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Aim. To evaluate the frequency and pattern of disease-associated mutations of ABCA4 gene among Greek patients with presumed Stargardt disease (STGD1). Materials and Methods. A total of 59 patients were analyzed for ABCA4 mutations using the ABCR400 microarray and PCR-based sequencing of all coding exons and flanking intronic regions. MLPA analysis as well as sequencing of two regions in introns 30 and 36 reported earlier to harbor deep intronic disease-associated variants was used in 4 selected cases. Results. An overall detection rate of at least one mutant allele was achieved in 52 of the 59 patients (88.1%). Direct sequencing improved significantly the complete characterization rate, that is, identification of two mutations compared to the microarray analysis (93.1% versus 50%). In total, 40 distinct potentially disease-causing variants of the ABCA4 gene were detected, including six previously unreported potentially pathogenic variants. Among the disease-causing variants, in this cohort, the most frequent was c.5714+5G>A representing 16.1%, while p.Gly1961Glu and p.Leu541Pro represented 15.2% and 8.5%, respectively. Conclusions. By using a combination of methods, we completely molecularly diagnosed 48 of the 59 patients studied. In addition, we identified six previously unreported, potentially pathogenic ABCA4 mutations.

Key Clinical Message Herein, we report a rare case of nyctalopia diagnosed in the first trimester of pregnancy due to vitamin A deficiency as a result of a bariatric gastrectomy. Low serum vitamin A levels establish the diagnosis and the patient was treated with oral vitamin A supplements. Moreover, due to the teratogenic effects of exceed Vitamin A levels in early pregnancy, supplements' dosages should be prescribed with respect to the safe limits. Our case aims to highlight the importance of checking micronutricients and vitamins levels before and during pregnancy in women that had a previous bariatric surgery. Abstract Vitamin A deficiency (VAD) has been identified as the predominant factor in the development of night blindness during pregnancy, a high‐risk for morbidity situation. Herein, we report a rare case of nyctalopia diagnosed in the first trimester of pregnancy due to VAD as a result of a bariatric gastrectomy. Our case aims to highlight the importance of checking micronutricients and vitamins levels before and during pregnancy in women that had a previous bariatric surgery. Low serum vitamin A levels establish the diagnosis and the patient was treated with oral vitamin A supplements. An uneventful antenatal course resulted in the birth of a healthy live neonatal at 38 weeks of gestation. In conclusion, nyctalopia is a rare condition in pregnant women that is often caused by VAD that poses significant health risks for both the mother and the infant, especially in women with a history of gastrointestinal bypass surgery, or any factors leading to malnutrition. Clinicians have to be alerted for micronutrients deficient in pregnant women who have a bariatric operation in their medical history.

Abstract In this study we examine the impact of cell confluency on gene expression. We focused on Argonaute (AGO) protein dynamics and associated gene and protein expression in HEK293, A375, and SHSY5Y cell lines. As a consequence of cell confluency, AGO2 protein translocates into the nucleus. Therefore, we generated transcriptomic data using RNA sequencing to compare gene expression in subconfluent versus confluent cells, which highlighted significant alterations in gene regulation patterns directly corresponding to changes in cell density. Our study also encompasses miRNA profiling data obtained through small RNA sequencing, revealing miRNA expressional changes dependent on cellular confluency, as well as cellular localization. Finally, we derived proteomic data from mass spectrometry analyses following AGO1-4 immunoprecipitation, providing a comprehensive view of AGO interactome in both nuclear and cytoplasmic compartments under varying confluency. These datasets offer a detailed exploration of the cellular and molecular dynamics, influenced by cell confluency, presenting a valuable resource for further research in cellular biology, particularly in understanding the basic mechanisms of cell density in cancer cells.

In this paper we explore the difficulties undergraduates from Greek Higher Educational Institutions faced during the transition to online learning due to the COVID-19 pandemic. By analyzing qualitative data from an online survey (N = 2093), we were able to identify the barriers undergraduates encountered during this transition and make inferences about the quality of the way online learning was implemented. The most frequently reported barriers include problems that undergraduates perceived as being caused by their lecturers, internet connection issues during an online lecture and the perceived limited social interactions that synchronous environments can afford. The paper argues that the way online learning was implemented by Greek Higher Educational Institutions did not result a meaningful learning experience for undergraduates. Our results are relevant to universities that are either forced in implementing emergency online protocols or wish to support their undergraduates' learning experience.

Primary school teachers are the educators responsible for introducing children into the world of mathematics. In the process of learning mathematics, children may experience negative emotions and develop negative attitudes or mathematics anxiety. Some authors approach these issues by focusing on primary teachers’ mathematics anxiety or proficiency in mathematics. In this article, we explore whether and how certain social and educational practices shape or not the development of mathematical thinking in prospective primary teachers, from a cultural-historical perspective. The study’s sample consists of twelve prospective primary teachers in their last year of studies. The participants were interviewed about their experience with mathematics throughout their educational years. By examining and contrasting the different developmental trajectories of the participants, we identified their “imprisonment” in situational thinking and some of the paradoxes that characterise their development. Adopting a historical perspective in analysing participants’ trajectories was crucial in uncovering the paradoxical nature of the development of mathematical thinking. We conclude by highlighting the socially mediated nature of mathematics and the obstacles posed by the competitive and exam-driven nature of educational practices

Background. Our knowledge regarding the epidemiology of pediatric cardiomyopathy is based on large national population studies reporting an annual incidence of 1 case per 100,000 children, with a higher incidence observed in infancy and among selected populations. The aim here is to document the epidemiology of pediatric cardiomyopathy in a Mediterranean population. Methods. Children younger than 18 years of age living on the Mediterranean island of Crete, Greece, who have been evaluated since the establishment of tertiary pediatric cardiology services (2002–2022) were included in this retrospective study. Results. A total of 40 children were included, corresponding to an average annual incidence of pediatric cardiomyopathy of 1.59 cases (95% CI: 1.4–2.3) and a prevalence of 26 cases per 100,000 children. In decreasing order of frequency, most cases corresponded to dilated (50%), followed by hypertrophic (42.5%), arrhythmogenic (5%), and restrictive (2.5%) cardiomyopathy. An etiology was identified in 40%, including a genetic diagnosis in 22.5%. Conclusions. The incidence of pediatric cardiomyopathy in the Mediterranean island of Crete is higher compared with that reported previously for other Caucasian populations. Further study is needed to investigate the exact prevalence and specific genetic factors associated with the epidemiology of pediatric cardiomyopathy in Mediterranean populations.

Abstract Background Heterogeneous nuclear ribonucleoprotein K (HNRNPK) regulates pre-mRNA processing and long non-coding RNA localization in the nucleus. It was previously shown that shuttling of HNRNPK to the cytoplasm promotes cell proliferation and cancer metastasis. However, the mechanism of HNRNPK cytoplasmic localization, its cytoplasmic RNA ligands, and impact on post-transcriptional gene regulation remain uncharacterized. Results Here we show that the intermediate filament protein Keratin 19 (K19) directly interacts with HNRNPK and sequesters it in the cytoplasm. Correspondingly, in K19 knockout breast cancer cells, HNRNPK does not localize in the cytoplasm, resulting in reduced cell proliferation. We comprehensively mapped HNRNPK binding sites on mRNAs and showed that, in the cytoplasm, K19-mediated HNRNPK-retention increases the abundance of target mRNAs bound to the 3’ untranslated region (3’UTR) at the expected cytidine-rich (C-rich) sequence elements. Furthermore, these mRNAs protected by HNRNPK in the cytoplasm are typically involved in cancer progression and include the p53 signaling pathway that is dysregulated upon HNRNPK knockdown (HNRNPK KD) or K19 knockout (KRT19 KO). Conclusions This study identifies how a cytoskeletal protein can directly regulate gene expression by controlling the subcellular localization of RNA-binding proteins to support pathways involved in cancer progression.

Paediatric cardiomyopathies form a heterogeneous group of disorders characterized by structural and electrical abnormalities of the heart muscle, commonly due to a gene variant of the myocardial cell structure. Mostly inherited as a dominant or occasionally recessive trait, they might be part of a syndromic disorder of underlying metabolic or neuromuscular defects or combine early developing extracardiac abnormalities (i.e., Naxos disease). The annual incidence of 1 per 100,000 children appears higher during the first two years of life. Dilated and hypertrophic cardiomyopathy phenotypes share an incidence of 60% and 25%, respectively. Arrhythmogenic right ventricular cardiomyopathy (ARVC), restrictive cardiomyopathy, and left ventricular noncompaction are less commonly diagnosed. Adverse events such as severe heart failure, heart transplantation, or death usually appear early after the initial presentation. In ARVC patients, high-intensity aerobic exercise has been associated with worse clinical outcomes and increased penetrance in at-risk genotype-positive relatives. Acute myocarditis in children has an incidence of 1.4–2.1 cases/per 100,000 children per year, with a 6–14% mortality rate during the acute phase. A genetic defect is considered responsible for the progression to dilated cardiomyopathy phenotype. Similarly, a dilated or arrhythmogenic cardiomyopathy phenotype might emerge with an episode of acute myocarditis in childhood or adolescence. This review provides an overview of childhood cardiomyopathies focusing on clinical presentation, outcome, and pathology.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the innate immune machinery through multiple viral proteins, including nonstructural protein 1 (NSP1). While NSP1 is known to suppress translation of host mRNAs, the mechanisms underlying its immune evasion properties remain elusive. By integrating RNA-seq, ribosome footprinting, and ChIP-seq in A549 cells we found that NSP1 predominantly represses transcription of immune-related genes by favoring Histone 3 Lysine 9 dimethylation (H3K9me2). G9a/GLP H3K9 methyltransferase inhibitor UNC0638 restored expression of antiviral genes and restricted SARS-CoV-2 replication. Our multi-omics study unravels an epigenetic mechanism underlying host immune evasion by SARS-CoV-2 NSP1. Elucidating the factors involved in this phenomenon, may have implications for understanding and treating viral infections and other immunomodulatory diseases.

Research exploring undergraduates' tool preferences in tertiary mathematics is currently limited. In this paper, we explore the tools mathematics and engineering students use when studying mathematics and the ways undergraduates combine these tools. Results from our survey (N = 628) showed that students in our sample use mostly their notes, the university's virtual learning environment (VLE), other students and textbooks. Mathematics students were found using more online encyclopaedias, the university's VLE, instant messaging and other students, whereas engineering students reported using more textbooks. By performing a cluster analysis, undergraduates were assigned to five distinct tool-use profiles: the peer-learning group (above average use of other students, instant messaging apps and social media); the online-learning group (above average use of online videos, online encyclopaedias, Wolfram Alpha and the university's VLE); the blended-learning group (above average use of all the tools at their disposal); the no-users group (below average use of all tools except textbooks); and the selective-learning group (above average use of textbooks, online videos and lecturers). The majority of mathematics students were distributed across the peer-learning, online-learning and blended-learning groups, whereas most of the engineering students were found in the blended-learning, no-users and selective-learning groups.

Abstract Background Homozygous truncating mutations located in the C-terminal region of the desmoplakin gene (DSP) are known to mainly cause Carvajal syndrome, an autosomal recessive syndromic form of arrhythmogenic cardiomyopathy with an extra-cardiac cutaneous phenotype. Case presentation Here we describe a female proband with a documented arrhythmogenic left ventricular cardiomyopathy and a syncopal episode at the age of 13, who was found homozygous for the novel DSP variant: NM_004415.4:c.8586delC, p.(Ser2863Hisfs*20) at the extreme C-terminal region of the protein, just 8 amino acids upstream the stop codon. She did not have any of the typical dermatological symptoms that characterize Carvajal syndrome. Her brother had died suddenly at the age of 18 during exercise and was found homozygous for the same variant at the post-mortem, while their parents were heterozygous. The region of origin of both parents was the same geographic area of Greece, but they were not aware of any common ancestor. Detailed clinical examination revealed that the mother displayed a mild arrhythmic phenotype, while the father was asymptomatic. Conclusion These observations pinpoint to a significant functional role of the extreme C-terminal tail of the protein.

The aim of the present prospective clinical study was to highlight the importance of the proper application of the manual detorsion (MD) in cases of intravaginal testicular torsion. Major complications such as ischemia, reperfusion injury and testicular compartment syndrome could be avoided.

The aim of this clinical study was to present our experience gained by using the intrascrotal incision through the mid raphe for the management of a variety of inguinoscrotal pathologies.

Hypertrophic cardiomyopathy (HCM) is the most common genetically inherited cardiomyopathy with an autosomal dominant inheritance pattern. A disease-causing gene is found between 34% and >60% of the times and the two most frequently mutated genes, which encode sarcomeric proteins, are MYBPC3 and MYH7. HCM is a diagnosis of exclusion since secondary causes of left ventricular hypertrophy should first be ruled out. These include hypertension, aortic stenosis, infiltrative disease, metabolic and endocrine disorders, mitochondrial cardiomyopathies, neuromuscular disorders, malformation syndromes and some chronic drug use. The disease is characterized by great heterogeneity of its clinical manifestations, however diastolic dysfunction and increased ventricular arrhythmogenesis are commonly seen. Current HCM therapies focus on symptom management and prevention of sudden cardiac death. Symptom management includes the use of pharmacological agents, elimination of medication promoting outflow track obstruction, control of comorbid conditions and invasive procedures, whereas in the prevention of sudden cardiac death, implantable cardiac defibrillators and antiarrhythmic drugs are used. A targeted therapy for LVOTO represented by allosteric cardiac myosin inhibitors has been developed. In terms of sport participation, a more liberal approach is recently recommended, after careful evaluation and common-shared decision. The application of the current therapies has lowered HCM mortality rates to

Key Clinical Message: Herein, we report a rare case of nyctalopia diagnosed in the first trimester of pregnancy due to vitamin A deficiency as a result of a bariatric gastrectomy. Low serum vitamin A levels establish the diagnosis and the patient was treated with oral vitamin A supplements. Moreover, due to the teratogenic effects of exceed Vitamin A levels in early pregnancy, supplements' dosages should be prescribed with respect to the safe limits. Our case aims to highlight the importance of checking micronutricients and vitamins levels before and during pregnancy in women that had a previous bariatric surgery. Vitamin A deficiency (VAD) has been identified as the predominant factor in the development of night blindness during pregnancy, a high‐risk for morbidity situation. Herein, we report a rare case of nyctalopia diagnosed in the first trimester of pregnancy due to VAD as a result of a bariatric gastrectomy. Our case aims to highlight the importance of checking micronutricients and vitamins levels before and during pregnancy in women that had a previous bariatric surgery. Low serum vitamin A levels establish the diagnosis and the patient was treated with oral vitamin A supplements. An uneventful antenatal course resulted in the birth of a healthy live neonatal at 38 weeks of gestation. In conclusion, nyctalopia is a rare condition in pregnant women that is often caused by VAD that poses significant health risks for both the mother and the infant, especially in women with a history of gastrointestinal bypass surgery, or any factors leading to malnutrition. Clinicians have to be alerted for micronutrients deficient in pregnant women who have a bariatric operation in their medical history. [ABSTRACT FROM AUTHOR]

In this paper we explore the difficulties engineering undergraduates encounter with tertiary mathematics. Results from our survey (N = 71) show that students in our sample face issues mostly related to the challenging nature of university mathematics, the absence of worked examples during lectures and the discontinuity of school and university mathematics curricula. By using third generation Activity Theory, we were able to interpret the identified difficulties as contradictions emerging between the school and university activity systems as well as within the university activity system, and we argue that these difficulties can be treated as stemming from the structural characteristics the two activity systems have.

Neural Style Transfer (NST) is a popular technique of computer vision where the content of an image is blended with the style of another, which results in a fused image with certain properties of both original images. This approach has practical applications in various domains and has garnered significant attention in both industry and academia. An interesting application of this technique is segmented style transfer where a segmentation algorithm is used to locate objects within an image and then the style transfer method is performed locally, producing images with different styles for different objects. This approach opens up possibilities for creating visually striking compositions by seamlessly blending various artistic styles onto specific objects within an image, allowing for a new level of creative expression. This paper proposes a novel method that combines Segment Anything Model (SAM), a state-of-the-art vision transformer-based image segmentation model developed by Facebook, with style transfer. Our approach includes performing localized style transfer in selected segmentation regions of an image using classical style transfer algorithms. To ensure smooth transitions between the stylized and non-stylized border we also develop our loss function with a border smoothing technique. Experimental results demonstrate the robustness and effectiveness of the proposed methodology, including the ability to infuse multiple artistic styles into different objects within an image. The contributions of this work include integrating SAM with style transfer, proposing a novel loss function, evaluating the segmented style transfer in multiple content regions, comparing with state-of-the-art approaches, and experimenting with multiple style images for diverse stylization. Our primary focus centers on creating a model that serves as a digital painter across a wide range of image genres and artistic styles.