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Öğe Refining partial gland ablation for localised prostate cancer: the FALCON project(2025) Rodriguez Sanchez, Lara; Cathelineau, Xavier; De Reijke, Theo; Stricker, Phillip; Emberton, Mark; del Pilar Laguna Pes, Maria; Sanchez Salas, RafaelObjectives: To provide a contemporary statement on focal therapy (FT) for localised prostate cancer (PCa) from an international and diverse group of physicians treating localised PCa, with the aim of overcoming the limitations of previous consensus statements, which were restricted to early adopters, and to offer direction regarding the various aspects of FT application that are currently not well defined. Materials and Methods: The FocAL therapy CONsensus (FALCON) project began with a 154-item online survey, developed following a steering committee discussion and literature search. Invitations to participate were extended to a large, diverse group of professionals experienced in PCa management. From 2022 to 2023, a Delphi consensus study consisting of three online rounds was conducted using the Modified Delphi method. A 1–9 Likert scale was used for the survey, which was followed by an in-person expert meeting. The threshold for achieving consensus was set at 70% agreement/disagreement. Six main aspects of FT were covered: (i) patient selection; (ii) energy source selection; (iii) treatment approach; (iv) treatment evaluation and follow-up; (v) treatment cost and accessibility; and (vi) future perspectives. Results: Of 246 initial participants, 148 (60%) completed all three rounds. Based on participant feedback, 27 new statements were added in the second round, and 33 questions related to personal expertise, for which consensus was not necessary, were excluded. After the third and final round, consensus had not been reached for 69 items. These items were discussed at the in-person meeting, resulting in a consensus of 57 additional items. Consensus was finally not reached on 12 items. Given the volume of data, the voting outcomes are summarised in this article, with a detailed breakdown presented in the form of figures and tables. Conclusions: The FALCON project delivered a significant consensus on the approach to FT for localised PCa. Additionally, it highlighted gaps in our knowledge that may provide guidance for future research.Öğe Multi-omics characterization of improved cognitive functions in parkinson's disease patients after the combined metabolic activator treatment: a randomized, double-blinded, placebo-controlled phase II trial(2025) Yuluğ, Burak; Altay, Özlem; Hanoğlu, Lütfü; Velioğlu, Halil Aziz; Coşkun, Ebru; Bayraktaroğlu, Zübeyir; Mardinoğlu, AdilParkinson’s disease is primarily marked by mitochondrial dysfunction and metabolic abnormalities. We recently reported that the combined metabolic activators improved the immunohistochemical parameters and behavioural functions in Parkinson’s disease and Alzheimer’s disease animal models and the cognitive functions in Alzheimer’s disease patients. These metabolic activators serve as the precursors of nicotinamide adenine dinucleotide and glutathione, and they can be used to activate mitochondrial metabolism and eventually treat mitochondrial dysfunction. Here, we designed a randomized, double-blinded, placebo-controlled phase II study in Parkinson’s disease patients with 84 days combined metabolic activator administration. A single dose of combined metabolic activator contains L-serine (12.35 g), N-acetyl-L-cysteine (2.55 g), nicotinamide riboside (1 g) and L-carnitine tartrate (3.73 g). Patients were administered either one dose of combined metabolic activator or a placebo daily for the initial 28 days, followed by twice-daily dosing for the next 56 days. The main goal of the study was to evaluate the clinical impact on motor functions using the Unified Parkinson’s Disease Rating Scale and to determine the safety and tolerability of combined metabolic activator. A secondary objective was to assess cognitive functions utilizing the Montreal Cognitive Assessment and to analyse brain activity through functional MRI. We also performed comprehensive plasma metabolomics and proteomics analysis for detailed characterization of Parkinson’s disease patients who participated in the study. Although no improvement in motor functions was observed, cognitive function was shown to be significantly improved (P < 0.0000) in Parkinson’s disease patients treated with the combined metabolic activator group over 84 days, whereas no such improvement was noted in the placebo group (P > 0.05). Moreover, a significant reduction (P = 0.001) in Montreal Cognitive Assessment scores was observed in the combined metabolic activator group, with no decline (P > 0.05) in the placebo group among severe Parkinson’s disease patients with lower baseline Montreal Cognitive Assessment scores. We showed that improvement in cognition was associated with critical brain network alterations based on functional MRI analysis, especially relevant to areas with cognitive functions in the brain. Finally, through a comprehensive multi-omics analysis, we elucidated the molecular mechanisms underlying cognitive improvements observed in Parkinson’s disease patients. Our results show that combined metabolic activator administration leads to enhanced cognitive function and improved metabolic health in Parkinson’s disease patients as recently shown in Alzheimer’s disease patients.Öğe Migrant women's perception toward cervical and breast cancer screening in Türkiye: a qualitative analysis(2025) Altaş, Zeynep Meva; Sezerol, Mehmet AkifIntroduction: This study aims to investigate the knowledge, attitudes, and behaviors of Syrian migrant women regarding breast and cervical cancer screenings in the Sultanbeyli district of Istanbul. Methods: The women were recruited from Extended Migrant Health Centre, which is a primary health care institution in Istanbul. In August 2024, face-to-face interviews were conducted using an open-ended, semi-structured question form administered by a nurse experienced in qualitative research. Sociodemographic information, their thoughts on cancer, information on the types of cancers screened and sources of information, their participation in cancer screenings, and their perspectives on cancer screenings were asked. Results: In depth interviews were conducted with 40 migrant women. Four main themes and thirteen sub-themes were identified. These themes include “Opinions about the cancers and information about the cancer screenings” “Attitudes about the cancer screening program” “Perspectives on preventive measures against cancers” and “Problems in access to health services”. Women mostly described cancer as a serious, incurable, and fatal disease. Despite this perception, almost half of the participants had not attended cancer screening programs. The majority said they did not undergo screening because they had no symptoms. The other main barriers for participation included lack of knowledge, fear of receiving a negative result, or fear of the procedures involved. Conclusions: Based on this study, migrant women have low level of attendance to breast and cervical cancer screening programs. Besides, they lack adequate information about breast cancer and cervical cancer, the screening protocols and preventive measuremets.Öğe AutoCOR: autonomous condylar offset ratio calculator for post-operative total knee arthroplasty radiographs(2025) Çakmak, Gülsade Rabia; Hamamcı, İbrahim Ethem; Yılmaz, Mehmet Kürşat; Alhajj, Reda; Azboy, İbrahim; Özdemir, Mehmet KemalBackground: This study aims to automate the measurement process of posterior condylar offset ratio (PCOR) and anterior condylar offset ratio (ACOR) to improve the Total Knee Arthroplasty (TKA) evaluation. Accurate calculation of PCOR and ACOR, performed manually by orthopedic surgeons, is crucial for assessing postoperative range of motion and implant positioning. Manual measurements, however, are time-consuming, prone to human error, and subject to variability. Automating this process could improve precision in clinical practice. Methods: We developed AutoCOR, a software system that autonomously calculates PCOR and ACOR by utilizing built-in function, employing k-means clustering, from the OpenCV library for image segmentation. The software detects key anatomical landmarks on true postoperative lateral radiographs. The definitions of PCOR and ACOR are PCO (posterior condylar offset) divided by femoral diameter, and ACOR is defined as ACO (anterior condylar offset) divided by femoral diameter, respectively. We tested the algorithm on 50 postoperative lateral radiographs of 32 patients from the Istanbul Kosuyolu Medipol Hospital, which included data from. The assessment process included calculating the mean, standard deviation and plotting the Bland-Altman plots, comparing AutoCOR's results against ground truth values. Results: The mean PCOR was 0.984 (SD 0.235) for AutoCOR and 0.972 (SD 0.164) for ground truth values, showing a strong correlation (Pearson r = 0.845, p < 0.0001). The mean ACOR was 0.107 (SD 0.092) for AutoCOR and 0.107 (SD 0.070) for ground truth values, with moderate correlation (Spearman's rs = 0.519, p = 0.0001). Conclusion: AutoCOR provides accurate measurements and shows potential to reduce variability in TKA evaluation, improving precision in clinical practice.Öğe Glow in the dark tumor: enhanced near-ir visualization and destruction of cancer with a self-quenched theranostic(2025) Güler, Selen İrem; Altan, Cem Levent; Demircioğlu, Emine Esma; Verimli, Nihan; Abisoğlu, Beyza; Bayraktaroğlu, Çiğdem; Erdem, Sultan SibelLate diagnosis is one of the major obstacles for the treatment of breast cancer which can be overcome with a system offering sensitive imaging and selective therapeutic effect. In this study, we developed a “dark-bright” multifunctional drug delivery system bringing real-time imaging and non-invasive therapy together. Theranostic ability of the system was delivered by Verteporfin (VP), serving as a fluorescence probe and a photosensitizer. To create a “dark state” system via self-quenching ability of VP, it was immobilized onto the superparamagnetic iron oxide nanoparticle (SPION) surface. Upon cellular uptake of the “dark state” system, release of VP led to fluorescence regain, switching the system to “bright state” after which photodynamic therapy (PDT) was initiated to lead to cell death. Theranostic feature of the system was evaluated in MCF-7 and MDA-MB-231 cell lines. Following internalization, fluorescence signal was increased up to ∼56-fold in MCF-7 cells. The IC50 value decreased ∼20-fold and ∼117-fold in MCF-7 and MDA-MB-231 cell lines, respectively. Moreover, the system significantly inhibited migration in the highly aggressive MDA-MB-231 cell line and induced apoptosis by caspase-3 activation. The developed “dark-bright” system is a promising multifunctional drug delivery vehicle with extraordinary theranostic features for the detection and destruction of micro tumors.Öğe Anticancer properties of phenylboronic acid in androgen-dependent (lncap) and androgen-independent (pc3) prostate cancer cells via map kinases by 2d and 3d culture methods(2025) Gürsoy Gürgen, Duygu; Güneş, Arzu; Köse, Oğuzhan; Kaplan, Arife Ahsen; Karabulut, Seda; Tunalı, Muzaffer Başak; Keskin, İlknurObjective: This study utilized three cell lines: normal prostate epithelial RWPE-1, androgen-dependent LNCaP, and androgen-independent PC3. We investigated the inhibitory effects of phenylboronic acid (PBA)’s inhibitory effect on cellular proliferation due to its ability to disrupt microtubule formation in prostate cancer cell lines. Additionally, this study aimed to assess the cytotoxic effects of PBA on prostate cancer cells using two-dimensional (2D) and three-dimensional (3D) cell culture models. Methods: The IC50 values of PBA and colchicine were determined through viability assays in 2D and 3D models. Colony formation, proliferation, and migration assays were conducted. Immunofluorescence intensity analysis of MAPKKK proteins (ERK, JNK, p38) was performed to explore the mechanism of cellular response to PBA. Results: The IC50 values were determined for each treatment group. After 48-hour of PBA treatment, migration was inhibited more effectively than with colchicine in both cancer cell lines. After 24-hour, PBA reduced colony formation and proliferation. PBA treatment for 24-hour decreased JNK expression in PC3 and LNCaP cells in 2D models. Both PBA and colchicine increased p38 expression in PC3 spheroids. PBA’s effects on cell deformation were visualized in semi-thin sections, marking the first ultrastructural observation of PBA-induced morphological defects in cancer cells. Conclusion: PBA exerts antimitotic effects by inhibiting proliferation and migration and triggers diverse metabolic responses across different cell lines. Furthermore, PBA’s low toxicity on RWPE-1 cells suggests its potential as a promising chemotherapeutic agent for future studies.Öğe Multi-omics characterization of improved cognitive functions in Parkinson’s disease patients after the combined metabolic activator treatment: a randomized, double-blinded, placebo-controlled phase II trial(2025) Yuluğ, Burak; Altay, Özlem; Hanoğlu, Lütfü; Velioğlu, Halil Aziz; Coşkun, Ebru; Bayraktaroğlu, Zübeyir; Mardinoğlu, AdilParkinson’s disease is primarily marked by mitochondrial dysfunction and metabolic abnormalities. We recently reported that the combined metabolic activators improved the immunohistochemical parameters and behavioural functions in Parkinson’s disease and Alzheimer’s disease animal models and the cognitive functions in Alzheimer’s disease patients. These metabolic activators serve as the precursors of nicotinamide adenine dinucleotide and glutathione, and they can be used to activate mitochondrial metabolism and eventually treat mitochondrial dysfunction. Here, we designed a randomized, double-blinded, placebo-controlled phase II study in Parkinson’s disease patients with 84 days combined metabolic activator administration. A single dose of combined metabolic activator contains L-serine (12.35 g), N-acetyl-L-cysteine (2.55 g), nicotinamide riboside (1 g) and L-carnitine tartrate (3.73 g). Patients were administered either one dose of combined metabolic activator or a placebo daily for the initial 28 days, followed by twice-daily dosing for the next 56 days. The main goal of the study was to evaluate the clinical impact on motor functions using the Unified Parkinson’s Disease Rating Scale and to determine the safety and tolerability of combined metabolic activator. A secondary objective was to assess cognitive functions utilizing the Montreal Cognitive Assessment and to analyse brain activity through functional MRI. We also performed comprehensive plasma metabolomics and proteomics analysis for detailed characterization of Parkinson’s disease patients who participated in the study. Although no improvement in motor functions was observed, cognitive function was shown to be significantly improved (P < 0.0000) in Parkinson’s disease patients treated with the combined metabolic activator group over 84 days, whereas no such improvement was noted in the placebo group (P > 0.05). Moreover, a significant reduction (P = 0.001) in Montreal Cognitive Assessment scores was observed in the combined metabolic activator group, with no decline (P > 0.05) in the placebo group among severe Parkinson’s disease patients with lower baseline Montreal Cognitive Assessment scores. We showed that improvement in cognition was associated with critical brain network alterations based on functional MRI analysis, especially relevant to areas with cognitive functions in the brain. Finally, through a comprehensive multi-omics analysis, we elucidated the molecular mechanisms underlying cognitive improvements observed in Parkinson’s disease patients. Our results show that combined metabolic activator administration leads to enhanced cognitive function and improved metabolic health in Parkinson’s disease patients as recently shown in Alzheimer’s disease patients.Öğe Facial hypertrichosis in the course of isotretinoin treatment: four-year retrospective observation(2024) Pekmezci, ErkinBackground: isotretinoin is a synthetic retinoid used in the treatment of acne. There are limited and inconsistent data about the effects of isotretinoin on hormones and hair growth. Aim: to investigate a probable connection, a single center four-year retrospective data of female acne patients who were treated with oral isotretinoin and developed facial hypertrichosis was reported. Methods: in the years 2019-2023, 327 female patients between 16-33 years of age (Mean ± Standard Deviation: 23.4 ± 4.7) were treated with 0.5-0.8 mg/kg/day isotretinoin, approximately for 6 months (6.2 ± 0.8). The patients who developed facial hypertrichosis were additionally analysed for dehydroepiandrosterone sulfate, prolactin and thyroid stimulating hormone values. Results: thirty one patients (9.5%) in all ages (22.9 ± 4.3) declared excessive hair growth on cheeks and/or chin during treatment. All declarations were between the 2nd and 4th months (2.6 ± 0.8). The mean values of analysed hormones were in normal ranges. Twenty seven of the thirty one patients (87%) stated that the excessive hair growth terminated completely at the end of 4th month (3.1 ± 0.7) after the cessation of the treatment, and the others declared it was diminished to a great extent. Conclusions: mainly due to normal mean values of the analysed hormones, it is hard to consider that the cause of hypertrichosis is hormonal irregularity. However, 9.5% is a considerable ratio. A more extensive prospective study should be performed to reveal the cause of this phenomenon.Öğe Evaluation of the relationship between air pollutants and emergency department admissions with childhood asthma(2024) Söğütlü, Yakup; Altaş, Uğur; Altıntaş, Tuğba; Altaş, Zeynep Meva; Akova, Sevgi; Özkars, Mehmet YaşarBackground: This study aims to evaluate the relationship between the number of visits to a pediatric emergency department due to asthma attacks and air pollutants. Methods: In this ecological study, all pediatric patients who visited the pediatric emergency department of a tertiary hospital in Istanbul with asthma between January 2016 and December 2023 were included. The effect of air pollution on the number of patient visits was analyzed using a negative binomial regression model. Results: Based on the negative binomial model, a one-unit increase in SO2 leads to a 0.020-unit decrease in the logarithm of the number of patient visits (p < 0.05). A one-unit increase in NO leads to a 0.040-unit increase in the logarithm of the number of patient visits (p < 0.05). According to factor analysis, as the levels of NO, NOx, PM2.5, NO2, and PM10 in the air increase, the number of patient visits also increases; however, as the level of SO2 increases, the number of patient visits decreases. Conclusions: Families should be informed about environmental exposures for disease management of children with asthma. The confounding factors may also play a role in SO2 level and the decrease in admissions due to asthma. Further studies are needed in this regard.Öğe The influence of obesogenic environments on diet self-efficacy and physical activity among healthcare workers: a multicenter study(2024) Sezerol, Mehmet Akif; Altaş, Zeynep Meva; Aslan, Melek Nur; Halaç, ŞeymaBackground: The aim of the study was to determine the level of dietary self-efficacy, physical activity and obesogenic environment in several districts of Istanbul and to examine the relationship between them. Methods: In this cross-sectional study, a questionnaire was administered to primary health care workers working in three different districts of Istanbul. Sociodemographic questions, Dieting Self-Efficiency Scale (DSES), The Assessment of the Obesogenic Environment Scale (AOES), and International Physical Activity Questionnaire (IPAQ) were used in the survey. p < 0.05 was determined as the level of statistical significance. Results: A total of 639 healthcare workers responded to the study. The median age of the participants was 39.0 years (min-max: 21.0–67.0). Male and single participants had significantly higher DSES scores (p = 0.014, p = 0.016, respectively). Male participants and those with lower income and education level had significantly higher scores on the AOES (p = 0.025, p = 0.024 and p = 0.024, respectively). According to the IPAQ, 56.8% (n = 283) of the participants were minimally physically active, 29.7% (n = 148) were inactive and 13.5% (n = 67) were very active. Those who were physically minimally active and very active had significantly higher DSES scores and significantly lower AOES scores than those who were inactive (p < 0.001 and p = 0.011). There was a significant negative correlation between the DSES and AOES (r=-0.263, p < 0.001). Conclusion: In this study, the evaluation of the concepts of dietary self-efficacy, physical activity level and obesogenic environment in healthcare professionals, who can be role models in the society, may contribute to the studies and intervention strategies for the whole society.Öğe Changes in secondary structure of protein in skeletal muscle due to high-carbohydrate or high-fat diets(2024) Ezer Özer, Nazlı; Doğan Mollaoğlu, AyçaObjective: Obesity, which arises from changes in lifestyle and feeding habits, poses a threat to human health. One essential contributor to the increase in obesity rates is the popularity of high-calorie diets. This study aims to investigate high-fat (HFD) and high-carbohydrate (HCD) diet-induced molecular changes in protein secondary structure in longissimus dorsi skeletal muscle tissues of female inbred C57BL/6J mice by utilizing Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy. Materials and Methods: Mice were fed a control diet, HCD, or HFD for 24 weeks. Their skeletal muscle tissues were collected, and their spectra were recorded using a Bruker Invenio S ATR-FTIR spectrometer in the 4000-400 cm-1 region. Results: The protein secondary structure profiles of the HCD group demonstrated a significant rise in antiparallel beta-sheet and beta-turn and a decline in parallel beta-sheets, together with the insignificant increase in aggregated beta-sheets and a decrease in alpha-helix. The impact of an HFD on protein conformation is less pronounced than HCD. The HFD diet led to an increase in antiparallel beta-sheets and a decrease in parallel beta sheets. Although insignificant, an increase was observed in beta-turn and alpha-helix. Conclusion: These results propose the appearance of protein aggregation and/or formation of protein- protein intermolecular interaction in skeletal muscle tissues of female inbred C57BL/6J mice. Collectively, these data suggest that both high-calorie diets impair secondary structures of protein in skeletal muscle that may affect its metabolic function.Öğe Splenic flexure mobilization: does body topography matter?(2025) Akyol, Habil Akansel; Arslan, Naciye Çiğdem; Koçak, Mehmet; Shahhosseini, Reza; Pekuz, Çağlar Kazım; Haksal, Mustafa; Öncel, MustafaBackground: Splenic flexure mobilization can be technically challenging, and its oncological benefits remain uncertain. This study aims to explore the relationship between patient and clinical characteristics and splenic flexure mobilization time as well as the implications of prolonged splenic flexure mobilization duration. Methods: This retrospective cohort study includes 105 patients who underwent laparoscopic distal colorectal cancer surgery between 2013 and 2018. The study analyzed patient characteristics, duration of surgical steps, and postoperative outcomes. Splenic flexure mobilization time was assessed using operation videos, and the impact of patient-related factors on splenic flexure mobilization complexity was examined. Results: The study identified significant correlations of higher body mass index (BMI) (p = 0.0086), weight (p = 0.002), and height (p = 0.043) with longer splenic flexure mobilization time. Gender did not significantly influence splenic flexure mobilization duration. Splenic flexure mobilization time was correlated with the durations of other individual surgical steps (Step 1: medial-to-lateral dissection [p = 0.0013], Step 2: pelvic dissection [p = 0.067], Step 3: dissection of white line and mobilization of descending colon [p = 0.0088], Step 5: stapling, resection, extraction of the specimen, and anastomosis [p = 0.04]) and the overall operation time (p < 0.0001). A 10-min cutoff point predicts the total operation time more efficiently than other potential thresholds. Conclusion: This research suggests that patient characteristics including BMI, weight, and height may serve as indicators for prolonged splenic flexure mobilization time in laparoscopic distal colorectal cancer surgery. Longer splenic flexure mobilization durations were correlated with extended durations of other surgical steps. A BMI-based approach to anticipate SFM duration may enhance preoperative planning, potentially aiding in surgical decision-making. Trial registration: E-10840098–772.02–61604 2.2.2019.Öğe Smartphone addiction and depression among health sciences students during covid-19 pandemic(2024) Kurnaz Ay, Merve; Topuzoğlu, Ahmet; Altaş, Zeynep MevaBackground: Previous studies indicate an increasing prevalence of depression among university students worldwide. Besides, university students are more likely to excessively use smartphones, making them more susceptible to smartphone addiction. Pandemic conditions can also have negative effects on mental health. Thus, this study aims to investigate the frequency of depression among university students during COVID-19 pandemic. Methods: The study population for this mixed-method research, which includes both qualitative and quantitative components, consists of students studying health sciences at a state university in Istanbul, Türkiye. No sample was selected for the quantitative data collection; instead, it was aimed to reach the entire population. Sociodemographic characteristics, the 10-item Smartphone Addiction Scale-Short Version (SAS-SV), and the 21-item Beck Depression Inventory (BDI) were used. In the qualitative part of our study, semi-structured online interviews were conducted with 12 students. Statistical significance level was set at p < 0.05. Results: The study, involving 819 students, found that 25.2% had moderate depression and 5.7% had severe depression. A statistically significant relationship was found between self-perceived smartphone addiction and the presence of moderate-severe depression (p < 0.001). Participants who spent more than 4 h a day on their smartphones, those who checked their smartphones more than 30 times a day, those who perceived themselves as smartphone addicts, and those who experienced smartphone-related sleep problems obtained statistically significantly higher scores from BDI compared to others (p < 0.05). According to our qualitative results, some participants thought that smartphone use could cause a depressive mood by isolating people, while others believed it could do so through the negative effects of social media. All participants reported that the quarantine period increased their smartphone usage. Conclusion: Our results suggest a potential interaction between smartphone addiction and depression. This indicates the potential benefit of assessing and addressing both conditions simultaneously.Öğe Temporal microbiome changes in axolotl limb regeneration: stage-specific restructuring of bacterial and fungal communities with a flavobacterium bloom during blastema proliferation(2024) Altın, Hanne; Delice, Büşra; Yıldırım, Berna; Demircan, Turan; Yıldırım, SüleymanThe intricate relationship between regeneration and microbiota has recently gained attention, spanning diverse model organisms. Axolotl (Ambystoma mexicanum) is a critically endangered salamander species and a model organism for regenerative and developmental biology. Despite its significance, a noticeable gap exists in understanding the interplay between axolotl regeneration and its microbiome. Here, we analyse in depth bacterial 16S rRNA amplicon dataset that we reported before as data resource and profile fungal community by sequencing ITS amplicons at the critical stages of limb regeneration (0–1–4–7–30–60 days post amputation, ‘dpa’). Results reveal a decline in richness and evenness in the course of limb regeneration, with bacterial community richness recovering beyond 30 dpa unlike fungi community. Beta diversity analysis reveals precise restructuring of the bacterial community along the three phases of limb regeneration, contrasting with less congruent changes in the fungal community. Temporal dynamics of the bacterial community highlight prevalent anaerobic bacteria in initiation phase and Flavobacterium bloom in the early phase correlating with limb blastema proliferation. Predicted functional analysis mirrors these shifts, emphasising a transition from amino acid metabolism to lipid metabolism control. Fungal communities shift from Blastomycota to Ascomycota dominance in the late regeneration stage. Our findings provide ecologically relevant insights into stage specific role of microbiome contributions to axolotl limb regeneration.Öğe Artificial intelligence meets the world experts; updates and novel therapies in autoimmunity - the 14th international congress on autoimmunity 2024 (AUTO14), Ljubljana(2025) Mahroum, Naim; Elsalti, Abdulrahman; Al Shawaf, Maisam; Darkhabani, Mohammad; Alwani, Abdulrahman; Seida, Ravend; Ertaş, Muhammet Tayfur; Şimşek, Ayşe Gülnihan; Awad, Mustafa; Habra, Mona; Alrifaai, Mohamad Aosama; Bogdanos, Dimitrios; Shoenfeld, YehudaThe bi-annual international congress on autoimmunity is a huge opportunity for the medical community to discuss the latest updates in the field. During the 14th congress 2024 (AUTO14) in Ljubljana, artificial intelligence (AI) occupied special attention due to its recent and ongoing unequivocal role in various medical fields including autoimmunity. For instance, through a challenging debate between world-experts and the most popular AI bot used (ChatGPT), several clinical cases including a case of vasculitis were discussed in the plenary sessions. ChatGPT agreed with the clinical decisions made by the experts nevertheless, the bot added additional aspects related to the specific case. In this regard, ChatGPT emphasized the need for osteoporosis prophylaxis in a patient planned to be treated with systemic steroids for a long time. Furthermore, AUTO14 included the newest updates on most autoimmune disorders, distributed among tens of sessions. Among others, infection and autoimmunity, the sequalae of the pandemic of COVID-19, as well as COVID-19 vaccines were discussed as well. Due to the high numbers of the works presented, and for ensuring that important updates are not missed; we divided our paper into sections. The subtitles throughout the paper correspond to different sessions of the congress, all presenting new updates in the field. A figure aiding in navigating throughout the paper was also provided.Öğe International alliance of urolithiasis (iau) consensus on miniaturized percutaneous nephrolithotomy(2024) Zeng, Guo Hua; Zhong, Wen; Mazzon, Giorgio; Zhu, Wei; Lahme, Sven; de la Rosette, Jean J. M. C. H.; Choong, SimonOver the past three decades, there has been increasing interest in miniaturized percutaneous nephrolithotomy (mPCNL) techniques featuring smaller tracts as they offer potential solutions to mitigate complications associated with standard PCNL (sPCNL). However, despite this growing acceptance and recognition of its benefits, unresolved controversies and acknowledged limitations continue to impede widespread adoption due to a lack of consensus on optimal perioperative management strategies and procedural tips and tricks. In response to these challenges, an international panel comprising experts from the International Alliance of Urolithiasis (IAU) took on the task of compiling an expert consensus document on mPCNL procedures aimed at providing urologists with a comprehensive clinical framework for practice. This endeavor involved conducting a systematic literature review to identify research gaps (RGs), which formed the foundation for developing a structured questionnaire survey. Subsequently, a two-round modified Delphi survey was implemented, culminating in a group meeting to generate final evidence-based comments. All 64 experts completed the second-round survey, resulting in a response rate of 100.0%. Fifty-eight key questions were raised focusing on mPCNLs within 4 main domains, including general information (13 questions), preoperative work-up (13 questions), procedural tips and tricks (19 questions), and postoperative evaluation and follow-up (13 questions). Additionally, 9 questions evaluated the experts’ experience with PCNLs. Consensus was reached on 30 questions after the second-round survey, while professional statements for the remaining 28 key questions were provided after discussion in an online panel meeting. mPCNL, characterized by a tract smaller than 18 Fr and an innovative lithotripsy technique, has firmly established itself as a viable and effective approach for managing upper urinary tract stones in both adults and pediatrics. It offers several advantages over sPCNL including reduced bleeding, fewer requirements for nephrostomy tubes, decreased pain, and shorter hospital stays. The series of detailed techniques presented here serve as a comprehensive guide for urologists, aiming to improve their procedural understanding and optimize patient outcomes.Öğe Chronic renal impairment predicts oncological outcomes in utuc patients undergoing rnu(2024) Wong, Chris Ho Ming; Sabuncu, Kubilay; Horuz, Rahim; Albayrak, Selami; del Pilar Laguna Pes, Maria; de la Rosette, Jean J. M. C. H.; Teoh, Jeremy Yuen ChunObjective: This study aims to explore the relationship between pre-existing renal impairment and oncological outcomes in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU) using data from a multicentre international registry. Patients and methods: Data on non-metastatic UTUC patients who underwent RNU were obtained from the Clinical Research Office of the Endourology Society Urothelial Carcinomas of the Upper Tract (CROES-UTUC) Registry. Patients were categorised into normal pre-operative renal function and chronic renal impairment (CKD) groups, with CKD defined as an estimated glomerular filtration rate below 60 mL/kg/1.73 m². Kaplan–Meier survival analysis was employed to investigate disease-free survival (DFS) and overall survival (OS). Multivariable Cox regression analysis was conducted to identify confounding variables. Results: A total of 1393 patients diagnosed with UTUC who underwent RNU between 2014 and 2019 were analysed. 875 patients (62.4%) had normal renal function, whilst 528 patients (37.6%) had CKD prior to RNU. The two groups had similar proportions of bladder cancer history, comparable cardiovascular comorbidity, similar tumour stage, and comparable proportions receiving laparoscopic or robotic-assisted RNU. In multivariable cox regression analysis, CKD was found to be associated with inferior DFS (HR = 1.419; 95%CI = 1.060–1.898; p = 0.019). Upon multivariable analysis, pre-existing renal impairment and higher T stage (HR = 4.613; 95%CI = 1.829–4.712; p < 0.001) and the use of adjuvant chemotherapy (HR = 1.858; 95%CI = 1.229–2.807; p = 0.003) were also found to associate with worse DFS. Significant cardiovascular disease and higher T stage were associated with worse OS. Existing renal impairment at baseline did not have any significant associated with OS. Conclusion: In this multicentre registry, preoperative chronic renal impairment was identified as an independent predictor of inferior DFS in patients undergoing RNU for non-metastatic UTUC. Preoperative CKD could serve as a clinical predictor of poorer oncological outcomes.Öğe Bioenergetic shift and proteomic signature induced by lentiviral-transduction of gfp-based biosensors(2024) Barakat, Sarah; Çimen, Şeyma; Miri, Seyed Mohammad; Vatandaşlar, Emre; Yelkenci, Hayriye Ecem; San Martín, Alejandro; Beker, Mustafa Çağlar; Kök, Kıvanç; Öztürk, Gürkan; Eroğlu, EmrahFluorescent proteins (FPs) stand as pivotal tools extensively employed across diverse biological research endeavors in various model systems. However, long-standing concerns surround their use due to the numerous side effects associated with their expression. Recent investigations have brought to light the significance of hydrogen peroxide (H2O2) that is associated with the maturation process of green fluorescent protein (GFP) fluorophores. The structural and functional impairments associated with GFP expression are possibly linked to this amount of H2O2. In this study, we assess the impact of the GFP-based HyPer7 biosensor on cellular homeostasis and proteome changes, aiming to identify potential risks related to oxidative stress responses that potentially risks the application of such tools. Cells expressing genome-integrated HyPer7 demonstrated altered mitochondrial membrane potential (MMP), which was alleviated by the addition of antioxidants or culturing cells at physiological normoxia (5 kPa O2). Additionally, HyPer7-expressing cells also exhibited significant impairment in mitochondrial oxidative respiration, suggesting broader mitochondrial dysfunction. Through untargeted proteomics analysis, we identified 26 proteins exhibiting differential expression in HyPer7-expressing cells compared to respective control cells. Functional annotation analysis showed that the list of the delineated proteins is associated with cellular responses to stress and the regulation of antioxidant mechanisms. Our findings underscore the significance of caution and validation in ensuring a thorough comprehension of cellular responses when using fluorescent protein-based tools, thereby enhancing the reliability of the results.Öğe Preliminary study on the impact of 900 MHz radiation on human sperm: an in vitro molecular approach(2024) Keskin, İlknur; Karabulut, Seda; Kaplan, Arife Ahsen; Alagöz, Murat; Akdeniz, Muhterem; Tüfekçi, Kıymet Kübra; Kaplan, SüleymanThe use of technologies that produce and emit electromagnetic fields (EMF) is growing exponentially worldwide. The biological effects of EMF-emitting equipment, such as mobile phones and other wireless devices, have been studied in the last decade using in vitro and in vivo methods. Infertility is a growing health problem, and nearly half of cases are because of male-factor. This study investigated the direct in vitro effects of 900 MHz radiation exposure on sperm parameters, genetic status, apoptotic markers, and the PI3K/AKT signaling pathway in healthy normozoospermic men. Semen samples were divided into four groups, two control (30 min and 1 h) and two EMF exposure (30 min and 1 h). Sperm parameters (motility, progressive motility, acrosomal index, morphology), genetic status (DNA fragmentation and chromatin integrity), apoptotic markers (cytokine-c and caspase-3 expression) and the PI3K/AKT signaling pathway (phosphoinoitide 3-kinase-PI3K- and phosphorylated AKT- p-AKT-) were analysed. Sperm motility were significantly reduced in 30 min EMF exposure while a significant increase in the expression of p-AKT were observed in 1 h EMF exposure group. An increased vacuolisation, acrosomal defect, extension of subacrosomal space, uncondensed chromatin structure, apoptotic signs and disrupted axoneme were observed in both EMF groups which were not observed in the control group. Other sperm parameters (morphology and acrosomal index), genetic status, apoptotic markers and the PI3K expression rates had no significant change.Öğe The potential role of boron in the modulation of gut microbiota composition: an in vivo pilot study(2024) Şentürk, Nermin Başak; Kasapoğlu, Burcu; Şahin, Eray; Özcan, Orhan; Ozansoy, Mehmet; Ozansoy, Muzaffer Beyza; Şahin, FikrettinBackground/Objectives: The role of the gut microbiome in the development and progression of many diseases has received increased attention in recent years. Boron, a trace mineral found in dietary sources, has attracted interest due to its unique electron depletion and coordination characteristics in chemistry, as well as its potential role in modulating the gut microbiota. This study investigates the effects of inorganic boron derivatives on the gut microbiota of mice. Methods: For three weeks, boric acid (BA), sodium pentaborate pentahydrate (NaB), and sodium perborate tetrahydrate (SPT) were dissolved (200 mg/kg each) in drinking water and administered to wild-type BALB/c mice. The composition of the gut microbiota was analyzed to determine the impact of these treatments. Results: The administration of BA significantly altered the composition of the gut microbiota, resulting in a rise in advantageous species such as Barnesiella and Alistipes. Additionally, there was a decrease in some taxa associated with inflammation and illness, such as Clostridium XIVb and Bilophila. Notable increases in genera like Treponema and Catellicoccus were observed, suggesting the potential of boron compounds to enrich microbial communities with unique metabolic functions. Conclusions: These findings indicate that boron compounds may have the potential to influence gut microbiota composition positively, offering potential prebiotic effects. Further research with additional analyses is necessary to fully understand the interaction between boron and microbiota and to explore the possibility of their use as prebiotic agents in clinical settings.
