventricular repolarisation heterogeneity on ECG. The aim of our study is to investigate the effect of acute CO poisoning on indirect parameters of ventricular repolarisation on ECG.
Sixty-seven patients were included in this case–control study. Thirty patients with acute CO poisoning were assigned to group 1 (19 females, mean age: 30.8 ± 11.3 years). A control group was formed with patients without known cardiac disease (group 2, n = 37; 25 females, mean age: 26.0 ± 5.2 years). Twelve-lead ECG and serum electrolyte levels were recorded in all patients. Also, carboxyhaemoglobin (COHb) levels were recorded in group 1. Tpeak–Tend (TpTe) interval, TpTe dispersion, TpTe/QT ratio, QT interval and QTd durations were measured as parameters of ventricular repolarisation. Corrected QT (QTc) and QTc dispersion (QTcd) intervals were determined with the Bazett’s formula.
The mean COHb level in group 1 was 27.6 ± 7.4% and mean duration of CO exposure was 163.5 ± 110.9 min. No statistically significant difference was found in age, gender, serum electrolytes or blood pressure levels between the groups. QRS, QT, QTc, TpTe interval and TpTe/QT ratio were similar between the groups (p > 0.05). QTcd (65.7 ± 64.4 vs 42.1 ± 14.2 ms, p = 0.003) and TpTe dispersion (40.5 ± 14.8 vs 33.2 ± 4.9 ms, p = 0.006) were significantly longer in group 1 than group 2. COHb level was moderately correlated with TpTe dispersion (r = 0.29; p = 0.01).
To our knowledge, this is the first study to investigate TpTe interval and dispersion in CO poisoning. Our results showed that TpTe dispersion and QTc dispersion increased after CO poisoning.
PMCID: PMC4120128  PMID: 25000439
carbon monoxide; electrocardiogram; dysrhythmia; ventricular repolarisation
17.  Cystoid Macular Edema in Bietti's Crystalline Retinopathy 
A 27-year-old man with progressive bilateral visual decline was diagnosed to have Bietti's crystalline dystrophy (BCD). Fluorescein angiography revealed bilateral petaloid type late hyperfluorescence implicating concurrent cystoid macular edema (CME). Optical coherence tomography exhibited cystoid foveal lacunas OU. During the follow-up of six years, intraretinal crystals reduced in amount but CME persisted angiographically and tomographically. CME is among the rare macular features of BCD including subfoveal sensorial detachment, subretinal neovascular membrane, and macular hole.
PMCID: PMC4037624  PMID: 24949209
18.  Malrotation-associated cholecystoduodenal fistula 
Patient: Female, 16
Final Diagnosis: Malrotation and cholecystoduodenal fistula
Symptoms: Abdominal pain • anorexia • fever • nausea • vomiting
Medication: —
Clinical Procedure: —
Specialty: Gastroenterology and Hepatology
Anatomical anomaly/variation
Cholecystoduodenal fistula (CDF) is the most common cholecystenteric fistula. It is a late complication of gallbladder disease with calculus and is mainly encountered in the elderly and females.
Case Report:
We report the case of a teenage patient with cholecystoduodenal fistula and malrotation. Direct plain abdominal x-ray demonstrated air in the biliary system. Computed tomography revealed CDF-associated with an anomaly of intestinal malrotation. She had gallstones (with a few stones in the gallbladder) and cholecystitis. CDF is caused by malrotation, and cholecystitis has not been reported before. In this regard our patient is the first and youngest reported case.
We suggest that CDF is probably a consequence of malrotation. The patient’s clinical features and operative management are presented and discussed with current literature.
PMCID: PMC3894915  PMID: 24454977
cholecystoduodenal fistula; cholecystitis; malrotation
19.  Small ubiquitin-like modifier 1-3 is activated in human astrocytic brain tumors and is required for glioblastoma cell survival 
Cancer science  2012;104(1):70-77.
Small ubiquitin-like modifier (SUMO1, 2, 3) is a group of proteins that conjugate to lysine residues of target proteins thereby modifying their activity, stability, and subcellular localization. A large number of SUMO target proteins are transcription factors and other nuclear proteins involved in gene expression. Furthermore, SUMO conjugation plays key roles in genome stability, quality control of newly synthesized proteins, proteasomal degradation of proteins and DNA damage repair. Any marked increase in levels of SUMO-conjugated proteins is therefore expected to have a major impact on the fate of cells. We show here that SUMO conjugation is activated in human astrocytic brain tumors. Levels of both SUMO1- and SUMO2/3-conjugated proteins were markedly increased in tumor samples. The effect was least pronounced in low-grade astrocytoma (WHO Grade II) and most pronounced in glioblastoma multiforme (WHO Grade IV). We also found a marked rise in levels of Ubc9, the only SUMO conjugation enzyme identified so far. Blocking SUMO1-3 conjugation in glioblastoma cells by silencing their expression blocked DNA synthesis, cell growth and clonogenic survival of cells. It also resulted in DNA-PK-dependent phosphorylation of H2AX, indicative of DNA double-strand damage, and G2/M cell cycle arrest. Collectively, these findings highlight the pivotal role of SUMO conjugation in DNA damage repair processes and imply that the SUMO conjugation pathway could be a new target of therapeutic intervention aimed at increasing the sensitivity of glioblastomas to radio- and chemotherapy.
PMCID: PMC3608476  PMID: 23078246
astrocytic brain tumors; DNA damage repair; DNA-PK; G2/M checkpoint; gene silencing; glioblastoma; H2AX; human; miRNA; SUMO conjugation; Ubc9
20.  Long-Term Follow-Up of the Postoperative Macular Fold following the Vitreoretinal Surgery with Air Tamponade 
A 64-year-old male who had a macula-on superior bullous retinal detachment in OD underwent scleral buckling, 20-gauge-pars plana vitrectomy, internal drainage of subretinal fluid with perfluorocarbon fluid, 360° endolaser and perflourocarbon-fluid-air exchange surgery. Patient sat upright immediately after the surgery for the night. At the first postoperative morning although the retina was attached, there was a macular fold extending toward the temporal retinal periphery. Patient denied further surgery. During the follow-up, retinal fold gradually became less visible and it could be noticeable only by fundus autoflorescence imaging at the sixth postoperative year with a subtle epiretinal membrane formation on the optical coherence tomographic section.
PMCID: PMC3800627  PMID: 24187636
21.  Intravitreal Dexamethasone Implant (Ozurdex) in Coats’ Disease 
Case Reports in Ophthalmology  2013;4(3):122-128.
We injected an intravitreal dexamethasone implant in two eyes of 2 pediatric patients with Coats’ disease in addition to other treatment modalities, such as intravitreal ranibizumab injection and indirect laser photocoagulation. In both eyes, intraocular pressure moderately rose in a temporary fashion. The dexamethasone implant seems to be a valuable addition to the armamentarium of treatment options for Coats’ disease as it necessitates fewer injections than anti-VEGF injections and thereby fewer sessions of general anesthesia in the pediatric population.
PMCID: PMC3806670  PMID: 24163679
Coats’ disease; Dexamethasone implant; Laser photocoagulation; Ranibizumab
22.  An easy technique for removal of knotted catheter in the bladder: percutaneous suprapubic cystoscopic intervention 
Uncontaminated urine samples are indispensable to precisely diagnose urinary tract infections in new-borns or infants. Among many clinical interventions for urine collection are described, the most common noninvasive practice is using sterile bags, associated with significant contamination of samples. In children, however, invasive methods i.e. catheterization, are generally needed for reliable urine specimens. Almost always all the inserted catheters are easily drawn back, nevertheless, might not work as expected, and lead to considerable problems that cannot be overcome. Herein, a case of a female newborn treated with a successful percutaneous suprapubic cystoscopic procedure for extracting knotted urinary catheter in the bladder is presented. The least invasive and easiest technic is suggested to be used when catheter is knotted in the bladder, as elaborately stated.
PMCID: PMC3731195  PMID: 23936602
Knotted urethral catheter; urinary catheterization; percutaneous cystoscopy
23.  Splitting of a Dexamethasone Implant (Ozurdex) following the Injection 
In this brief report, we share our observations on a splitted Dexamethasone implant (Ozurdex) which we discovered a week after the injection. It is likely that implant splitting neither changes the efficacy of the implant nor creates a mishap for the patient.
PMCID: PMC3745943  PMID: 23984139
24.  Artificial neural network analysis for evaluating cancer risk in multinodular goiter 
The aim of this study was to create a diagnostic model using the artificial neural networks (ANNs) to predict malignancy in multinodular goiter patients with an indeterminate cytology.
Materials and Methods:
Out of 623 patients, 411 evaluated for multinodular goiter between July 2004 and March 2010 had a fine-needle aspiration biopsy. All patients underwent total thyroidectomy. The interpretation was consistent with an indeterminate lesion in 116 (18.6%) patients. Patient's medical records including age, sex, dominant nodule size, pre-operative serum thyroid-stimulating hormone level, thyroid hormone therapy and final pathologic diagnosis were collected retrospectively.
The mean age of the patients was 44.6 years (range, 17-78 years). About 104 (89.7%) were female and 12 (10.3%) were male patients. Final pathology revealed 24 malignant diseases (20.7%) and 92 (79.3%) benign diseases. After the completion of training, the ANN model was able to predict diagnosis of malignancy with a high degree of accuracy. The area under the curve of ANNs was 0.824.
The ANNs technique is a useful aid in diagnosing malignancy and may help reduce unnecessary thyroidectomies in multinodular goiter patients with an indeterminate cytology. Further studies are needed to construct the optimal diagnostic model and to apply it in the clinical practice.
PMCID: PMC3897020  PMID: 24516485
Artificial neural network; fine-needle aspiration; ındeterminate cytology; multinodular goiter; thyroid
25.  Efficacy of sorafenib in patients with gastrointestinal stromal tumors in the third- or fourth-line treatment: A retrospective multicenter experience 
Oncology Letters  2013;6(2):605-611.
Sorafenib is a multi-targeted tyrosine kinase receptor inhibitor used to treat patients with advanced gastrointestinal stromal tumors (GISTs). The present study evaluated the efficacy and tolerability of sorafenib therapy for patients with GISTs. Between January 2001 and November 2012, 25 patients, from multiple centers, who had received sorafenib as the third- or fourth-line treatment for GISTs were investigated retrospectively. In total, 17 patients were male and eight were female. The median age was 54.0 years (range, 16–82 years). From the patients, 21 received imatinib for longer than six months and four received it for less than six months. The clinical benefit rate of sorafenib was 40.0%. Treatment-related adverse events were reported in 72% of patients. These adverse events were generally mild to moderate in intensity. The median progression-free survival (PFS) and overall survival (OS) times of the patients who received sorafenib were 7.2 and 15.2 months, respectively. The duration of imatinib usage was an independent prognostic factor for PFS and OS. Sorafenib is an effective treatment in patients with GISTs showing a clinical benefit rate of 40.0% and an acceptable tolerability.
PMCID: PMC3789037  PMID: 24137379
sorafenib; gastrointestinal stromal tumors; efficacy

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