PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Plasma Proteomic Markers of Interleukin-1β Pathway Associated With Incident Age-Related Macular Degeneration in Persons With Aids(Elsevier, 2025) Hunt, Peter W.; Olshen, Adam B.; Murad, Natalia; Ambayec, Gabrielle C.; Sezgin, Efe; Schneider, Michael F.; Jabs, Douglas A.Objective To evaluate the associations of plasma inflammatory proteins with age-related macular degeneration (AMD) in persons with the AIDS, using a discovery-based proteomics approach. Design A nested case-control study (analysis 1) and nested cohort study (analysis 2). Participants Persons with AIDS enrolled in the Longitudinal Study of the Ocular Complications with AIDS (LSOCA). Methods Cryopreserved plasma specimens obtained at baseline were assayed for inflammatory proteins using the Olink Inflammation Explore Panel 1. In analysis 1, baseline proteomic profiles for 26 persons with AIDS and incident intermediate-stage AMD 5 to 10 years after baseline and 49 matched controls (matched for age, biologic sex, race/ethnicity, and follow-up) without AMD were compared. In analysis 2, 475 persons from LSOCA with baseline plasma inflammatory proteomic profile measurements were followed for incident cataract and mortality. Main Outcome Measures Incident intermediate-stage AMD; incident cataract; and mortality. Results Of 365 measurable plasma inflammatory proteins, 118 (32%) were associated with incident intermediate-stage AMD at the false discovery rate-adjusted Q < 0.05 level after adjustment for smoking, CD4+ T count, and plasma human immunodeficiency virus RNA level. Gene ontology pathway enrichment analysis identified the interleukin (IL)-1 beta pathway and wound healing pathways, including tissue inhibitor of metalloproteinase 3, as significantly associated with incident AMD. These associations were qualitatively different from those associated with incident cataracts, where elevated levels of inflammatory proteins were associated with a decreased risk of cataracts. A much broader number of inflammatory pathways, including those related to the adaptive immune system, were associated with mortality. Conclusions Upregulation of the IL-1 beta pathway appears to be associated with an increased risk of incident AMD in persons with AIDS. Given the availability of inhibitors of this pathway, inhibition of the IL-1 beta pathway may provide a therapeutic avenue for treatment of AMD. Financial Disclosure(s) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. Ophthalmology Science 2025;5:100794 (c) 2025 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Article Citation - WoS: 1Citation - Scopus: 1Comparison of Magnetic Seed and Rfid Methods in the Localization of Non-Palpable Breast Lesions(Wolters Kluwer Medknow Publications, 2024) Sanli, Ahmet Necati; Sanli, Deniz E. Tekcan; Golshan, Mehra; Sezgin, Efe; Celik, Varol; Aydogan, FatihBackground: Many methods have been developed for localizing non-palpable breast lesions. This study investigated the success rate and surgical results of the magnetic seed (Magseed) and radiofrequency identification (RFID) method, which are relatively new compared to standard wire-guided localizations. Materials and Methods: 20 simulation (10 Magseed, 10 RFID) models were created using turkey breasts and raisins. Raisins containing magnetic seed and RFID tags were placed on the turkey breast. Sentimag (R) probe was used for the Magseed group, and Faxitron LOCalizer (TM) System device was used in the RFID group. Both methods were evaluated in terms of accuracy in detecting breast lesion localization, operation times, excised tissue weights, total resection volume, surgical margin negativity, and re-excision rates. Results: Lesion localization success in both techniques was 100%. While procedure times were statistically significantly shorter in the Magseed group, incision lengths were shorter in the RFID group (P = 0.013, P = 0.007, respectively). No statistically significant difference was found between the groups for the weight of the removed parts, total resection volume, and surgical margin distance (P > 0.05). Conclusion: In this feasibility study, it was concluded that neither the RFID nor Magseed methods had a significant advantage over each other, in terms of localization detection and surgical margin negativity, and both methods could be used successfully for localization.Article Citation - WoS: 1Citation - Scopus: 1Altitude Shapes Gut Microbiome Composition Accounting for Diet, Thyroid Hormone Levels, and Host Genetics in a Subterranean Blind Mole Rat(Frontiers Media Sa, 2024) Solak, Halil Mert; Kreisinger, Jakub; Cizkova, Dagmar; Sezgin, Efe; Schmiedova, Lucie; Murtskhvaladze, Marine; Yanchukov, AlexeyThe animal gut microbiome acts as a crucial link between the host and its environment, playing a vital role in digestion, metabolism, physiology, and fitness. Using 16S rRNA metabarcoding, we investigated the effect of altitude on the microbiome composition of Anatolian Blind Mole Rats (Nannospalax xanthodon) across six locations and three altitudinal groups. We also factored in the host diet, as well as host microsatellite genotypes and thyroid hormone levels. The altitude had a major effect on microbiome composition, with notable differences in the relative abundance of several bacterial taxa across elevations. Contrary to prior research, we found no significant difference in strictly anaerobic bacteria abundance among altitudinal groups, though facultatively anaerobic bacteria were more prevalent at higher altitudes. Microbiome alpha diversity peaked at mid-altitude, comprising elements from both low and high elevations. The beta diversity showed significant association with the altitude. Altitude had a significant effect on the diet composition but not on its alpha diversity. No distinct altitude-related genetic structure was evident among the host populations, and no correlation was revealed between the host genetic relatedness and microbiome composition nor between the host microbiome and the diet. Free thyroxine (FT4) levels increased almost linearly with the altitude but none of the bacterial ASVs were found to be specifically associated with hormone levels. Total thyroxine (TT4) levels correlated positively with microbiome diversity. Although we detected correlation between certain components of the thyroid hormone levels and the microbiome beta diversity, the pattern of their relationship remains inconclusive.Article Citation - WoS: 6Citation - Scopus: 5Basidiomycota Species in Drosophila Gut Are Associated With Host Fat Metabolism(Nature Research, 2023) Bozkurt, Berkay; Terlemez, Gamze; Sezgin, EfeThe importance of bacterial microbiota on host metabolism and obesity risk is well documented. However, the role of fungal microbiota on host storage metabolite pools is largely unexplored. We aimed to investigate the role of microbiota on D. melanogaster fat metabolism, and examine interrelatedness between fungal and bacterial microbiota, and major metabolic pools. Fungal and bacterial microbiota profiles, fat, glycogen, and trehalose metabolic pools are measured in a context of genetic variation represented by whole genome sequenced inbred Drosophila Genetic Reference Panel (DGRP) samples. Increasing Basidiomycota, Acetobacter persici, Acetobacter pomorum, and Lactobacillus brevis levels correlated with decreasing triglyceride levels. Host genes and biological pathways, identified via genome-wide scans, associated with Basidiomycota and triglyceride levels were different suggesting the effect of Basidiomycota on fat metabolism is independent of host biological pathways that control fungal microbiota or host fat metabolism. Although triglyceride, glycogen and trehalose levels were highly correlated, microorganisms’ effect on triglyceride pool were independent of glycogen and trehalose levels. Multivariate analyses suggested positive interactions between Basidiomycota, A. persici, and L. brevis that collectively correlated negatively with fat and glycogen pools. In conclusion, fungal microbiota can be a major player in host fat metabolism. Interactions between fungal and bacterial microbiota may exert substantial control over host storage metabolite pools and influence obesity risk. © 2023, Springer Nature Limited.Article Citation - WoS: 11Citation - Scopus: 10Molecular Evolution and Population Genetics of Glutamate Decarboxylase Acid Resistance Pathway in Lactic Acid Bacteria(Frontiers Media S.A., 2023) Sezgin, Efe; Tekin, BurcuGlutamate decarboxylase (GAD) pathway (GDP) is a major acid resistance mechanism enabling microorganisms’ survival in low pH environments. We aimed to study the molecular evolution and population genetics of GDP in Lactic Acid Bacteria (LAB) to understand evolutionary processes shaping adaptation to acidic environments comparing species where the GDP genes are organized in an operon structure (Levilactobacillus brevis) versus lack of an operon structure (Lactiplantibacillus plantarum). Within species molecular population genetic analyses of GDP genes in L. brevis and L. plantarum sampled from diverse fermented food and other environments showed abundant synonymous and non-synonymous nucleotide diversity, mostly driven by low frequency changes, distributed throughout the coding regions for all genes in both species. GAD genes showed higher level of replacement polymorphism compared to transporter genes (gadC and YjeM) for both species, and GAD genes that are outside of an operon structure showed even higher level of replacement polymorphism. Population genetic tests suggest negative selection against replacement changes in all genes. Molecular structure and amino acid characteristics analyses showed that in none of the GDP genes replacement changes alter 3D structure or charge distribution supporting negative selection against non-conservative amino acid changes. Phylogenetic and between species divergence analyses suggested adaptive protein evolution on GDP genes comparing phylogenetically distant species, but conservative evolution comparing closely related species. GDP genes within an operon structure showed slower molecular evolution and higher conservation. All GAD and transporter genes showed high codon usage bias in examined LAB species suggesting high expression and utilization of acid resistance genes. Substantial discordances between species, GAD, and transporter gene tree topologies were observed suggesting molecular evolution of GDP genes do not follow speciation events. Distribution of operon structure on the species tree suggested multiple independent gain or loss of operon structure in LABs. In conclusion, GDP genes in LABs exhibit a dynamic molecular evolutionary history shaped by gene loss, gene transfer, negative and positive selection to maintain its active role in acid resistance mechanism, and enable organisms to thrive in acidic environments.Erratum Correction: Intervention for Hepatic and Pulmonary Metastases in Breast Cancer Patients: Prospective, Multi-Institutional Registry Study–imet, Protocol Mf 14-02(Springer, 2023) Soran, Atilla; Özbaş, Serdar; Özçınar, Beyza; Işık, Arda; Doğan, Lütfi; Şenol, Kazım; Sezgin, EfeThe authors‘ given names are correct as reflected here. © Society of Surgical Oncology 2022.Erratum Correction To: Excessive Replacement Changes Drive Evolution of Global Sheep Prion Protein (prnp) Sequences (heredity, (2022), 128, 5, (377-385), 10.1038/S41437-022-00520-6)(Springer, 2023) Teferedegn, Eden Yitna; Yaman, Yalçın; Sezgin, Efe; Ün, CemalIn this article the affiliation details for Author Cemal Ün were incorrectly given as Armauer Hansen research institute, Biotechnology and Bioinformatic Directorate, Addis Ababa, Ethiopia but should have been Department of Biology, Molecular Biology Division, Ege University, Izmir, Turkey. The original article has been corrected. © 2022, The Author(s), under exclusive licence to The Genetics Society.Article Citation - WoS: 2Citation - Scopus: 2Diverse Selection Pressures Shaping the Genetic Architecture of Behçet Disease Susceptibility(Frontiers Media S.A., 2022) Sezgin, Efe; Kaplan, ElifBehçet disease (BD) is a polygenic, multifactorial, multisystem inflammatory condition with unknown etiology. Global distribution of BD is geographically structured, highest prevalence observed among East Asian, Middle Eastern, and Mediterranean populations. Although adaptive selection on a few BD susceptibility loci is speculated, a thorough evolutionary analysis on the genetic architecture of BD is lacking. We aimed to understand whether increased BD risk in the human populations with high prevalence is due to past selection on BD associated genes. We performed population genetics analyses with East Asian (high BD prevalence), European (low/very low BD prevalence), and African (very low/no BD prevalence) populations. Comparison of ancestral and derived alleles’ frequencies versus their reported susceptible or protective effect on BD showed both derived and ancestral alleles are associated with increased BD risk. Variants showing higher risk to and more significant association with BD had smaller allele frequency differences, and showed less population differentiation compared to variants that showed smaller risk and less significant association with BD. Results suggest BD alleles are not unique to East Asians but are also found in other world populations at appreciable frequencies, and argue against selection favoring these variants only in populations with high BD prevalence. BD associated gene analyses showed similar evolutionary histories driven by neutral processes for many genes or balancing selection for HLA (Human Leukocyte Antigen) genes in all three populations studied. However, nucleotide diversity in several HLA region genes was much higher in East Asians suggesting selection for high nucleotide and haplotype diversity in East Asians. Recent selective sweep for genes involved in antigen recognition, peptide processing, immune and cellular differentiation regulation was observed only in East Asians. We conclude that the evolutionary processes shaping the genetic diversity in BD risk genes are diverse, and elucidating the underlying specific selection mechanisms is complex. Several of the genes examined in this study are risk factors (such as ERAP1, IL23R, HLA-G) for other inflammatory diseases. Thus, our conclusions are not only limited to BD but may have broader implications for other inflammatory diseases.Article Citation - WoS: 1Aso Visual Abstract: Intervention for Hepatic and Pulmonary Metastases in Breast Cancer Patients-Prospective, Multi-Institutional Registry Study: Imet; Protocol Mf 14-02(Springer, 2022) Soran, Atilla; Özbaş, Serdar; Özçınar, Beyza; Işık, Arda; Doğan, L.; Şenol, Kazım; Dağ, Ahmet; Karanlık, Hasan; Aytaç, Özgür; Karadeniz Çakmak, Güldeniz; Dalcı, Kubilay; Doğan, Mutlu; Sezer, Atakan Y.; Gökgöz, Şehsuvar; Özyar, Enis; Sezgin, EfeThe aim of our prospective, multicenter registry study was to investigate the importance of interventions for operable lung and/or liver metastasis for breast cancer (BC) survival (https://doi.org/10.1245/s10434-022-12239-z). The results reveal that surgical resection or ablative interventions may contribute to survival in patients with BC with limited number and operable metachronous hepatic/pulmonary metastases. Ultimately, randomized studies will determine whether intervention on lung and liver metastatic sites should be performed. In the meantime, such interventions can be considered on select patients.Article Citation - WoS: 8Citation - Scopus: 10Factors Associated With the Occurrence and Healing of Umbilical Pilonidal Sinus: a Rare Clinical Entity(Lippincott Williams and Wilkins Ltd., 2022) Işık, Arda; Wysocki, Arkadiusz Peter; Memiş, Ufuk; Sezgin, Efe; Yezhikova, Assel; Islambekov, YersultanObjective: Pilonidal sinus disease (PSD) is a chronic inflammatory condition of skin that is thought to be related to implanted loose hair. Although PSD is most frequently seen in the sacrococcygeal region, it can also occur at the axilla, perineum, suprapubic regions, hands, and umbilicus. The aim of this project was to find factors influencing the development and treatment of umbilical PSD. Methods: In this retrospective study, the authors evaluated 82 patients (19 women, 63 men) with a history of umbilical PSD between 2012 and 2020 to determine predisposing factors and treatment modalities. Results: There was a 20% concordance with intergluteal PSD. Smoking was the only modifying factor for recurrence. The three different treatment methods studied (conservative treatment, surgical treatment, silver nitrate) did not differ in recurrence rate (P =.57). Conclusions: Because of its rare nature, umbilical PSD can be misdiagnosed or underdiagnosed. Key aspects of treatment include smoking cessation and a conservative approach.
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