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© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.Background: Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency and cytotoxic T-lymphocyte protein-4 (CTLA-4) insufficiency are recently described disorders that present with susceptibility to infections, autoimmunity, and lymphoproliferation. Clinical and immunological comparisons of the diseases with long-term follow-up have not been previously reported. We sought to compare the clinical and laboratory manifestations of both diseases and investigate the role of flow cytometry in predicting the genetic defect in patients with LRBA deficiency and CTLA-4 insufficiency. Methods: Patients were evaluated clinically with laboratory assessments for lymphocyte subsets, T follicular helper cells (TFH), LRBA expression, and expression of CD25, FOXP3, and CTLA4 in regulatory T cells (Tregs) at baseline and 16 h post-stimulation. Results: LRBA-deficient patients (n = 29) showed significantly early age of symptom onset, higher rates of pneumonia, autoimmunity, chronic diarrhea, and failure to thrive compared to CTLA-4 insufficiency (n = 12). In total, 29 patients received abatacept with favorable responses and the overall survival probability was not different between transplanted versus non-transplanted patients in LRBA deficiency. Meanwhile, higher probability of survival was observed in CTLA-4-insufficient patients (p = 0.04). The T-cell subsets showed more deviation to memory cells in CTLA-4-insufficiency, accompanied by low percentages of Treg and dysregulated cTFH cells response in both diseases. Cumulative numbers of autoimmunities positively correlated with cTFH frequencies. Baseline CTLA-4 expression was significantly diminished in LRBA deficiency and CTLA-4 insufficiency, but significant induction in CTLA-4 was observed after short-term T-cell stimulation in LRBA deficiency and controls, while this elevation was less in CTLA-4 insufficiency, allowing to differentiate this disease from LRBA deficiency with high sensitivity (87.5%) and specificity (90%). Conclusion: This cohort provided detailed clinical and laboratory comparisons for LRBA deficiency and CTLA-4 insufficiency. The flow cytometric approach is useful in predicting the defective gene; thus, targeted sequencing can be conducted to provide rapid diagnosis and treatment for these diseases impacting the CTLA-4 pathway.

Okul çağı çocukluk döneminde kazanılan sağlıksız beslenme alışkanlıkları ve yeme davranışları yetişkinliğe kadar devam edebilmekte, obezite ve Tip 2 diyabet gibi kronik hastalıkların gelişme riskini artırabilmektedir. Özellikle okul çağı çocuklarda yeme alışkanlıklarında erken yapılan doğru değişikliklerin sağlığı geliştirebileceği ve sonraki yaşamda hastalık geliştirme riskini azaltabileceği belirtilmektedir. Bu nedenle okul temelli beslenme eğitim programları da dâhil olmak üzere erken dönemde sağlıklı beslenmeyi destekleyen programların önemi artmaktadır. Çeşitli araştırmalar, cinsiyet, yaş, sosyoekonomik durum ve yaşanılan ülke gibi demografik özelliklerden bağımsız olarak, ebeveynlerin beslenme alışkanlıklarının çocukların beslenme davranışları üzerinde büyük bir etkisi olduğunu gözlemlemiştir. Aile ile birlikte yeme, ebeveynlerin rol model olması, ebeveyn beslenme bilgi düzeyi, ebeveyn teşvikinin artması ve aşırı baskının azalmasının çocukların beslenme davranışlarını olumlu yönde etkileyebileceğini düşündürmektedir. Ebeveynleri tarafından sağlıklı beslenme konusunda teşvik edilen çocukların okul temelli beslenme eğitim programlarından edindikleri bilgileri daha uzun süre kullanım potansiyelleri vardır. Bu durum, ev ortamının çocuklarda sağlıklı beslenme davranışını desteklemedeki önemli rolünü vurgulamaktadır. Ebeveyn katılımlı çocuk besleme eğitimlerinin, diyetle ilgili hastalıkları önlemek için gelecekte uygulanacak diyet müdahalelerinin ve politikalarının tasarlanmasına yardımcı olabilecek değiştirilebilir risk faktörleri olarak değerlendirildiği çalışmalar artırılmalıdır. Bu derleme de, ebeveyn beslenme eğitiminin okul çağı çocuklarında verilen beslenme eğitimine etkisinin değerlendirildiği çalışmalar incelenmiştir.

Fractures of the triquetrum are the second most common form of isolated carpal bone fracture after the scaphoid. However, data on triquetrum morphology and morphometry are sparse. The aim of this study was to describe the morphology of triquetrum using anatomical landmarks, evaluate its morphometric features, and determine its vascular entry points. The morphological and morphometrical features of 87 adult dry triquetral bones (39 left, 48 right) were determined by measuring length, width and thickness. The number and locations of nutrient foramina wider than 0.5 mm were recorded. Mean length, width and thickness were 17.37 mm (range, 14.26-22.13), 12.65 mm (range, 10.37-15.85) and 11.41 mm (range, 8.98-18.23), respectively. The facet articulating with the pisiform was oval in 40 bones, round in 8 and amorphous (neither round nor oval) in 39. The mean length of the interarticular ridge was 7.09 ± 0.9 mm. The mean number of nutrient foramina was significantly greater on the dorsal than on the other aspects. The dorsal predominance of nutrient foramina makes the bone weaker in the dorsal region, which could explain why fractures are more common in this region. Also, the dorsal aspect is rich in blood supply, which could explain why avascular necrosis is less common in triquetral fractures. As most of the vascularization is on the dorsal side, there is need for caution when performing triquetrum surgery. LEVEL OF EVIDENCE: Level 2.

Bazı kelimelerin anlam kapasiteleri bazılarına nazaran daha geniş ve çeşitlidir. Bu tür kelimeler ifadeye zenginlik ve derinlik kattıkları için rağbet görürler. Fakat aynı gerekçe kastedilen anlamın kapalı kalmasına da yol açabilmektedir. Anlam çerçevesi geniş olan bu kabil kelimeler ekseriyetle yabancı kökenli kelimelerdir. Türkler İslâmiyeti kabul ettikten sonra yeni dinî kavramlarla karşılaşmışlardır. Bu kavramların Türkçede karşılıkları olmadığı için Arapça ve Farsçadan kelimeler alınmıştır. Örnekleri az olmayan bu kelimelerden biri “himmet” kelimesidir. Arapça kökenli olan bu kelime Türkçeye Farsça üzerinden gelmiştir. Himmet kelimesi Türkçede Arapçadaki anlamından daha farklı bir anlamda kullanılmaktadır. Bu çalışmada himmet kelimesinin Türkçede hangi anlamda kullanıldığı üzerinde durulacaktır. Bunun için öncelikle sözlükler incelenmiştir. Ayrıca Türk edebiyatının kadim metinlerinden olan Dîvân-ı Hikmet ve Garib-nâme’de himmet kelimesinin hangi anlamlarla yer aldığı üzerinde durulmuştur. he semantic capacity of some words are wider and more diverse than others. Such words are widely used since they add amplitude and depth to the expression. However, the same reason may cause the meaning to be implicit. These words, which have a wide semantic framework, are mostly words of foreign origin. After the Turks emberaced Islam, they encountered new religious concepts. Since these concepts do not have equivalents in Turkish, words were loaned from Arabic and Persian. One of these words, whose examples are not few, is the word “himmet”. The word himmet, which is of Arabic origin, came to Turkish through Persian. The word himmet is used in a different meaning in Turkish than in Arabic. In this study, it will be emphasized in which sense the word himmet is used in Turkish. For this purpose, firstly, dictionaries were examined. In addition, the meaning of the word himmet in Dîvân-ı Hikmet and Garib-nâme, which are among the earliest texts of Turkish literature, is dwelled on.

Küçük hücre dışı akciğer kanserlerinde cerrahi başarı, iyi bir anatomik rezeksiyon sonrası makroskobik ve mikroskobik olarak temiz gelen cerrahi sınır olması ve lenf nodlarında yayılım görülmemesidir. Cerrahi, akciğer kanserlerinde özellikle erken evrelerde en büyük tedavi şansını oluştururken tümör ve komşu dokuların birlikte anblok rezeksiyonları, cerrahi sınırda tümör dokusunun kalmayışı en uzun süreli sağkalımı sağlamaktadır. Küçük hücreli dışı akciğer kanserli hastaların yaklaşık %70’inde kullanılan lobektomi standart bir anatomik rezeksiyondur. Uygulanan teknik pulmoner venlerin, arterin ve bronşun ayrı ayrı serbestleştirilmesi ve ardından mutlak bir şekilde hiler lenf nodları ve lenfatiklerin dikkatli diseksiyonudur. Akciğer rezeksiyonu geçirecek bütün hastalar için rezeksiyon öncesi evreleme; hastalığın seyri ve onkolojik girişimlerin algoritması için mutlaka yapılmalıdır.

Bu çalışma Türkmenistan ekonomisi için 1996-2019 döneminde doğrudan yabancı yatırımların, kaynak gelirlerinin ve kamu harcamalarının iktisadi büyümeye olan etkisini araştırmaktadır. Bu çerçevede söz konusu ilişki VAR analizi ile test edilmiştir. Eşbütünleşme analizinin bulgularına göre reel büyüme ile söz konusu üç değişken arasında uzun dönemli bir ilişki mevcuttur. Diğer taraftan Granger nedensellik testine göre kısa dönemde %10 anlam düzeyinde reel büyümeden DYY ’ye ve kamu harcamalarından DYY ’ye doğru pozitif bir nedensellik ilişkisi bulunmaktadır. Bunun yanında kaynak gelirleri ile büyüme arasında çift yönlü pozitif nedensellik ilişkisi bulunmaktadır. Diğer değişkenler arasında ise nedensellik ilişkisi yoktur. Çalışmanın etki-tepki analizi ile ulaşılan üçüncü bulgusu ise büyümenin üzerinde özellikle doğrudan yabancı yatırımların etkisinin nispeten büyük olduğudur. Ek olarak Varyans ayrıştırmasında doğrudan yabancı yatırımların büyüme üzerindeki etkisinin nispeten daha önemli olduğu sonucuna ulaşılmıştır.

Severe combined immunodeficiency is an inborn error of immunity characterized by impairments in the numbers and functions of T and B lymphocytes due to various genetic causes, and if it remains untreated, patients succumb to infections during the first 2 years of life. Purpose and Methods: This study reported retrospective data from 72 infants diagnosed with SCID including their major clinical features, HSCT characteristics, and outcomes over a 20-year period (1997–2017). Results: Sixty-one of 72 SCID patients in the study underwent HSCT from 1997 to 2017. Median ages at the time of diagnosis and transplantation were 3.5 months and 5 months, respectively. Consanguinity was present in 68% of the patients, and T − B − NK + phenotype was predominantly identified. The overall survival was 80.3% over a 20-year period. However, the patients transplanted during an active infection had a lower survival rate of 73.9% compared to 100% for patients transplanted infection-free or with a previous infection that had resolved. The survival rate was significantly higher among recipients of HLA-identical transplants (92.9%), compared to recipients of mismatched related transplants (70%). The overall survival increased from 50 (1997–2006) to 85% (2007–2017) during the last 10 years. Conclusions: This is one of the largest single-center studies in Turkey with extensive experience about SCID patients. Early diagnosis of SCID patients before the onset of an infection and early transplantation are shown to be extremely important factors affecting the outcome and increasing the survival regardless of the donor type based on the results of this study. WOS:000659780700002 34114123 Q1

The objectivity of physical and electrodiagnostic tests is limited in detecting carpal tunnel syndrome and its recurrence. Predicting the median nerve blood supply using superb microvascular imaging will allow exact diagnosis and a good follow-up system. The aims of this study include using superb microvascular imaging to correlate with electromyographic diagnosis, and to determine the impact of surgery on improvement in superb microvascular imaging.Between July of 2019 and January of 2020, 32 wrists of 21 patients were evaluated prospectively. After preoperative electrodiagnostic studies and vascular index measurement with superb microvascular imaging, open carpal tunnel release was performed by a single surgeon, and 3 months later standardized superb microvascular imaging was performed. Preoperative vascular indexes were compared with the mild, moderate, and severe electrodiagnostic study results. Preoperative and postoperative vascular index results were compared.The average of the preoperative and postoperative imaging groups was 2.77 and 1.48, respectively, and there was a statistically significant difference between the two groups (p0.05). Although no significant difference was found between preoperative and postoperative vascular index values in patients presenting with mild carpal tunnel syndrome (p0.05), there was a significant decrease in vascular index values in patients presenting with moderate and severe carpal tunnel syndrome after surgical decompression.Superb microvascular imaging is emerging as a groundbreaking, new, and reliable technique. Evaluation of the median nerve blood supply is a reliable method that would be helpful for early diagnosis, planning treatment, determining the severity of carpal tunnel syndrome, and postoperative follow-up.Diagnostic, IV.

Tarihsel mirasında kurumsal vergi sistemine sahip olmayan ekonomiler bağımsızlıklarıyla birlikte vergi sistemi tesisi arayışına girmişlerdir. Böyle bir sistemin esas unsuru olan vergi yapısı ise geçiş ekonomilerinin serbest piyasa reformlarının finansmanı anlamına gelmektedir. Çalışmanın amacı, 31 geçiş ekonomisinin mevcut vergi yapısını değerlendirmektir. Ek olarak, vergi yapısı ve vergi sisteminin kurumsal yapısının etkinliğini değerlendirmek amacıyla 24 geçiş ekonomisinde yolsuzluk ile toplam vergi yükü, kişi başına düşen GSYH, dışa açıklık, ekonomik özgürlük, kurumlar-gelir-tüketim vergisi oranları ilişkisi incelenmiştir. Bu amaçla statik ve dinamik panel veri analizi yapılmıştır. Sonuçlarına göre ekonomik özgürlük endeksi düşük olan ülkelerde yolsuzluk yüksek seyretmektedir. Benzer şekilde yolsuzluğun yüksek olduğu ekonomilerde kişi başına düşen GSYH düşüktür. Vergi yükünün yüksek, gelir dağılımında adaletin düşük ve vergi idarelerinin kurumsal zayıflığı gibi nedenlerden dolayı geçiş ekonomilerinde rüşvet, verginin ikamesi olarak görüldüğü söylenebilir. Bu çerçevede statik analiz bulgularına göre geçiş ekonomilerinde kişi başına düşen gelirde bir birimlik artış yolsuzluğu %0,0371, dışa açıklık %0,0134, ekonomik özgürlük %0,0394 ve gelir vergisi oranı %0,0122 pozitif etkilemektedir. Dinamik analizin bulgularına göre yolsuzluğu negatif etkileyen iki değişken bulunmaktadır. Bunlardan ekonomik özgürlük yolsuzluğu %0,073 ve tüketim vergileri %0,108 negatif etkilemektedir. Diğer taraftan vergi gelirleri (0,064), kişi başına düşen gelir (0,056), ticari açıklık (0,073) ve gelir vergisi oranı (0,063) yolsuzluğu pozitif etkilemektedir., Economies that do not have a corporate tax system in their historical heritage have sought to establish a tax system with their independence. The tax structure means the financing free-market reforms of transition economies. The study aims to evaluate the current tax structure of 31 transition economies. Also, the relationship between corruption and total tax burden, GDP per capita, openness, economic freedom, corporate-income-consumption tax rates in 24 transition economies were examined to evaluate the tax structure and the effectiveness of the institutional structure of the tax system. Corruption is high-ranking in countries with a low economic freedom index. GDP per capita is lower in economies with high corruption. Bribery in transition economies is seen as a substitute for tax due to reasons such as high tax burden, low justice in income distribution, and institutional weakness of tax administrations. According to static analysis, a one-unit increase in income per capita in transition economies positively affects corruption at 0.0371%, openness at 0.0134%, economic freedom at 0.0394%, and income tax rate at 0.0122%. According to dynamic analysis, two variables negatively affect corruption. Economic freedom negatively affects the corruption index by 0.073% and excise taxes by 0.108%. On the other hand, tax revenues (0.064), per capita income (0.056), the trade deficit (0.073), and income tax rate (0.063) positively affect corruption.

Aim: Nuss procedure for pectus excavatum and Abramson procedure for pectus carinatum are used as minimally invasive methods for surgical treatment of chest wall defomities. The aim of this study is to investigate the causes of bar-related complications, and to present technical details of their management. Materials and Methods: Patients who underwent minimally invasive correction surgery with the diagnosis of pectus excavatum and pectus carinatum between 2011-2020 in our clinic were included in this study. The surgical treatments, bar related complications, and follow-up records of patients were recorded and analyzed retrospectively. Results: 141 patients with a mean age of 16.08 ± 4.38 were included in the study. Postoperative bar-related complications were encountered in 28 (19.8%) of all patients. There were no life-threatening early or late complications. The most common complication was skin reaction in 7 (4.9%) cases. Conclusion: Bar-related complications are problems that can cause morbidity and disrupt patient comfort, thus management of complications should be focused on.

The convergence of various technologies, such as smartwatches, smartphones, etc. has proven to be beneficial, although poses various security and privacy risks. In this paper, we explore one such risk where a smartwatch can be exploited to infer what a user is typing on a physical keyboard while wearing the smartwatch. We exploited the acoustic emanations of the keyboard as recorded by the smartwatch to perform the proposed attack-SIA. To address various environment-related challenges, SIA employs four stages: Noise Cancelling, Keystroke Detection, Key Identification, and Word Correction, where several digital signal processing, machine learning, and natural language processing techniques are utilized to produce the final inference. Our results show that an acoustic emanation of a physical keyboard captured by a smartwatch recovers up to 98% of the typed text. We also showed that utilizing the noise cancellation, SIA is robust to the changes in the attack environment, which further boosts the practicality of the attack. The findings are alarming and call for further investigation on methods to cope with inference attacks due to the convergence of those technologies.

Objective: In this study, we aimed to observe whether short-term weight loss program changes dietary carbon footprint (CF) and its effect on the risk of chronic disease. Design: This study was carried out between April 2019- January 2020. Participants received a diet intervention for four weeks. Their anthropometric measurements and food records were evaluated before and at the end of the study. Participants: 61 individuals (51 female; 10 male) aged 19-59 years and with a Body Mass Index (BMI) of ≥25 kg/m2. Results: Their dietary CF of sweets/snacks, drinks, potatoes/bread/pasta, meat, and butter/oil also decreased statistically significantly according to the eight major food groups. The total dietary CF increased in this study (p=0.018). This increase resulted from the increase in the consumption of dairy/egg food group. At the end of the study the body weight, BMI, waist, hip and neck circumference, waist-hip ratio, and the waist-height ratio of participants decreased statistically significantly after the weight loss program (p

Background: In this study, we aimed to examine the development of knowledge on pectus deformities through a meticulous analysis of the 100 most-cited articles published on this topic. Methods: Publications related to pectus deformities from January 1975 to April 2020 were scanned using the Web of Science Core Collection database. The publications were ranked from maximum to minimum according to the number of citations and were examined in detail. Results: The 100 articles were published in 27 different journals and received a total of 8,290 citations. The average of the impact factors of journals in 2018 was 4.441. The mean citation density of all articles was 5.1±3.8. In the past years, a surgical technique definition and experience transfer were more frequently used, while complications and technical details were started to be presented in recent years. Conclusion: Our study results suggest that the studies of pectus deformities would continue and, from now on, issues such as complications and technical details would come to the forefront in the articles.

Maternal beslenme birçok bulaşıcı olmayan kronik hastalığın gelişiminde belirleyici bir rol oynamaktadır. Gebelik boyunca maternal beslenme durumu programlanmada değişikliklere neden olup yetişkin dönem hastalıklarının gelişimine katkıda bulunabilir. Plasenta yetmezliği, glukokortikoidlere maruz kalma, beslenme yetersizlikleri ya da fazlalıkları ve stres gibi çeşitli perinatal sorunlar ile birlikte maternal intestinal mikrobiyom fetusun/yavrunun gelişimini değiştirerek kronik bulaşıcı olmayan hastalıkların oluşmasında yatkınlığa yol açabilir. Aynı zamanda gebelik sürecince yapılan beslenme müdahaleleri, programlama sürecinin tersine çevrilerek bulaşıcı olmayan hastalıkların önlenmesini amaçlayan yeni stratejilerin oluşturabilmesi için çok değerlidir. Fetal gelişim sırasında gen ekspresyonu epigenetik mekanizmalardan etkilenebilir. Özellikle deoksiribonükleik asit metilasyonunda rol alan genlerin epigenetik modifikasyonları, histon modifikasyonları ve mikroRNA’lar hayatın sonraki dönemlerinde metabolik hastalıkların gelişimine katkıda bulunabilir. Bu derlemede epidemiyolojik çalışmalar ve hayvan modellerinden elde edilen veriler ışığında maternal beslenmenin fetal programlama üzerine etkilerinin altında yatan mekanizmalardan biri olan epigenetik mekanizmalar ele alınmıştır.

Patients with autosomal recessive protein kinase C delta (PKC delta) deficiency suffer from childhood-onset autoimmunity, including systemic lupus erythematosus. They also suffer from recurrent infections that overlap with those seen in patients with chronic granulomatous disease (CGD), a disease caused by defects of the phagocyte NADPH oxidase and a lack of reactive oxygen species (ROS) production. We studied an international cohort of 17 PKC delta-deficient patients and found that their EBV-B cells and monocyte-derived phagocytes produced only small amounts of ROS and did not phosphorylate p40(phox) normally after PMA or opsonized Staphylococcus aureus stimulation. Moreover, the patients' circulating phagocytes displayed abnormally low levels of ROS production and markedly reduced neutrophil extracellular trap formation, altogether suggesting a role for PKC delta in activation of the NADPH oxidase complex. Our findings thus show that patients with PKC delta deficiency have impaired NADPH oxidase activity in various myeloid subsets, which may contribute to their CGD-like infectious phenotype. Yale Center for Mendelian Genomics - National Human Genome Research Institute [UM1HG006504]; National Institute of Allergy and Infectious DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [5R01AI089970, 5R37AI095983, R01AI127564-01]; National Center for Research ResourcesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR); National Center for Advancing Translational Sciences of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Advancing Translational Sciences (NCATS) [8UL1TR001866]; Rockefeller University; St. Giles Foundation; INSERMInstitut National de la Sante et de la Recherche Medicale (Inserm)European Commission; University of Paris; French Foundation for Medical ResearchFondation pour la Recherche Medicale [EQU201903007798]; Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence [ANR-10-LABX-62-IBEID]; SCOR Corporate Foundation for Science; French National Research Agency (ANR) under the Investments for the future programFrench National Research Agency (ANR) [ANR-10-IAHU-01]; ANR-IFNPHOX [ANR-13-ISV3-0001-01]; ANR-GENMSMDFrench National Research Agency (ANR) [ANR-16-CE17-0005-01]; ANR-GENCMCD [ANR-11-BSV3-005-01]; ANR-HGDIFDFrench National Research Agency (ANR) [ANR-14-CE15-0006-01]; Bettencourt Schueller Foundation; International PhD program of the Imagine Institute; Japanese Foundation; EURO-CMC project [ANR-14-RARE-0005-02]; Societe Nationale Francaise de Medecine Interne (Bourse Marcel Simon); INSERM PhD program for medical doctors (poste d'accueil INSERM); Fulbright grant (Franco-American commission); MD-PhD program of Imagine Institute; Consejo Nacional de Ciencia y Tecnologa National PhD Fellowship Program; National Institute for Health Research Biomedical Research CentreNational Institute for Health Research (NIHR); Great Ormond Street Hospital Charity; Deutsche Forschungsgemeinschaft under Germany's Excellence StrategyGerman Research Foundation (DFG) [EXC 2155, 390874280]; REBIRTH Center for Translational Regenerative Medicine through the State of Lower Saxony [MWK: ZN3440] This paper is dedicated to the memory of Prof. Asghar Agha-mohammadi, who passed away in November 2020, and made immense contributions to the understanding and treatment of primary immunodeficiencies. We thank all patients, their relatives, and the treatment teams for their cooperation in this study. We thank all the members of the Laboratory of Human Genetics of Infectious Diseases for helpful discussions. We also thank Christine Rivalain, Cecile Pa-tissier, Lazaro Lorenzo-Diaz, Dominick Papandrea, Dana Liu, and Yelena Nemirovskaya for administrative assistance and Gaspard Kerner for statistical advice. We thank the Necker Institute Imaging Facility for technical advice. The graphical abstract was created with BioRender.com under subscription. This research was supported by the Yale Center for Mendelian Genomics funded by the National Human Genome Research Insti-tute (UM1HG006504) . The Howard Hughes Medical Institute lab-oratory was funded in part by the National Institute of Allergy and Infectious Diseases (grants 5R01AI089970, 5R37AI095983, and R01AI127564-01) , the National Center for Research Resources, and the National Center for Advancing Translational Sciences of the National Institutes of Health (grant 8UL1TR001866 for J-L. Casa-nova) , the Rockefeller University, the St. Giles Foundation, INSERM, the University of Paris, the French Foundation for MedicalResearch (EQU201903007798) , the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID) , the SCOR Corporate Foundation for Science, and the French National Research Agency (ANR) under the Investments for the future program (grant ANR-10-IAHU-01) , ANR-IFNPHOX (grant ANR-13-ISV3-0001-01 for J. Bustamante) , ANR-GENMSMD (grant ANR-16-CE17-0005-01 for J. Bustamante) , ANR-GENCMCD (grant ANR-11-BSV3-005-01 for A. Puel) , and ANR-HGDIFD (grant ANR-14-CE15-0006-01 for J. Bustamante) . A-L. Neehus was sup-ported by the Bettencourt Schueller Foundation and the Interna-tional PhD program of the Imagine Institute, K. Moriya by a Japanese Foundation for Pediatric Research fellowship grant and EURO-CMC project (grant ANR-14-RARE-0005-02 for J. Bustamante) , R. Levy by the Societe Nationale Francaise de Medecine Interne (Bourse Marcel Simon) , the INSERM PhD program for medical doctors (poste d'accueil INSERM) , and the Fulbright grant (Franco-American commission) , T. Le Voyer by the Bettencourt Schueller Foundation and the MD-PhD program of Imagine Institute, and A. Nieto-Patlan by the Consejo Nacional de Ciencia y Tecnologa Na-tional PhD Fellowship Program. All research at the Great Ormond Street Hospital National Health Service Foundation Trust is sup-ported by the National Institute for Health Research Biomedical Research Centre. P.A. Brogan also acknowledges support from the Great Ormond Street Hospital Charity. N. Lachmann acknowledges support from the Deutsche Forschungsgemeinschaft under Ger-many's Excellence Strategy-EXC 2155-project number 390874280 and the REBIRTH Center for Translational Regenerative Medicine funded through the State of Lower Saxony (MWK: ZN3440) . Author contributions: A-L. Neehus, J-L. Casanova, A. Puel, and J. Bustamante conceived and designed the study. A-L. Neehus, K. Moriya, T. Le Voyer, A. Nieto-Patlan, R. Levy, M. Roynard, K. Haake, M. Migaud, and K. Dorgham performed the experiments. A. ozen, E. Karakoc-Aydiner, S. Baris, A. Yildiran, E. Altundag, F. Dogu, S. Has-kologlu, E. Ince, G. Uzel, A. Kiykim, K. Boztug, M.R. Roderick, M. Shahrooei, P.A. Brogan, H. Abolhassani, G. Hancioglu, N. Parvaneh, A.; Belot, and A. Ikinciogullari were the treating physicians respon-sible for clinical diagnosis, deep phenotyping, sample collection, and patient follow-up. G. Gorochov, L. Abel, N. Lachmann, J. El-Benna, and A. Belot provided conceptual advice. A-L. Neehus, J-L. Casanova, A. Puel, and J. Bustamante analyzed the results and wrote the man-uscript. All authors revised the manuscript and approved the final manuscript as submitted. Disclosures: P.A. Brogan reported personal fees from Sobi, No-vartis, Roche, and GSK, and grants from Sobi outside the sub-mitted work. No other disclosures were reported.

CCNE1 gene amplification is associated with overexpression of Cyclin E1 protein and is an important oncogenic driver. CCNE1 amplification is common in high grade serous ovarian carcinomas (HGSOC) and is associated with platinum resistance and poor patient outcomes. Importantly, Cyclin E1 overexpression can also occur in the absence of gene amplification in ovarian cancer. Overexpression of Cyclin E1 increases CDK2 activity and accelerates entry into S phase of cell cycle, resulting in replication stress and rendering cells more dependent on DNA repair. WEE1 participates in the DNA damage response by controlling essential checkpoints of the cell cycle, preventing cells from entering mitosis and allowing for DNA repair before cell cycle progression. Thus, we hypothesize that ovarian cancers overexpressing Cyclin E1, either via CCNE1 gene amplification or through other independent mechanisms, are more sensitive to WEE1 inhibition. Here, we tested this hypothesis in a range of preclinical cancer models using azenosertib, a novel, selective, and orally bioavailable WEE1 inhibitor currently in clinical development. Ovarian cancer cell lines overexpressing Cyclin E1 protein (Cyclin E1high) were more sensitive to azenosertib than ovarian cancer cell lines with lower levels of Cyclin E1 protein (Cyclin E1low) inducing significant cytotoxic effects (GRmax < -0.5). In Cyclin E1low ovarian cancer cell lines, overexpression of Cyclin E1 increased sensitivity to azenosertib. In contrast, silencing of CDK2 in Cyclin E1high cells reduced sensitivity to azenosertib. In vivo, higher levels of baseline expression of Cyclin E1 in tumor cells were associated with better response to azenosertib, with tumor growth inhibition (TGI) ranging from 51.5% in a Cyclin E1low SKOV3 model to 88% in a Cyclin E1high OVCAR3 model. Azenosertib synergized with chemotherapy agents in multiple ovarian cancer models. In vitro, we report that Cyclin E1high cancer cells were more sensitive to the combination of azenosertib and chemotherapeutics than Cyclin E1low cancer cells. In vivo, the synergy between azenosertib and paclitaxel was stronger in Cyclin E1high OVCAR3 model (46% reduction of initial tumor volume/104% TGI) than Cyclin E1low A2780 model (85% TGI). Taken together, these data suggest that Cyclin E1 overexpression via gene amplification or independent mechanisms sensitize ovarian cancer cells to azenosertib alone or in combination with chemotherapy. This observation supports the use of Cyclin E1 expression to enrich for azenosertib responders in ovarian cancer and possibly other tumor types. Two subsets of Cyclin E1-driven platinum resistant ovarian cancer patients, as defined by gene amplification or protein overexpression, are being enrolled in an azenosertib monotherapy trial. Citation Format: Jianhui Ma, Wen Liu, Heekyung Chung, Hooman Izadi, Petrus DeJong, Olivier Harismendy, Jia li, Fernando Doñate, Ahmed Samatar, Mark Lackner, Laure Escoubet, Kevin Bunker, Daehwan Kim, Nathan Jameson, Tugba Yildiran Ozmen, Kangjin Jeong, Dong Zhang, Wen-An Pan, Gordon Mills. Cyclin E1 protein overexpression sensitizes ovarian cancer cells to ZN-c3, a novel, selective and oral bioavailable inhibitor of Wee1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2153.

Eğitim yapılarında aydınlatma, dersliklerde gün boyu devam eden eğitim süreci nede-niyle görsel konfor ve enerji tüketimi açısında önemli bir konudur. Bu etkenler düşünül-düğünde gün ışığı aydınlatma için en iyi çözümdür. Ancak yetersiz kaldığı durumlarda doğru tasarlanmış yapay aydınlatma ile desteklenmelidir. Doğal aydınlatma, güneşin günlük ve mevsimsel hareketlerine bağlı olarak, sabit aydın-lık düzeyi sağlamaz. Bu değişkenlik sebebiyle dersliklerde düzgün dağılımlı aydınlatma düzeyi oluşturmak ve enerji tasarrufu sağlamak üzere tasarlanacak aydınlatma sistem-lerinin türü, miktarı, gücü, konumu önemlidir. Bu bağlamda Mimarlıkta Enerji Etkin Ta-sarım yüksek lisans dersi kapsamında gerçekleştirilen çalışmada Kocaeli Üniversitesi Mimarlık Fakültesi’nde belirlenen atölyelerde mevcut aydınlık seviyesi ve dağılımı tespit edilmiş, sonuçlar standartlar ile karşılaştırılıp değerlendirilmiştir. Bu değerlendirmeye göre görsel konfor koşullarını arttırmak, enerji tüketimini azaltmak üzere uygun aydın-latma sistemlerinin seçimi ve kullanım biçimlerinin belirlenmesine yönelik çalışma ger-çekleştirilmiştir. Belirlenen atölyelerden en riskli verilere sahip olan Atölye A, DIALux Evo programında modellenmiştir. Farklı aydınlatma gücü ve türünde elemanlarının kullanıldığı öneriler getirilmiştir. Bu öneriler, enerji tüketim miktarı ve görsel konfor koşulları üzerinden de-ğerlendirilmiş, atölye için en uygun aydınlatma planı önerilmiştir.

Purpose The purpose of this study is to evaluate the perception and knowledge of standard food/meal portion size and related factors in young adults. Design/methodology/approach The present study was conducted on 1,000 volunteer young adults, consisting of 504 men and 496 women (18 and 28 years). The portion size of food/meal, amount of food measuring utensils and also nutritional knowledge were evaluated via a questionnaire and some visual materials. Findings Knowledge of portion sizes, amount of food each utensil holds and nutrition was evaluated via a questionnaire and some visual materials. Knowledge of portion size with respect to food groups (p = 0.015), meals (p < 0.001) and food measuring utensils (p = 0.002) and nutritional knowledge scores (p = 0.011) differed based on body mass indexes (BMI). Women had on mean a higher nutritional knowledge score than men (2.0 ± 1.3, 1.9 ± 1.1 points, respectively). The probability of having knowledge about food measuring utensils was 1.4-fold greater for individuals who had been previously educated about nutrition (p = 0.034). Individuals of the faculty of health sciences had higher mean scores for all portion scores (p < 0.05). Originality/value The study findings highlighted that portion knowledge and perception of young adults were affected by gender, BMI, enrolled faculty and nutritional knowledge status. This is the first study, through which the portion knowledge and perception subcomponents (food, meal and measuring utensils) are evaluated, indicating each subcomponent to be affected by distinct factors.

Şeker, hem enerji içeriği hem de tadı nedeniyle beynimizdeki ödül sistemini tetikleyen lezzetli bir besindir ve yiyecek bağımlılığına neden olan işlenmiş besinlerin ana yüzünü oluşturmaktadır. Şekerin beyindeki, genel etkileri ve özellikle de beynin ödül yolaklarında etkileri yoğun bir araştırma ve tartışma alanı olmuştur. Şeker tüketimi, mezokortikolimbik sistemi madde kullanımıyla benzer şekilde aktive eder. Şeker alımına bağlı olarak beyinde dopamin D1 reseptör bağlanmasında artış ve D2 reseptör bağlantısında azalma olmakta ve dopamin seviyelerinde oluşan bu değişiklik önce yoksunluğa, ardından devam eden şeker alımına yol açabilmektedir. Kanda yüksek şeker seviyeleri periferik olarak salınan iştah hormonlarının düzenlenmesinin yanı sıra, hipotalamik iştah peptitlerini de etkilemektedir. Beyin nörokimyasında şeker alımıyla oluşan bu değişiklikler büyüklük bakımından daha küçük olmasına rağmen madde kullanımı ile meydana gelen değişikliklere benzerdir. Şekerin insan sağlığı üzerinde yarattığı olumsuz sonuçlar göz önünde bulundurulduğunda oluşturabileceği bağımlılığın ciddi sonuçlar yaratacağı açıktır. Bu sebeplere dayanarak, şeker tüketiminin azaltılması adına, hem bireysel hem de toplum sağlığına yönelik, devletin ve endüstrinin birlikte hareket ettiği adımlar atılması önem taşımaktadır.

Today, pancreatic cancer ranks second after the cardiovascular system among the causes of death. The pancreatic cancer which is an aggressive type progressing without giving too many symptoms. In addition, factors such as difficulty in early diagnosis, rapid metastasis and non-response to traditional treatments cause a low survival rate in this type of cancer. Therefore, many studies are carried out to develop alternative diagnosis and treatment methods. Focus is put on target-oriented studies to increase the survival rate and eliminate other negative effects. The gene therapy method is at the forefront of such studies. RNA interference (RNAi) molecules are crucial in this method. From among these molecules, small non-coding RNA (siRNA) are used in studies as a therapeutic agent by its delivery to the target gene by various mechanisms. Studies are carried out with different biological and chemical agents to deliver the molecules to the target cell efficiently. This study aimed to silence the c-Myc gene using gold nanoparticle (AuNP)-siRNA in the Capan-1 cell line. We performed Real-Time PCR, Dual Staining and gel electrophoresis using gold nanoparticles (2X, 4X, 8X) and siRNA (25 nM) at concentrations determined in the Capan-1 cell line. The data obtained from the analysis suggested that the nanoparticle siRNA complex could be used effectively in silencing the target gene. Nevertheless, effective results could be obtained with more knowledge on this subject.

Araştırmada devlet üniversitesinde görev yapmakta olan öğretim üyelerinin iç girişimcilik ve yenilik yönelimi arasındaki ilişkileri incelenmek istenmiş olup, iç girişimcilik ve alt boyutları ile yenilik yönelimi arasındaki ilişkiler tespit edilmeye çalışılmıştır. Ayrıca demografik değişkenler ile iç girişimcilik ve yenilik yönelimi arasındaki farklılıklar saptanmaya çalışılmıştır. Araştırmanın amacı kapsamında Karabük Üniversitesi’ndeki 280 öğretim üyesinden anket aracılığı ile veriler toplanmıştır. Toplanan verilerin analizleri için Bağımsız Örneklem T-Testi, Tek Yönlü ANOVA ve Pearson Korelasyon yöntemlerinden yararlanılmıştır. Araştırmanın temel hipotezi olan iç girişimcilik ve yenilik yönelimi arasında ilişkinin olduğu savı istatistiksel olarak kanıtlanamamıştır. İç girişimcilik ve yenilik yönelimi arasında ilişkinin demografik değişkenlere göre farklılaştığına yönelik oluşturulan hipotezler de istatistiki açıdan kısmen kanıtlanmıştır., In the research, it was aimed to investigate the relations between intrapreneurship and innovation orientation of faculty members working at a state university, and the relations between internal entrepreneurship and its sub-dimensions and innovation orientation were tried to be determined. Furthermore, the differences between demographic variables, intrapreneurship and innovation orientation were attempted to be defined. Within the scope of the research, data were collected from 280 faculty members at Karabuk University through a questionnaire. Independent Sample T-Test, One-Way ANOVA and Pearson Correlation methods were employed for the analysis of the collected data. The claim that there is a relationship between intrapreneurship and innovation orientation, which is the main hypothesis of the research, could not be proved statistically. The hypothesis that the relationship between intrapreneurship and innovation orientation differs according to demographic variables has also been partially proven statistically.

Circadian rhythms, also known as circadian clocks, are cyclic endogenous biological patterns of an approximately 24-hour cycle which regulate the timing of physiology, metabolism, and behavior. Recent research in the field of circadian science has suggested that the timing of food intake may also play a role in markers of health, in addition to food choice and food quantity. There is emerging evidence suggesting that the timing of dietary intake, so-called chrono-nutrition, may be influenced by an individuals chronotype. For example, the evening type has been linked to unhealthy diet, which could indicate a higher possibility of obesity. On the other hand, the continuum of chronotype diversity is largely mediated by genes. The presence of single nucleotide polymorphisms (SNP) of clock genes have been associated with obesity, chronotype, metabolic disturbances, and dietary habits (e.g., breakfast skipping, meal timing, energy/macronutrient intake). In this review, we outline the current knowledge of the interactions between clock genes, chronotype, dietary intake and chrono-nutrition.Additionally, it is emphasized that the COVID-19 pandemichas had a significant impact on the circadian system, dietary choices and meal timing. For this reason, the current review aims to focus on how chronotype/sleep and chrono-nutrition are affected during the COVID-19 pandemic.