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Item A Local Search Heuristic with Self-tuning Parameter for Permutation Flow-Shop Scheduling Problem(2009) Dengiz, Berna; Alabas-Uslu, Cigdem; Sabuncuoglu, IhsanIn this paper, a new local search metaheuristic is proposed for the permutation flow-shop scheduling problem. In general, metaheuristics are widely used to solve this problem due to its NP-completeness. Although these heuristics are quite effective to solve the problem, they suffer from the need to optimize parameters. The proposed heuristic, named STLS, has a single self-tuning parameter which is calculated and updated dynamically based on both the response surface information of the problem field and the performance measure of the method throughout the search process. Especially, application simplicity of the algorithm is attractive for the users. Results of the experimental study show that STLS generates high quality solutions and outperforms the basic tabu search, simulated annealing, and record-to-record travel algorithms which are well-known local search based metaheuristics.Item A Highly Potent SARS-CoV-2 Blocking Lectin Protein(2022) Ahan, Recep E.; Hanifehnezhad, Alireza; Kehribar, Ebru S.; Oguzoglu, Tuba C.; Foldes, Katalin; Ozcelik, Cemile E.; Filazi, Nazlican; Oztop, Sidika; Palaz, Fahreddin; Onder, Sevgen; Bozkurt, Eray U.; Ergunay, Koray; Ozkul, Aykut; Seker, Urartu Ozgur Safak; https://orcid.org/0000-0001-5653-6080; 35426678; AAJ-7911-2020The COVID-19 (coronavirus disease-19) pandemic affected more than 180 million people around the globe, causing more than five million deaths as of January 2022. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the new coronavirus, has been identified as the primary cause of the infection. The number of vaccinated people is increasing; however, prophylactic drugs are highly demanded to ensure secure social contact. A number of drug molecules have been repurposed to fight against SARS-CoV-2, and some of them have been proven to be effective in preventing hospitalization or ICU admissions. Here, we demonstrated griffithsin (GRFT), a lectin protein, to block the entry of SARS-CoV-2 and its variants, Delta and Omicron, into the Vero E6 cell lines and IFNAR(-/-) mouse models by attaching to the spike protein of SARS-CoV-2. Given the current mutation frequency of SARS-CoV-2, we believe that GRFT protein-based drugs will have a high impact in preventing the transmission of both the Wuhan strain as well as any other emerging variants, including Delta and Omicron variants, causing the high-speed spread of COVID-19.Item Insights on Lipomatosis after Platinum-Based Chemotherapy Use in Pediatric Oncology: A Case Report(2022) Boeriu, Estera; Boc, Alexandra Georgiana; Borda, Alexandra; Negrean, Rodica Anamaria; Feciche, Bogdan; Boeriu, Amalia Iulia; Horhat, Florin George; Mot, Ion Cristian; Horhat, Ioana Delia; Ravulapalli, Madhavi; Sabuni, Omar; Adi, Abduljabar; Anjary, Adnan; Arghirescu, Smaranda Teodora; 0000-0002-6147-6518; 36556917Agents of platinum-based chemotherapy, such as cisplatin or carboplatin, are used in the treatment of a wide range of malignancies that affect children, such as brain tumors, osteosarcoma, neuroblastoma, hepatoblastoma, and germ cell tumors (GCTs). The Cyclophosphamide Equivalent Dose (CED) calculator for reproductive risk does not take platinum-based chemotherapy into account, despite the fact that it accounts for the majority of chemotherapy medications that are typically administered for pediatric GCTs. As a result, exposure to platinum-based drugs throughout infancy can have predictable long-term effects such as infertility, as well as other rare encounters such as lipoma formation and lipomatosis. Lipomas are the most prevalent benign soft tissue tumor subtype. They may be either solitary entities or engaged in multiple lipomatosis, which may have a familial origin or be an acquired disorder. Chemotherapy is a possible cause of lipomatosis. Chemotherapy based on cisplatin has been linked to a variety of long-term consequences, including kidney damage, neurotoxicity, and pulmonary toxicity, and may even create secondary cancers. However, lipoma development is known to occur in fewer than 1 in 100 individuals, and only a few examples of multiple cutaneous lipomatosis triggered by this therapy have been documented. Here we present a very rare case of lipomatosis in a pediatric patient with GCT under cisplatin therapy, which might be the third report of this kind affecting children.Item Triplet or Doublet Chemotherapy Regimens in Metastatic Gastric Cancer(2022) Yildirim, Serkan; Yilmaz, CengizChemotherapy is the most important treatment option for patients diagnosed at an advanced stage. Chemotherapy both prolongs survival and increases the quality of life. Today, there is still no definite information about whether doublet or triplet chemotherapy should be chosen in empirical therapy. Therefore, we designed our study to evaluate first-line treatment options in metastatic gastric cancer.Our study is retrospective and involves five centers in Turkey. Inclusion criteria were the presence of metastatic gastric adenocarcinoma pathology, not having received treatment for local gastric cancer (surgery, chemotherapy, or radiotherapy), having received chemotherapy (patients with two or more combinations of drugs were included in the study, and patients who received single-drug chemotherapy were not included) for metastatic disease and being HER-2 negative. The survival of the triplet chemotherapy group was significantly longer when compared with the patients who received oxaliplatin-based doublet chemotherapy (11.1 vs. 8.1 months p=0.007). When the patients who received triplet chemotherapy and those who received cisplatin-based doublet chemotherapy were compared, there was no statistically significant difference (11.13 vs. 10.57 months p=0.665).If chemotherapy will be chosen as the first-line treatment in metastatic gastric cancer, choosing triplet chemotherapy regimens if possible, and if doublet chemotherapy will be given for any reason, choosing cisplatin-based regimens may be more appropriate, especially for the patient population in Turkey.Item p16(INK4a), and p14(ARF) Expressions in Carcinogenesis of Squamous Cell Carcinoma of the Lip(2022) Akatli, Ayse Nur; Ayva, Ebru Sebnem; Bozdogan, OnderThe goal of this study was to clarify the role of p16(INK4a), p14(ARF), and p53 protein expressions in carcinogenesis in squamous cell carcinomas of the lip. The expressions of the p53, p16(INK4a), and p14(ARF) proteins were examined in 46 formaline-fixed paraffin embedded tissue specimens, which included 19 cases of squamous cell carcinoma of the lip, 14 cases of actinic cheilitis, and 13 cases of normal mucosa. Immunoreactivity in the peritumoral epithelium adjacent to squamous cell carcinomas was also evaluated. p16(INK4a) expression was increased in actinic cheilitis in comparison with normal mucosa (p=0.001). p14(ARF) expression progressively increased from normal mucosa to actinic cheilitis (p=0.001) and was observed to decrease significantly during the process of transition from actinic cheilitis to carcinoma (p=0.003). p53 values progressively increased from normal mucosa to actinic cheilitis (p=0.001) and carcinoma (p=0.008). A significant positive correlation was found between p14(ARF) and p53 in the peritumoral epithelium adjacent to carcinomas. Our findings indicated that p16(INK4a) and p14(ARF) immunohistochemistry does not determine whether or not actinic cheilitis has the potential to develop carcinoma. The p14(ARF) /p53 pathway is activated in the peritumoral epithelium adjacent to carcinoma; however, this activation would not be adequate to prevent carcinogenesis.Item Who Desires To Stay? The Role Of Relational Job Crafting On The Intention To Stay With The Mediating Role Of Workplace Friendship(2022) Cinar, Esra; Basim, H. NejatDrawing on theory of reasoned action and identity theory, we examined the mediating effect of workplace friendship on the association between relational job crafting and the intention to stay. The hypotheses were tested by analysing the data collected from 228 participants. We found positive and significant relationships between the intention to stay and relational job crafting, as well as with workplace friendship. Furthermore, a positive and significant relationship between relational job crafting and workplace friendship was found. The results also indicate that workplace friendship has a partial mediating effect on the relationship between relational job crafting and the intention to stay.Item Can CT Pelvimetry Be Used to Predict Circumferential Resection Margin Positivity in Laparoscopic Resection of Middle and Lower Rectum Cancer?(2022) Gojayev, Afig; Yuksel, Cemil; Akbulut, Serkan; Ersen, Ogun; Bakirarar, Batuhan; Gulpinar, Basak; Coruh, Aysegul Gursoy; Unal, Ali Ekrem; Demirci, Salim; 36569682Background Previous studies have shown that pelvimetry can be valuable in predicting surgical difficulties in rectal cancer operations. However, its usability in predicting circumferential resection margin (CRM) involvement remains debatable. This study investigated the factors affecting CRM status and the importance of computed tomography (CT) pelvimetry in predicting CRM involvement in laparoscopic resection of middle and lower rectal cancer.Methodology In this study, we retrospectively investigated the data of 111 patients who underwent a laparoscopic operation for middle and lower rectum cancer at Ankara University Faculty of Medicine, Department of Surgical Oncology between January 2014 and January 2020. The predictive value of CT pelvimetry and other variables on the CRM status was analyzed.Results The following four pelvic parameters differed significantly between the genders: transverse diameter of the pelvic inlet (p = 0.024), anteroposterior diameter of the pelvic outlet (p = 0.003), transverse diameter of the pelvic outlet (p < 0.001), and pelvic depth (p < 0.001). The effect of pelvic anatomic parameters on CRM involvement was not found to be significant. It was found that tumor height from the anal verge (p = 0.004), tumor size (p < 0.001), and gender (p = 0.033) were significant risk factors for CRM involvement. Survival was poor in patients with male gender (p = 0.032), perineural invasion (p < 0.001), and grade 3 tumor.Conclusions In this study, no benefit was found in predicting CRM positivity from CT pelvimetry in the laparoscopic resection of middle and lower rectal cancer. Besides, tumor height from the anal verge, tumor size, and gender were important factors for CRM positivity. Although our study sheds light on this issue, prospective randomized studies with larger sample sizes are needed.Item Development of Electrochemical Biosensor Platforms for Determination of Environmental Viral Structures(2022) Ekici, Rumeysa; Bozdogan, Betul; Denkbas, Emir BakiInfectious diseases caused by viruses (such as influenza, Zika, human immunodeficiency, Ebola, dengue, hepatitis, and COVID-19 virus) are diseases that have been on the agenda of the whole world for the last quarter of a century and have become one of the most important problems for people. Urgent identification of the people infected with a disease will allow these people who have contracted the disease to be treated effectively. In this context, the polymerase-chain-reaction (PCR)-based methods have been the most common and widely used method that responds with sensitivity. However, due to some disadvantages encountered in PCR applications (in particular, the test protocol is comprehensive, not fast in terms of time, not economical, requires user expertise, is not suitable for field/on-site measurements, etc.), a new generation (which can give fast results, are economical, sensitive, suitable for on-site application, etc.) of systems that can provide solutions are needed. On the subject of different test-diagnostic applications used in a large number of test-based analysis methods and techniques, electroanalytical systems have some advantages. Within the scope of this presentation, low-cost, miniaturized electrochemical platforms for surface-printed electrodes by using appropriate biochemical and viral structures of the electrode surfaces decorated with suitable agents are explained. These platforms can be used in the determination of some particular viral proteins for the understanding of viral pathogenic diseases. In this study, a copper-modified graphite electrode was developed and characterized with SEM. Afterwards, an antibody of the N protein of COVID-19 was decorated surrounding this electrode to measure the amount of that protein in the samples. The square wave voltammetry (SWV) technique was used for the electrochemical detection of SARS-CoV-2. When the results of the analyses were examined, the best analytical sensitivity and linearity were obtained by incubating the antibody-modified electrode and virus antigen for 10 min. The measurements showed linearity with a high correlation coefficient (R-2 = 0.9917). The detection limit (LOD) was calculated as 508 pg/mL. The measurement limit (LOQ) was calculated as 1.54 ng/mL. With the pencil tip, which is an easily accessible material for the modified electrode system we designed, a very precise measurement was provided for the rapid detection of the N protein of the SARS-CoV-2 virus at very low concentrations.Item Metagenomics Next Generation Sequencing (mNGS): An Exciting Tool for Early and Accurate Diagnostic of Fungal Pathogens in Plants(2022) Gokdemir, Fatma Seyma; Iseri, Ozlem Darcansoy; Sharma, Abhishek; Achar, Premila N.; Eyidogan, Fusun; https://orcid.org/0000-0003-2951-848X; 36422016Crop output is directly impacted by infections, with fungi as the major plant pathogens, making accurate diagnosis of these threats crucial. Developing technology and multidisciplinary approaches are turning to genomic analyses in addition to traditional culture methods in diagnostics of fungal plant pathogens. The metagenomic next-generation sequencing (mNGS) method is preferred for genotyping identification of organisms, identification at the species level, illumination of metabolic pathways, and determination of microbiota. Moreover, the data obtained so far show that this new approach is promising as an emerging new trend in fungal disease detection. Another approach covered by mNGS technologies, known as metabarcoding, enables use of specific markers specific to a genetic region and allows for genotypic identification by facilitating the sequencing of certain regions. Although the core concept of mNGS remains constant across applications, the specific sequencing methods and bioinformatics tools used to analyze the data differ. In this review, we focus on how mNGS technology, including metabarcoding, is applied for detecting fungal pathogens and its promising developments for the future.Item The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort(2022) Eyuboglu, Fusun Oner; 0000-0002-5525-8207; 36117966; AAR-4338-2020Background and objectivesAlthough several repurposed antiviral drugs have been used for the treatment of COVID-19, only a few such as remdesivir and molnupiravir have shown promising effects. The objectives of our study were to investigate the association of repurposed antiviral drugs with COVID-19 morbidity. MethodsPatients admitted to 26 different hospitals located in 16 different provinces between March 11-July 18, 2020, were enrolled. Case definition was based on WHO criteria. Patients were managed according to the guidelines by Scientific Board of Ministry of Health of Turkey. Primary outcomes were length of hospitalization, intensive care unit (ICU) requirement, and intubation. ResultsWe retrospectively evaluated 1,472 COVID-19 adult patients; 57.1% were men (mean age = 51.9 +/- 17.7years). A total of 210 (14.3%) had severe pneumonia, 115 (7.8%) were admitted to ICUs, and 69 (4.7%) were intubated during hospitalization. The median (interquartile range) of duration of hospitalization, including ICU admission, was 7 (5-12) days. Favipiravir (n = 328), lopinavir/ritonavir (n = 55), and oseltamivir (n = 761) were administered as antiviral agents, and hydroxychloroquine (HCQ, n = 1,382) and azithromycin (n = 738) were used for their immunomodulatory activity. Lopinavir/ritonavir (beta [95% CI]: 4.71 [2.31-7.11]; p = 0.001), favipiravir (beta [95% CI]: 3.55 [2.56-4.55]; p = 0.001) and HCQ (beta [95% CI]: 0.84 [0.02-1.67]; p = 0.046) were associated with increased risk of lengthy hospital stays. Furthermore, favipiravir was associated with increased risks of ICU admission (OR [95% CI]: 3.02 [1.70-5.35]; p = 0.001) and invasive mechanical ventilation requirement (OR [95% CI]: 2.94 [1.28-6.75]; p = 0.011). ConclusionOur findings demonstrated that antiviral drugs including lopinavir, ritonavir, and favipiravir were associated with negative clinical outcomes such as increased risks for lengthy hospital stay, ICU admission, and invasive mechanical ventilation requirement. Therefore, repurposing such agents without proven clinical evidence might not be the best approach for COVID-19 treatment.