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Objectives: This study aimed to evaluate the potential efficacy of 68 Ga-fibroblast activation protein inhibitor (FAPi) positron emission tomography/computed tomography (PET/CT) for detecting, staging, and restaging digestive system malignancies that are 18 F-fluorodeoxyglucose ( 18 F-FDG) negative or show equivocal 18 F-FDG uptake., Methods: We conducted a prospective analysis of 30 patients with pathologically confirmed primary tumors or metastases of the digestive system. Participants underwent 68 Ga-FAPi PET/CT and 18 F-FDG PET/CT imaging for staging or restaging purposes within the same week. The efficacy of 68 Ga-FAPi PET/CT was assessed by comparing its ability to detect lesions and influence disease staging with that of 18 F-FDG PET/CT., Results: 68 Ga-FAPi PET/CT imaging was performed in 30 patients with 18 F-FDG-negative or indeterminate lesions. Of the 30 patients, 23 had gastric cancer and 7 had colorectal cancer. Among all patients, histopathological diagnosis of signet ring cell carcinoma was present in 15 (50%) patients. Primary tumor or local recurrence was detected in 19 (63%) patients, lymph node metastasis in 8 (27%) patients, visceral metastasis in 4 (13%) patients, peritoneal metastasis in 14 (47%) patients, and bone metastasis in 3 (10%) patients on 68 Ga-FAPi PET/CT images. All patients underwent histopathological confirmation on 68 Ga-FAPi PET/CT images. The disease stage was upgraded in 20 patients (67%) after 68 Ga-FAPi PET/CT imaging. Of the 20 patients, 12 had no evidence of recurrence or metastasis on 18 F-FDG PET/CT., Conclusion: Based on our study, 68 Ga-FAPi PET/CT alters the disease stage in the majority of gastrointestinal malignancies with negative or equivocal 18 F-FDG PET/CT findings. 68 Ga-FAPi PET/CT appears to be effective in both staging and restaging of gastrointestinal malignancies, such as signet-ring cell carcinomas of the stomach that frequently show low 18 F-FDG -avidity., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (Copyright© 2025 The Author. Published by Galenos Publishing House on behalf of the Turkish Society of Nuclear Medicine.)

Objective: Evaluation of the biomarkers and their relations with sleep in attention deficit hyperactivity disorder (ADHD) is important for understanding the impairments in cognitive functioning. In this study, we aimed to investigate the brain-derived neurotrophic factor (BDNF) and sialic acid (Sia) levels, and their possible relations with chronotypes in ADHD., Methods: The study included 100 drug-naive children with ADHD and 74 healthy children as controls. Conners' Parent Rating Scale-Revised (CPRS-R) scores were used for the severity assessment. Morningness Eveningness Questionnaire (MEQ) was used to determine the chronotypes of participants. ELISA kits were used for the assessment of BDNF and Sia plasma levels., Results: Levels of BDNF and Sia were found to be statistically significantly higher in the ADHD group compared to healthy children (p < 0.001, p < 0.001, respectively). BDNF and Sia levels were found to be higher in the ADHD group with eveningness chronotype (p = 0.045, p = 0.038). The binary logistic regression model was statistically significant (p = 0.033), higher BDNF and Sia levels were assessed as predictive factors for the diagnosis of ADHD. Also, eveningness chronotype was found as a predictive factor of BDNF and Sia levels in ADHD., Conclusion: The results indicate that BDNF and Sia levels, which are related to cognitive functions and sleep, increase with the age of ADHD. Eveningness chronotype, connected with the severity of ADHD, is related to BDNF and Sia levels. There is a need for further studies to confirm these results., (© 2024 International Society for Developmental Neuroscience.)

Friction and wear characteristics play a critical role in the functionality and durability of prosthetic sockets, which are essential components in lower-limb prostheses. Traditionally, these sockets are manufactured from bulk polymers or composite materials reinforced with advanced carbon, glass, and Kevlar fibres. However, issues of accessibility, affordability, and sustainability remain, particularly in less-resourced regions. This study investigates the potential of self-reinforced polymer composites (SRPCs), including poly-lactic acid (PLA), polyethylene terephthalate (PET), glass fibre (GF), and carbon fibre (CF), as sustainable alternatives for socket manufacturing. The tribological behaviour of these self-reinforced polymers (SrPs) was evaluated through experimental friction tests, comparing their performance to commonly used materials like high-density polyethylene (HDPE) and polypropylene (PP). Under varying loads and rotational speeds, HDPE and PP exhibited lower coefficients of friction (COF) compared to SrPLA, SrPET, SrGF, and SrCF. SrPLA recorded the highest average COF of 0.45 at 5 N and 240 rpm, while SrPET demonstrated the lowest COF of 0.15 under the same conditions. Microscopic analysis revealed significant variations in wear depth, with SrPLA showing the most profound wear, followed by SrCF, SrGF, and SrPET. In all cases, debris from the reinforcement adhered to the steel ball surface, influencing the COF. While these findings are based on friction tests against steel, they provide valuable insights into the durability and wear resistance of SRPCs, a crucial consideration for socket applications. This study highlights the importance of tribological analysis for optimising prosthetic socket design, contributing to enhanced functionality and comfort for amputees. Further research, including friction testing with skin-contact scenarios, is necessary to fully understand the implications of these materials in real-world prosthetic applications.

Objective: Neurodevelopmental disorders (NDDs) are the most common psychiatric disorders in childhood, and there are many factors in their etiology. In recent years, many biomarkers have been studied to elucidate the etiology of these disorders. In this study, it was aimed to investigate the levels of nerve growth factor (NGF) and angiotensin converting enzyme 2 (ACE2) in attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID)., Methods: The study included 74 children with NDDs (the number of patients in ADHD, ASD and ID groups were 24, 25 and 25 respectively) and 30 healthy controls (HCs). Serum NGF and ACE2 levels were studied with ELISA kits, also complete blood count (CBC), levels of fasting glucose and serum lipids were assessed., Results: ACE2 levels were found to be lower in NDD group than HCs in girls. In boys with ASD, triglyceride levels were significantly higher than other groups. Also a positive correlation was found between ACE2 and NGF levels when all sample assessed together., Conclusions: This study is a premise for investigating ACE2 and NGF in NDDs. The role of these markers in ADHD, ASD, ID and other NDDs and their associations with gender should be assessed by studies in which both larger sample groups and more disorders.

Background: Internet gaming disorder (IGD) has become increasingly prevalent worldwide and is recognized as a significant public health concern because of its negative consequences on individuals mental and physical health, social relationships, academic performance and overall well-being. While research on IGD has gained significant momentum in the past decade, the neural substrates underlying this disorder remains unclear. This study aims to investigate resting-state cortical activation in male subjects with IGD using a concurrent functional near infrared spectroscopy (fNIRS) and electroencephalography (EEG) hybrid system., Methods: Twenty-two male individuals with IGD (18-23 years old) and twenty-two male healthy, age-matched healthy controls were included in the study. Mean oxygenation of the prefrontal cortex (PFC) and whole head neural activity were measured using fNIRS and EEG respectively, during eyes-open and eyes-closed conditions at the resting state. EEG signals were decomposed into distinct frequency sub-bands with wavelet transform, followed by the analysis of the power spectral density within each band. Mean oxygenation of PFC is measured using a multichannel fNIRS system., Results: Results revealed that the individuals with IGD had significantly higher beta power in the frontal region compared to the control group. Individuals with IGD showed significantly increased PFC oxygenation compared to healthy controls. Additionally, both frontal beta power and PFC oxygenation were significantly correlated with IGD severity. However, there were no significant correlations observed between oxygenation and beta powers., Conclusion: This study is the first to examine resting-state cortical activation using multimodal EEG-fNIRS system in young adults with IGD. Moreover, it provides an important contribution to the understanding of the underlying neural mechanisms of IGD and offer new insights for the diagnosis and intervention of the disorder using multimodal EEG-fNIRS system. Further studies should aim to replicate the findings of this study using a larger and more culturally diverse sample to support the neurophysiological basis of IGD., Competing Interests: Declaration of competing interest Meltem Izzetoglu has a small share in fNIRS Devices, LLC that produced the fNIRS system used in this work. The other authors declare that they have no conflicts of interest to report., (Copyright © 2024. Published by Elsevier Ltd.)

Dyslexia is a specific learning disability that is neurobiological in origin and is characterized by reading and/or spelling problems affecting the development of language-related skills. The aim of this study is to reveal functional markers based on dyslexia by examining the functions of brain regions in resting state and reading tasks and to analyze the effects of special education given during the treatment process of dyslexia. A total of 43 children, aged between 7 and 12, whose native language was Turkish, participated in the study in three groups including those diagnosed with dyslexia for the first time, those receiving special education for dyslexia, and healthy children. Independent component analysis method was employed to analyze functional connectivity variations among three groups both at rest and during the continuous reading task. A whole-brain scanning during task fulfillment and resting states revealed that there were significant differences in the regions including lateral visual, default mode, left frontoparietal, ventral attention, orbitofrontal and lateral motor network. Our results revealed the necessity of adding motor coordination exercises to the training of dyslexic participants and showed that training led to functional connectivity in some brain regions similar to the healthy group. Additionally, our findings confirmed that impulsivity is associated with motor coordination and visuality, and that the dyslexic group has weaknesses in brain connectivity related to these conditions. According to our preliminary results, the differences obtained between children with dyslexia, group of dyslexia with special education and healthy children has revealed the effect of education on brain functions as well as enabling a comprehensive examination of dyslexia., (© 2024. The Author(s).)

Background/aim: Strengthening the muscles of the lumbar region in individuals with neck pain may be protective against future back problems. In addition, telerehabilitation applications, which gained momentum in the literature and clinical practice during the COVID-19 pandemic, are among the applications preferred by patients thanks to their various advantages. This study aimed to compare the effects of telerehabilitation and spinal stabilization exercises applied with face-to-face approaches on the thickness of the transversus abdominis (M.TrA) and lumbar multifidus (M.LM) muscles in patients with nonspecific neck pain., Materials and Methods: The primary outcomes were the thickness of the M.TrA and M.LM. Neck pain intensity and neck disability were secondary outcomes. Muscle thickness was evaluated with an ultrasound device, neck pain intensity was assessed with a visual analog scale, and disability was assessed with the Neck Disability Index. Patients were randomly assigned to the telerehabilitation group (TRG) (n = 13) or the control group (CG) (n = 13). While the TRG did the exercises with live videos and video recordings, the CG did exercises face-to-face in the clinic. Both groups performed the same exercises for 45 minutes per session 3 days a week for 8 weeks., Results: At the end of the treatment, the thicknesses of the M.TrA and M.LM were increased and neck pain intensity and neck disability were decreased in both groups (p < 0.05). The groups were similar in terms of these variables (p > 0.05)., Conclusion: Telerehabilitation and face-to-face spinal stabilization exercises are both beneficial for spinal muscle architecture and clinical variables as a preventive measure against future lower back problems in individuals with neck pain., Competing Interests: Conflict of interest: The authors declare that there is no conflict of interest., (© TÜBİTAK.)

Development of an orphan-designated drug has been more challenging and financially less attractive than that of other drugs due to low prevalence of the condition, poorly defined biomarkers and lack of experience of healthcare providers in diagnosing and treating the condition. Guidance and incentives in some countries support the sponsors in developing orphan-designated drugs despite the challenges. Expedited regulatory programs as offered by the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) support the development of drugs, provide shorter marketing application review times or provide preliminary approval. In this study, we analyze marketing application review times in the US and in the European Union (EU) and clinical development times for novel, i.e., containing new molecular entity, orphan-designated drugs that were approved in the US between 1 June 2020 and 31 May 2023, and their correlation with expedited regulatory programs. Seventy-three marketing applications for novel orphan-designated drugs were approved by the FDA, and 39 also received a positive opinion from the EMA. The marketing application review time by the FDA for the 73 novel orphan-designated drugs approved in the US was 244 days ( n  = 73, median), and the marketing application review time by the EMA for the 39 drugs that were also approved in the EU was 353 days ( n  = 39, median). The typical clinical development time for a novel orphan-designated drug was 7.2 years ( n  = 72)., Competing Interests: ED, JK, and LF were employed by Pharming Group N.V. The paper was created based on data from various sources but is neither a legal interpretation nor a statement reflecting any policy, view, or opinion of contributing data sources. The views expressed in the paper are those of the authors alone, and do not reflect the view or opinion of the data suppliers., (Copyright © 2024 Demirci, Knicley and Fiorentino.)

Background/Objectives: Paroxysmal atrial fibrillation (PAF) is an important cause that is thought main potential factor in Embolic stroke of undetermined source (ESUS). Extended Holter ECG is an expensive and time-consuming examination. It needs another tools for predicting PAF in ESUS patients. In this study, serum galectin-3 levels, ECG parameters (PR interval, P wave time and P wave peak time) LA volume index, LA global peak strain and atrial electromechanical conduction time values were investigated for predicting PAF. Methods: 150 patients with ESUS and 30 volunteers for the control group were recruited to study. 48-72 h Holter ECG monitoring was used for detecting PAF. Patients were divided into two groups (ESUS + PAF and ESUS-PAF) according to the development of PAF in Holter ECG monitoring. Results: 30 patients with ESUS whose Holter ECG monitoring showed PAF, were recruited to the ESUS + PAF group. Other 120 patients with ESUS were recruited to the ESUS-PAF group. PA lateral, PA septum, and PA tricuspid were higher in the ESUS + PAF group ( p < 0.001 for all). Serum galectin-3 levels were significantly higher in ESUS + PAF than in ESUS-PAF and control groups (479.0 pg/mL ± 435.8 pg/mL, 297.8 pg/mL ± 280.3 pg/mL, and 125.4 ± 87.0 pg/mL, p < 0.001, respectively). Serum galectin-3 levels were significantly correlated with LAVI, PA lateral, and global peak LA strain (r = 0.246, p = 0.001, p = 0.158, p = 0.035, r = -0.176, p = 0.018, respectively). Conclusion: Serum galectin-3 levels is found higher in ESUS patients which developed PAF and Serum galectin-3 levels are associated LA adverse remodeling in patients with ESUS.

Sandwich structures made with fibre-reinforced plastics are commonly used in maritime vessels thanks to their high strength-to-weight ratios, corrosion resistance, and buoyancy. Understanding their mechanical performance after moisture uptake and the implications of moisture uptake for their structural integrity and safety within out-of-plane loading regimes is vital for material optimisation. The use of modern methods such as acoustic emission (AE) and machine learning (ML) could provide effective techniques for the assessment of mechanical behaviour and structural health monitoring. In this study, the AE features obtained from quasi-static indentation tests on sandwich structures made from E-glass fibre face sheets with polyvinyl chloride foam cores were employed. Time- and frequency-domain features were then used to capture the relevant information and patterns within the AE data. A k -means++ algorithm was utilized for clustering analysis, providing insights into the principal damage modes of the studied structures. Three ensemble learning algorithms were employed to develop a damage-prediction model for samples exposed and unexposed to seawater and were loaded with indenters of different geometries. The developed models effectively identified all damage modes for the various indenter geometries under different loading conditions with accuracy scores between 86.4 and 95.9%. This illustrates the significant potential of ML for the prediction of damage evolution in composite structures for marine applications.

In the context of Turkiye's most recent parliamentary and presidential elections ("seçim" in Turkish), social media has played an important role in shaping public debate. It is of utmost importance to capture social media trends during the 2023 Turkish elections, since it uncovers a great deal of information of election propaganda, political debates, smear campaigns, and election manipulation by domestic and international actors. We provide a comprehensive dataset for social media researchers to study Turkish elections, develop tools to prevent online manipulation, and gather novel information to inform the public. We are committed to continually improving the data collection and updating it regularly leading up to the election. Using the #Secim2023 dataset, researchers can examine the social and communication networks between political actors, track current trends, and investigate emerging threats to election integrity. Our dataset and analysis code available through Harvard Dataverse and Github, respectively., (© 2024. The Author(s).)

This study aimed to develop an equine-derived hyperimmune serum against SARS-CoV-2 and evaluate its efficacy as a potential immunotherapy tool for the treatment of known and potential variants of COVID-19 in preclinical trials. The novelty of this study is the whole virus and ALUM gel adjuvant formula. The horses were immunized using a whole inactivated SARS-CoV-2 antigen, and the final purified hyperimmune serum showed high plaque reduction neutralization (PRNT 50) neutralizing titers. The efficacy of the hyperimmune serum was evaluated histopathologically and biochemically in the lungs, hearts, and serum of K18 hACE2 transgenic mice (n=45), which is an accepted model organism for SARS-CoV-2 studies and was challenged with live SARS-CoV-2. Serum treatment improved the general condition, resulting in lower levels of proinflammatory cytokines in the blood plasma, as well as reduced viral RNA titers in the lungs and hearts. Additionally, it reduced oxidative stress significantly and lessened the severity of interstitial pneumonia in the lungs when compared to infected positive controls. The study concluded that equine-derived anti-SARS-CoV-2 antibodies could be used for COVID-19 prevention and treatment, especially in the early stages of the disease and in combination with antiviral drugs and vaccines. This treatment will benefit special patient populations such as immunocompromised individuals, as specific antibodies against SARS-CoV-2 can neutralize the virus before it enters host cells. The rapid and cost-effective production of the serum allows for its availability during the acute phase of the disease, making it a critical intervention in preventing the spread of the disease and saving lives in new variants where a vaccine is not yet developed., (© 2024 The Authors. This is an open access article under the CC BY-NC-ND 4.0 license.)

Objective: The metabolic equivalent (MET) and Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) score are two parameters with known cardiovascular prognostic significance. In this study, we aimed to investigate the direct relationship between MET and SYNTAX score in patients with chronic coronary syndrome (CCS)., Method: This retrospective study included 200 patients over 18 years of age who underwent coronary angiography and had a positive exercise electrocardiography test result. Patients were divided into two groups: Group 1 with a low SYNTAX score and Group 2 with a medium-high SYNTAX score. MET values were then compared between these groups., Results: Baseline demographic characteristics and laboratory values were similar between the groups. The mean MET values in the low and medium-high SYNTAX score groups were 9.36 ± 2.38 and 8.78 ± 2.43, respectively. No statistical difference was observed (P = 0.086). Additionally, there was no statistical difference between the two groups in terms of MET values being 10 ≤ or 10 > (P = 0.172)., Conclusion: The main conclusion of our study is that there is no correlation between the SYNTAX score and functional MET value in CCS.

Objective: : Pathways associated with glutamate receptors are known to play a role in the pathophysiology of attention-deficit hyperactivity disorder (ADHD). However, cyclin-dependent kinase 5 (CDK5), microtubule-associated protein-2 (MAP2), guanylate kinase-associated protein (GKAP), and postsynaptic density 95 (PSD95), all of which are biomarkers involved in neurodevelopmental processes closely related to glutamatergic pathways, have not previously been studied in patients with ADHD. The main purpose of this study was to evaluate the plasma levels of CDK5, MAP2, GKAP, and PSD95 in children with ADHD and investigate whether these markers have a role in the etiology of ADHD., Methods: : Ninety-six children with ADHD between 6 and 15 years of age and 72 healthy controls were included in the study. Five milliliters of blood samples were taken from all participants. The samples were stored at -80°C until analyzed by the enzyme-linked immunosorbent assay method., Results: : Statistically significantly lower CDK5 levels were observed in children with ADHD than in healthy controls ( p = 0.037). The MAP2, GKAP, and PSD95 levels were found to be statistically significantly higher in the ADHD group than in healthy controls ( p = 0.012, p = 0.009, and p = 0.024, respectively). According to binary regression analysis, CDK5 and MAP2 levels were found to be predictors of ADHD., Conclusion: : In conclusion, we found that a close relationship existed between ADHD and glutamatergic pathways, and low levels of CDK5 and high levels of MAP2 and GKAP played a role in the etiopathogenesis of ADHD.

Elevated CX3CL1 is associated with severe COVID-19 and neurologic symptoms. We aimed to investigate the potential protective effects of selective CX3CR1 antagonist AZD8797 on SARS-CoV-2-induced neuronal damage, and to identify the underlying mechanisms. K18-hACE2 transgenic mice (n = 37) were randomly divided into control groups and SARS-CoV-2 groups, with and without intraperitoneal administration of vehicle or AZD8797 (2.5 mg/mL/day), following exposure to either a single dose of SARS-CoV-2 inhalation or no exposure. Object recognition and hole board tests were performed to assess memory function. Postinfection 8 days, brain tissues were analyzed for histopathological changes, viral, glial, apoptotic, and other immunohistochemical markers, along with measuring malondialdehyde, glutathione, and myeloperoxidase activities. Serum samples were analyzed for proinflammatory cytokines. The SARS-CoV-2 group showed significant weight loss, neuronal damage, oxidative stress, and impaired object recognition memory, while AZD8797 treatment mitigated some of these effects, especially in weight, apoptosis, glutathione, and MCP-1. Histopathological analyses supported the protective effects of AZD8797 against SARS-CoV-2-induced damage. The CX3CL1-CX3CR1 signaling pathway could offer a promising target for reducing SARS-CoV-2's neurological impact, but additional research is needed to confirm these findings in combination with other therapies and assess the clinical significance., Competing Interests: Conflict of Interest The authors declare that they have no competing interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Microscopy Society of America.)

Internet addiction (IA), one of the behavioral addictions, is also related to impulsivity. Although studies on its etiology and risks continue, the number of studies is limited. In this study, we aimed to assess the roles of behavioral systems, emotional regulation (ER), and impulsivity in the development of IA in adolescents and also to assess the relationship between all these clinical parameters and brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY). Forty-two adolescents with IA and 30 healthy controls (ages 12 -17) were included in the study. Self-reported measures included the Internet Addiction Scale. (IAS), Behavioral Activation and Behavioral Inhibition Scale (BAS/BIS), Barratt. Impulsiveness Scale-11 (BIS-11), and Difficulties in Emotion Regulation Scale-16 (DERS-16) were used for the assessment of the participants. The levels of plasma brain BDNF and NPY were evaluated with the ELISA method. BAS/BIS subscale scores, BIS-11, and DERS-16 scale total scores were found to be statistically significantly higher, while BDNF and NPY levels were found to be lower in adolescents with IA compared to the healthy controls. IA severity was not found to correlate with both BDNF and NPY. IA was found to be more related to BIS than to BAS. There is a need for further studies evaluating developmental features and possible diagnostic biomarkers that may be associated with IA in adolescents., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Comorbidity of Internet addiction (IA) with sleep disruptions is common in adolescents. There is evidence that the levels of brain injury markers could be affected by sleep disruptions. In this study, we aimed to evaluate the relationship between sleep quality and these biomarkers within the framework of the relationship between IA and sleep disruptions., Methods: A total of 65 drug-free adolescents with newly diagnosed IA, aged 12 to 18 years, were included in the study, and they were divided into two groups considering the comorbidities of attention-deficit/hyperactivity disorder (ADHD) and social anxiety. The control group consisted of 30 healthy children. The participants were asked to complete the Young Internet Addiction Scale, Pittsburgh Sleep Quality Index (PSQI), Morningness Eveningness Questionnaire, Beck's Depression Inventory, Beck's Anxiety Inventory, and Barratt Impulsiveness Scale-11. Blood samples were taken between 8 and 9 am to analyze S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) levels with enzyme-linked immunosorbent assay., Results: Plasma S100B and NSE levels were found to be statistically significantly higher in the IA with ADHD and the IA with anxiety groups than in healthy controls. NSE and S100B levels were found to be correlated with PSQI scores in both the IA groups. Also, there was a positive correlation between these biomarkers and IA severity., Conclusions: Decreased sleep quality and daily sleep duration in IA might cause brain injury, resulting in an increase in the severity of the addiction. Prospective studies with large samples are needed to better explain the IA-sleep-brain injury relationship., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to evaluate the stability, safety, and efficacy of alpha-targeted therapy with [ 225 Ac]Ac-DOTATATE in patients with grade 1/2 metastatic neuroendocrine tumors (NETs)., Methods: This retrospective cohort included patients (n=11) with metastatic NETs from different primary sites (bronchial, pancreatic, nonpancreatic gastroenteropancreatic NETs, paraganglioma, and unknown primary site) treated with [ 225 Ac]Ac-DOTATATE with a mean activity of 8.2±0.6 MBq (range: 7.5-10.0 MBq) at our institution between November 2019 and March 2022. The in vivo and in vitro stability of [ 225 Ac]Ac-DOTATATE was calculated. The safety profile was evaluated according to the CTCAE-v5.0. Treatment efficacy was evaluated according to [ 68 Ga] Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) images and the RECIST 1.1 criteria., Results: Patients had 73% (n=8) lymph node metastases, 91% (n=10) liver metastases, 36% (n=4) lung metastases, and 73% (n=8) bone metastases. All but one patient was refractory to treatment with [ 177 Lu]Lu-DOTATATE. [ 225 Ac]Ac-DOTATATE was stable for at least 5 h in vitro (in saline) and 3 h in vivo (urine and blood samples). Grade 2 renal toxicity and grade 2 hematotoxicity were observed in one patient. No grade 3-4 toxicities were reported. According to post-treatment [ 68 Ga]Ga-DOTATATE PET/CT (n=9), 11% (n=1) had progressive disease, 44.4% (n=4) had stable disease, and 44.4% (n=4) had a partial response. The disease control rate was 89% (n=8). The median progression-free survival estimated according to Kaplan-Meier analysis was 12 months., Conclusion: The preliminary results of this study suggest that [ 225 Ac]Ac-DOTATATE is stable, safe, and effective for treating advanced and [ 177 Lu] Lu-DOTATATE-refractory NETs. However, prospective studies are needed to determine the impact of treatment on overall survival and to uncover potential side effects., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2023 by the Turkish Society of Nuclear Medicine / Molecular Imaging and Radionuclide Therapy published by Galenos Publishing House.)

The aim of this study is to determine the functioning of adults with autism spectrum disorders (ASDs) diagnosed in childhood and depression and burnout levels among their parents. A total of 261 adults with ASDs and their parents were recruited for the study. Both parents completed the Beck Depression and Maslach Burnout Inventories and reported the functioning of their adult offspring with ASDs. Only 5.4 % of our sample reported "good" or "very good" outcomes. The most common psychiatric comorbidities were intellectual disabilities and attention-deficit/hyperactivity disorder. Maternal burnout and depression scores were significantly elevated compared to those of fathers. There is an undeniable urgent need for more research to identify the needs of adults and families suffering from ASD. Modifications for those with ASD may have to be made for support in workplaces, achieving driving licenses, using public transportation and attendance at tertiary education., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

For patients with advanced-stage metastatic castration-resistant prostate cancer (mCRPC) who do not respond to [ 177 Lu]Lu-PSMA therapy, there are limited treatment options. Clinical results obtained with [ 225 Ac]Ac-PSMA are promising. We retrospectively analyzed the outcomes of patients treated with [ 225 Ac]Ac-PSMA between December 2018 and October 2022. Methods: We evaluated the treatment results of 23 patients (mean age, 70.3 ± 8.8 y) with mCRPC who were refractory to treatment with [ 177 Lu]Lu-PSMA (2-9 cycles). The safety profile was assessed according to Common Technology Criteria for Adverse Events version 5.0. Treatment efficacy was assessed using prostate-specific membrane antigen PET progression criteria and prostate-specific antigen (PSA) response according to Prostate Cancer Working Group 2 criteria after the first cycle of [ 225 Ac]Ac-PSMA treatment. Results: All patients received androgen-deprivation therapy, whereas 22 (96%) and 19 (83%) patients received chemotherapy and second-generation antiandrogen therapy, respectively. One patient received 4 cycles, 2 received 3 cycles, 8 received 2 cycles, and 12 received 1 cycle of [ 225 Ac]Ac-PSMA. The median interval between cycles was 13 wk (range, 8-28 wk). [ 225 Ac]Ac-PSMA was administered with a mean activity of 7.6 MBq (range, 6.2-10.0 MBq) in each cycle. Patients were at an advanced stage of disease, and tumor burden was very high. Although the best PSA response was observed in 5 patients (26%) after [ 225 Ac]Ac-PSMA treatment, there was at least some level of decline in PSA observed in 11 patients (58%; n = 19). Treatment response was assessed in patients who underwent [ 68 Ga]Ga-PSMA PET/CT imaging. After the first cycle of treatment ( n = 18), 50% of patients ( n = 9) showed disease progression according to prostate-specific membrane antigen PET progression criteria, and the disease control rate was calculated to be 50%. Median progression-free survival was 3.1 mo, and median overall survival was 7.7 mo. Grade 3 hematologic toxicity occurred in 1 patient, and grade 3 nephrotoxicity was observed in another patient. Parotid SUV max decreased by 33%, although all patients complained of dry mouth before treatment. Conclusion: We observed that [ 225 Ac]Ac-PSMA therapy was safe and showed potential even in cases with advanced-stage mCRPC in which all other treatment options were completed., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: The COVID-19 is an ongoing health problem with millions of cases and deaths worldwide. Although the virus is transmitted with droplets through the respiratory system, the involvement of different organs has been reported., Objectives: The pandemic caused urological procedures to be postponed when patient is infected with SARS-CoV-2. However, the reliability of 1 month postpone period and long-term complications of the virus, such as a possible erectile dysfunction (ED) is not clarified. We aimed to compare the corpus cavernosum of patients 1 and 7 months after COVID-19 infection with control patients who had not COVID-19 and search for SARS-CoV-2 in tissues using immunohistochemistry and electron microscopy., Materials and Methods: Three groups of subjects underwent penile prosthesis implantation and Nesbit procedure for Peyronie's disease 1 and 7 months after COVID-19 infection and control group without previous COVID-19 infection. We searched for SARS-CoV-2 in penile tissue using RT-PCR, electron microscopy and immunohistochemistry., Results: Electron microscopy and immunohistochemical staining showed SARS CoV-2 virus in the penile corpus cavernosum of patients 1 month after COVID-19 recovery. Immunohistochemical staining intensity correlated with the severity of previous infection. Transmission electron microscopy revealed intracellular virtual particles of about 80 nm with a typical morphology of prominent spikes and electron-dense dots of nucleocapsid in addition to vesicles filled with virus-like particles. Cells showed increased membrane trafficking. The 1 month after COVID-19 group showed an increased number of fibroblasts. The 7 months after COVID-19 group had similar morphology and immunoreactivity as control group., Discussion: This is the first study of late post-COVID examination of penis and the second study of early post-COVID examination of corpus cavernosum. For 1 month post-COVID patients, the aetiology of ED could be the viral infection that is also affecting corpora cavernosa. We hypothesize that viral infection affects the endocytic and exocytic pathways, hence the metabolic activity of cells that can be the reason of altered functions in some post-COVID patients., Conclusion: This study is important because it did not detect any virus residue in the tissue samples at the seventh month. In addition, we can say that the penile surgeries should be postponed more than 1 month after the COVID infection according to this study. But, there is a need for new studies with large series and high levels of evidence that can show how long the virus remains in the corpus cavernosum. Patients should be followed in this respect., (© 2022 American Society of Andrology and European Academy of Andrology.)

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorders that begin in early childhood. Mutations in α-synuclein (SNCA) gene have been shown to result in the accumulation of α-synuclein, which occurs in many neurodegenerative diseases. Our aim was to determine the changes in the expression profile and protein level of this gene by comparing the autistic children with their healthy siblings, their mothers and healthy controls in order to elucidate the possible contribution of the SNCA gene to the etiology of ASD. 50 autistic patients, their mothers, siblings and 25 healthy controls and their mothers were enrolled to determine SNCA gene expression and serum α-synuclein levels. It was determined that α-synuclein serum levels decreased in the autistic patients. Similarly, it was found that SNCA gene expression and serum α-synuclein levels were significantly decreased in the mothers of the patients. Significant negative correlation was observed between the SNCA gene and protein expression amounts in the 6-8 age of the patients. This family-based study is the first in the literature, with both gene expression and serum levels of α-synuclein. The relationship between ASD severity and α-synuclein level needs to be confirmed in larger-scale studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The use of fibre-reinforced plastics (FRPs) in various industrial applications continues to increase thanks to their good strength-to-weight ratio and impact resistance, as well as the high strength that provides engineers with advanced options for the design of modern structures subjected to a variety of out-of-plane impacts. An assessment of the damage morphology under such conditions using non-destructive techniques could provide useful data for material design and optimisation. This study investigated the damage mechanism and energy-absorption characteristics of E-glass laminates and sandwich structures with GFRP face sheets with PVC cores under quasi-static indentation with conical, square, and hemispherical indenters. An acoustic emission (AE) technique, coupled with a k-means++ pattern-recognition algorithm, was employed to identify the dominant microscopic and macroscopic damage mechanisms. Additionally, a post-mortem damage assessment was performed with X-ray micro computed tomography and scanning electron microscopy to validate the identified clusters. It was found that the specific energy absorption after impact with the square and hemispherical indenters of the GFRP sandwich and the plain laminate differed significantly, by 19.29% and 43.33%, respectively, while a minimal difference of 3.5% was recorded for the conical indenter. Additionally, the results obtained with the clustering technique applied to the acoustic emission signals detected the main damaged modes, such as matrix cracking, fibre/matrix debonding, delamination, the debonding of face sheets/core, and core failure. The results therefore could provide a methodology for the optimisation and prediction of damage for the health monitoring of composites.

The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) offer expedited regulatory approval programs for drugs with high potential patient value applicable at different stages leading to marketing authorization: (i) drug development (fast track designation (FTD), breakthrough therapy designation (BTD), regenerative medicine advanced therapy designation in the United States, and priority medicines scheme in the European Union), (ii) review of marketing authorization application (priority review in the United States and accelerated assessment in the European Union), (iii) approval of drug (accelerated approval in the United States and conditional approval in the European Union). Typical clinical development time of 76 new anticancer drugs, for which the EMA gave a positive opinion between January 2010 and December 2019, was 6.7 years: 5.8 years for small molecules and 7.7 years for biotechnology-derived products. Drugs following only BTD (5.6 years) typically had a shorter clinical development time than drugs following only FTD (6.4 years) or both FTD and BTD (6.4 years), compared to drugs not following any expedited regulatory approval program at the drug development stage (7.7 years). Drugs following an expedited regulatory approval program at the stage of drug development and accelerated approval in the United States (FDA1 [4.5 years] and FDA3 [5.6 years]), and drugs following the standard procedure at the stage of drug development and conditional approval in the European Union (EMA5 [5.5 years] and EMA7 [4.5 years]) typically had a reduced clinical development time. These findings provide insight for the industry into combinations of expedited regulatory approval programs correlated with shorter clinical development time of new anticancer drugs., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Purpose: The aim of this study is to evaluate the prevalence of anxiety disorders, its correlation with sociodemographic characteristics, its comorbidities with other psychiatric disorders and its predictors in school-aged children., Methods: This study is part of a representative, multi-centered national study that is planned by the Turkish Association of Child and Adolescent Mental Health to evaluate the prevalence of psychopathology among elementary school students in Turkey between the years 2014-2015. Children are screened via Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children Present and Lifetime Version. Impairment is assessed by a 3-point Likert type scale independently by the parent and the teacher. The final sample included 5842 children with the mean age of 8.7 years., Results: The prevalence of any anxiety disorder without considering impairment is 16.7% and considering impairment is 5.2% in children according to our study. We found significant differences for comorbid Attention Deficit Hyperactivity Disorder, Disruptive Behavior Disorder, Mood Disorders, Tic Disorders, Obsessive Compulsive Disorder, Enuresis Nocturna, Encopresis, and Intellectual Disability. Having a history of paternal physical disorder, living in the regions of Marmara, Mediterranean and Black Sea were found to be the main predictors of having childhood anxiety disorders according to the logistic regression analysis., Conclusion: Better understanding of childhood anxiety disorders, comorbid conditions and predictors will result in earlier diagnosis and more appropriate treatment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Cubilin is one of the receptor proteins responsible for reabsorption of albumin in proximal tubules and is encoded by the CUBN gene. We aimed to evaluate clinical and genetic characterization of six patients with proteinuria who had CUBN mutations., Methods: Patients' characteristics, serum creatinine, albumin, vitamin B 12 levels, urine analysis, spot urine protein/creatinine, microalbumin/creatinine, beta-2 microglobulin/creatinine ratios, estimated glomerular filtration rates (eGFR), treatments, kidney biopsies, and genetic analyses were evaluated., Results: Six patients (2 female, 4 male) with an incidental finding of proteinuria were evaluated. Mean admission age and follow-up time were 7.3 ± 2.9 and 6.5 ± 5.6 years, respectively. Serum albumin, creatinine, and eGFR were normal; urine analysis revealed no hematuria, and C3, C4, ANA, and anti-DNA were negative; kidney ultrasonography was normal for all patients. Urine protein/creatinine was 0.9 ± 0.3 mg/mg, and microalbumin was high in all patients. Serum vitamin B 12 was low in two patients and normal in four. Kidney biopsy was performed in four patients, three demonstrated normal light microscopy, and there was one focal segmental glomerulosclerosis (FSGS). Genetic tests revealed four homozygous and two compound heterozygous mutations in the C-terminal part of cubilin. All patients had normal eGFR and still had non-nephrotic range proteinuria at last visit., Conclusions: CUBN gene mutations should be considered in patients with isolated non-nephrotic range proteinuria and normal kidney function. Diagnosing these patients, who are thought to have a better prognosis, is important in terms of avoiding unnecessary treatment and predicting prognosis. CUBN gene mutations may also present as FSGS which extends the spectrum of renal manifestation of these patients. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: There are studies on the effects of Ramadan fasting (RF), which is one of the intermittent fasting diets, on both hypertension and endothelial function. However, the relationship between possible improvements in endothelial function and blood pressure after RF is not clear. In this study, we aimed to evaluate the effects of RF on blood pressure and endothelial dysfunction in patients with arterial hypertension (HT)., Methods: : Sixty-four HT patients, aged 45-65, who were followed up in the Cardiology Department of Kayseri City Hospital and fasted during Ramadan between 13 April and 13 May 2021 with their self-consents were enrolled to study. Body mass index (BMI), blood pressure, and flow-mediated dilatation (FMD) were assessed before and after Ramadan. Also, 5 mL venous blood samples were taken between 8:00 and 8:30 a.m. from all participants to assess cortisol, C-reactive protein (CRP), and other laboratory data., Results: : In patients, FMD values were found to be higher after Ramadan compared to values before the fasting period (p < 0.001). CRPand cortisol levels decreased after fasting, and the decrease in CRP (95% CI for B = -1.685 - -0.334, p = 0.009) and cortisol levels (95% CI for B = -0.392 - 0.092, p = 0.039) were determined as the predictive factors for FMD after RF., Discussion: Endothelial functions as determined by FMD improved after 30 days of intermittent fasting. The decreased CRP and cortisol levels may contribute to the improvement in FMD after RF.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is clinically defined as myocardial infarction in the absence of obstructive atherosclerosis on coronary angiography. Diagnosis may require multiple diagnostic tools in addition to standard coronary angiography, including cardiac imaging or provocative tests, according to clinical suspicion. We assessed the usefulness of the DETERMINE (Defibrillators to Reduce Risk by Magnetic Resonance Imaging Evaluation) score for distinguishing patients with MINOCA from those with non-ST segment elevation myocardial infarction with obstructive coronary artery disease (NSTEMI-CAD) in a single-center observational study. The patients were divided into two groups according to coronary angiography findings. The study included 277 patients: 227 with NSTEMI-CAD and 50 with MINOCA. The DETERMINE score (6.1 ± 3.7 vs 1.9 ± 2.1, P<.001) was significantly higher in the NSTEMI-CAD than MINOCA group. Logistic regression analysis revealed that the DETERMINE score (OR=0.591, P<0.001) was an independent predictor of MINOCA. The incidence of diabetes mellitus and glucose levels were significantly higher in the NSTEMI-CAD group; however, ejection fraction was significantly higher in the MINOCA group (P<0.05). Our findings suggest that the DETERMINE score constitutes a simple and inexpensive tool for the assessment of MINOCA.

Background: Although it has been reported that the intermittent fasting (IF) diet has positive effects on heart health and improvement in blood pressure, it has not been sufficiently clarified how it could have these positive effects yet., Objective: We aimed to evaluate the effects of IF on the autonomic nervous system (ANS) and renin-angiotensin system (RAS), which are closely related to blood pressure., Methods: Seventy-two hypertensive patients were included in the study, and the data of 58 patients were used. All the participants fasted for about 15-16 hours for 30 days. Participants were evaluated with 24-hour ambulatory blood pressure monitoring and Holter electrocardiography before and after IF; also, 5 ml venous blood samples were taken for assessment of Serum angiotensin I (Ang-I) and angiotensin II (Ang-II) levels and angiotensin-converting enzyme (ACE) activity. For data analysis, the p-value <0.05 was accepted as significant., Results: Compared to pre-IF, a significant decrease was observed in the patients' blood pressures in post-IF. An increase in high-frequency (HF) power and the mean root square of the sum of squares of differences between adjacent NN intervals (RMSSD) were observed after the IF protocol (p=0.039, p=0.043). Ang-II and ACE activity were lower in patients after IF (p=0.034, p=0.004), and decreasing Ang-II levels were determined as predictive factors for improvement of the blood pressure, like the increase in HF power and RMSSD., Conclusion: The present findings of our study demonstrated an improvement in blood pressure and the relationship of blood pressure with positive outcomes, including HRV, ACE activity, and Ang-II levels after the IF protocol.

The analysis of fibrous structures using micro-computer tomography (µCT) is becoming more important as it provides an opportunity to characterise the mechanical properties and performance of materials. This study is the first attempt to provide computations of fibre crimp for various random fibrous networks (RFNs) based on µCT data. A parametric algorithm was developed to compute fibre crimp in fibres in a virtual domain. It was successfully tested for six different X-ray µCT models of nonwoven fabrics. Computations showed that nonwoven fabrics with crimped fibres exhibited higher crimp levels than those with non-crimped fibres, as expected. However, with the increased fabric density of the non-crimped nonwovens, fibres tended to be more crimped. Additionally, the projected fibre crimp was computed for all three major 2D planes, and the obtained results were statistically analysed. Initially, the algorithm was tested for a small-size, nonwoven model containing only four fibres. The fraction of nearly straight fibres was computed for both crimped and non-crimped fabrics. The mean value of the fibre crimp demonstrated that fibre segments between intersections were almost straight. However, it was observed that there were no perfectly straight fibres in the analysed RFNs. This study is applicable to approach employing a finite-element analysis (FEA) and computational fluid dynamics (CFD) to model/analyse RFNs.

Objective: Aspirin is an essential drug in the prevention of atherosclerotic cardiovascular disease (ASCVD). It is ultimately indicated in a patient with ASCVD. However, its role is debated in primary prevention. We aimed to investigate the appropriateness of aspirin use in diabetic patients according to recommendations of recent guidelines., Patients and Methods: ASSOS was a multicenter observational study investigating aspirin use in cardiology outpatient clinics. We evaluated aspirin use in diabetic patients in primary prevention from the ASSOS study. We also assessed the appropriate use of aspirin according to the European Society of Cardiology (ESC), American College of Cardiology/American Heart Association (ACC/AHA), American Diabetes Association (ADA), Consensus Statement of Endocrinology, Cardiology, and Nephrology (ENCARNE), and the United States Preventive Services Task Force (USPTF)., Results: A total of 5,007 patients of whom 1,537 had type 2 diabetes mellitus (DM) were included in the study. 1,132 of the total participants used aspirin for primary prevention; 313 of them had type 2 DM. Only 248 (76.7%), 132 (40.8%), and 128 (39.6%) diabetic patients indicated aspirin use according to the ESC/INCARNE, ACC/AHA, and ADA/USPTF guidelines, respectively., Conclusions: Inappropriate aspirin use was common among diabetic patients, according to clinical practice guideline recommendations. In addition, the differences between the indications for the use of aspirin in diabetic patients according to the guidelines were remarkable. Guidelines that minimize these differences are needed for clinicians, and compliance with these guidelines in clinical practice could reduce inappropriate aspirin use.

Objective: Serum ACE2 level in the acute phase of ST-segment elevation myocardial infarction may be an indicator of heart failure, however, limited studies have reported conflicting results. Therefore, in our study, we aimed to evaluate the relationship between serum ACE2 level and infarct size in the acute phase of ST-segment elevation myocardial infarction and compare the predictive value of ACE2 level with classical biomarkers., Patients and Methods: Sixty-six patients after the primary percutaneous coronary intervention were included in the study. For the measurement of serum ACE2 levels, blood samples were taken twice from the patients: in the first 24 hours and on the 5th day of the infarction, and once from 30 healthy volunteers. hs-cTnT, BNP, and CRP levels were measured daily, and their peak values were taken. On the 7th day of ST-segment elevation myocardial infarction, gSPECT was used with the 99mTc-MIBI method for assessment of infarct size., Results: Baseline ACE2 values were found to be higher in patients compared to controls, and ACE2 values obtained on the 5th day were found to be higher than the baseline values in the patients. There was no significant correlation between serum ACE2 levels and the RSS (%), while peak levels of hs-cTnT, BNP, and CRP were assessed as predictive factors for the RSS (%)., Conclusions: Although serum ACE2 levels increased in the acute phase of ST-segment elevation myocardial infarction, this increase was not associated with infarct size. Serum ACE2 level did not provide additional benefit to classical biomarkers for infarct size-related prognosis prediction.

Background: Imaging modalities are used to diagnose and clinical grading of clinically significant prostate cancer. In this study, 68Ga-PSMA PET/CT (PSMA) and multiparametric prostate MRI (mp-MRI) were compared in regard to locating intraprostatic tumor and locoregional staging., Methods: After ethics committee approval, a total of 49 patients with prostate cancer who had mp-MRI and PSMA before radical prostatectomy were included. Preoperative and postoperative PSA, transrectal ultrasound-guided prostate biopsy (TRUS-Bx) ISUP grade, radical prostatectomy ISUP grade, body mass index (BMI), TRUS prostate volume, mp-MRI tumor mapping, PSMAtumor mapping, pathologic tumor mapping, extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymph node invasion (LNI), and bladder neck invasion (BNI)were retrospectively evaluated. Index tumor was located by uroradiologist, nuclear medicine specialist, and uropathologist on a 12-sector prostate pathology map and compared with each other in terms of accuracy and locoregional clinical staging., Results: Mean age of the patients was 66.18 ± 6.67 years and the mean of preoperative PSA results was 21.11 ± 32.56 ng/ml. Nearly half of the patients' (44.9%) pathology was reported as ISUP grade 4 and 5% and 18.4% of patients were surgical margin positive. According to the pathological findings, 362 out of 588 sectors were tumor-positive, 174 out of 362 sectors were tumor-positive in mp-MRI, and 175 out of 362 sectors were tumor-positive in PSMA. Both PSMA and mp-MRI were comparable (p = 0.823) and accurate to detect the location of the intraprostatic index tumor (AUC = 0.66 vs. 0.69 respectively, p = 0.82). The sensitivity and the specificity of the PSMA and mp-MRI for localizing intraprostatic index tumors were 42.5% versus 49.5% and 90.7% versus 88.6% respectively. mp-MRI was more accurate than PSMA in terms of EPE (AUC = 0.8 vs. AUC = 0.57 respectively, p = 0.027) and both methods were comparable in terms of SVI (AUC = 0.75 vs. AUC = 0.75, p = 0.886) and BNI (AUC = 0.51 vs. AUC = 0.59, p = 0.597). PSMA and mp-MRI were comparable in terms of LNI (AUC = 0.76 vs. AUC = 0.64, p = 0.39)., Conclusion: mp-MRI should be considered for its high accuracy in the diagnosis of EPE, especially before decision-making for nerve-sparing surgery in high-risk patients. Both imaging modalities were accurate for localizing intraprostatic index tumor. PSMA is accurate for detecting LNI., (© 2022 Wiley Periodicals LLC.)

Dyslexia is a learning disability in acquiring reading skills, even though the individual has the appropriate learning opportunity, adequate education, and appropriate sociocultural environment. Dyslexia negatively affects children's educational development; hence, early detection is highly important. Electrooculogram (EOG) signals are one of the most frequently used physiological signals in human-computer interfaces applications. EOG is a method based on the examination of the electrical potential of eye movements. The advantages of EOG-based systems are non-invasive, affordable, easy to record, and can be processed in real time. In this paper, a novel 1D CNN approach using EOG signals is proposed for the diagnosis of dyslexia. The proposed approach aims to diagnose dyslexia using EOG signals that are recorded simultaneously during reading texts, which are prepared in different typefaces and fonts. EOG signals were recorded from both horizontal and vertical channels, thus comparing the success of vertical and horizontal EOG signals in detecting dyslexia. The proposed approach provided an effective classification without requiring any hand-crafted feature extraction techniques. The proposed method achieved classifier accuracy of 98.70% and 80.94% for horizontal and vertical channel EOG signals, respectively. The results show that the EOG signals-based approach gives successful results for the diagnosis of dyslexia., (© 2022. International Federation for Medical and Biological Engineering.)

Background: Attention deficit hyperactivity disorder (ADHD), one of the most common neurodevelopmental disorders in childhood, is diagnosed clinically by assessing the symptoms of inattention, hyperactivity, and impulsivity. Also, there are limited objective assessment tools to support the diagnosis. Thus, in this study, a new electrooculography (EOG) based on visual stimulus tracking to support the diagnosis of ADHD was proposed., Methods: Reference stimulus one-to-one tracking numbers (RSOT) and colour game detection (CGD) were applied to 53 medication-free children with ADHD and 36 healthy controls (HCs). Also, the test was applied six months after the treatment to children with ADHD. Parameters obtained during the visual stimulus tracking test were analyzed and Higuchi fractal dimension (HFD) and Hjorth parameters were calculated for all EOG records., Results: The average test success rate was higher in HCs than in children with ADHD. Based on machine learning algorithms, the proposed system can distinguish drug-free ADHD patients from HCs with an 89.13% classification performance and also distinguish drug-free children from treated children with an 80.47% classification performance., Discussion: The findings showed that the proposed system could be helpful to support the diagnosis of ADHD and the follow-up of the treatment.

Quantitative analysis of fibre orientation in a random fibrous network (RFN) is important to understand their microstructure, properties and performance. 2D fibre orientation distribution presents an in-plane fibre orientation without any information on fibre orientation in thickness direction. This research introduces a fully parametric algorithm for computing 3D fibre orientation as thickness is important for high-density or thick fibrous networks. The algorithm is tested for 3 major classes of nonwoven fabrics called low- (L), medium- (M) and high-density (H) ones. H fabric density is 6-8 times larger than the L fabric density. M fabric density (traditional intermediate fabric density) is 3-4 times larger than the L fabric density. Voxel models of experimental nonwoven webs were generated by an X-ray micro-CT (µCT) system and evaluated with the algorithm. Statistical results showed that a fraction of fibres orientated along the thickness direction increases as fibre density grows. To validate the accuracy of findings, deterministic voxelated virtual fibrous structures, created using mathematical functions were used. This novel algorithm is able to produce a 3D orientation distribution function (ODF) for any RFN including, models of nonwovens produced with various manufacturing parameters, experimentally verified and validated with X-ray µCT. Also, it can compute 2D ODFs of various types of RFNs to evaluate 2D behaviour of fibrous structures. The obtained results are useful for applications in many fields including finite element analysis, computational fluid dynamics, additive manufacturing, etc., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The aim of this study was to assess the effect of expedited regulatory approval programs used by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), type of product (small molecule or biotechnology-derived product) and consulting scientific advisory committees on the regulatory review time of the marketing authorization applications (MAAs) for new anticancer drugs. A dataset composed of 76 new anticancer drugs was constructed. The date of submission of the MAAs in the United States and the European Union were comparable. The typical review time of MAAs was 136 days shorter in the United States (201 days [median]) than in the European Union (337 days [median]). The type of product did not have a high impact on the review time. The review time of the MAAs for drugs undergoing priority review in the United States or accelerated assessment in the European Union at the stage of review of MAA was generally shorter than that for drugs following the standard regulatory pathway. The regulatory pathway using at least one expedited regulatory program at the stages of drug development, review of MAA, and approval of drug in the United States (172 days [median]), and that at the stages of review of MAA and approval of drug in the European Union (183 days [median]) enabled the shortest review time of MAAs. Referral to advisory committee meeting increased the review time of MAAs for drugs undergoing one or more expedited regulatory approval programs in the United States and the European Union close to that for drugs undergoing the standard regulatory approval pathway., (© 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objective: Although several genes have previously been studied about the treatment of Attention Deficit Hyperactivity Disorder (ADHD), the number of studies investigating the effects of genes on atomoxetine (ATX) treatment is very limited. In this study, we aimed to investigate the effect of CYP2C19 polymorphisms, which have a role in ATX biotransformation, on the treatment response and also to assess whether there is a relationship between BDNF and treatment response in children and adolescents with ADHD., Methods: One hundred children with ADHD and 100 healthy controls (HCs) were included in this study. The treatment response was assessed 2 months after the start of the ATX treatment. DNA samples from peripheral venous blood were replicated using PCR and analyzed using the ILLUMINA next-generation sequencing method. The resulting fastqs were analyzed using Basespace's Variant Interpreter Program. Plasma BDNF levels were evaluated with ELISA kits., Results: Treatment response was found to be lower in both heterozygous and homozygous carriers of the c.681G > A (CYP2C19*2) polymorphism. When the BDNF level was compared, it was found to be significantly higher in the ADHD group compared to HCs. Also, BDNF has a stronger predictive value for assessing resistance to ATX treatment., Conclusions: To our knowledge, this is the first study to assess the effects of CYP2C19 polymorphisms and BDNF levels together on ATX treatment in children. Further studies with an extensive population are needed to better understand the effects of CYP2C19 polymorphisms on treatment and side effects, as well as the effects of BDNF levels., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: We aimed to present the characteristics, genetic analysis results, long-term progno- sis of our patients with distal kidney tubular acidosis, and the relationship between hyperam- monemia and distal kidney tubular acidosis., Materials and Methods: Biochemical, clinical, and imaging findings were collected at presen- tation and the last clinic visit, and results of the genetic analysis were recorded., Results: Our study included 9 patients (3 female, 33%). The median age at diagnosis was 3 months, and the median follow-up period was 111 months. Height standard deviation scores were less than -2 in 4 (44%) patients at presentation and in 3 (33%) at the last clinic visit. The median estimated glomerular filtration rate was 98 mL/min/1.73 m2 at presentation and 126 mL/min/1.73 m2 at the last clinic visit. We have found 8 different types of mutations of 2 genes, including 6 in the ATP6V0A4 gene, 2 in the SLCA4A1 gene, and 2 of them were novel. At the time of presentation, nephrocalcinosis and hypercalciuria were present in all our patients, but at the last visit, only 1 patient had hypercalciuria. Sensorineural hearing loss was found in 4 of our patients with a mutation in the ATP6V0A4 gene. Serum ammonia levels were found to be high in 3 patients with mutations in the ATP6V0A4 gene., Conclusion: Adequate metabolic control is essential for optimal growth and preserved kidney function in distal kidney tubular acidosis patients. Distal kidney tubular acidosis may be associ- ated with hyperammonemia. We recommend keeping potassium levels at high-normal levels to reduce ammonia levels, especially in the absence of acidosis.

Neuroendocrine tumors (NETs) are being seen increasingly frequently, and the only known curative treatment method is surgical resection. Peptide receptor radionuclide therapy (PRRT) is a treatment option that the most contributes to progression-free survival and overall survival in metastatic cases.β-emitting radionuclides are traditionally used for PRRT. Nowadays, alpha particle-emitting radionuclides are being developed, with advantages in terms of very high energy and a short path length, which should theoretically show higher efficacy. In this case; in a patient with NET diagnosis who had multiple (>50) lesions in the abdomen, almost all the lesions disappeared with a single dose application. This paper aims to present a case in which we observed the efficacy of 225 Ac-DOTATATE treatment, which is an alpha treatment., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2022 by Turkish Society of Nuclear Medicine, Molecular Imaging and Radionuclide Therapy published by Galenos Yayınevi.)

Research Question: The cryopreservation of prepubertal testicular tissue is important for children who are to undergo gonadotoxic treatment. There is ongoing debate around the optimal carrier for an inexpensive and rapid vitrification technique. How efficient would a novel, practical and sterilizable metal brush be when compared with previously used carriers?, Design: The testicular tissues of prepubertal rats were vitrified using four different carriers and evaluated by light microscopy and transmission electron microscopy., Results: Nuclei were easily discriminated in the metal brush, aluminium foil and high-security straw groups, but there was decreased discrimination of structures in the metal wire group. Minimal cytoplasmic degeneration, vacuolization and mild reversible degenerative effects were seen in spermatogonial stem cells and Sertoli cells in the metal brush group. Mild to moderate structural changes were found in the aluminium foil group. Severe pyknosis of the nuclei, a high degree of swelling, expansion of the endoplasmic reticulum, and swelling and blurring of the mitochondria were seen in the metal wire and high-security straw groups. The cell viabilities in the metal brush, aluminium foil, metal wire and high-security straw groups were 91.6 ± 3.85%, 83.0 ± 4.06%, 76.0 ± 3.16% and 68.6 ± 4.93%, respectively., Conclusions: The metal brush is a promising new carrier for prepubertal testis vitrification., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: Atomoxetine (ATX), one of the most commonly used drugs after stimulants in attention deficit hyperactivity disorder (ADHD) treatment, is an inhibitor of the norepinephrine transporter ( NET/SLC6A2 ), which is also associated with the etiology of ADHD. In this study, we aimed to investigate the effect of NET gene polymorphisms on response to ATX treatment and to find the answers to the questions about whether there is a relationship between the severity of the disorder and the observed side effects in children with ADHD., Method: About 100 children with ADHD and 80 healthy controls (HCs) were included in this study. The dose of ATX was started at 0.5 mg/kg/day and titrated at 1.2 mg/kg/day. Response to treatment of 78 patients was evaluated 2 months after the beginning of the treatment. After whole blood samples were obtained, DNAs were isolated, and samples were stored at -80°C. Two single-nucleotide polymorphisms (SNPs) (rs12708954 and rs3785143) were analyzed by real-time quantitative PCR (qRT-PCR)., Results: The patients with both rs12708954 and rs3785143 heterozygous genotype had better treatment response and more side effects than patients with wild type. There was not found any association between any of the investigated NET polymorphisms and ADHD severity., Conclusion: It was, however, found that the NET rs12708954 and rs3785143 genotypes affect the treatment response to ATX in our study; thus, further studies with a large population are needed to understand the effects of NET polymorphisms on treatment, side effects, and also the severity of ADHD.

In this study, we aimed to determine endothelial dysfunction and ischemia-modified albumin (IMA) levels in patients diagnosed with erectile dysfunction (ED) and to examine the relationship between these and diabetes disease. 86 male patients (46 patients with diabetes, age: 51.5 ± 9.2 and 40 patients with nondiabetes (control group), age: 54.78 ± 12.2) were included in the study. IMA, a new indicator of tissue ischemia and oxidative stress, was checked. Superoxide dismutase (SOD) activity, another oxidative stress indicator, was examined. Endothelin-1 (ET-1), one of the parameters of endothelial dysfunction, was measured. Additionally, endothelial function was evaluated with flow-mediated vasodilatation (FMD). Student's t -test was used for statistical evaluation. p values less than 0.05 were considered statistically significant. SOD activity was significantly lower in the diabetic group than in the control group, and ET-1 was significantly higher ( p < 0.001). IMA was found to be significantly higher in the diabetic group than the control group ( p < 0.001). FMD was significantly lower in diabetic group compared to the control group ( p < 0.002). According to our findings, the co-occurrence of erectile dysfunction and diabetes demonstrates a complex condition that includes endothelial dysfunction, oxidative stress, and tissue ischemia. When the correlation of indicators, which are markers, was examined, the severity of the co-occurrence of diabetes and erectile dysfunction was again demonstrated., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Hasan Anıl Kurt et al.)

Background: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences., Methods: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension., Results: Aspirin use for primary prevention was higher in patients with hypertension compared to patients without hypertension [328 (21.3%); 1046 (30.2%); P < .001]. Treatment with a dose of 150 mg aspirin (n=172, 5%) was mostly preferred by internists for hypertensive patients (n =226, 6.5%); however, a daily dose of 80-100 mg aspirin therapy (n=1457, 94.6%) was mostly prescribed by cardiologists (n=1347, 87.5%) for patients without hypertension., Conclusion: Aspirin was found to be used commonly among patients with hypertension for primary prevention despite the current European Society of Cardiology Arterial Hypertension Guideline not recommending aspirin for primary prevention in patients with hypertension.

Background: Septic cardiomyopathy increases mortality by 70% to 90% and results in mechanical dysfunction of cells., Methods: Here, we created a LPS-induced in-vitro sepsis model with mouse embryonic stem cell-derived cardiomyocytes (mESC-CM) using the CellDrum technology which simultaneously measures mechanical compliance and beat frequency of mESCs. Visualization of reactive oxygen species (ROS), actin stress fibers, and mRNA quantification of endothelial protein C receptor (EPCR) and protease-activated receptor 1 (PAR1) before/after LPS incubation were used for method validation. Since activated protein C (APC) has cardioprotective effects, samples were treated with human recombinant APC (rhAPC) with/-out LPS predamage to demonstrate the application in therapeutic studies., Results: Twelve hours LPS treatment (5 μg/mL) increased ROS and decreased actin stress fiber density and significantly downregulated EPCR and PAR1 compared to control samples (0.26, 0.39-fold respectively). rhAPC application (5 μg/mL, 12 h) decreased ROS and recovered actin density, EPCR, and PAR1 levels were significantly upregulated compared to LPS predamaged samples (4.79, 3.49-fold respectively). The beat frequencies were significantly decreased after 6- (86%) and 12 h (73%) of LPS application. Mechanical compliance of monolayers significantly increased in a time-dependent manner, up to eight times upon 12-h LPS incubation compared to controls. rhAPC incubation increased the beat frequency by 127% (6h-LPS) and 123% (12h-LPS) and decreased mechanical compliance by 68% (12h-LPS) compared to LPS predamaged samples., Conclusion: LPS-induced contraction dysfunction and the reversal effects of rhAPC were successfully assessed by the mechanical properties of mESC-CMs. The CellDrum technology proved a decent tool to simulate sepsis in-vitro., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.)

The tumor microenvironment (TME) surrounding tumor cells is a complex and highly dynamic system that promotes tumorigenesis. Cancer-associated fibroblasts (CAFs) are key elements in TME playing a pivotal role in cancer cells' proliferation and metastatic spreading. Considering the high expression of the fibroblast activation protein (FAP) on the cell membrane, CAFs emerged as appealing TME targets, namely for molecular imaging, leading to a pan-tumoral approach. Therefore, FAP inhibitors (FAPis) have recently been developed for PET imaging and radioligand therapy, exploring the clinical application in different tumor sub-types. The present review aimed to describe recent developments regarding radiolabeled FAP inhibitors and evaluate the possible translation of this pan-tumoral approach in clinical practice. At present, the application of FAPi-PET has been explored mainly in single-center studies, generally performed in small and heterogeneous cohorts of oncological patients. However, preliminary results were promising, in particular in low FDG-avid tumors, such as primary liver and gastro-entero-pancreatic cancer, or in regions with an unfavorable tumor-to-background ratio at FDG-PET/CT (i.e., brain), and in radiotherapy planning of head and neck tumors. Further promising results have been obtained in the detection of peritoneal carcinomatosis, especially in ovarian and gastric cancer. Data regarding the theranostics approach are still limited at present, and definitive conclusions about its efficacy cannot be drawn at present. Nevertheless, the use of FAPi-based radio-ligand to treat the TME has been evaluated in first-in-human studies and appears feasible. Although the pan-tumoral approach in molecular imaging showed promising results, its real impact in day-to-day clinical practice has yet to be confirmed, and multi-center prospective studies powered for efficacy are needed.

Unlike constitutively secreted proteins, peptide hormones are stored in densely packed secretory granules, before regulated release upon stimulation. Secretory granules are formed at the TGN by self-aggregation of prohormones as functional amyloids. The nonapeptide hormone vasopressin, which forms a small disulfide loop, was shown to be responsible for granule formation of its precursor in the TGN as well as for toxic fibrillar aggregation of unfolded mutants in the ER. Several other hormone precursors also contain similar small disulfide loops suggesting their function as a general device to mediate aggregation for granule sorting. To test this hypothesis, we studied the capacity of small disulfide loops of different hormone precursors to mediate aggregation in the ER and the TGN. They indeed induced ER aggregation in Neuro-2a and COS-1 cells. Fused to a constitutively secreted reporter protein, they also promoted sorting into secretory granules, enhanced stimulated secretion, and increased Lubrol insolubility in AtT20 cells. These results support the hypothesis that small disulfide loops act as novel signals for sorting into secretory granules by self-aggregation., (© 2022 Reck et al.)

Introduction: Restriction of salt intake is advised in the general population to reduce cardiovascular risk. Daily higher salt intake may contribute to high coronary artery disease (CAD) prevalence in the Turkish population, although there is limited data regarding salt intake and urinary sodium (Na) extraction in patients with CAD. In this study, we aimed to assess the relationship between urine Na, potassium (K), protein and creatine levels in patients with CAD., Methods: One hundred participants, aged 30-65, who underwent coronary angiography under elective conditions were enrolled in this study between May 2019 and August 2019. Patients who had known CAD before, acute coronary syndrome, hypertension, congestive heart failure, diabetes mellitus (DM), structural heart disease, malignancy, renal failure, and severe comorbid states were excluded from the study. Coronary angiograpy revealed CAD in 61 patients and normal coronary arteries in 39 patients who were classified as the control group. Morning urine samples were collected for analysis. The 24-hour urine sodium was calculated using the KAWASAKI method., Results: Spot urinary protein extraction and spot urinary micro-protein/creatinine ratio were significantly higher in the CAD group than in the control group (p=0.035, p=0.031, respectively). Also, serum creatinine (Cr) was found to be higher while glomerular filtration rate (GFR) and Na levels were found to be lower in the CAD group than in the control group (p=0.014, p=0.012, p=0.016 respectively). The logistic regression model was statistically significant, χ2(25)=41.45, p=0.021 and GFR, Na levels, spot urinary micro-protein/creatinine, and HDL levels were assessed as predictive factors for CAD.CONCLUSİON: Urinary Na and K extraction is not affected by the presence of CAD. Also, spot urinary Na/ K ratio and 24-hour sodium extraction were similar between patients with and without CAD. However, decreased GFR and increased urinary micro-protein/creatinine ratio could be risk factors for CAD. Furter studies with large samples are needed to assess this relationship (Tab. 6, Ref. 16).