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Phase 1 Trial Of Alrn-6924, A Dual Inhibitor Of Mdmx And Mdm2, In Patients With Solid Tumors And Lymphomas Bearing Wild-Type Tp53, Guilherme Rabinowits

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Abstract

Purpose: We describe the first-in-human dose-escalation trial for ALRN-6924, a stabilized, cell-permeating peptide that disrupts p53 inhibition by MDM2 and MDMX to induce cell cycle arrest or apoptosis in TP53 wild-type tumors.

Methods: Two schedules were evaluated for safety, pharmacokinetics, pharmacodynamics, and anti-tumor effects in patients with solid tumors or lymphomas: In arm A, patients received ALRN-6924 by intravenous infusion once-weekly for 3 weeks every 28 days; arm B, was twice-weekly for 2 weeks every 21 days.

Results: Seventy-one patients were enrolled: 41 in arm A (0.16-4.4 mg/kg), 30 in arm B (0.32-2.7 mg/kg). ALRN-6924 showed dose-dependent pharmacokinetics and …

Lycopene Sensitizes The Cervical Cancer Cells To Cisplatin Via Targeting Nuclear Factorkappab (Nf-��B) Pathway, Oktay Hali̇t Aktepe, Taha Koray Şahi̇n, Gürkan Güner, Zafer Arik, Şuayi̇b Yalçin

Turkish Journal of Medical Sciences

Background/aim: Lycopene is associated with anticancer effects in various tumor types. However, the exact underlying mechanisms of action of lycopene in human cervical cancer remain to be determined. This study aimed to determine anticancer efficacy and mechanism of lycopene in human cervical carcinoma (HeLa) cells. Materials and methods: HeLa cells were treated with cisplatin (1 μM) alone, lycopene (10 μM) alone, and in combination for 72 h. The cell viability of HeLa cells was assessed via MTS assay. Western blot was used to analyze the expression levels of the nuclear factor-kappa B (NF-ΚB), B-cell-associated X protein (Bax), nuclear factor erythroid …

Cover And Contents

Turkish Journal of Medical Sciences

No abstract provided.

The Effect Of Induction Loop System Use Training On Adults With Hearing Aids, Merve Burcu Özay, Hüseyi̇n Özay, Selhan Gürkan, Serpi̇l Mungan Durankaya, Tahsi̇n Oğuz Başokçu, Günay Kirkim

Turkish Journal of Medical Sciences

Background/aim: The study aimed to investigate the effect of training on hearing aid users to benefit from induction loop systems. Materials and methods: A five-question scale was developed to evaluate whether individuals using hearing aids could use the induction loop system effectively. In the first step, validity-reliability studies were performed with 264 individuals using hearing aids. In the second step, 30 individuals using hearing aids were given verbal and hands-on training on the induction loop system. Before and after training with hearing aids (noiseless, noise, noise + induction system active) in three different environments, questions on the scale were asked …

Turkish Reliability And Validity Study Of The Medical Outcomes Study (Mos) Sleep Scale Inpatients With Obstructive Sleep Apnea, Bülent Devri̇m Akçay, Duygu Akçay, Si̇nan Yetki̇n

Turkish Journal of Medical Sciences

Background/aim: The purpose of the present study was to evaluate the Turkish reliability and validity of the medical outcomes study (MOS) sleep scale in patients who have obstructive sleep apnea. Materials and methods: The data of the study were collected from 120 adult patients with obstructive sleep apnea and from 90 healthy individuals between March 04 and May 31, 2019. Results: The Cronbach's α internal consistency reliability coefficient of the MOS sleep scale was found as 0.82. The test-retest reliability was acceptable (r = 0.76-0.94). Six factors were identified by the factor analysis. These were the same as those in …

Muc1 And Muc5ac Implication In Tunisian Colorectal Cancer Patients, Meriam Hazgui, Marwa Weslati, Rahma Boughriba, Donia Ounissi, Dhouha Bacha, Saadia Bouraoui

Turkish Journal of Medical Sciences

Background/aim: Mucins, such as MUC1 and MUC5AC, are known for their protective and moisturizing role in intestinal epithelium. Their expression is tightly controlled given their essential role in normal tissue homeostasis, whereas their deregulation leads to chronic inflammation, and even cancer. This study aimed to assess the expression profiles of MUC1 and MUC5AC and their implications in colorectal carcinogenesis. Materials and methods: A retrospective study of 202 patients who underwent colorectal cancer (CRC) surgery was conducted. The expression of MUC1 and MUC5AC was investigated by immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR). Statistical analysis of mucin expression pattern, as well …

Diagnostic Efficacy Of Apparent Diffusion Coefficient Measurements In Differentiation Ofmalignant Intra-Axial Brain Tumors, İlker Eyüboğlu, İsmet Mi̇raç Çakir, Serdar Aslan, Ahmet Sari

Turkish Journal of Medical Sciences

Background/aim: To evaluate diagnostic efficacy of the apparent diffusion coefficient measurements from tumor (ADCt) and tumor circumference hyperintensities (ADCtch) in different types of malignant intra-axial brain tumors. Materials and methods: Between April 2013 and June 2017, 125 patients (52 females (41.6%) and 73 males (58.4%); mean age: 53 years, age range: 14-81 years), who underwent diffusion-weighted imaging (DWI) with intracranial mass, were retrospectively evaluated. The mean ADCt and ADCtch values and ratios were measured. Results: Of the 125 patients, 22 (17.6%) had a low-grade glioma (LGG), 55 (44%) had a high-grade glioma (HGG), 32 (25.6%) had metastasis, and 16 (12.8%) …

Efficacy, Retention, And Safety Of Tofacitinib In Real-Life: Hur-Bio Monocentric Experience, Emre Bi̇lgi̇n, Furkan Ceylan, Emi̇ne Duran, Bayram Fari̇soğullari, Ertuğrul Çağri Bölek, Gözde Kübra Yardimci, Levent Kiliç, Ali̇ Akdoğan, Ömer Karadağ, Şazi̇ye Şule Apraş Bi̇lgen, Sedat Ki̇raz, Ali̇ İhsan Ertenli̇, Umut Kalyoncu

Turkish Journal of Medical Sciences

Background/aim: To assess the real-life efficacy, retention rate, and safety data of tofacitinib in rheumatoid arthritis (RA) patients. Materials and methods: We analyzed all patients registered in the HURBİO database who received at least 1 dose of tofacitinib. Patients who received at least one dose were included in retention analysis; patients with at least 1 control visit were included in efficacy and safety analysis. Factors predicting good response at the last follow-up visit were analyzed by logistic regression analysis. Drug retention rates were calculated using the Kaplan-Meier method and predictors of drug retention were determined by Cox proportional hazard model. …

Joint Optimization Of Target Wake Time Mechanism And Scheduling For Ieee802.11ax, Mehmet Karaca

Turkish Journal of Electrical Engineering and Computer Sciences

IEEE 802.11ax as the newest wireless local area networks (WLANs) standard brings enormous improvements in network throughput, coverage and energy efficiency in densely populated areas. Unlike previous IEEE 802.11 WLAN standards where power saving mechanisms have a limited capability and flexibility, 802.11ax comes with a different mechanism called target wake time (TWT) where stations (STAs) wake up only after each TWT interval and different STAs can wake up at different time instance depending on their application requirements. As an example, for a periodic data arrival occurring in IoT applications, STA can wake up by following the data period and go …

Impact Of Hybrid Power Generation On Voltage, Losses, And Electricity Cost Indistribution Networks, Yavuz Ateş, Tayfur Gökçek, Ahmet Yi̇ği̇t Arabul

Turkish Journal of Electrical Engineering and Computer Sciences

Energy and its capacity has emerged as one of the biggest distribution challenges all over the world. The existing grid becomes insufficient along with the expansion of the consumption. Therefore, the number of distributed generation (DG) in distribution networks increases and it allows us to sell back the extra energy. However, the efficiency of energy must be maintained into optimal values from the grid to the end-users. In spite of a lot of advantages of DG units, there are some disadvantages like fluctuations in voltage, increments of power losses, wrong protection coordination, harmonic and energy quality issues etc.. If the …

Analysis And Simulation Of Efficiency Optimized Ipm Drives In Constant Torqueregion With Reduced Computational Burden, Mi̇kai̇l Koç, Selçuk Emi̇roğlu, Bünyami̇n Tamyürek

Turkish Journal of Electrical Engineering and Computer Sciences

Moving from internal combustion engine based towards electric based transportation is crucial for wide societies as they facilitate the use of green energy technologies such as wind and solar. Interior mounted permanent magnet (IPM) machines, also known as salient brushless alternating current (AC) machines, are commonly employed in traction applications as they have superior features, such as high efficiency operation, high torque, and power densities. The efficiency optimization in IPM drives is achieved by obtaining and operating at accurate and unique current angle for a certain electromagnetic torque demand. In conventional drives, the optimum current angle is obtained by online …

Determination Of Pneumonia In X-Ray Chest Images By Using Convolutionalneural Network, Özlem Polat, Zümray Ölmez, Tamer Ölmez

Turkish Journal of Electrical Engineering and Computer Sciences

Pneumonia is one of the major diseases that cause a lot of deaths all over the world. Determining pneumonia from chest X-ray (CXR) images is an extremely difficult and important image processing problem. The discrimination of whether pneumonia is of bacterium or virus origin has also become more important during the pandemic. Automatic determination of the presence and origin of pneumonia is crucial for speeding up the treatment process and increasing the patient's survival rate. In this study, a convolutional neural network (CNN) framework is proposed for detection of pneumonia from CXR images. Two different binary CNNs and a triple …

Power-Based Modelling And Control: Experimental Results On A Cart-Pole Doubleinverted Pendulum, Tuğçe Yaren, Selçuk Ki̇zi̇r

Turkish Journal of Electrical Engineering and Computer Sciences

This paper is concerned with the modeling framework based on power and control for a mechanical system that has nonlinear, unstable, and under-actuated characteristic features, based on an analogy, which is developed by using the Brayton and Moser's (BM) equations between mechanical and electrical systems. The analogy is based on a mixed-potential function generalized for BM. The mixed-potential function for a cart - pole double inverted pendulum (CPDIP) system is used as a new building block for modeling, analysis, and controller design. The analogy allows for the exact transfer of results from electrical circuit synthesis and analysis to the mechanical …

Control Synthesis For Parametric Timed Automata Under Reachability, Ebru Aydin Göl

Turkish Journal of Electrical Engineering and Computer Sciences

Timed automata is a fundamental modeling formalism for real-time systems. During the design of such real-time systems, often the system information is incomplete, and design choices can vary. These uncertainties can be integrated to the model via parameters and labelled transitions. Then, the design can be completed by tuning the parameters and restricting the transitions via controller synthesis. These problems, namely parameter synthesis and controller synthesis, are studied separately in the literature. Herein, these are combined to generate an automaton satisfying the given specification by both parameter tuning and controller synthesis, thus exploring all design choices. First, it is shown …

Information Retrieval-Based Bug Localization Approach With Adaptive Attributeweighting, Mustafa Erşahi̇n, Semi̇h Utku, Deni̇z Kilinç, Buket Erşahi̇n

Turkish Journal of Electrical Engineering and Computer Sciences

Software quality assurance is one of the crucial factors for the success of software projects. Bug fixing has an essential role in software quality assurance, and bug localization (BL) is the first step of this process. BL is difficult and time-consuming since the developers should understand the flow, coding structure, and the logic of the program. Information retrieval-based bug localization (IRBL) uses the information of bug reports and source code to locate the section of code in which the bug occurs. It is difficult to apply other tools because of the diversity of software development languages, design patterns, and development …

Novel Ofdm Transmission Scheme Using Generalized Prefix With Subcarrierindex Modulation, Yusuf Acar

Turkish Journal of Electrical Engineering and Computer Sciences

The cyclic prefix (CP) is a prefix technique widely used in orthogonal frequency division multiplexing (OFDM) systems in order to eliminate the intersymbol interference (ISI) caused by the dispersion of wireless channels. However, CP reduces the number of symbols that can be transmitted in one OFDM symbol. Therefore, CP is one of the bottlenecks of OFDM systems limiting their spectral efficiency (SE). This limitation on the SE of the classical CP-based OFDM system is the main motivation for this work to introduce a novel method. In this paper, the design of a new CP structure, which is based on the …

Subcapsular Local Anesthesia Approach In Percutaneous Liver Biopsy: Less Pain, Morecomfort, Özgür Çakir, Can Aksu

Turkish Journal of Medical Sciences

Background/aim: To compare the subjective level of pain in patients who underwent an ultrasound-guided percutaneous liver biopsy (PLB) after either pericapsular anesthesia (PA) or subcapsular anesthesia (SA), based on the numeric rating scale (NRS). Materials and methods: A total of 323 patients, mean age 51, range 21-82 years; 160 (49.5%) male, referred to the Interventional Radiology Clinic of Kocaeli University Faculty of Medicine for image-guided PLB, between June 2019 and May 2020 were included and randomized into two groups by anesthetic type; the first (n = 171) consisted of patients undergoing SA while the second (n = 152) included patients …

What Is The Predictive Value Of Preoperative Ca 125 Level On The Survival Rate Of Type 1endometrial Cancer?, Şafak Yilmaz Baran, Songül Alemdaroğlu, Gülşen Doğan Durdağ, Seda Yüksel Şi̇mşek, Fi̇li̇z Bolat, Fati̇h Köse, Hüsnü Çeli̇k

Turkish Journal of Medical Sciences

Background/aim: To investigate the utility of preoperative serum cancer antigen 125 (CA 125) levels in type 1 endometrial carcinoma (EC) as a marker for determining poor prognostic factors and survival. Material and methods: All patients with endometrial cancer, who had been treated between 2012 and 2020, were retrospectively reviewed, and finally, 256 patients with type 1 endometrium carcinoma were included in the study. The relationship between the clinicopathological characteristics, CA 125 level, and survival rates were analyzed. The cut-off value for the preoperative serum CA 125 level was defined as 16 IU/L. Results: The median serum CA 125 levels were …

Effective Dose Of Intravenous Oxycodone Depending On Sex And Age For Attenuation Ofintubation-Related Hemodynamic Responses, Keum Young So, Ki Tae Jung, Bo Hyun Jang, Sang Hun Kim

Turkish Journal of Medical Sciences

Background/aim: Preoperative intravenous oxycodone may help to prevent or attenuate intubation-related hemodynamic responses (IRHRs), but its pharmacokinetics differs according to age and sex. Therefore, we investigated the 95% effective dose (ED95) of intravenous oxycodone for attenuating all IRHRs, depending on the age and sex of the study population. Materials and methods: All patients were allocated to one of 6 groups: 1) 20-40 year old males, 2) 41-65yearold males, 3) 66-80 year old males, 4) 20-40 year old females, 5) 41-65yearold females, and 6) 66-80 year old females (groups YM, OM, EM, YF, OF, and EF, respectively). Using Dixon's up-and-down method, …

Exenatide Improves Cardiovascular Risk Factors In Obese Patients With Type 2 Diabetesmellitus: A Prospective Study, Derya Köseoğlu, Sali̇h Süha Koparal, Özden Özdemi̇r Başer, Di̇lek Berker

Turkish Journal of Medical Sciences

Background/aim: The aim of this study was to evaluate the effects of a 6-month treatment regimen with exenatide on the lipid profile, high-sensitivity C-reactive protein (hsCRP), carotid intima media thickness (CIMT), visceral adiposity, and nonalcoholic fatty liver disease (NAFLD), all of which are important cardiovascular risk factors. Materials and methods: This study included 45 obese patients with type 2 diabetes mellitus (T2DM). Baseline clinical findings, laboratory parameters, and ultrasonography findings were recorded. An exenatide recipe was given twice daily to the patients and, after 6 months of therapy, the same variables were compared. The compared parameters were lipid profiles, hsCRP, …

The Evaluation Of Intracellular Energy Metabolism In Prediabetic Patients And Patientsnewly Diagnosed With Type 2 Diabetes Mellitus, Erkan Dulkadi̇roğlu, Hüseyi̇n Özden, Hüseyi̇n Demi̇rci̇

Turkish Journal of Medical Sciences

Background/aim: Increased susceptibility to infections is a serious problem in diabetics. Impairment in the energy metabolism of the immune system is the main source of the problem. Early diagnosis of the impairment in energy metabolism is crucial. Our study aimed to investigate the energy metabolism in leukocytes in patient groups such as prediabetics and patients newly diagnosed with type 2 diabetes mellitus. Materials and methods: Our study included 21 newly diagnosed type 2 diabetic patients (NDDP), 30 prediabetic patients, and 22 adult volunteers. 75 g oral glucose tolerance test (OGTT) was applied to all patients included in the study. Blood …

Clinicopathological Characteristics And Mutational Profile Of Kras And Nras Intunisian Patients With Sporadic Colorectal Cancer, Donia Ounissi, Marwa Weslati, Rahma Boughriba, Meriam Hazgui, Saadia Bouraoui

Turkish Journal of Medical Sciences

Background/aim: Colorectal cancer (CRC) is a major public health problem worldwide and in Tunisia due to its increasing rate of incidence. KRAS and NRAS mutations have become a pivotal part of CRC diagnosis, given their association to treatment resistance with antiepidermal growth factor receptor (EGFR) monoclonal antibodies. In this study, we aimed to screen for mutations in KRAS and NRAS genes in Tunisian patients with CRC and explore their correlations with clinicopathological features. Materials and methods: AmoyDx KRAS and NRAS mutation real-time PCR kits were used to screen for mutations in KRAS (exon 2) and NRAS (exons 2, 3, and …

Evaluating The Persian Versions Of Two Psoriatic Arthritis Screening Questionnairesearly Arthritis For Psoriatic Patients Questionnaire (Earp) And Psoriasis Epidemiologyscreening Tool (Pest) In Iranian Psoriatic Patients, Vahide Lajevardi, Seyed Zahra Ghodsi, Mahdieh Shafiei, Amir Teimourpour, Ifa Etesami

Turkish Journal of Medical Sciences

Background/aim: The majority of psoriatic arthritis (PsA) patients present at dermatology clinics with cutaneous psoriasis up to 10 years prior to arthritis onset; therefore, applying a suitable screening tool to detect PsA early is essential for dermatologists. This study aimed to validate and evaluate the Persian version of two PsA screening questionnaires, the early arthritis for psoriatic patients questionnaire (EARP) and the psoriasis epidemiology screening tool (PEST) in Iranian psoriatic patients. Materials and methods: In this cross-sectional study, psoriatic patients who presented to the dermatology clinic without a previously established PsA were asked to fill out the Persian version of …

A Survey Of Bullous Diseases In A Turkish University Hospital: Clinicoepidemiologicalcharacteristics And Follow-Up, Zekayi̇ Kutlubay, Ayşegül Sevi̇m Keçi̇ci̇, Uğur Çeli̇k, Mehmet Cem Mat

Turkish Journal of Medical Sciences

Background/aim: Autoimmune bullous diseases, if left untreated, are life-threatening conditions affecting primarily skin and mucous membranes. These blistering disorders are characterized by epidermal or subepidermal detachment. Autoimmunity plays a key role in pathogenesis; therefore, immunosuppressive agents are the treatment of choice. The aim of this study is to document relative frequencies of different autoimmune bullous diseases, patient characteristics, treatment options, and side effects in patients presenting to our bullous skin disease center at İstanbul University, Cerrahpaşa, Cerrahpaşa Medical Faculty. Materials and methods: Medical files were examined retrospectively for all patients with autoimmune bullous diseases who were followed up between 2003 …

Determining Overfitting And Underfitting In Generative Adversarial Networksusing Fréchet Distance, Enes Eken

Turkish Journal of Electrical Engineering and Computer Sciences

Generative adversarial networks (GANs) can be used in a wide range of applications where drawing samples from a data probability distribution without explicitly representing it is essential. Unlike the deep convolutional neural networks (CNNs) trained for mapping an input to one of the multiple outputs, monitoring the overfitting and underfitting in GANs is not trivial since they are not classifying but generating a data. While training set and validation set accuracy give a direct sense of success in terms of overfitting and underfitting for CNNs during the training process, evaluating the GANs mainly depends on the visual inspection of the …

A Case Study On Player Selection And Team Formation In Football With Machinelearning, Di̇dem Abi̇di̇n

Turkish Journal of Electrical Engineering and Computer Sciences

Machine learning has been widely used in different domains to extract information from raw data. Sports is one of the popular domains for researchers to work on recently. Although score prediction for matches is the most preferred application area for artificial intelligence, player selection, and team formation is also an application area worth working on. There are some studies in the literature about player selection and team formation which are examined in this study. The study has two important contributions: First one is to apply seven different machine learning algorithms on our dataset to find the best player combination for …

Analysis Of Optical Gyroscopes With Vertically Stacked Ring Resonators, Dooyoung Hah

Turkish Journal of Electrical Engineering and Computer Sciences

Without any moving part, optical gyroscopes exhibit superior reliability and accuracy in comparison to mechanical sensors. Microring-resonator-based optical gyroscopes emerged as alternatives for bulky conventional Sagnac interferometer sensors, especially attractive for applications with limited footprints. Previously, it has been reported that planar incorporation of multiple resonators does not bring about improvement in sensitivity for a given area because the increase in Sagnac phase accumulation does not outrun the increase of area. Therefore, it was naturally suggested to consider vertical stacking of ring resonators because then, the resonators can share the same footprint. In this work, sensitivity performances of such configurations …

Ige-Mediated Food Allergy Throughout Life, Ebru Çelebi̇oğlu, Ayşegül Akarsu, Ümi̇t Murat Şahi̇ner

Turkish Journal of Medical Sciences

No abstract provided.

Distribution Of Nuchal Translucency Thickness At 11 To 14 Weeks Of Gestation In A Normalturkish Population, Gülseren Di̇nç, İlker Eyüboğlu

Turkish Journal of Medical Sciences

Background/aim: The aim of this study was to determine fetal nuchal translucency (NT) thickness nomogram values in first trimester in a Turkish population and compare them with previously reported European and Asian nomogram data. Material and methods: Ultrasonographic measurements of crown-rump length (CRL) and NT thicknesses were obtained from 11 to 14 weeks of gestation in a normal Turkish population. Pregnant women with singleton pregnancy and fetal CRL between 45 and 84 mm were included in the study. The mean 1st, 3rd, 5th, 50th, 90th, 95th, 97th, and 99th percentiles and fixed cut off values of ≥ 2.5 mm, ≥ …

Comprehensive Assessment Of Levodopa-Carbidopa Intestinal Gel For Turkish Advancedparkinson's Disease Patients, Yeşi̇m Sücüllü Karadağ, Tuğçe Saltoğlu, Fadi̇me Erdoğan Küçükdağli, Ömer Öztürk, Hasan Tankut Köseoğlu, Emi̇n Altiparmak

Turkish Journal of Medical Sciences

Background/aim: Levodopa-carbidopa intestinal gel (LCIG) is an effective treatment modality in the management of advanced Parkinson's disease (PD) despite frequent adverse events and different rates of dropouts. Efficacy and safety data regarding Turkish patients on LCIG are limited. This study aims to report in detail the efficacy and adverse effect profile of LCIG among advanced PD patients from a Turkish center for movement disorders. Materials and methods: Twenty-two patients (50% male) who started receiving LCIG between December 2014 and March 2020 were recruited. The efficacy of LCIG was assessed with the Unified Parkinson's Disease Rating Scale (UPDRS III), Clinical Global …