Basic Findings Research Articles

Clinical and mechanistic insights into the roles of DDX41 in haematological malignancies.

DEAD-box Helicase 41 (DDX41) is a member of the DExD/H-box helicase family that has a variety of cellular functions. Of note, germline and somatic mutations in the DDX41 gene are prevalently found in myeloid malignancies. Here, we present a comprehensive and analytic review covering relevant clinical, translational and basic science findings on DDX41. We first describe the initial characterisation of DDX41 mutations in patients affected by myelodysplastic syndromes, their associated clinical characteristics, and current treatment modalities. We then cover the known cellular functions of DDX41, spanning from its discovery in Drosophila as a neuroregulator through its more recently described roles in inflammatory signalling, R-loop metabolism and snoRNA processing. We end with a summary of the identified basic functions of DDX41 that when perturbed may contribute to the underlying pathology of haematologic neoplasms.

Diagnostic Accuracy of Magnetic Resonance Imaging With 3-Dimensional T2-SPACE Techniques for Preganglionic Injury of the Brachial Plexus

An accurate diagnosis of the site and severity of a brachial plexus injury is imperative for selecting the appropriate management. Conventional magnetic resonance imaging (MRI) does not allow for the precise interpretation of preganglionic injuries (pre-GIs), especially intravertebral canal injuries. We developed 4 MRI sequences of conventional 1.5-tesla 3-dimensional T2-weighted turbo spin echo sampling perfection with the application of optimized contrasts using different flip angles evolution (T2-SPACE) images to clearly visualize each component of the brachial plexus. The purpose of this study was to introduce basic normal and pathologic findings of our current MRI approach, focusing on its diagnostic accuracy for pre-GIs. We initially examined 119 patients with brachial plexus injuries who underwent surgical exploration by MRI using 4 sequences of the 1.5-tesla 3-dimensional T2-SPACE technique. We obtained coronal, transverse, coronal oblique, and coronal cuts of T2 short time inversion recovery. The images of 595 roots were interpreted by multiple-image synchronizing techniques of the 4 views to precisely interpret the presence of spinal cord edema, numbers of anterior and posterior rootlets, sites of ganglions, meningeal cysts, and the "black line sign" (displaced ruptured dura or bundles of ruptured rootlets). We assessed the accuracy, sensitivity, and specificity of these abnormal findings with regard to diagnosing pre-GIs by comparing surgical exploration. The absence or decreased numbers of anterior and posterior rootlets and displacement of ganglions were definitive evidence of pre-GIs and the other findings, like spinal cord edema, meningeal cysts, and black line signs, were predictive signs. The synchronizing techniques of the four 1.5-tesla 3-dimensional T2-SPACE images provided high diagnostic accuracy of pre-GIs. Diagnostic II.

Cerebrospinal fluid findings in adult patients with obsessive-compulsive disorder: A retrospective analysis of 54 samples

Objectives Obsessive-compulsive disorder (OCD) can rarely be associated with immunological aetiologies, most notably in Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections and possibly in autoimmune encephalitis. As cerebrospinal fluid (CSF) analysis is a sensitive method for assessing neuroinflammation, this retrospective study analysed basic CSF parameters and well-characterised as well as novel neuronal autoantibodies in OCD to screen for signs of autoimmunity. Methods Basic CSF findings of 54 adult OCD patients suspected of an organic aetiology were retrospectively compared to a control group of mentally healthy patients (N = 39) with idiopathic intracranial hypertension. Further subgroup analysis included testing for well-characterised neuronal IgG autoantibodies and tissue-based assays using indirect immunofluorescence to screen for novel brain autoantibodies. Results Elevated protein in the CSF of OCD patients compared to the control group (p = 0.043) was identified. Inflammatory markers (pleocytosis/oligoclonal bands/increased IgG-index) were detected in 7% of all patients with OCD. Well-characterised neuronal autoantibodies were not found in any OCD patient, whereas 6/18 (33%) CSF samples showed binding on mouse brain sections in tissue-based assays (binding to neuropil in the basal ganglia/brainstem, cilia of granule cells, blood vessels, nuclear/perinuclear structures). Conclusions While elevated CSF protein is merely a weak indicator of blood CSF barrier dysfunction, the presence of inflammatory CSF changes and novel brain autoantibodies in CSF may indicate OCD subtypes with inflammatory pathomechanism and supports the hypothesis of a rare “autoimmune OCD” subtype.

Network Pharmacology Research and Dual-omic Analyses Reveal the Molecular Mechanism of Natural Product Nodosin Inhibiting Muscle-Invasive Bladder Cancer in Vitro and in Vivo.

Bladder cancer, specifically, muscle-invasive bladder cancer (MIBC), is among the most common malignant tumors. Patients with MIBC who cannot tolerate standard drugs require novel treatments. Targeting apoptosis may help treat cancer, which may be achieved with the use of some natural products. Nodosin, found in Isodon serra (Maxim.) Kudo (known as Xihuangcao), may inhibit bladder cancer cells. Transcriptomics and proteomics dual-omic analyses revealed the network pharmacological mechanism: (1) blocking the S phase by up-regulating RPA2, CLSPN, MDC1, PDCD2L, and E2F6 gene expressions, suppressing cancer cell proliferation; (2) inducing apoptosis and autophagy and restraining ferroptosis by up-regulating HMOX1, G0S2, SQSTM1, FTL, SLC7A11, and AIFM2 gene expressions; (3) preventing cancer cell migration by down-regulating NEXN, LIMA1, CFL2, PALLD, and ITGA3 gene expressions. In vivo, nodosin inhibited bladder cancer cell growth in a model of xenograft tumor in nude mice. This study is the first to report basic research findings on the network pharmacological mechanism of cytotoxicity of bladder cancer cells by nodosin, providing novel evidence for the application of nodosin in the field of oncology; however, other mechanisms may be involved in the effects of nodosin for further research. These findings provide a foundation for the development of novel MIBC drugs.

Increased open fracture complications following pediatric all-terrain vehicle accidents

BackgroundATV (All-Terrain Vehicle) related open fractures are often high energy and may be highly contaminated. We asked whether they were more complicated than other open fractures in pediatric patients. MethodsA retrospective chart review was performed comparing ATV associated open fractures to open fractures sustained in non-ATV related accidents. 97 pediatric open fractures from 2015 to 2021 were identified based on ICD-10 codes. Of these fractures, 62 were non-ATV related and 35 were ATV related. Charts were reviewed to collect basic demographics, fracture pattern, Gustilo-Anderson classification, procedures performed, operative findings, and complications. ResultsOur cohort was predominantly male (71% in the ATV group and 76% in the non-ATV group). White race was more common in both the ATV (28 (80%)) and non-ATV (50(78%)) groups. The distribution of AO/OTA fractures was significantly different (p = 0.046), with humerus fractures being more common in the ATV group (8 (22%)) vs. non-ATV group (6 (9.3%)). The ATV group had a higher proportion of more severe type II and III open fractures with 77.1% (n = 27), versus 56% (n = 35) in the non-ATV group (p = 0.020).. Revision and reoperation were more likely in the ATV group (16 (23%)) vs. the non-ATV group (12 (15%)), as was malunion (ATV group 3 (4.3%) Vs. non-ATV 0 (0%)). ConclusionOpen fractures resulting from ATV injuries tend to be more complex and have higher rates of revision and malunion. This information supports the large body of evidence on the dangers of ATVs to children and can help guide expectations of both clinicians and family members of patients presenting with these injuries.

Metabolic targeting of malignant tumors: a need for systemic approach.

Dysregulated metabolism is now recognized as a fundamental hallmark of carcinogenesis inducing aggressive features and additional hallmarks. In this review, well-established metabolic changes displayed by tumors are highlighted in a comprehensive manner and corresponding therapeutical targets are discussed to set up a framework for integrating basic research findings with clinical translation in oncology setting. Recent manuscripts of high research impact and relevant to the field from PubMed (2000-2021) have been reviewed for this article. Metabolic pathway disruption during tumor evolution is a dynamic process potentiating cell survival, dormancy, proliferation and invasion even under dismal conditions. Apart from cancer cells, though, tumor microenvironment has an acting role as extracellular metabolites, pH alterations and stromal cells reciprocally interact with malignant cells, ultimately dictating tumor-promoting responses, disabling anti-tumor immunity and promoting resistance to treatments. In the field of cancer metabolism, there are several emerging prognostic and therapeutic targets either in the form of gene expression, enzyme activity or metabolites which could be exploited for clinical purposes; both standard-of-care and novel treatments may be evaluated in the context of metabolism rewiring and indeed, synergistic effects between metabolism-targeting and other therapies would be an attractive perspective for further research.

Mechanistic Approach to Reveal Interaction of Uranyl Ions in Alkyltriphenylphosphonium Bromide-Based Deep Eutectic Solvent.

Speciation is known to control fundamental aspects of metal processing and electrochemical behavior such as solubility and redox potentials. Deep eutectic solvents (DESs) are an emerging class of green, low-cost and designer solvents and are being explored as alternatives for recycling nuclear fuel and critical materials. However, there is a lack of knowledge about the behavior of metals in them. Here, for the first time, we synthesized three new DESs based on alkyltriphenylphosphonium bromide (CnPPh3Br), with varied alkyl chain lengths (n), as the hydrogen-bond acceptor along with decanoic acid (DA) as the hydrogen-bond donor and explored the redox speciation of uranyl nitrate. The changes in the Fourier transform infrared and NMR spectra helped elucidate the formation of hydrogen bonds in DES. The absorption maxima of uranyl in DES was red-shifted by 10 nm compared to the free uranyl, with concomitant increase in intensity and luminescence lifetime, which suggested a strong interaction of uranyl nitrate with DES. Cyclic voltammetry was probed to understand the redox thermodynamics, transport properties, and heterogeneous electron transfer kinetics of the irreversible electron transfer of uranyl ions in the three DESs. Electrochemical and spectroscopic techniques together with density functional theory calculations unlocked microscopic insights into the solvation and speciation of UO22+ ions in three DESs and also the associated unusual trends observed in the physical properties of the DESs. The hydrogen-bonded structure of DES plays a crucial role in the redox behavior of the UO22+ ion due to its strong potent complexation with its components. The basic findings of the present work can have far-reaching consequences for the extraction, electrochemical separation, and future development of redox-based separation processes in the nuclear fuel cycle.

Adult patients with allied disorders of Hirschsprung's disease in emergency department: An 11-year retrospective study.

BACKGROUNDIn the past years, only a few studies with a limited number of adult patients analyzed clinical features of allied disorders of Hirschsprung’s disease (ADHD), most of which were individual case reports or lacked detailed clinical information. Although many studies have reported patients presenting to the emergency department (ED) with recurrent abdominal symptoms for a number of disorders, there are few data involving ADHD. However, owing to a lack of awareness of the disease, misdiagnoses and mistreatments are common. Severe complications such as perforation, bleeding, malabsorption, and even death in ADHD had been reported by many studies.AIMTo assist ED clinicians in having a more comprehensive understanding of this disease and making an early suspected diagnosis of ADHD more effectively.METHODSWe enrolled 53 patients who visited the ED and were eventually diagnosed with ADHD over the past 11 years in our hospital. Their basic information, clinical manifestations, and imaging findings were analyzed. Blood indices were compared between the ADHD and irritable bowel syndrome (IBS) groups.RESULTSAdult patients with ADHD had a mean age of 48.8 ± 14.3 years, and 77.4% had been treated before admission. The transverse colon was the most common dilated part (73.6%), and constipation (67.9%) was the most common symptom. ADHD patients can present with uncommon symptoms and false-negative imaging findings. Logistic regression analysis indicated that body mass index (BMI) [odds ratio (OR) = 0.786, P = 0.013], cholinesterase (per 1000 units; OR = 0.693, P = 0.008), and blood chlorine (OR = 0.816, P = 0.022) were determined to be independent related factors between the ADHD and IBS groups. The area under the receiver operating characteristics curve of these three indices combined was 0.812 (P < 0.001).CONCLUSIONEmergency physicians should be vigilant regarding patients with chronic constipation, abdominal pain, or abdominal distension, and consider the possibility of ADHD despite its rarity. Abdominal computed tomography examination is recommended as a useful tool in the suspected diagnosis of ADHD. BMI, cholinesterase, and blood chlorine have good discriminative abilities between ADHD and IBS. The nutritional status of adult patients with ADHD is worthy of further attention. Surgical treatment for adult patients with ADHD is important and inevitable.

Precision Medicine Highlights Dysregulation of the CDK4/6 Cell Cycle Regulatory Pathway in Pediatric, Adolescents and Young Adult Sarcomas.

Simple SummaryThis review provides an overview of clinical features and current therapies in children, adolescents, and young adults (AYA) with sarcoma. It highlights the basic and clinical findings on the cyclin-dependent kinases 4 and 6 (CDK4/6) cell cycle regulatory pathway in the context of the precision medicine-based molecular profiles of the three most common types of pediatric and AYA sarcomas—osteosarcoma (OS), rhabdomyosarcoma (RMS), and Ewing sarcoma (EWS).Despite improved therapeutic and clinical outcomes for patients with localized diseases, outcomes for pediatric and AYA sarcoma patients with high-grade or aggressive disease are still relatively poor. With advancements in next generation sequencing (NGS), precision medicine now provides a strategy to improve outcomes in patients with aggressive disease by identifying biomarkers of therapeutic sensitivity or resistance. The integration of NGS into clinical decision making not only increases the accuracy of diagnosis and prognosis, but also has the potential to identify effective and less toxic therapies for pediatric and AYA sarcomas. Genome and transcriptome profiling have detected dysregulation of the CDK4/6 cell cycle regulatory pathway in subpopulations of pediatric and AYA OS, RMS, and EWS. In these patients, the inhibition of CDK4/6 represents a promising precision medicine-guided therapy. There is a critical need, however, to identify novel and promising combination therapies to fight the development of resistance to CDK4/6 inhibition. In this review, we offer rationale and perspective on the promise and challenges of this therapeutic approach.

A synopsis of global frontiers in fertility preservation.

Since 2007, the Oncofertility Consortium Annual Conference has brought together a diverse network of individuals from a wide range of backgrounds and professional levels to disseminate emerging basic and clinical research findings in fertility preservation. This network also developed enduring educational materials to accelerate the pace and quality of field-wide scientific communication. Between 2007 and 2019, the Oncofertility Consortium Annual Conference was held as an in-person event in Chicago, IL. The conference attracted approximately 250 attendees each year representing 20 countries around the world. In 2020, however, the COVID-19 pandemic disrupted this paradigm and precluded an in-person meeting. Nevertheless, there remained an undeniable demand for the oncofertility community to convene. To maintain the momentum of the field, the Oncofertility Consortium hosted a day-long virtual meeting on March 5, 2021, with the theme of “Oncofertility Around the Globe” to highlight the diversity of clinical care and translational research that is ongoing around the world in this discipline. This virtual meeting was hosted using the vFairs ® conference platform and allowed over 700 people to participate, many of whom were first-time conference attendees. The agenda featured concurrent sessions from presenters in six continents which provided attendees a complete overview of the field and furthered our mission to create a global community of oncofertility practice. This paper provides a synopsis of talks delivered at this event and highlights the new advances and frontiers in the fields of oncofertility and fertility preservation around the globe from clinical practice and patient-centered efforts to translational research.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10815-022-02570-5.

Gender-Diverse Inclusion in Immunological Research: Benefits to Science and Health.

The differences between male and female immune systems are an under-researched field, ripe for discovery. This is evidenced by the stark sex biases seen in autoimmunity and infectious disease. Both the sex hormones (oestrogen and testosterone), as well as the sex chromosomes have been demonstrated to impact immune responses, in multiple ways. Historical shortcomings in reporting basic and clinical scientific findings in a sex-disaggregated manner have led not only to limited discovery of disease aetiology, but to potential inaccuracies in the estimation of the effects of diseases or interventions on females and gender-diverse groups. Here we propose not only that research subjects should include both cis-gender men and cis-gender women, but also transgender and gender-diverse people alongside them. The known interaction between the hormonal milieu and the sex chromosomes is inseparable in cis-gender human research, without the confounders of puberty and age. By inclusion of those pursuing hormonal affirmation of their gender identity- the individual and interactive investigation of hormones and chromosomes is permitted. Not only does this allow for a fine-tuned dissection of these individual effects, but it allows for discovery that is both pertinent and relevant to a far wider portion of the population. There is an unmet need for detailed treatment follow-up of the transgender community- little is known of the potential benefits and risks of hormonal supplementation on the immune system, nor indeed on many other health and disease outcomes. Our research team has pioneered the inclusion of gender-diverse persons in our basic research in adolescent autoimmune rheumatic diseases. We review here the many avenues that remain unexplored, and suggest ways in which other groups and teams can broaden their horizons and invest in a future for medicine that is both fruitful and inclusive.

Aftershock Regions of Aleutian‐Alaska Megathrust Earthquakes, 1938–2021

AbstractWith five earthquakes (1938, 1946, 1957, 1964, and 1965), the Aleutian‐Alaska subduction plate boundary ruptured a length of 3,548 km. We revisit these five earthquakes—first studied in detail by Sykes (1971, https://doi.org/10.1029/JB076i032p08021)—through probabilistic relocation of carefully selected mainshocks and aftershocks. Our final catalog of 324 events is established from a set of 12 mainshocks that includes all Mw ≥ 7.7 megathrust earthquakes. Using the relocated catalog, we create revised aftershock regions delimited both parallel and normal to the trench. These aftershock regions exhibit significant differences from previous studies, with the following basic findings: the 10 November 1938 Mw 8.3 earthquake extended further west, to the Shumagin Islands, and further east, into the Kodiak region, relative to the prevailing aftershock region established by McCann et al. (1979, https://doi.org/10.1007/978-3-0348-6430-5_2). The 01 April 1946 Mw 8.6 sequence was anomalously concentrated near the trench, which implies near‐trench coseismic slip that contributed to the exceptionally large tsunami. The 09 March 1957 Mw 8.6 aftershocks spanned a 1,230 km length with numerous aftershocks within the outer‐rise region of the incoming Pacific plate. The 28 March 1964 Mw 9.2 aftershocks extended east into the Pamplona thrust system (south of Icy Bay, Alaska), suggesting coseismic rupture into this region; this is consistent with coseismic static displacements, as well as current estimates of interseismic locking. The post‐1965 events we examine are all smaller than the earlier events, but since they occurred in an era of improved data collection (seismic, geodetic, and tsunami), they provide a better opportunity for assessing the link between the distribution of aftershocks and the occurrence of coseismic, postseismic, and interseismic slip.

Hemispheric asymmetries in the amygdala: A comparative primer.

The amygdala is a core structure in the neuronal network underlying emotion processing in the vertebrate brain. Its structure and function have been extensively studied in both neuroimaging studies in human volunteers and comparative studies in animal models. Across different studies and research questions regarding the amygdala, one often-encountered finding is that the left and the right amygdala are not equivalent in terms of function and structure. Hemispheric asymmetries in the amygdala have been reported on many different levels, yet a systematic integration of these findings has been missing from the literature. Researchers in both cognitive and clinical neurosciences are often puzzled why they find a specific effect or association for the left but not the right amygdala, or vice versa. In this review article, we provide an integrated overview of existing basic and clinical findings regarding amygdala asymmetries in structure, connections, and functions. Importantly, the literature suggests that functional amygdala lateralization is determined by temporal characteristics, emotional valence, and perceptual properties. Furthermore, we highlight alterations of amygdala asymmetries reported in different patient groups, thereby allowing for a deeper understanding of atypical amygdala asymmetries. Lastly, we aim to provide guidelines and approaches concerning the interpretation of results for researchers investigating amygdala asymmetries.

19th International Symposium on Epstein-Barr Virus and Associated Diseases, 29-30 July 2021, Asahikawa, Japan.

Simple SummaryNovel insights into the basic and translational findings on Epstein–Barr virus-related diseases were presented at the “19th International Symposium on Epstein–Barr Virus and Associated Diseases” in Asahikawa, Japan.Novel insights into Epstein–Barr virus (EBV) pathogenicity were presented at the “19th International Symposium on Epstein-Barr Virus and Associated Diseases” in Asahikawa, Japan. In addition, basic and translational findings on EBV-associated tumors, including natural killer (NK)/T-cell lymphoma, gastric cancer, and nasopharyngeal cancer, were presented by an international group of scientists and clinicians.

DIPG-55. Increasing the drug-tumor resonance time in DMG murine models significantly extends survival

H3K27-altered diffuse midline glioma (DMG) is a uniformly lethal CNS cancer that predominately occurs in children. In the last decade, while studies revealing the molecular underpinnings of the disease have paved the way for novel therapeutic strategies, this tumor remains a death sentence. Our lab and others have identified numerous drugs of high interest for treating this devasting disease, however, every trial has failed to show benefit. Is our failure to translate these laboratory findings due to the fact we have not found the right drugs or treatment regimens yet? Or is this a failure to get the drugs to the tumor? Or is this simply a very bad disease to treat? The answer is likely multifactorial. Our lab, in collaboration with others, have strong data to show that simply getting drugs to the tumor will not result in a positive benefit. Most drugs are rapidly cleared from their target space. Utilizing techniques that increase the drug-tumor resonance time is necessary to translate our basic science findings to our patients. Picking the right drug and the delivery mechanism is not enough for a positive effect. Here, we assessed the efficacy of a previously identified inhibitor, alisertib, delivered by short-term convection-enhanced delivery or a continuous osmotic pump and found that continuous, direct delivery results in a significant increase in survival (p = 0.0002). Furthermore, long-term survivors showed a decreased tumor burden and on-target drug effects. These data support that translation into patients must consider three factors: 1) selection of a potent therapy, 2) selection of the proper delivery method for that therapy, 3) modulation to ensure that the therapy remains in the targeted tissue long enough for desired effect. Keeping these basic tenets at the forefront of development may finally lead to a more effective treatment strategy for this devastating disease

Targeting Glioblastoma Stem Cells to Overcome Chemoresistance: An Overview of Current Therapeutic Strategies.

Glioblastoma (GBM) is the most malignant primary brain tumor. The current standard approach in GBM is surgery, followed by treatment with radiation and temozolomide (TMZ); however, GBM is highly resistant to current therapies, and the standard of care has not been revised over the last two decades, indicating an unmet need for new therapies. GBM stem cells (GSCs) are a major cause of chemoresistance due to their ability to confer heterogeneity and tumorigenic capacity. To improve patient outcomes and survival, it is necessary to understand the properties and mechanisms underlying GSC chemoresistance. In this review, we describe the current knowledge on various resistance mechanisms of GBM to therapeutic agents, with a special focus on TMZ, and summarize the recent findings on the intrinsic and extrinsic mechanisms of chemoresistance in GSCs. We also discuss novel therapeutic strategies, including molecular targeting, autophagy inhibition, oncolytic viral therapy, drug repositioning, and targeting of GSC niches, to eliminate GSCs, from basic research findings to ongoing clinical trials. Although the development of effective therapies for GBM is still challenging, this review provides a better understanding of GSCs and offers future directions for successful GBM therapy.

Investigation of studies on pre-school coding education in Turkey

Bu çalışmanın amacı, okul öncesi dönemde kodlama eğitimine ilişkin Türkiye’de yapılan bilimsel çalışmaların sistematik inceleme yöntemi ile incelenerek, konu ile ilgili araştırmaların yöntemsel eğilimlerinin, konularının, incelenen değişkenlerinin ve temel bulgularının ortaya çıkarılmasıdır. Bu doğrultuda, YÖK Tez Merkezi, TR Dizin ve Google Akademik veri tabanları üzerinde yapılan aramalar sonucunda belirlenen 30 çalışma (14 Tez, 14 Makale ve 2 Konferans Bildirisi), içerik analizi yöntemi ile analiz edilmiştir. Çalışma sonucunda, okul öncesi dönemde kodlama eğitimine ilişkin Türkiye’de yapılan çalışma sayısında istenen düzeyde olmasa da son yıllarda artış olduğu tespit edilmiştir. İncelenen çalışmalarda en çok nitel ve nicel araştırma desenlerinin kullanıldığı ve örneklem grubu olarak genellikle 5-6 yaş arasındaki okul öncesi öğrencilerinin seçildiği belirlenmiştir. İncelenen çalışmaların, çoğunlukla sınıf ortamında, kodlama derslerinde ve 8 ile 10 hafta arasında süren uygulamalarla gerçekleştirildiği tespit edilmiştir. Ayrıca çalışmalarda kodlama eğitimi ile genellikle algoritma tasarımı, sıralama, döngü, komut ve koşul gibi kodlama sürecinin temel kavramlarının öğretildiği görülmüştür. Bunlara ek olarak, çalışmalarda en çok problem çözme becerisi değişkeninin araştırıldığı ve sıklıkla bilgisayarsız kodlama etkinliklerinin kullanıldığı tespit edilmiştir. Ayrıca, robotik kodlamada en çok Bee-Bot aracının, blok tabanlı kodlamada ise en çok code.org platformunun kullanıldığı belirlenmiştir. İncelenen çalışmalar sonucunda, okul öncesi dönemde kodlama eğitiminin en sık belirtilen avantajının öğrencilere problem çözme becerisinin kazandırılması, en sık belirtilen zorluğunun ise döngü yapıları konusunun öğrencilerin anlamakta zorluk yaşamaları olduğu tespit edilmiştir. Son olarak sistematik incelemeden elde edilen bulgular doğrultusunda uygulayıcılara ve araştırmacılara yönelik çeşitli öneriler sunulmuştur.

A Digital Diplomacy Irony: Donald Trump

The concept of digital diplomacy includes the use of digital communication techniques both in interstate diplomacy and in the relationship between a state and foreign public opinion groups. This study is a qualitative research to determine how the 45th President of the USA, Donald John Trump, uses Twitter in terms of content in the context of digital diplomacy. The general purpose of the study is to evaluate Trump's digital diplomacy activities on Twitter. In this context, examining the styles and forms of the role of digital diplomacy constitutes the main research question of this study. The question of how Trump's digital diplomacy practices on Twitter are, constitutes the main problematic to focus on in the research. In the study, firstly, the literature on the subject was searched, and then Trump's tweets containing diplomacy issues between January 20, 2017 and January 20, 2021 were taken as a basis in the selection of the data needed for the research. In the process of collecting data within the scope of the research, document analysis method was used. In the content analysis carried out on the determined sample, categories were produced based on the diplomacy actors that are frequently repeated in the literature, and each analyzed tweet was analyzed within the relevant category. One of the most basic findings obtained as a result of the research is the fact that the language he uses while using social media is quite far from the language of diplomacy due to Trump's tweets. In addition, it is noteworthy that Trump exhibits a racist attitude and uses hate language with tweets he sends to both himself and other countries' citizens and administrations on Twitter, one of his social media channels. Looking at the data, it is seen that soft power elements are not used in the content of Trump's tweets, therefore, there is no national and international dialogue environment, and it is concluded that his tweets have reached the level of sarcastic, insulting and even hate crime, and therefore it can be called digital diplomacy irony.

The Oxidative Damage and Inflammation Mechanisms in GERD-Induced Barrett's Esophagus.

Barrett’s esophagus is a major complication of gastro-esophageal reflux disease and an important precursor lesion for the development of Barrett’s metaplasia and esophageal adenocarcinoma. However, the cellular and molecular mechanisms of Barrett’s metaplasia remain unclear. Inflammation-associated oxidative DNA damage could contribute to Barrett’s esophagus. It has been demonstrated that poly(ADP-ribose) polymerases (PARPs)-associated with ADP-ribosylation plays an important role in DNA damage and inflammatory response. A previous study indicated that there is inflammatory infiltration and oxidative DNA damage in the lower esophagus due to acid/bile reflux, and gastric acid could induce DNA damage in culture esophageal cells. This review will discuss the mechanisms of Barrett’s metaplasia and adenocarcinoma underlying oxidative DNA damage in gastro-esophageal reflux disease patients based on recent clinical and basic findings.

Towards an Ontology-Based Phenotypic Query Model

Clinical research based on data from patient or study data management systems plays an important role in transferring basic findings into the daily practices of physicians. To support study recruitment, diagnostic processes, and risk factor evaluation, search queries for such management systems can be used. Typically, the query syntax as well as the underlying data structure vary greatly between different data management systems. This makes it difficult for domain experts (e.g., clinicians) to build and execute search queries. In this work, the Core Ontology of Phenotypes is used as a general model for phenotypic knowledge. This knowledge is required to create search queries that determine and classify individuals (e.g., patients or study participants) whose morphology, function, behaviour, or biochemical and physiological properties meet specific phenotype classes. A specific model describing a set of particular phenotype classes is called a Phenotype Specification Ontology. Such an ontology can be automatically converted to search queries on data management systems. The methods described have already been used successfully in several projects. Using ontologies to model phenotypic knowledge on patient or study data management systems is a viable approach. It allows clinicians to model from a domain perspective without knowing the actual data structure or query language.