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A new high-performance liquid chromatography method andvalidation for the determination of pomalidomide inpharmaceutical preparations
Get PDFMultipl miyelom hastalığı kemik iliği kanseri olarak adlandırılan kötü huylu olan bir kan hastalığıdır. Pomalidomid, multipl-miyelom tedavisinde yaygın olarak kullanılan bir ilaç etken maddesidir. Bu çalışmanın amacı, pomalidomidin farmasötik preparatlarda tayini için yeni bir ters faz yüksek performanslı sıvı kromatografisi yöntemi (HPLC) geliştirmek ve valide etmektir. Validasyon çalışmaları, analitik metodun seçicilik, doğruluk, doğrusallık, kesinlik, tekrarlanabilirlik ve sağlamlık parametreleri üzerine odaklanmıştır. Geliştirilen HPLC yönteminde, silika C18 kolon (250 mm × 4,6 mm, 5 μ), mobil faz A olarak asetonitril: 0,1M fosforik asit çözeltisi (10:90) ve mobil faz B olarak asetonitril: 0,1M fosforik asit çözeltisi (70:30) olarak belirlenmiştir. Mobil faz akış hızı 1,2 mL/dakikadır. Çalışmada fotodiyot dedektör (PDA) kullanılmış ve dalga boyu 230 nm seçilmiştir. Doğrusal aralık konsantrasyon 0,03 mg/mL ile 0,09 mg/mL arasında bulunmuştur. Doğruluk çalışmaları 0,04 mg/mL ve 0,07 mg/mL arasında yapılmıştır. Kapsüllerden geri kazanım değeri ortalama %101,1'dir. Geliştirilen yöntem ICH kurallarına göre valide edildikten sonra pomalidomidin kapsül preparatlarda miktar tayinine başarı ile uygulanmıştır ve pomalidomidin kalite kontrol süreçlerinde güvenilir bir miktar tayini metodu olarak kullanılabilirliğini desteklemektedir.Multiple myeloma is a malignant blood disease referred to as bone marrow cancer. Pomalidomide is an active pharmaceutical ingredient widely used in the treatment of multiple myeloma. The objective of this study is to develop and validate reverse-phase high-performance liquid chromatography (HPLC) method for the determination of Pomalidomide in pharmaceutical preparations. The validation studies focused on the selectivity, accuracy, linearity, precision, repeatability, and robustness parameters of the analytical method. The developed HPLC method utilized a C18 silica column (250 mm × 4.6 mm, 5 μm), with mobile phase A comprising acetonitrile: 0.1M phosphoric acid solution (10:90) and mobile phase B comprising acetonitrile: 0.1M phosphoric acid solution (70:30). The mobile phase flow rate was set at 1.2 mL/min. A photodiode array (PDA) detector was used with a wavelength of 230 nm. The linear range was determined between concentrations of 0.03 mg/mL and 0.09 mg/mL. Accuracy studies were conducted between 0.04 mg/mL and 0.07 mg/mL, with a mean recovery value from capsules of 101.1%. After validation according to ICH guidelines, the developed method was successfully applied for the quantification of pomalidomide in capsule formulations and demonstrated its reliability as a quantitative method in quality control processes for pomalidomide
Gelatins derived from aronia-supplemented fish diets: Structural effect and molecular simulation
No full textFish gelatin, a sustainable substitute for mammalian gelatin, frequently exhibits weaker gel strength and thermal stability, limiting its industrial uses. This study investigated an in vivo method to improve functional characteristics by supplementing Nile tilapia diets with Aronia extract. The control diet (A0) contained no Aronia extract, while the remaining four diets consisted of commercial pelleted feed enriched with 250 mg/kg (A250), 500 mg/kg (A500), 750 mg/kg (A750), and 1000 mg/kg (A1000) of Aronia extract. The gelatin samples revealed thermo-reversible behavior with increasing temperature. A250 exhibited the highest melting temperature of 29.65 degrees C, compared to 27.43 degrees C for A0. The gelation temperature for A250 was 17.56 degrees C, indicating a relatively stable gelatin structure. The elastic modulus (G') was the highest in A250, suggesting an improved gel network compared to the other samples. The gelation rate constant (kgel) was highest in A250 (540.67 Pa), followed by A750 (447.32 Pa), A500 (393.85 Pa), and A1000 (370.97 Pa), compared to 391.15 Pa for A0. The gel strength was improved, with A250 showing the highest value at 133.9 g, followed by A750, A1000, and A500, while A0 was 102.1 g. The glass transition temperatures (Tg) for A250, fish gelatin (FG), bovine gelatin (BG), and A0 were 76.72 degrees C, 74.31 degrees C, 70.71 degrees C, and 73.52 degrees C, respectively. Molecular docking studies revealed strong binding interactions between A250 and phenolic compounds, which contributed to the observed structural enhancements. These findings suggest that supplementing fish diets with Aronia extract can substantially enhance gelatin quality, offering a promising alternative to traditional gelatin sources
RUMELİ’DE ASİ BİR VOYVODA: MACAR ALİ AĞA (1792-1798)
No full textSelim III's reign was full of rebellions in various provinces of the Ottoman Empire, one after another. In this respect, Rumelia was one of the regions where rebellions occurred intensely. Especially the mountainous rebellions that took place between 1791-1808 caused the central authority in Rumelia to disappear at certain intervals. In this period, in addition to the bandit activity, state officials and high-ranking figures who joined the outlawed elements expanded the scope of the mountainous rebellions. One of the important figures in Rumelia who spread the mountainous rebellions and naturally the mountainous banditry from Vidin to the Rusçuk/Silistre line was Ali the Madjar, known as the commander of Pazvandoğlu Osman. However, despite his influence, the information about Ali Aga in the literature is quite limited. Therefore, in the existing sources, Ali Aga's role in the mountainous rebellions is generally monotonous. However, Ali Aga's life was built on two different identities. In this respect, the identities of Selvi Voivode Ali Aga and Madjar Ali shed light on the Mountaineer rebellions in Rumelia from two different fronts. As a matter of fact, Ali Aga's identity as voivode is as effective in the struggle against the mountaineer rebellions as his identity as Madjar Ali, the commander of Pazvandoğlu Osman, is very important in the spread of the rebellions. In this respect, an independent study on Ali Aga is essential for recent Ottoman and Balkan history. This article will use documents from the Ottoman archives of the Presidency of the Republic to evaluate the dynamics under which Ali Aga, a state official, turned into a vigilante and to reveal the extent to which this transformation affected the ongoing mountaious rebellions in Rumelia.III. Selim’in saltanatı, Osmanlı Devleti’nin çeşitli eyaletlerinde birbiri ardına ortaya çıkan isyan hadiseleriyle doludur. Bu doğrultuda Rumeli, isyan hadiselerinin yoğun olarak yaşandığı bölgelerin başında gelmektedir. Özellikle 1791-1808 yılları arasında meydana gelen dağlı isyanları, Rumeli’de merkezi otoritenin belli aralıklarla ortadan kalkmasına neden olmuştur. Bu dönem eşkıya hareketliliğinin yanında kanun dışı unsurlar arasına katılan devlet görevlileri ve üst düzey simalar, dağlı isyanlarının hareket sahasını genişletmiştir. Rumeli’de dağlı isyanlarını ve doğal olarak dağlı eşkıyasını Vidin’den Rusçuk/Silistre hattına kadar yayan önemli isimlerden biri de Pazvandoğlu Osman’ın komutanı olarak bilinen Macar Ali’dir. Ancak yaratmış olduğu etkiye rağmen Ali Ağa hakkında literatüre yansıyan bilgi oldukça kısıtlıdır. Bundan dolayı var olan kaynaklarda Ali Ağa’nın dağlı isyanları içindeki rolü genellikle tekdüze bir anlatım içermektedir. Halbuki Ali Ağa’nın yaşamı iki farklı kimlik üzerinde inşa edilmiştir. Bu bakımdan Selvi Voyvodası Ali Ağa ve Macar Ali kimlikleri Rumeli’deki dağlı isyanlarına iki farklı cepheden de ışık tutmaktadır. Nitekim Ali Ağa’nın voyvoda kimliği, dağlı isyanlarına karşı mücadelede ne kadar etkinse Pazvandoğlu Osman’ın komutanı olan Macar Ali kimliği de isyanların yayılmasında oldukça önemlidir. Bu bakımdan Ali Ağa’ya dair bağımsız bir çalışmanın yapılması, yakın dönem Osmanlı ve Balkan tarihi açısından elzemdir. Makalede Cumhurbaşkanlığı Osmanlı arşivi belgeleri kullanılarak bir devlet görevlisi olan Ali Ağa’nın hangi dinamikler çerçevesinde kanun dışı unsura dönüştüğü değerlendirilecek ve bu dönüşümün Rumeli’de devam eden dağlı isyanlarını hangi boyutta etkilediği ortaya koyulmaya çalışılacaktır
Effects of neoadjuvant and adjuvant chemotherapy on survival in muscle-invasive bladder cancer: A multicenter study
Get PDFAmaç: Kasa invaze mesane kanserinin tedavisinde yüksek metastaz riski nedeniyle sistemik tedavi önerilmektedir. Neoadjuvan veya adjuvan tedaviyi karşılaştıran yeterli çalışma olmaması nedeniyle bu çalışmada amacımız lokal ileri evre mesane kanserinde neoadjuvan veya adjuvan tedavi alan hastaların tedavi etkinliğini karşılaştırmaktır. Gereç ve Yöntemler: Radikal sistektomi yapılan ve perioperatif kemoterapi alan 6 merkezden 107 mesane kanseri hastası retrospektif olarak çalışmaya dahil edildi. Hastalar 2 kategoriye ayrıldı: (i) neoadjuvan kemoterapi (n=54) ve (ii) adjuvan kemoterapi (n=53). Ortanca takip süresi 31.6 aydı (%95CI 21.8-41.4). 30. ay hastalıksız sağkalım oranı (HSO) tüm grupta %58.9, neoadjuvanda %56.3 ve adjuvanda %61.5 idi. Neoadjuvan tedavi sonrası 30.ay HSS evrelemeye göreAim: Muscle-invasive bladder cancer requires systemic treatment due to its high risk of metastasis. However, studies comparing neoadjuvant and adjuvant therapy regimens are currently limited. Our goal in this study was to compare the treatment efficacy of patients receiving neoadjuvant or adjuvant treatment in locally advanced bladder cancer. Material and Methods: We retrospectively included 107 bladder cancer patients from 6 centres who underwent radical cystectomy and received perioperative chemotherapy. Patients were divided into 2 categories: (i) neoadjuvant chemotherapy (n=54) and (ii) adjuvant chemotherapy (n=53). Results: Median follow-up was 31.6 months (95%CI 21.8-41.4). 30-month disease-free survival (DFS) was 58.9% in the whole group, 56.3% in neoadjuvant and 61.5% in adjuvant. 30-month DFS after neoadjuvant treatment was 70.1% i
Lacunary statistical soft convergence in soft topology
Get PDFStatistical convergence and some related types of convergence are a generalisation of topological convergence. Similarly, soft set theory, introduced by Molodtsov to deal with uncertainty in various scientific fields, is a generalisation of the classical concept of sets. Although both concepts have found extensive applications to various mathematical structures, the investigation of statistical convergence within soft topological spaces has not yet been undertaken. This study examines the lacunary statistical convergence of sequences of soft points in soft topological spaces, employing a density defined by an unbounded modulus function. Basic results and inclusion theorems concerning this convergence are presented. © The Author(s) 2025.Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, TÜBİTA
Evaluation of T-cell repertoire by flow cytometric analysis in primary immunodeficiencies with DNA repair defects
Get PDFThe group of patients with DNA-repair-defects increases susceptibility to infections due to impaired repertoire diversity. In this context, we aimed to investigate the TCRv beta-repertoire by flow cytometric analysis and its correlation with clinical entities in a group of IEI patients with DNA repair defects. Peripheral lymphocyte subset and TCRv beta-repertoire analyses were performed by flow cytometric analysis. The aim was to explore the changing TCR-V beta-repertoire that can predict some clinical entities by investigating the repertoire using flow-cytometric-analysis-based TCR-V beta and its interaction with clinical entities in a group of IEI patients with DNA repair defects. TCR-repertoire of the patients with DNA-repair-defects and healthy controls was analysed with flow-cytometer. The potential of flow-cytometric analysis of the TCR repertoire as a practical and easily accessible clinical prediction method was investigated. Thirty-nine-IEI patients with DNA-repair-defects and 15 age-matched healthy-controls were included in this study. Peripheral lymphocyte subset and TCR-V beta repertoire analyses were performed by flow cytometry. Compared to the control group, 9 out of 24 clones (37.5%) exhibited a statistically significant reduction, while only 3 clones showed a statistically significant increase (p < 0.05). Preferential use of v beta-genes was associated with some clinical entities. Lower TCR-v beta-9 and TCR-v beta 23, higher TCR-v beta 7.2 were found in the patients with pneumonia (n = 13) (p = 0.018, p = 0.044 p = 0.032). AT patients with pneumonia had lower TCR-v beta-9 clone than patients without pneumonia (p = 0.008). Skewed proliferation of most TCR-v beta clones was seen DNA-repair-defects, especially AT. In addition, this study showed that preferential use of TCR-v beta genes could be predictive for some clinical entities.Istanbul Universitesi-CerrahpasaIstanbul Universitesi-Cerrahpas
Trade Openness, Economic Growth, Capital, and Financial Globalization: Unveiling Their Impact on Renewable Energy Consumption
Get PDFRenewable energy sources are becoming increasingly popular due to their advantages over fossil fuels, their economic benefits, and growing environmental concerns. Researchers are particularly focused on understanding the factors that affect the efficiency of various energy sources. This paper explores the relationship between renewable energy consumption and trade openness from 1990 to 2018 among the top 15 countries that consume the most renewable energy. The study also considers economic growth, natural resources, capital, and financial globalization as additional factors influencing renewable energy use. To analyze the data, the paper utilizes advanced panel data techniques, including the dynamic Seemingly Unrelated Regression (DSUR) and Dimutrescu-Hurlin panel bootstrap causality methods. The findings reveal cross-sectional dependence and slope heterogeneity in the model. The results show that trade openness, economic growth, and capital investment promote renewable energy consumption, while financial globalization tends to reduce it. Additionally, the study finds one-way causality from trade openness, economic growth, natural resources, capital, and financial globalization to renewable energy consumption. These insights can inform the development of renewable energy policies in the countries examined.The John Paul II Catholic University of Lublin, Poland; John Paul II Catholic University of Lublin, PolandThe APC was funded by The John Paul II Catholic University of Lublin, Poland
The Importance of Body Mass Index on Prognostic Factors for Urinary Incontinence in Asymptomatic Nulliparous Women
No full textIntroductionMeasurements of levator hiatal area (LHA) by pelvic floor ultrasound examination were shown to be associated with symptoms and signs of prolapse and urinary incontinence. Body mass index (BMI) is a modifiable risk factor which has shown to be related with urinary incontinence. Our aim in this study was to observe and to understand the relation between BMI and weight with LH and other transperineal ultrasound parameters such as bladder neck mobility and bladder-urethra angles in asymptomatic nulliparous women.Materials and MethodsThis study was a cross-sectional study in a gynecology outpatient clinic of a tertiary center after receiving ethical approval. Nulliparous women presenting to the gynecology outpatient clinic without any uro-gynecological complaint were invited to participate.ResultsDuring study period, 167 women met the eligibility criteria. Our data showed that weight and BMI are correlated with hiatal dimensions, gamma angle and bladder neck descent even in asymptomatic nulliparous women.DiscussionThese findings may explain why weight loss is associated with improvements in stress incontinence symptoms and why we should encourage women in weight control which is the only modifiable factor in the etiology of incontinence
Letter: Relationships Between Inflammatory Parameters and Quantitative Flow Ratio May Be Misleading Because of Many Confounding Factors
No full text[No abstract available
A fuzzy Kano model proposal for sustainable product design: Mobile application feature analysis
No full textCompanies aim to maximize profits by effectively designing mobile applications to promote their services in a competitive market. However, identifying the design features that significantly impact mobile applications is challenging due to their subjective nature. Traditional Kano approaches face limitations, such as information loss caused by considering only the most frequent values. To address these limitations, this study proposes a novel fuzzy Kano approach to better manage the subjectivity in human judgments and the uncertainty in user preferences. This approach uncovers hidden preference levels, accounts for uncertainties, resolves dual classification issues, compares membership degrees, and emphasizes subtle details that may otherwise be overlooked. The fuzzy Kano approach was applied to survey data from 100 participants, covering 33 mobile application features. By classifying these features, the fuzzy Kano model examined their influence on user satisfaction and quality perception. The results demonstrated the feasibility and effectiveness of the proposed method, identifying key features—such as Product Details, Order Management and Returns, and Product Opinions and Reviews—that, if absent, could lead to customer dissatisfaction. Additionally, the findings revealed significant differences between the fuzzy and traditional Kano models and highlighted variations in mobile application characteristics across different demographic groups, providing valuable insights for mobile application design. © 2025 Elsevier B.V.Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, TÜBİTAK, (222M229