bluuebunny/crossref_metadata_2025 huggingface dataset:
BİLİM İNSANI HATİCE ÖRCÜN BARIŞTA’NIN TÜRK SANATINA KATKILARI
Authors: GÜMÜŞ İlker
Published: November 2022

Bilim insanı ve bilim, toplum için vazgeçilmez etmenler arasındadır. Bir ülkenin gelişmişliği, bilgi üreten bireyler yetiştirmesi ile artar. Toplum olarak bilimi ve bilim insanlarını anlamak önemlidir. Bilim insanı, toplumu ileri noktaya taşıyabilmek için mantık çerçevesinde araştırma yapan, sabırlı, meraklı, kendine güvenen, sürekli not tutan, okuyan, mütevazı olan, tarafsız ve objektif davranan bir kimliğe sahip olmalıdır.

Türkiye’de, Türk sanatı üzerine bilimsel çalışmalar yapan bilim insanları yeterince tanıtılmamaktadır. Bu da alandaki önemli bir eksik olarak karşımıza çıkmaktadır. Türkiye’de, Türk sanatı araştırmaları ile özellikle geleneksel Türk sanatı çalışmaları konusunda akademik çevrede ilk akla gelen Hatice Örcün Barışta’dır. 1977 yılında başlayıp 2017 yılına kadar devam eden 47 yıllık akademik yaşamında yaptığı bilimsel çalışmaları Türk toplumunun yararına sunmuş, bunlarla Türk kültür ve sanatını tanıtmayı hedeflemiştir. Barışta, Ankara Üniversitesi Sanat Tarihi Bölümünün yetiştirdiği önemli bilim insanlarından biridir. Türk el sanatları ve işleme sanatları hakkında yaptığı çalışmalar ile bilim dünyasına katkı sağlamıştır. Türk sanatı sahasının problemlerini çok yönlü bakış açısıyla çözmeye uğraşmıştır. Araştırmalarındaki detaycılığı ve nitelikli yayınları, onu Türk sanatının geleneksel sanatlar alanında önde gelen bilim insanı hâline getirmiştir.

Bu nedenle bu çalışma da sürekli bilginin peşinde koşan değerli bilim insanı Hatice Örcün Barışta’nın Türk sanatı ve düşünce dünyasına bırakmış olduğu izleri ortaya çıkarmak ve onu anlayabilmek amacıyla kaleme alınmıştır.
-ARAK/-EREK, -A…-A, -E…-E (-E…-A), -MADAN/-MEDEN, -MAKSIZIN/-MEKSİZİN, -CASINA/-CESİNE ZARF-FİİL EKLERİNİN TÜRKÇEDEN RUSÇAYA ÇEVİRİSİ
Authors: YILMAZ Murat
Published: November 2022

Bu çalışmanın amacı, Türkçedeki zarf-fiil yapılarını anlatmak, bunları Rusçadaki zarf-fiil yapılarıyla karşılaştırarak benzerliklerini ve farklılıklarını ortaya çıkarmak, konuya çeviri temelinde yaklaşmaktır. Bu konunun çeviribilim açısından pek fazla incelenmemiş olması çalışmanın yapılmasını gerekli kılmıştır. Özellikle Türkçeden Rusçaya çeviride çokça karşımıza çıkan zarf-fiil yapılarının Rusçaya aktarımında ortaya çıkan sorunların çözümüne yönelik konu ele alınmış buna yönelik çözümler sunulmuştur. Her dilin kendine özgü yapıda olması bunu hedef dile çevirirken bazı zorlukların ortaya çıkmasına neden olmaktadır. Çeviri esnasında kaynak ve hedef dillerin gramer, stilistik ve semantik yapılarının incelenerek nasıl bir yol izlenmesi gerektiği burada ayrıca vurgulanmaktadır. Türkçe ve Rusçanın farklı dil ailelerine mensup olması kendilerine özgü kurallarda çeşitliliğe neden olmaktadır. Bundan dolayı her iki dilin dilsel özelliklerini göz önünde bulundurarak belirlenen zarf-fiillerin Rusçaya çevirisinde izlenmesi gereken yol anlatılmaktadır. Bu yapıların Rusçadaki eşdeğerlilikleri analiz edilmektedir. Bu çalışmanın amaçlarından biri de Rusçayı yabancı bir dil olarak öğrenen öğrenciler başta olmak üzere herkese Türkçedeki gramer yapılarının Rusçaya çevirisinde izlenmesi gereken yolları göstermek ve anlatmaktır.
DİJİTALLEŞEN DÜNYADA MEDYANIN DÖNÜŞÜMÜ: GELENEKSEL MEDYADAN YENİ MEDYAYA GEÇİŞ VE TÜRKİYE’DE İNTERNET HABERCİLİĞİ
Authors: BENDAŞ Kadır
Published: November 2022

Günümüzde dijitalleşmeyle birlikte kitle iletişim araçlarının işleyişinde meydana gelen değişikliklerin altında yatan temel neden teknolojideki yeni gelişmeler ve özellikle internet kullanımının tüm dünyada artmasıdır. Haberin okuyucuya veya izleyiciye iletilmesinde geçmişte internet haberciliği alternatif bir iletişim aracı olmaktayken günümüzde bu durum değişmiş ve insanlar artık haberi ve bilgiyi en hızlı bir şekilde internet sayesinde elde edebilecek duruma gelmiştir. Türkiye’de de son yıllarda bu alanda kayda değer gelişmeler yaşanmıştır. Yapılan bu çalışmayla iletişim teknolojilerinde meydana gelen gelişmelere paralel olarak insanların haber izleme alışkanlıklarının geleneksel medyadan neden yeni medyaya kaymasının ardındaki gerekçeler ve Türkiye’de son yıllarda internet haberciliği alanındaki gelişmeler irdelenmektedir. Türkiye’de geleneksel medyadan yeni medyaya geçiş ve internet haberciliğinin gelişimi 2000’li yılların başından itibaren hızla artmaya başladığı için örneklem olarak 2000 yılından günümüze kadar olan süreç betimsel bir yaklaşımla değerlendirmeye alınmıştır. Yapılan çalışma sonucunda internetin ve internet haberciliğinin dünyada ve Türkiye’de alternatif bir kaynak olmaktan çıkarak asıl bilgi kaynağına dönüştükleri anlaşılmıştır.
GAZETECİ FERİDUN KANDEMİR’İN AŞKALE GÖZLEMLERİ
Authors: TOSUN Ulvi Ufuk
Published: November 2022

Feridun Kandemir, gazeteci ve yazardır. Gerek Millî Mücadele Dönemi’nde ve gerekse Cumhuriyet kurulduktan sonra aktif şekilde basın hayatının içerisinde yer almıştır.

11 Kasım 1942’de Varlık Vergisi Kanunu çıkarılmıştır. Bu Kanun’un icrasında, vergisini ödemeyen bir kısım gayrimüslim mükellef, zorunlu çalışma uygulamasına tabi tutulmuştur. Söz konusu bu mükellefler, zorunlu çalışma yeri olarak ilk önce Erzurum’un Aşkale ilçesine sevk edilmiştir. Tasviri Efkâr gazetesi muhabiri Feridun Kandemir de onlarla birlikte 30 Ocak 1943 tarihinde Aşkale’ye gelmiştir. Kandemir, Aşkale’de sözü edilen mükelleflerin yaşamlarını gözlemleyerek bunları Tasviri Efkâr gazetesinde yayımlamıştır. Bu gözlemlerin önemli bir kısmı da o günkü Aşkale ile ilgilidir. Kandemir, yazılarında Aşkale’nin iklimi, çevresel özellikleri, burada çalışan bir kısım devlet görevlilerinin isimleri gerek ilçe halkından gerekse mükelleflerin kaldıkları Pırnakapan köyünden bazı vatandaşlar ile kendi arasında geçen ilginç diyaloglar gibi farklı farklı konulardan söz etmiştir. Kandemir’in burada hem mükellefler hem de ilçe hakkında yaptığı gözlemleri, Tasviri Efkâr gazetesinde yayımlanmıştır.

Bu çalışmada, Tasviri Efkâr gazetesi muhabiri Feridun Kandemir’in Aşkale hakkındaki gözlemleri üzerinde odaklaşılarak bir gazetecinin gözünden ilçenin o günkü tarihine bir nebze projektör tutulmak istenmiştir.
Macera Rekreasyonunda Heyecan Arayışı ve Serbest Zaman Doyumu Arasındaki İlişkinin İncelenmesi: Çok Hafif Hava Araçları (ÇHHA) Pilot Örneği
Authors: Beşikçi Tolga , Dinç Sırrı Cem
Published: November 2022

Bu araştırmanın amacı, maceraya dayalı hava sporlarından olan Yamaç Paraşütü, Yelken Kanat, Planör gibi Çok Hafif Hava Araçlarını (ÇHHA) kullanan pilotların heyecan arama düzeylerinin belirlenmesi ve serbest zaman doyumu ile arasındaki ilişkisinin incelenmesidir. Araştırmanın evrenini Türkiye’ de ÇHHA pilotluğuyla ilgilenen bireyler oluşturmaktadır. Örneklem grubunu ise yaşları 18 ila 67 yaş arası değişkenlik gösteren 118 kadın, 488 erkek katılımcı olmak üzere toplam 606 ÇHHA pilotu oluşturmaktadır. Katılımcılar hava sporları ile ilgili THK onaylı kuruluşlar, üniversite kulüpleri, özel eğitim veren okullar, hava sporları ile ilgili forum, blog ve internet üzerinden oluşturulan gruplara kayıtlı üyeler arasından olasılıklı örnekleme tekniklerinden basit tesadüfi örnekleme yöntemiyle seçilmiştir. Araştırmada veri toplama araçları olarak araştırmacılar tarafından hazırlanan kişisel bilgi formu ve Zuckerman (1994) tarafından geliştirilen Heyecan Arama Ölçeği (HAÖ) ile Beard ve Ragheb (1980) tarafından geliştirilen Serbest Zaman Doyum Ölçeği (SZDÖ) kullanılmıştır. Veri analizinde öncelikle tanımlayıcı istatistik ve frekans analizleri yapılmıştır. “Levene” değerleri incelenerek varyansların homojenliği doğrulanmış daha sonra “bağımsız örneklem t testi” ve “tek yönlü varyans analizi” (ANOVA) uygulanmıştır. “Doğrusal regresyon analizi” ile ölçekler arasındaki etki test edilmiştir. Elde edilen bulgular doğrultusunda, pilotların heyecan arama düzeyleri ve serbest zaman doyumlarına bağlı olarak cinsiyet, yaş, medeni durum, eğitim durumu ve gelir seviyesi değişkenlerinde anlamlı farklılıklar bulunmuştur. Doğrusal regresyon analizi sonucunda heyecan aramanın (β=.12, t=3.24, p=.00) serbest zaman doyumunu olumlu yönde etkilediği sonucuna varılmıştır.
Current Management of Adult Acute Lymphoblastic Leukaemia: Emerging Insights and Outstanding Questions
Authors: Thomas Xavier , Le Jeune Caroline
Published: November 2022

Less than 50% of patients with adult acute lymphoblastic leukaemia (ALL) experience long-term survival and for those adults >60 years old, long-term survival rates are only 10%. However, significant advances have been reported over the last decade. Both the efficacy of chemotherapy and the safety of transplants have improved. Improved outcomes have been seen in younger adults treated with paediatric-inspired chemotherapy regimens. Minimal residual disease has been identified as an independent predictor of relapse risk and is currently widely used for risk-adapted treatment. Newly developed targeted therapies have been developed to improve treatment outcomes. Tyrosine kinase inhibitors (TKI) have become an integral part of front-line therapy for Philadelphia (Ph) chromosome positive ALL. Ph-positive ALL serves as the first example of truly targeted treatment, although the choice of the most effective TKI is not yet settled. The last few years have also seen a surge in immune therapies for B cell lineage ALL. The success of the anti-CD20 monoclonal antibody rituximab provided proof-of-principle for exploiting the immune system therapeutically. Novel immune therapies recruit (bispecific T cell engager) or modify (chimeric antigen receptor T cells) the patient’s own T cells to fight leukaemic cells. These new approaches led us to predict that ALL therapy might be based heavily on non-chemotherapeutic approaches in the near future. The role of allogeneic stem cell transplantation is also increasingly called into question. Herein, we review the background and development of these distinct treatments, and assess the current clinical knowledge of their efficacy and safety.
Hepatitis B Care Pathway in the United Arab Emirates: Current Situation, Gaps, and Actions
Authors: Al Zaabi Mohamed , Al Quraishi Huda , Al Rifai Ahmad , Abdelaziz Moustafa , Mansour Eid , Snehanshu Snehanshu , Bassil Nathalie , Kozma Sam , Taha Mazen
Published: November 2022

Introduction: Hepatitis B virus (HBV) infection remains a worldwide public health problem. The last major review of the epidemiology and management of HBV in the Middle East was published in 2011. This paper aims to assess the current situation of the HBV care pathway in the United Arab Emirates (UAE), identify gaps in our knowledge and barriers therein, and recommend initiatives to be taken to improve the management of such patients.

Methods: A literature search was conducted in PubMed as well as through free internet searches. Interviews and group discussions were held with key opinion leaders and HBV experts.

Results: The national prevalence of HBV is estimated to be approximately 1.0–1.5%; however, prevalence is expected to be higher in those >25 years of age born before the introduction of the HBV vaccination programme. There is limited data on the burden of HBV-related hepatocellular carcinoma in the country.

Discussion: Awareness of various aspects of the disease is perceived to be low among the general population and medium among healthcare providers. There are several mandated national screening structures present; however, there are no country-specific HBV guidelines regarding diagnosis, linkage-to-care, treatment, and follow-up. Improvements have been made in the past 30 years in the UAE, evident through a decline in prevalence. The burden attributable to HBV complication and the coverage of screening and treatment remain unclear.

Conclusion: Key stakeholders in all areas of the HBV care pathway must reduce morbidity and
mortality in the UAE population, and interventions should be supported by research.
Protesting is Not Everything: Analyzing Twitter Use During Electoral Events in Non-democratic Contexts
Authors: Kermani Hossein , Rasouli Fatemeh
Published: November 2022

Despite the fact that during political protests, Twitter usage has been substantially studied in various contexts, there are still some significant gaps in our understanding of the ways that this microblogging network is employed in regular political happenings, e.g., elections, particularly in authoritarian countries. As a result, it remains unclear if citizens in non-democratic countries use Twitter to protest at the time of regular political events as the time of uprisings or not. This investigation tries to address this gap by providing some empirical evidence from the Iranian Twittersphere during the 2017 presidential election. Having employed networked framing theory, we combined textual and network analytic approaches to investigate a sample of 10,416 tweets of the most influential users in the retweet (RT) network. Findings demonstrate that Iranian users did not significantly challenge the regime and power relations in Iran. They framed the election in a non-critical way dealing with routine political and election frays and debates. They also preferred to attack politicians rather than discuss contentious and deliberate politics. Thus, this research reveals that Twitter is not always a tool for protesting against non-democratic regimes. At the time of electoral events, it could be used as an ordinary communication platform.
Bregman iterative regularization using model functions for nonconvex nonsmooth optimization
Authors: Yang Haoxing , Zhang Hui , Wang Hongxia , Cheng Lizhi
Published: November 2022

In this paper, we propose a new algorithm called ModelBI by blending the Bregman iterative regularization method and the model function technique for solving a class of nonconvex nonsmooth optimization problems. On one hand, we use the model function technique, which is essentially a first-order approximation to the objective function, to go beyond the traditional Lipschitz gradient continuity. On the other hand, we use the Bregman iterative regularization to generate solutions fitting certain structures. Theoretically, we show the global convergence of the proposed algorithm with the help of the Kurdyka-Łojasiewicz property. Finally, we consider two kinds of nonsmooth phase retrieval problems and propose an explicit iteration scheme. Numerical results verify the global convergence and illustrate the potential of our proposed algorithm.
Microbial detoxification of lignocellulosic biomass hydrolysates: Biochemical and molecular aspects, challenges, exploits and future perspectives
Authors: Ujor Victor C. , Okonkwo Christopher C.
Published: November 2022

Valorization of lignocellulosic biomass (LB) has the potential to secure sustainable energy production without impacting food insecurity, whist relieving over reliance on finite fossil fuels. Agro-derived lignocellulosic residues such as wheat straw, switchgrass, rice bran, and miscanthus have gained relevance as feedstocks for the production of biofuels and chemicals. However, the microorganisms employed in fermentative conversion of carbohydrates to fuels and chemicals are unable to efficiently utilize the sugars derived from LB due to co-production of lignocellulose-derived microbial inhibitory compounds (LDMICs) during LB pretreatment. LDMICs impact microbial growth by inhibition of specific enzymes, cause DNA and cell membrane damage, and elicit cellular redox imbalance. Over the past decade, success has been achieved with the removal of LDMICs prior to fermentation. However, LDMICs removal by chemical processes is often accompanied by sugar losses, which negatively impacts the overall production cost. Hence, in situ removal of LDMICs by fermentative organisms during the fermentation process has garnered considerable attention as the “go-to” approach for economical LDMICs detoxification and bio-chemicals production. In situ removal of LDMICs has been pursued by either engineering more robust biocatalysts or isolating novel microbial strains with the inherent capacity to mineralize or detoxify LDMICs to less toxic compounds. While some success has been made along this line, efficient detoxification and robust production of target bio-chemicals in lignocellulosic hydrolysates (LHs) under largely anaerobic fermentative conditions remains a lingering challenge. Consequently, LB remains an underutilized substrate for bio-chemicals production. In this review, the impact of microbial LH detoxification on overall target molecule production is discussed. Further, the biochemical pathways and mechanisms employed for in situ microbial detoxification of furanic LDMICs [e.g., furfural and 5-hydroxymethylfurfural (HMF)] and phenolic LDMICs (e.g., syringaldehyde, p-coumaric acid, 4-hydroxybenzaldehyde, vanillin, and ferulic acid) are discussed. More importantly, metabolic engineering strategies for the development of LDMIC-tolerant and bio-chemicals overproducing strains and processes are highlighted.
The application of mechanobiotechnology for immuno-engineering and cancer immunotherapy
Authors: Yoon Chi Woo , Pan Yijia , Wang Yingxiao
Published: November 2022

Immune-engineering is a rapidly emerging field in the past few years, as immunotherapy evolved from a paradigm-shifting therapeutic approach for cancer treatment to promising immuno-oncology models in clinical trials and commercial products. Linking the field of biomedical engineering with immunology, immuno-engineering applies engineering principles and utilizes synthetic biology tools to study and control the immune system for diseases treatments and interventions. Over the past decades, there has been a deeper understanding that mechanical forces play crucial roles in regulating immune cells at different stages from antigen recognition to actual killing, which suggests potential opportunities to design and tailor mechanobiology tools to novel immunotherapy. In this review, we first provide a brief introduction to recent technological and scientific advances in mechanobiology for immune cells. Different strategies for immuno-engineering are then discussed and evaluated. Furthermore, we describe the opportunities and challenges of applying mechanobiology and related technologies to study and engineer immune cells and ultimately modulate their function for immunotherapy. In summary, the synergetic integration of cutting-edge mechanical biology techniques into immune-engineering strategies can provide a powerful platform and allow new directions for the field of immunotherapy.
How to fulfill the expert role in public dialogue: The Dutch dialogue on human germline genetic modification as a case
Authors: Reincke Cathelijne M. , Bredenoord Annelien L. , van Baalen Sophie , van Mil Marc H. W.
Published: November 2022

Over the last decades science communication theory appears to have evolved at a much faster pace than science communication practice. Scientists seem willing to step into the public domain, but a genuine two-way interaction with the public is only rarely observed. We argue that part of this discrepancy between theory and practice may actually be caused by the lacking of a clear description of the modern expert role; the role a scientist should take in contemporary science communication. In this contribution we use an example of good practice—the Dutch dialogue on human germline genetic modification—to inform theory. We analyse guiding principles for the design and execution of this dialogue and observe expert behavior in three separate dialogue sessions. With the combined findings, we present a detailed description of the modern expert role in terms of three responsibilities, with for each responsibility three prompts for behavior. For the responsibility to share these are to select expert knowledge that is relevant to the goal; to present expert knowledge in a meaningful and accessible language; and to be cautious in sharing personal considerations. For the responsibility to listen and learn these are to consider interactions with members of the public as opportunities to learn; to be patient and supportive; and to assist in stimulating in-depth dialogue. For the responsibility to invest in relationships these are to assist in creating an ambiance of safety and relevance; to preserve trust; and to convey respect for every contribution and every point of view. Each behavioral prompt is further concretized with concomitant actions and practice examples as collected from observing experts in action. The implications for scientists engaging in contemporary science communication, as well as for science communication trainers, are discussed.
Protein engineering of amine transaminases
Authors: Meng Qinglong , Ramírez-Palacios Carlos , Wijma Hein J. , Janssen Dick B.
Published: November 2022

Protein engineering is a powerful and widely applied tool for tailoring enzyme properties to meet application-specific requirements. An attractive group of biocatalysts are PLP-dependent amine transaminases which are capable of converting prochiral ketones to the corresponding chiral amines by asymmetric catalysis. The enzymes often display high enantioselectivity and accept various amine donors. Practical applications of these amine transaminases can be hampered by enzyme instability and by their limited substrate scope. Various strategies to improve robustness of amine transaminases and to redirect their substrate specificity have been explored, including directed evolution, rational design and computation-supported engineering. The approaches used and results obtained are reviewed in this paper, showing that different strategies can be used in a complementary manner and can expand the applicability of amine transaminases in biocatalysis.
Takotsubo cardiomyopathy Afatinib-related in a non-small cell lung cancer patient: Case report
Authors: Ramos German E. , Caglevic Christian , Bulnes Juan F. , Panay Sergio E. , Zapata Mario I. , Daniele Andrés J. , Rodríguez Manuel E.
Published: November 2022

Endothelial Growth Factor Receptor (EGFR) mutations are frequently found among NSCLC patients. Second-generation Tyrosine Kinase Inhibitor (TKI) Afatinib is frequently used in this population of patients achieving better results than cytotoxic chemotherapy in terms of survival and progression. Afatinib-related cardiotoxicity has been rarely reported. Here we comment on a clinical case of a Takotsubo Cardiomyopathy Afatinib-induced in an NSCLC patient.
Geophysical data fusion of ground-penetrating radar and magnetic datasets using 2D wavelet transform and singular value decomposition
Authors: Oliveira Rui Jorge , Caldeira Bento , Teixidó Teresa , Borges José Fernando , Bezzeghoud Mourad
Published: November 2022

This work addresses the problem of the lack of perceptibility that geophysical data may have. Data fusion allows us to combine datasets, providing an improved and more informative source of information about structures buried in the ground. After testing different approaches, a strategy was developed using ground-penetrating radar and magnetic datasets collected over the same area. Data collected at the Roman Villa of Pisões (Beja, Portugal), which is a place of easy application of geophysical methods, were used to test the method, but with problems caused by the properties of the soil. The approach was based on processing operations that allow the fusion of images obtained by different equipment widely used in medical imaging for tumor detection and image processing. The goal is to create an improved image with data fusion that has higher quality than the input images, allowing a better understanding of the object of the study. The approach is composed of two stages: pre-processing and data fusion. Pre-processing is applied to enhance the input data. It consists of removing background noise through singular value decomposition applied in the spectral domain. Then the calculation of the data entropy will highlight the differences corresponding to the spatial alignments compatible with buried structures. Then, both entropy maps of the two datasets are fused in the second processing step to produce the final image. This step involves applying the 2D wavelet transform to each entropy map, decomposing them into sub-bands. Algorithms to calculate multiresolution singular value decomposition and the image gradient are applied to the sub-bands. The processed sub-band pairs are then fused using specific fusion rules. The fused image is obtained by applying the inverse of the wavelet transform. Data fusion with the proposed approach allows us to obtain a detailed image that is sharper and of better quality than the input datasets. The increase in sharpness and quality can be quantified through the sharpness index and the BRISQUE quality index in several steps of the processing. The obtained values confirm the graphical results. Images produced by the proposed data fusion approach suggest that the perceptibility has increased, allowing us to provide conclusions about the existence of buried structures.
Spatio-temporal evolution of ground motion intensity caused by reservoir-induced seismicity at the Pertusillo artificial lake (southern Italy)
Authors: Picozzi Matteo , Serlenga Vincenzo , Stabile Tony Alfredo
Published: November 2022

We investigate the spatiotemporal evolution of ground motion caused by reservoir-induced seismicity at the Pertusillo artificial lake in southern Italy. The area has a strong seismogenic potential, having been affected in the past by the 1857, Mw 7.0 Basilicata earthquake. We consider ∼1,000 microearthquakes that occurred from 2001 to 2018 and were recorded by a local network of nine seismic stations. The ground motion intensity associated with microseismicity allows us to identify two periods, each lasting approximately 2 years. They are characterized by a high rate of events but exhibit different source properties and spatial distributions. In the first period, the seismicity is spatially clustered close to the lake, on faults with different orientations and kinematics. In the second period, the seismicity is distributed along the Monti della Maddalena faults. Comparing the ground motion intensities of the two periods, we observe that events that occurred in the first period are associated with higher stress levels than others, in agreement with the b-values of the respective frequency-magnitude distributions. We compare the temporal evolution of the ground motion intensity with the rainfall and water levels measured at the artificial lake, as well as with the discharge of a ∼80 km distant spring, which is strictly controlled by climate trends. The results provide information about the regional processes acting on the southern Apennines. Our results show that the microseismicity is clearly associated with the Pertusillo artificial lake in the first period, whereas in the second period is a result of a combination of local effects due to water table oscillations of the lake itself, regional tectonics, and the poroelastic and elastic phenomena associated with carbonate rocks hosting aquifers.
The role of Nrf2 in periodontal disease by regulating lipid peroxidation, inflammation and apoptosis
Authors: Ma Fengyu , Luo Shangdie , Lu Chunting , Jiang Xinrong , Chen Kexiao , Deng Jianwen , Ma Shuyuan , Li Zejian
Published: November 2022

Nuclear factor E2-related factor 2(Nrf2) is a transcription factor that mainly regulates oxidative stress in the body. It initiates the expression of several downstream antioxidants, anti-inflammatory proteins and detoxification enzymes through the Kelch-like ECH-associating protein 1 (Keap1) -nuclear factor E2-related factor 2(Nrf2) -antioxidant response element (ARE) signaling pathway. Its anti-apoptosis, anti-oxidative stress and anti-inflammatory effects have gradually become the focus of periodontal disease research in recent years. In this paper, the structure and function of Nrf2 pathway and its mechanism of action in the treatment of periodontitis in recent years were analyzed and summarized, so as to further clarify the relationship between Nrf2 pathway and oxidative stress in the occurrence and development of periodontitis, and to provide ideas for the development of new treatment drugs targeting Nrf2 pathway.
AnnotaPipeline: An integrated tool to annotate eukaryotic proteins using multi-omics data
Authors: Maia Guilherme Augusto , Filho Vilmar Benetti , Kawagoe Eric Kazuo , Teixeira Soratto Tatiany Aparecida , Moreira Renato Simões , Grisard Edmundo Carlos , Wagner Glauber
Published: November 2022

Assignment of gene function has been a crucial, laborious, and time-consuming step in genomics. Due to a variety of sequencing platforms that generates increasing amounts of data, manual annotation is no longer feasible. Thus, the need for an integrated, automated pipeline allowing the use of experimental data towards validation of in silico prediction of gene function is of utmost relevance. Here, we present a computational workflow named AnnotaPipeline that integrates distinct software and data types on a proteogenomic approach to annotate and validate predicted features in genomic sequences. Based on FASTA (i) nucleotide or (ii) protein sequences or (iii) structural annotation files (GFF3), users can input FASTQ RNA-seq data, MS/MS data from mzXML or similar formats, as the pipeline uses both transcriptomic and proteomic information to corroborate annotations and validate gene prediction, providing transcription and expression evidence for functional annotation. Reannotation of the available Arabidopsis thaliana, Caenorhabditis elegans, Candida albicans, Trypanosoma cruzi, and Trypanosoma rangeli genomes was performed using the AnnotaPipeline, resulting in a higher proportion of annotated proteins and a reduced proportion of hypothetical proteins when compared to the annotations publicly available for these organisms. AnnotaPipeline is a Unix-based pipeline developed using Python and is available at: https://github.com/bioinformatics-ufsc/AnnotaPipeline.
Novel insight of N6-methyladenosine modified subtypes in abdominal aortic aneurysm
Authors: Wang Kangjie , Kan Qinghui , Ye Yanchen , Qiu Jiachong , Huang Lin , Wu Ridong , Yao Chen
Published: November 2022

Background: N6-methyladenosine (m6A) is the most prevalent non-cap reversible modification present in messenger RNAs and long non-coding RNAs, and its dysregulation has been linked to multiple cardiovascular diseases, including cardiac hypertrophy and atherosclerosis. Although limited studies have suggested that m6A modification contributes to abdominal aortic aneurysm (AAA) development, the full landscape of m6A regulators that mediate modification patterns has not been revealed.

Methods: To distinguish the m6A methylation subtypes in AAA patients, an unsupervised clustering method was carried out, based on the mRNA levels of 17 m6A methylation regulators. Differentially expressed genes were identified by comparing clusters. An m6Ascore model was calculated using principal component analysis and structured to assess the m6A methylation patterns of single samples. Subsequently, the relationship between the m6Ascore and immune cells and the hallmark gene set was analyzed. Finally, pairs of circRNA-m6A regulators and m6A regulators-m6A related genes were used to establish a network.

Results: We identified three m6A methylation subtypes in the AAA samples. The m6Acluster A and C were characterized as more immunologically activated because of the higher abundance of immune cells than that in m6Acluster B. The m6Acluster B was less enriched in inflammatory pathways and more prevalent in pathways related to extracellular matrix stability. Subsequently, we divided the individual samples into two groups according to the m6Ascore, which suggested that a high m6Ascore predicted more active inflammatory pathways and higher inflammatory cell infiltration. A network consisting of 9 m6A regulators and 37 circRNAs was constructed.

Conclusion: This work highlighted that m6A methylation modification was highly correlated with immune infiltration of AAA, which may promote the progression of AAA. We constructed an individualized m6Ascore model to provide evidence for individualized treatments in the future.
Shared genetic mechanism between type 2 diabetes and COVID-19 using pathway-based association analysis
Authors: Wu Kevin Chun Hei , He Qian , Bennett Adam N. , Li Jie , Chan Kei Hang Katie
Published: November 2022

Recent studies have shown that, compared with healthy individuals, patients with type 2 diabetes (T2D) suffer a higher severity and mortality of COVID-19. When infected with this retrovirus, patients with T2D are more likely to face severe complications from cytokine storms and be admitted to high-dependency or intensive care units. Some COVID-19 patients are known to suffer from various forms of acute respiratory distress syndrome and have a higher mortality risk due to extreme activation of inflammatory cascades. Using a conditional false discovery rate statistical framework, an independent genome-wide association study data on individuals presenting with T2D (N = 62,892) and COVID-19 (N = 38,984) were analysed. Genome-wide association study data from 2,343,084 participants were analysed and a significant positive genetic correlation between T2D and COVID-19 was observed (T2D: r for genetic = 0.1511, p-value = 0.01). Overall, 2 SNPs (rs505922 and rs3924604) shared in common between T2D and COVID-19 were identified. Functional analyses indicated that the overlapping loci annotated into the ABO and NUS1 genes might be implicated in several key metabolic pathways. A pathway association analysis identified two common pathways within T2D and COVID-19 pathogenesis, including chemokines and their respective receptors. The gene identified from the pathway analysis (CCR2) was also found to be highly expressed in blood tissue via the GTEx database. To conclude, this study reveals that certain chemokines and their receptors, which are directly involved in the genesis of cytokine storms, may lead to exacerbated hyperinflammation in T2D patients infected by COVID-19.
Transcriptomic meta-analysis reveals unannotated long non-coding RNAs related to the immune response in sheep
Authors: Bilbao-Arribas Martin , Jugo Begoña M.
Published: November 2022

Long non-coding RNAs (lncRNAs) are involved in several biological processes, including the immune system response to pathogens and vaccines. The annotation and functional characterization of lncRNAs is more advanced in humans than in livestock species. Here, we take advantage of the increasing number of high-throughput functional experiments deposited in public databases in order to uniformly analyse, profile unannotated lncRNAs and integrate 422 ovine RNA-seq samples from the ovine immune system. We identified 12302 unannotated lncRNA genes with support from independent CAGE-seq and histone modification ChIP-seq assays. Unannotated lncRNAs showed low expression levels and sequence conservation across other mammal species. There were differences in expression levels depending on the genomic location-based lncRNA classification. Differential expression analyses between unstimulated and samples stimulated with pathogen infection or vaccination resulted in hundreds of lncRNAs with changed expression. Gene co-expression analyses revealed immune gene-enriched clusters associated with immune system activation and related to interferon signalling, antiviral response or endoplasmic reticulum stress. Besides, differential co-expression networks were constructed in order to find condition-specific relationships between coding genes and lncRNAs. Overall, using a diverse set of immune system samples and bioinformatic approaches we identify several ovine lncRNAs associated with the response to an external stimulus. These findings help in the improvement of the ovine lncRNA catalogue and provide sheep-specific evidence for the implication in the general immune response for several lncRNAs.
The mechanisms underlying the immune control of Zika virus infection at the maternal-fetal interface
Authors: Espino Ana , Gouilly Jordi , Chen Qian , Colin Philippe , Guerby Paul , Izopet Jacques , Amara Ali , Tabiasco Julie , Al-Daccak Reem , El Costa Hicham , Jabrane-Ferrat Nabila
Published: November 2022

Unlike other Flaviviruses, Zika virus (ZIKV) infection during the first trimester of pregnancy causes severe pregnancy outcomes including the devastating microcephaly and diseases associated with placental dysfunctions. We have previously reported that the maternal decidua basalis, the major maternal-fetal interface, serves as a replication platform enabling virus amplification before dissemination to the fetal compartment. However, the rate of congenital infection is quite low, suggesting the presence of a natural barrier against viral infection. Using primary cells from first-trimester pregnancy samples, we investigated in this study how the maternal decidua can interfere with ZIKV infection. Our study reveals that whether through their interactions with dNK cells, the main immune cell population of the first-trimester decidua, or their production of proinflammatory cytokines, decidual stromal cells (DSCs) are the main regulators of ZIKV infection during pregnancy. We also validate the functional role of AXL as a crucial receptor for ZIKV entry in DSCs and demonstrate that targeted inhibition of ligand-receptor interaction at the early stage of the infection is effective in drastically reducing virus pathogenesis at the maternal-fetal interface. Collectively, our results provide insights into the mechanisms through which ZIKV infection and spreading can be limited. The strategy of circumventing viral entry at the maternal-fetus interface limits virus dissemination to fetal tissues, thereby preventing congenital abnormalities.
IL-17A and TNF-α inhibitors induce multiple molecular changes in psoriasis
Authors: Dong Qiang , Li Dan , Xie Bi Bo , Hu Li Hua , Huang Jia , Jia Xiao Xiao , Tang Yan Li , Liu Gan Hong , Shen Ning Ning , Yu Xiao Bing
Published: November 2022

Adalimumab and secukinumab are commonly used for moderate to severe psoriasis vulgaris (PV). Although distinct individual responses to and impaired effectiveness of these biological agents occur occasionally, little is known about the underlying reasons. Here, we report a proteomic analysis of psoriatic lesions from patients treated with these drugs using data-independent acquisition mass spectrometry (DIA-MS). Thousands of differentially expressed proteins (DEPs) changed over 12 weeks of treatment. Network analysis showed that DEPs could interact and induce transformation in matrix components, metabolic regulation, and immune response. The results of parallel reaction monitoring (PRM) analysis suggested that S100s, STAT1, KRT2, TYMP, SOD2, HSP90AB1, TFRC, and COL5A1 were the most significantly changed proteins in both groups. There was a positive association between the Psoriasis Area and Severity Index (PASI) score and three proteins (TFRC, IMPDH2, KRT2). Our study findings suggest that inhibition of IL-17A and TNF-α can induce changes in multiple molecules in psoriatic lesions and have an overlapping influence on the immune response and process through direct or indirect effects.
Pediatric versus adult high grade glioma: Immunotherapeutic and genomic considerations
Authors: Aggarwal Payal , Luo Wen , Pehlivan Katherine C. , Hoang Hai , Rajappa Prajwal , Cripe Timothy P. , Cassady Kevin A. , Lee Dean A. , Cairo Mitchell S.
Published: November 2022

High grade gliomas are identified as malignant central nervous tumors that spread rapidly and have a universally poor prognosis. Historically high grade gliomas in the pediatric population have been treated similarly to adult high grade gliomas. For the first time, the most recent classification of central nervous system tumors by World Health Organization has divided adult from pediatric type diffuse high grade gliomas, underscoring the biologic differences between these tumors in different age groups. The objective of our review is to compare high grade gliomas in the adult versus pediatric patient populations, highlighting similarities and differences in epidemiology, etiology, pathogenesis and therapeutic approaches. High grade gliomas in adults versus children have varying clinical presentations, molecular biology background, and response to chemotherapy, as well as unique molecular targets. However, increasing evidence show that they both respond to recently developed immunotherapies. This review summarizes the distinctions and commonalities between the two in disease pathogenesis and response to therapeutic interventions with a focus on immunotherapy.
Innate and adaptive immune response in SARS-CoV-2 infection-Current perspectives
Authors: Zhu Qiugang , Xu Yan , Wang Ting , Xie Feiting
Published: November 2022

Coronavirus disease 2019 (COVID-19) has been a global pandemic, caused by a novel coronavirus strain with strong infectivity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the in-depth research, the close relationship between COVID-19 and immune system has been dug out. During the infection, macrophages, dendritic cells, natural killer cells, CD8+ T cells, Th1, Th17, Tfh cells and effector B cells are all involved in the anti-SARS-CoV-2 responses, however, the dysfunctional immune responses will ultimately lead to the excessive inflammation, acute lung injury, even other organ failure. Thus, a detailed understanding of pertinent immune response during COVID-19 will provide insights in predicting disease outcomes and developing appropriate therapeutic approaches. In this review, we mainly clarify the role of immune cells in COVID-19 and the target-vaccine development and treatment.
A novel signature based on CeRNA and immune status predicts prognostic risk and drug sensitivity in gastric cancer patients
Authors: Cao Wei , Zhou Weiguo , Li Mengying , Zhang Zehua , Zhang Xun , Yang Kang , Yang Shiyi , Cao Guodong , Chen Bo , Xiong Maoming
Published: November 2022

Background

At present, there is increasing evidence that both competitive endogenous RNAs (ceRNAs) and immune status in the tumor microenvironment (TME) can affect the progression of gastric cancer (GC), and are closely related to the prognosis of patients. However, few studies have linked the two to jointly determine the prognosis of patients with GC. This study aimed to develop a combined prognostic model based on ceRNAs and immune biomarkers.

Methods

First, the gene expression profiles and clinical information were downloaded from TCGA and GEO databases. Then two ceRNA networks were constructed on the basis of circRNA. Afterwards, the key genes were screened by univariate Cox regression analysis and Lasso regression analysis, and the ceRNA-related prognostic model was constructed by multivariate Cox regression analysis. Next, CIBERSORT and ESTIMATE algorithms were utilized to obtain the immune cell infiltration abundance and stromal/immune score in TME. Furthermore, the correlation between ceRNAs and immunity was found out through co-expression analysis, and another immune-related prognosis model was established. Finally, combining these two models, a comprehensive prognostic model was built and visualized with a nomogram.

Results

The (circRNA, lncRNA)-miRNA-mRNA regulatory network of GC was constructed. The predictive power of ceRNA-related and immune-related prognosis models was moderate. Co-expression analysis showed that the ceRNA network was correlated with immunity. The integrated model of combined ceRNAs and immunity in the TCGA training set, the AUC values of 1, 3, and 5-year survival rates were 0.78, 0.76, and 0.78, respectively; in the independent external validation set GSE62254, they were 0.81, 0.79, and 0.78 respectively; in GSE15459, they were 0.84, 0.88 and 0.89 respectively. Besides, the prognostic score of the comprehensive model can predict chemotherapeutic drug resistance. Moreover, we found that plasma variant translocation 1 (PVT1) and infiltrating immune cells (mast cells) are worthy of further investigation as independent prognostic factors.

Conclusions

Two ceRNA regulatory networks were constructed based on circRNA. At the same time, a comprehensive prognosis model was established, which has a high clinical significance for prognosis prediction and chemotherapy drug selection of GC patients.
Epigenetic therapy reprograms M2-type tumor-associated macrophages into an M1-like phenotype by upregulating miR-7083-5p
Authors: Vadevoo Sri Murugan Poongkavithai , Gunassekaran Gowri Rangaswamy , Yoo Jae Do , Kwon Tae-Hwan , Hur Keun , Chae Sehyun , Lee Byungheon
Published: November 2022

Reprogramming M2-type, pro-tumoral tumor-associated macrophages (TAMs) into M1-type, anti-tumoral macrophages is a key strategy in cancer therapy. In this study, we exploited epigenetic therapy using the DNA methylation inhibitor 5-aza-2’-deoxycytidine (5-aza-dC) and the histone deacetylation inhibitor trichostatin A (TSA), to reprogram M2-type macrophages into an M1-like phenotype. Treatment of M2-type macrophages with the combination of 5-aza-dC and TSA decreased the levels of M2 macrophage cytokines while increasing those of M1 macrophage cytokines, as compared to the use of either therapy alone. Conditioned medium of M2 macrophages treated with the combination of 5-aza-dC and TSA sensitized the tumor cells to paclitaxel. Moreover, treatment with the combination inhibited tumor growth and improved anti-tumor immunity in the tumor microenvironment. Depletion of macrophages reduced the anti-tumor growth activity of the combination therapy. Profiling of miRNAs revealed that the expression of miR-7083-5p was remarkably upregulated in M2 macrophages, following treatment with 5-aza-dC and TSA. Transfection of miR-7083-5p reprogrammed the M2-type macrophages towards an M1-like phenotype, and adoptive transfer of M2 macrophages pre-treated with miR-7083-5p into mice inhibited tumor growth. miR-7083-5p inhibited the expression of colony-stimulating factor 2 receptor alpha and CD43 as candidate targets. These results show that epigenetic therapy upon treatment with the combination of 5-aza-dC and TSA skews M2-type TAMs towards the M1-like phenotype by upregulating miR-7083-5p, which contributes to the inhibition of tumor growth.
Modeling-informed Engineered Genetic Incompatibility strategies to overcome resistance in the invasive Drosophila suzukii
Authors: Sychla Adam , Feltman Nathan R. , Hutchison William D. , Smanski Michael J.
Published: November 2022

Engineered Genetic Incompatibility (EGI) is an engineered extreme underdominance genetic system wherein hybrid animals are not viable, functioning as a synthetic speciation event. There are several strategies in which EGI could be leveraged for genetic biocontrol of pest populations. We used an agent-based model of Drosophila suzukii (Spotted Wing Drosophila) to determine how EGI would fare with high rates of endemic genetic resistance alleles. We discovered a surprising failure mode wherein field-generated females convert an incompatible male release program into a population replacement gene drive. Local suppression could still be attained in two seasons by tailoring the release strategy to take advantage of this effect, or alternatively in one season by altering the genetic design of release agents. We show in this work that data from modeling can be utilized to recognize unexpected emergent phenomena and a priori inform genetic biocontrol treatment design to increase efficacy.