WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
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Article Comprehensive Proteomic and Metabolomic Analysis of Novel Substituted Fluoroquinolone Derivatives in Escherichia Coli Isolates(John Wiley and Sons Ltd, 2026) Nigiz Ş.; Kulabaş N.; Türe A.; Kablan S.; Koçak E.; Özkul C.; Küçükgüzel İ.; Koçak, Engin; Nigiz, Şeyma; Kablan, Sevilay Erdoğan; Özkul, Ceren; Kulabaş, Necla; Küçükgüzel, İlkay; Türe, AslıAntimicrobial resistance is one of the most important global problems, and new antibiotic requirements have been emerging as a key point in this issue. In the present work, we focused on the efficiency of two novel promising fluoroquinolone derivatives on resistant Escherichia coli isolates at the molecular level. Their mode of action and adaptation process were evaluated by using proteomics and metabolomics analysis. Proteomics analysis showed that two compounds have an effect mainly on the ribosomal process and energy metabolism. Moreover, we observed compounds that affect various important antimicrobial targets, such as ribosomal subunits, phosphotransacetylase, and chaperone proteins. In metabolomics analysis, we found that compounds altered bacterial metabolism directly. Pathway analysis showed that cofactor biosynthesis and energy metabolism were affected mainly by undertreated groups. Our experiments demonstrated that novel fluoroquinolone derivatives have promising results at the molecular level and results will contribute to further studies. © 2026 John Wiley & Sons Ltd.Article Fully Synthetic, Nature-Inspired Exosome-Mimetics for Melanoma Therapy(Elsevier B.V., 2026) Arda Ozturk N.Z.; Majchrzak O.B.; Ulivi G.; Kirmizibayrak P.B.; Borchard G.; Patrulea V.; Ozer O.; Ozturk, Nahide Zeren Arda; Borchard, Gerrit; Ozer, Ozgen; Patrulea, Viorica; Majchrzak, Oliwia Barbara; Arda Ozturk, Nahide Zeren; Kirmizibayrak, Petek Ballar; Ulivi, GianlucaFully synthetic exosome-mimetics (FSEMs) represent a nature-inspired drug delivery system designed to replicate the key physicochemical and biological properties of natural exosomes, while offering the potential to address limitations in scalability and reproducibility associated with natural exosomes. In this study, we prepared FSEMs at the laboratory scale. We loaded them with (–)-epigallocatechin-3-gallate (EGCG) and microRNA-23a (miR-23a), aiming to co-deliver therapeutic small molecules and nucleic acids for the treatment of melanoma. FSEMs were fabricated using three methods: thin-film hydration, ethanol injection, and microfluidics. They were surface-functionalized with either CD9, a tetraspanin involved in membrane fusion, or TSP-1, an adhesion protein promoting cellular interactions. Through physicochemical characterization via dynamic light scattering, we found that FSEMs were ∼ 100 nm in size, of low polydispersity (∼0.2) and showed a negative zeta potential (∼–55 mV). Both EGCG and miR-23a were efficiently encapsulated. SDS-PAGE analysis confirmed successful protein incorporation and correct positioning. In vitro release studies showed minimal premature leakage, supporting their suitability for cellular uptake-mediated delivery. When tested on melanoma cells (MDA-MB-435) and progenitor human dermal fibroblasts (FE002-SK2), FSEMs selectively killed melanoma cells while sparing fibroblasts. Importantly, EGCG within FSEMs was more effective than the free compound. Compared to conventional DOTAP-based liposomes, FSEMs were more selective and induced less off-target cytotoxicity. This study presents a proof-of-concept for fully synthetic, protein-functionalized FSEMs as dual carriers for both chemical and gene-based agents, offering a safer and potentially more effective alternative to traditional cationic liposomes. These results lay the groundwork for future in vivo validation and translational cancer research. © 2026 The Author(s)Article Investigation of the Susceptibility Rates to Ceftazidime-Avibactam and Colistin, Clonal Relationships, and Clinical Data of Patients with Carbapenem-Resistant Klebsiella Pneumoniae Isolates Detected in the ICUs of a Hospital in İstanbul(K Faisal Special Hospital Research Centre, 2026) Akkaya, Yuksel; Aydin, Irfan; Harmankaya, Sebile; Karakul, Mehmet; Aydin, Mehtap; Erdin, Begum Nalca; Kilic, Ibrahim Halil; Karakuş, MehmetBACKGROUND: The increase in carbapenem-resistant K. pneumoniae (CR-Kp) in intensive care units (ICUs) causes treatment difficulties and increases risk in mortality. OBJECTIVES: The aim of this study was to investigate the susceptibility rates of CR-Kp isolates obtained from ICUs to ceftazidime-avibactam (CAZ-AVI) and colistin, carbapenem resistance genes, clonal relationships and clinical characteristics of the patients. DESIGN: Retrospective cohort SETTING: Single-center, University of Health Sciences, & Uuml;mraniye Training and Research Hospital MATERIALS AND METHODS: This study was conducted between June 2023 and December 2024. Isolates were identified using VITEK MS v.3.2, and antibiotic susceptibility testing was performed using the VITEK 2 Compact system. CAZ-AVI susceptibility was determined using disk diffusion, and colistin susceptibility was determined using broth microdilution to determine minimum inhibitory concentration (MIC) values. Carbapenem resistance genes were determined using multiplex real-time polymerase chain reaction (RT-PCR) and clonal relationship arbitrarily primed-polymerase chain reaction (AP-PCR). MAIN OUTCOME MEASURES: Resistance genes of CR-Kp isolates, clonal relationships, CAZ-AVI and colistin resistance, and clinical characteristics of patients SAMPLE SIZE: Ninety-seven isolates from 76 patients RESULTS: Among patients with CR-Kp isolates, central venous catheter use was detected in 59 cases (78%), ventilator-associated pneumonia in 44 cases (58%), and bacteremia in 39 cases (51%), respectively. It was determined that 53 of the patients (70%) died. Using the AP-PCR method, 60 different genotypes were identified among 97 isolates, and clustering was determined in 42 of the isolates (46%). It was determined that 36 (37%) of the isolates were resistant to colistin and 42 (45%) were resistant to CAZ-AVI. NDM+OXA-48, OXA-48, KPC, KPC+NDM, and NDM genes were detected in 40 (43%), 32 (35%), 10 (11%), 2 (2%), and 3 (3%) isolates, respectively. It was determined that 30 (75%) of the isolates with NDM+OXA-48 and only 4 (12%) of the isolates with OXA-48 were resistant to CAZ-AVI. CONCLUSION: In addition to OXA-48, an increase in the frequency of CR-Kp isolates containing the NDM, NDM+OXA-48, KPC+NDM, and OXA-48+KPC genes were also detected. It was also determined that resistance to colistin and CAZ-AVI is increasing. The AP-PCR method can also be used to investigate infections. LIMITATIONS: Single center,Pulsed Field Gel Electrophoresis (PFGE) could not be performed together with AP-PCRArticle Does Localization Change Management in Complicated Right and Left-Sided Diverticulitis(Baishideng Publishing Group Inc, 2025) Acar, Turan; Sur, Yunus; Acar, Nihan; Tekindal, Mustafa Agah; Dilek, Osman NuriBACKGROUND Distribution of the colonic diverticula differs in different populations, and right-sided colon diverticulitis (RCD) and left-sided colon diverticulitis (LCD) manifest distinct clinical features. Complicated diverticulitis (CD) mostly requires hospitalization and can be treated within a spectrum from observation to surgery. Treatment choice is formed depending on the patient's general condition, the presence of diffuse peritonitis, the localization of diverticulitis, Hinchey stage, and responsiveness to the prior treatment. Clinical disparities regarding right and LCD also led to the differences in the incidences of both emergency surgery and future elective surgery. AIM To evaluate the clinical features of CD, display the differences according to colonic localizations, and present treatment approaches. METHODS This was a retrospective study from a single centre analysing data from a prospective database. The 253 patients with history of hospitalization for CD were included and divided into two groups: RCD and LCD. To compare the differences between the two groups, the Student's t-test was used when the parametric test prerequisites were fulfilled, and the Mann-Whitney U test was used when such requirements were not fulfilled. RESULTS The 208 (82.2%) patients were found to have LCD, and 45 (17.8%) had RCD. The majority of the patients had Hinchey 1A diverticulitis (49.8%). Male gender was significantly more common in patients who underwent surgery for LCD. While persistent abdominal pain was the main prior finding in the conservative treatment of both localizations, surgery was most performed due to abscess in RCD and perforation in LCD. The presence of an accompanying malignancy during colonoscopy was significantly more common in LCD cases who underwent surgery. Hartmann's procedure was the most performed technique in emergency settings (56.3%), while laparoscopic colectomy with anastomosis was in elective settings (53.9%). In addition, surgery was found to prolong the mean length of hospital stay in LCD patients. CONCLUSION Although diverticulitis is a benign condition, the need for an individualized and evidence-based approach makes management challenging. Localization of the disease has an important role in determining the appropriate treatment.Article Citation - WoS: 1Safety and Efficacy of Depatuxizumab Mafodotin Monotherapy or in Combination With Temozolomide in Patients With/Without EGFR-Amplified Recurrent Glioblastoma: A Systematic Review(Lippincott Williams & Wilkins, 2025) Moghib, Khaled; Hassan, Malak A.; Eljadid, Ghaith Y.; Salomon, Izere; Algazar, Mansour A.; Abu Arafeh, Muhannad Wael; Ibrahim, Ismail A.This study aimed to assess the safety and efficacy of depatuxizumab mafodotin as a monotherapy or in combination with temozolomide in patients with recurrent epidermal growth factor receptor (EGFR)-amplified glioblastoma multiforme, focusing on overall survival (OS) and progression-free survival (PFS). A comprehensive literature search was conducted across PubMed, Cochrane Library, Web of Science, and Scopus databases up to August 2024. Randomized controlled trials (RCTs) and observational studies were included, comparing depatuxizumab mafodotin alone or with temozolomide in patients with and without EGFR amplification. Data extraction encompassed participant demographics, treatment regimens, and clinical outcomes. Of 102 screened publications, 10 RCTs and cohort studies involving 1431 patients met the inclusion criteria. The included studies examined depatuxizumab mafodotin as a standalone therapy and in combination with other agents, revealing OS ranging from 5 to 14 months and considerable variability in PFS. While depatuxizumab mafodotin shows the potential to improve survival outcomes, the heterogeneity in results highlights the need for further research. Future studies should refine patient selection criteria and explore alternative therapeutic combinations, such as depatuxizumab mafodotin with gemcitabine or cisplatin, to optimize treatment strategies.Article Machine Learning Model for Predicting Multidrug Resistance in Clinical Escherichia Coli Isolates: A Retrospective General Surgery Study(Multidisciplinary Digital Publishing Institute (MDPI), 2025) Tolan, H.K.; Aydın, İ.; Tanyildizi-Kökkülünk, H.; Karakuş, M.; Akkaya, Y.; Kaya, O.; Işman, F.K.Background/Objectives: Escherichia coli is one of the leading causes of surgical site infections (SSIs) and poses a growing public health concern due to its increasing antimicrobial resistance. High rates of extended-spectrum beta-lactamase (ESBL) production among E. coli strains complicate treatment outcomes and emphasize the need for effective surveillance and control strategies. Methods: A total of 691 E. coli isolates from general surgery clinics (2020–2025) were identified using MALDI-TOF MS. Antibiotic susceptibility data and patient variables were cleaned, encoded, and used to predict resistance using the Random Forest, CatBoost, and Naive Bayes algorithms. SMOTE addressed class imbalance, and model performance was assessed through various validation methods. Results: Among the three machine learning models tested, Random Forest (RF) showed the best performance in predicting antibiotic resistance of E. coli, achieving median accuracy, precision, recall, and F1-scores of 0.90 and AUC values up to 0.99 for key antibiotics. CatBoost performed similarly but was less stable with imbalanced data, while Naive Bayes showed lower accuracy. Feature importance analysis highlighted strong inter-antibiotic resistance links, especially among β-lactams, and some influence of demographic factors. Conclusions: This study highlights the potential of simple, high-performing models using structured clinical data to predict antimicrobial resistance, especially in resource-limited clinical settings. By incorporating machine learning into antimicrobial resistance (AMR) surveillance systems, our goal is to support the advancement of rapid diagnostics and targeted antimicrobial stewardship approaches, which are essential in addressing the growing challenge of multidrug resistance. © 2025 by the authors.Article Ludwig's Angina in a 6-Year Child: Case Report(Wiley, 2025) Akbari, Negarin; Razavi, Ali; Sabzi, Zahra; Parhiz, JabbarLudwig's angina is a rare but potentially fatal cellulitis that affects the submandibular, sublingual, and submental spaces, typically triggered by dental infections. This case report details a severe presentation of Ludwig's angina in a 6-year-old girl who presented with submandibular swelling, fever, voice alterations, and respiratory distress. Diagnosis was based on clinical evaluation, supported by CT imaging, revealing significant airway narrowing and lymphadenopathy. The patient was promptly intubated to secure the airway, followed by emergency surgical drainage and intravenous antibiotics. Postoperative care included sedation, ongoing monitoring in the PICU, and close follow-up by multiple specialties. After a 10-day hospitalization, the patient showed significant recovery with no complications. The case underscores the importance of early diagnosis and intervention in preventing severe complications such as airway obstruction, sepsis, and mediastinal spread. It highlights the critical role of interdisciplinary collaboration, including pediatric infectious disease specialists, surgeons, and anesthesiologists, in managing this life-threatening condition effectively.Article Citation - WoS: 1Technical Approaches for Preservation of the Temporalis Muscle in Neurosurgery: A Systematic Review(Lippincott Williams & Wilkins, 2025) Azab, Mohammed A.; Sarhan, Khalid; Atallah, Oday; Hernandez-Hernandez, Alan; Ibrahim, Ismail A.; Shama, Mohsen Nabih; Kammoun, BrahimBackground:The temporalis muscle is commonly dissected and mobilized during craniotomy. Cosmetic and functional complications may arise from the improper handling of this muscle. Surgery for recurrent pathologies may be challenging due to adhesions and muscle damage.Material and methods:A systematic review following PRISMA guidelines was conducted to consolidate literature on the potential techniques used for preserving the temporalis muscle during neurosurgical interventions. PubMed, Scopus, and Web of Science were systematically searched using predefined criteria from inception to 2025. A qualitative synthesis was done summarizing the primary cranial pathology, type of surgical approach, the technical clue for temporalis muscle preservation, follow up and complications.Results:We included 27 eligible articles with a total number of 811 patients. About 508 (62.6%) of patients underwent pterional approach, while 150 (18.4%) patients had decompressive craniotomies. Aneurysm clipping was the surgical indication in 172 (21.2%) patients, while decompressive surgery was done for traumatic brain injuries in about 48 (5.9%) patients. Osteoplastic temporalis muscle flap was used in 178 (21.9%) patients, while some authors sutured the temporalis muscle to the cranioplasty plate in 79 (9.7%) patients. Fixation of the temporalis muscle to the bone using sutures through small holes was done in 100 (12.33%) patients. No chewing problems were recorded among all the patients analyzed. Temporalis muscle atrophy was observed in only 13 (1.6%) patients.Conclusion:Proper manipulation of the temporalis muscle during surgery is crucial for the vitality of its fibers and to prevent postoperative functional or cosmetic drawbacks.Article Post-Covid Neutropenia in an Infant With Thalassemia Minor: Case Report(Wiley, 2025) Elsherif, Yasmine; Elsherif, Omar; Karimi, Mehran; Ibrahim, Ismail A.; Abukhadijah, Hana J.This case of an 11-month-old female who developed severe neutropenia following COVID-19 infection underscores the need for heightened vigilance and monitoring of hematological parameters in infants post-COVID-19. The exact mechanism of COVID-19-induced neutropenia is not fully understood, but it may involve cytokine-induced suppression of hematopoiesis and bone marrow repression due to the inflammatory response. Given the potential for serious clinical implications, including increased susceptibility to infections, it is crucial to effectively identify and manage neutropenia in this vulnerable population. Further research is necessary to elucidate the underlying mechanisms and optimize treatment strategies for COVID-19-related hematological complications in infants.Article A Guide To Facilitate the Creation of a Femoral Tunnel for Arthroscopic Ligamentum Teres Reconstruction: a Three-Dimensional Computed Tomography Study(Oxford Univ Press, 2024) Ismailoglu, Abdul Veli; Ismailoglu, Pelin; Zeynalov, Samir, I; Ozdogmus, Omer; Yildizhan, Saliha Elif; Bayramoglu, Alp; Kayaalp, AsimThe ideal femoral tunnel passing through the centre of the femoral neck targeted to the footprint of the ligamentum teres (LT) is established during the LT reconstruction surgery with the free-hand technique. We aimed to quantitatively determine the entry site and define the angular orientation of the ideal femoral tunnel with its relevance to the femoral valgus angle (FVA) and the femoral anteversion angle (FAA) to facilitate the creation of an ideal femoral tunnel during the LT reconstruction surgery. A total of 60 randomly selected CT images were obtained to reconstruct three-dimensional femur models. A virtual reamer representing the ideal femoral tunnel was placed in the femur models. The femur length, FVA, FAA, the femoral tunnel anterior angle, the femoral tunnel superior angle and the skin- and bony-entry sites were measured. The femoral tunnel angular orientation was strongly correlated with the FVA and the FAA. Mathematical formulas were defined by which entry site of the reamer and the anterior and superior angulation of the femoral tunnel could be estimated before the surgery. The mean skin-entry site was 67.3 mm distal and 0.1 mm anterior to the centre of the greater trochanter's superior border. The angular orientation of the femoral tunnel using FVA and FAA can be easily estimated using mathematical formulas before LT reconstruction surgery. The entry site and angular orientation of the femoral tunnel described in this study can be used to reduce dependency on the usage of fluoroscopy and the workload on the surgeon during the LT reconstruction surgery.