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Real-world survival outcomes following metastasectomy in ras wild-type mcrc: Insights from a multicentre national cohort study
No full textBackground: Metastasectomy is a cornerstone of multimodal management in metastatic colorectal cancer (mCRC), yet contemporary real-world data focusing specifically on RAS wild-type (RAS-WT) disease remain limited. We aimed to evaluate survival outcomes and prognostic factors associated with metastasectomy in patients with RAS-WT mCRC using a large national multicentre registry. Methods: This retrospective cohort study utilized data from the ONKO-KOLON T & uuml;rkiye registry. A total of 1079 patients with pathologically confirmed KRAS/NRAS wild-type mCRC were identified and categorized according to receipt of metastasectomy. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared with log-rank tests across multiple clinically relevant time origins, including metastatic diagnosis, initial colorectal cancer diagnosis, and time of metastasectomy. Prognostic factors within the metastasectomy cohort were assessed using univariate Cox proportional hazards models. Serum CEA and CA19-9 were analyzed after log10 transformation. Results: Among 1079 patients, 185 (17.1%) underwent metastasectomy. Patients receiving metastasectomy demonstrated significantly longer OS compared with those managed non-surgically when survival was calculated from the time of metastatic diagnosis (hazard ratio [HR] for death 0.36, 95% CI 0.27-0.47; p < 0.001), as well as improved PFS (HR for progression or death 0.39, 95% CI 0.30-0.52; p < 0.001). The survival advantage remained consistent when OS was measured from the time of initial colorectal cancer diagnosis (HR 0.37, 95% CI 0.25-0.50; p < 0.001). Median OS following metastasectomy was 43 months (95% CI 31.4-45.6). In univariate analyses within the metastasectomy cohort, higher baseline CA19-9 levels were significantly associated with inferior OS when analyzed both as a continuous variable (per log10 increase; HR 1.81, 95% CI 1.20-2.75; p = 0.005) and as a categorical variable (above vs. below threshold; HR 0.37, 95% CI 0.16-0.86; p = 0.021). Other clinicopathologic factors, including age, CEA, tumor sidedness, grade, MSI status, and metastatic burden, were not significantly associated with survival. Conclusions: In this large, real-world national cohort of RAS-WT mCRC, metastasectomy was strongly associated with prolonged survival across multiple clinically relevant time frames. Within surgically treated patients, baseline CA19-9 emerged as the most informative prognostic marker, while traditional clinicopathologic variables showed limited discriminatory value. These findings highlight the importance of careful patient selection and support further prospective studies integrating molecular and biomarker-based strategies to refine prognostication and optimize surgical decision-making in RAS-WT mCRC
Investigation of the potential roles of IL-9 cytokine in the regulation of ATP adenosine metabolism
No full textHücresel enerji döngüsünün önemli bir parçası olan adenozin trifosfat (ATP), aynı zamanda doku hasarı ve enflamasyon gibi durumlarda önemli bir sinyal molekülü olarak görev yapar. ATP’nin hücre dışına salınımı ve CD39 ile CD73 gibi ektonükleotidazlar aracılığıyla adenozine dönüştürülmesi, immün yanıtların düzenlenmesinde kritik bir metabolik yolak oluşturur. Bu çalışmada, IL-9’un ATPadenozin metabolizması üzerindeki düzenleyici potansiyeli ve bu etkinin özellikle T hücre yanıtları üzerindeki yansımalarının sistematik olarak incelenmesi amaçlanmıştır. Sağlıklı bireylerden izole edilen periferik kan mononükleer hücreleri (PKMH), IL-9'un neden olduğu fenotipik, fonksiyonel ve metabolik değişiklikleri karakterize etmek ve altta yatan mekanizmaları araştırmak amacıyla Akan Hücre Ölçer (AHÖ) ve Enzim Bağımlı İmmünosorbent Yöntem (ELISA) teknikleriyle analiz edildi. Bulgularımız, IL-9’un ana T hücre popülasyonlarının frekansını değiştirmemesine karşın, CD39 ve CD73 ekspresyonunu artırarak ATP’nin adenozine dönüşümünü hızlandırdığını göstermiştir. Bu mekanizma, özellikle regülatör T (Treg) hücrelerde immünosüpresif bir mikroçevre oluşumuna katkı sağlamıştır. IL-9 ayrıca proenflamatuvar sitokin üretimini baskılarken, antienflamatuvar sitokinleri artırmış ve T hücre proliferasyonunu sınırlamıştır. Eksojen ATP’nin varlığında Treg frekansında azalma olmasına rağmen IL-9’un etkileri korunmuş olup Treg gelişimini teşvik etmiştir. Kültür ortamındaki ATP düzeyleri IL-9 ile azalırken, adenozin artış eğilimi göstermiştir. Bu etkilerin büyük çoğunluğu CD39/CD73 ektonükleotidaz aktivitelerinin inhibisyonuyla tersine çevrilmiştir. Sonuç olarak çalışmamız, IL-9’un CD39 ve CD73 ektonükleotidazları aracılığıyla ATP–adenozin metabolizmasını modüle edebildiği ve bu yolla gelişen pürinerjik sinyallemenin T hücre yanıtlarını şekillendirebildiğine dair literatüre özgün bir katkı sunmaktadır. Elde edilen bulgular, IL-9’un özellikle kronik enflamasyon, otoimmün hastalıklar ve kanser gibi patolojilerde, immünoterapötik yaklaşımların geliştirilmesine yönelik hedeflenebilecek potansiyel bir molekül olduğunu ortaya koymaktadır.Adenosine triphosphate (ATP), which is an important component of the cellular energy cycle, also functions as a key signaling molecule under conditions such as tissue damage and inflammation. The release of ATP into the extracellular space and its conversion into adenozine through ectonucleotidases such as CD39 and CD73 constitutes a critical metabolic pathway in the regulation of immune responses. In this study, it was aimed to systematically investigate the regulatory potential of IL-9 on ATP–adenosine metabolism and the reflections of this effect, particularly on T cell responses. Peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals were analyzed using Flow Cytometry (FCM) and Enzyme-Linked Immunosorbent Assay (ELISA) techniques in order to characterize the phenotypic, functional, and metabolic changes induced by IL-9 and to investigate the underlying mechanisms. Our findings demonstrated that although IL-9 did not alter the frequency of major T cell populations, it enhanced the conversion of ATP to adenosine by increasing CD39 and CD73 expression. This mechanism contributed to the formation of an immunosuppressive microenvironment, particularly within regulatory T (Treg) cells. IL-9 also suppressed proinflammatory cytokine production while increasing antiinflammatory cytokines and limiting T cell proliferation. Although a decrease in Treg frequency was observed in the presence of exogenous ATP, the effects of IL-9 were preserved and promoted Treg development. While ATP levels in the culture medium decreased with IL-9 treatment, adenosine levels showed a tendency to increase. The majority of these effects were reversed by inhibition of CD39/CD73 ectonucleotidase activities. In conclusion, our study provides an original contribution to the literature by demonstrating that IL-9 can modulate ATP–adenosine metabolism through CD39 and CD73 ectonucleotidases, and that the resulting purinergic signaling can shape T cell responses. The obtained findings reveal that IL-9 is a potential molecule that may be targeted for the development of immunotherapeutic approaches, particularly in pathologies such as chronic inflammation, autoimmune diseases, and cancer
The alignment of the book ‘’Science in the Child's World: Activities for Meaningful Learning’’ with the objectives of the Turkish Ministry of National Education Science Curriculum and the evaluation of sample activities
No full textBu araştırmanın amacı, Prof. Dr. Olga Jarrett tarafından kaleme alınan Çocuğun Dünyasında Bilim: Anlamlı Öğrenme İçin Etkinlikler adlı eserde yer alan örnek uygulamaların, Millî Eğitim Bakanlığı (MEB) 2018 İlkokul Fen Bilimleri Dersi Öğretim Programı hedefleri, kazanımları ve öğrenme-öğretme yaklaşımı ile uyumunu incelemek; ayrıca bu uygulamaların ilkokul öğrencilerinin bilimsel süreç becerileri ile fen bilimlerine yönelik ilgi ve öğrenme süreçlerine katkısını değerlendirmektir. Araştırma, nitel araştırma yaklaşımı kapsamında durum çalışması deseni ile yürütülmüştür. Bu kapsamda, ilgili kitapta yer alan etkinlikler ile MEB 2018 İlkokul Fen Bilimleri Dersi Öğretim Programı’nın amaçları, kazanımları ve temel yaklaşımları karşılaştırmalı olarak incelenmiştir. Bu süreçte etkinlikler, araştırma-sorgulamaya dayalı öğrenme anlayışı, bilimsel süreç becerileri ve program temelli ölçütler doğrultusunda incelenmiştir. Araştırma kapsamında, etkinliklerin uygulanması sürecinde öğrencilerin gözlem yapma, tahmin yürütme, ölçme, veri toplama, karşılaştırma, verileri yorumlama ve sonuç çıkarma gibi bilimsel süreç becerilerini kullanma düzeyleri incelenmiştir. Elde edilen bulgular, kitapta yer alan etkinliklerin MEB Fen Bilimleri Dersi Öğretim Programı ile yüksek düzeyde uyumlu olduğunu ve araştırma-sorgulamaya dayalı öğrenme yaklaşımını desteklediğini göstermektedir. Ayrıca basit ve günlük yaşamdan seçilen materyallerle gerçekleştirilen etkinliklerin, öğrencilerin bilimsel süreç becerilerini kullanmalarını desteklediği; fen bilimleri dersine yönelik ilgi ve motivasyonlarına ilişkin öğrencilerin olumlu görüşler ortaya koyduğu; öğrenme sürecini anlamlı hâle getirdiği belirlenmiştir. Sonuç olarak, Çocuğun Dünyasında Bilim: Anlamlı Öğrenme İçin Etkinlikler adlı eserde yer alan etkinliklerin, ilkokul fen öğretiminde öğretim programı ile uyumlu, uygulanabilir ve öğretmenler için tamamlayıcı bir kaynak niteliği taşıdığı sonucuna ulaşılmıştır.The aim of this research is to examine the compatibility of the sample applications in the book "Science in the Child's World: Activities for Meaningful Learning" by Prof. Dr. Olga Jarrett with the objectives, learning outcomes, and learning-teaching approach of the 2018 Primary School Science Curriculum of the Ministry of National Education (MEB); and to evaluate the contribution of these applications to primary school students' scientific process skills and their interest and learning processes in science. The research was conducted using a case study design within the scope of a qualitative research approach. In this context, the activities in the book were examined comparatively with the objectives, learning outcomes, and basic approaches of the 2018 Primary School Science Curriculum of the MEB. In this process, the activities were examined in line with the inquiry-based learning understanding, scientific process skills, and program-based criteria. Within the scope of the research, the level at which students use scientific process skills such as observation, prediction, measurement, data collection, comparison, data interpretation, and drawing conclusions during the implementation of the activities was examined. The findings indicate that the activities in the book are highly compatible with the Ministry of National Education's Science Curriculum and support an inquiry-based learning approach. Furthermore, it was determined that the activities, carried out using simple materials selected from daily life, support students in using their scientific process skills; students expressed positive opinions regarding their interest and motivation towards science lessons; and the learning process is made meaningful. In conclusion, it was determined that the activities in the book "Science in the Child's World: Activities for Meaningful Learning" are compatible with the curriculum in primary school science education, applicable, and serve as a complementary resource for teachers
Bulky auricular folliculotropic mycosis fungoides: Dramatic response and rechallenge efficacy with extended brentuximab vedotin therapy
No full textFibrosis-4 score and postoperative outcomes in metabolic dysfunction-associated steatotic liver disease
No full textBackground/Aims: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing globally. The Fibrosis-4 (FIB-4) score is a noninvasive biomarker used for assessing potential advanced fibrosis. The study aimed to evaluate the role of the FIB-4 score in predicting postoperative complications and mortality in patients undergoing surgery. Materials and Methods: This multicenter retrospective study included 11 072 patients who underwent surgery under general anesthesia. Demographic and clinical data-including age, gender, comorbidities, FIB-4 scores, American Society of Anesthesiologists classification, postoperative complications, and mortality-were analyzed. Results: A total of 1667 MASLD patients were included. Patients were classified based on FIB-4 scores: 70% (n = 1167) had FIB-4 = 2.67. Due to the limited number of patients with possible advanced fibrosis (FIB-4 >= 2.67), propensity score (PS) matching was performed. After PS matching, patients with a high FIB-4 score exhibited a significantly higher rate of postoperative complications (P < .001), and 12-month mortality was elevated (11%), although the difference was not statistically significant (P = .481). Conclusion: A high FIB-4 score may serve as a predictive marker for postoperative complications in patients with MASLD undergoing surgery
Suva-based modelling of thmfp under ozonation using regression and ann approaches
No full textDrinking-water treatment systems must effectively control natural organic matter (NOM), a major precursor of regulated disinfection by-products (DBPs). Specific ultraviolet absorbance (SUVA) is widely used as an operational surrogate for NOM aromaticity and hydrophobicity; however, ozonation and subsequent filtration can disrupt the linear relationship between SUVA and trihalomethane formation potential (THMFP). This study evaluates whether SUVA can reliably predict THMFP under two ozonation configurations frequently applied in drinking-water treatment: pre-ozonation prior to coagulation-filtration and final ozonation following filtration. Experimental data were analyzed using conventional linear regression and artificial neural network (ANN) models, with SUVA employed as the sole predictor variable. Across all treatment configurations, reductions in SUVA were consistently more pronounced than corresponding decreases in THMFP, indicating a decoupling between chromophoric loss and chlorine-reactive precursor dynamics under ozonation-dominated conditions. Linear regression models exhibited only moderate predictive performance (R2 = 0.63-0.76), reflecting the limitations of proportional surrogate-based approaches when NOM undergoes oxidative and adsorptive transformation. In contrast, single-parameter ANN models captured the nonlinear SUVA-THMFP relationship with substantially higher accuracy across both pre- and final-ozonation regimes (R2 = 0.88-0.99), successfully resolving process-dependent patterns embedded within optically compressed SUVA signals. These findings demonstrate that, although SUVA alone cannot linearly represent the multistep transformation of NOM during ozonation and adsorption, it retains process-relevant structure information on DBP precursor reactivity that can be effectively extracted using nonlinear modelling. The results highlight the potential of integrating ANN-driven tools into advanced monitoring and DBP-control strategies in modern drinking-water treatment systems
Participation across public programs among children in low-income families: Public preschool, child care subsidies, and the supplemental nutrition assistance program
No full textEarly care and education (ECE) and nutrition assistance programs expand opportunity during early childhood. Although prior research examines participation in individual ECE programs, few investigate how families combine support across programs despite overlap in eligibility, or how nutrition assistance influences these decisions. Using linked administrative data from Virginia (2015–2019), this study examines how low-income families bundle public preschool with child care subsidies, and the extent to which the Supplemental Nutrition Assistance Program (SNAP) changes these bundles during the pre-K year. We explore who combines which ECE programs, when combinations occur, and how these patterns relate to hours in ECE using a sample of 176,773 first-time kindergarteners eligible for free or reduced-price lunch. We then focus on 98,965 of these children who participated in SNAP during the pre-K year. Child care subsidy participation is greatest among lowincome children in private ECE, but also common among public pre-K participants, suggesting mismatches between preschool and parent work schedules. Subsidy participation is associated with greater weekly hours in licensed ECE across public, private, and other settings. Black children from low-income households are most likely to attend public ECE and participate in subsidies, whereas Hispanic children are least likely to participate in public ECE, subsidies, and SNAP. We show subsidy timing varies by ECE type: utilization peaks during the academic year for those in private ECE and declines in summer, but ticks up in summer for those in public ECE or other settings. Findings highlight the importance of public program coordination in supporting low-income families.Version of Recor
Prediction of ammonia mitigation efficiency in sodium bisulfate-treated broiler litter using artificial neural networks
No full textThe increasing demand for poultry meat, driven by its favorable nutritional profile, including low cholesterol and high protein content, has resulted in intensified production volumes and, consequently, elevated ammonia (NH3) emissions. Artificial intelligence-based predictive approaches offer an effective alternative to conventional treatment-oriented methods by enabling faster and more accurate estimation of NH3 removal performance. This study aimed to predict the ammonia removal efficiency of broiler litter generated during a production cycle under controlled laboratory-scale conditions using artificial neural networks (ANNs) trained with different learning algorithms. Four ANN models were developed based on the Levenberg-Marquardt (LM), Fletcher-Reeves (FR), Scaled Conjugate Gradient (SCG), and Bayesian Regularization (BR) algorithms. The results showed that the LM-based model with 12 hidden neurons achieved the highest predictive performance (R2 = 0.9777; MSE = 0.0033; RMSE = 0.0574; MAPE = 0.0833), while the BR-based model with 10 neurons showed comparable accuracy. In comparison with the FR and SCG models, the LM algorithm demonstrated superior predictive accuracy and generalization capability. Overall, the findings suggest that ANN-based modeling is a reliable, data-informed approach for estimating NH3 removal efficiency, providing a potential decision-support framework for ammonia mitigation strategies in poultry production systems