bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced IFN Sensing by Aggressive Chronic Lymphocytic Leukemia Cells
Authors: Luo Tina YuXuan , Shi Yonghong , Wang Guizhi , Spaner David E 
Published: October 2022

Abstract
Type I IFN is made by cells in response to stress. Cancer cells exist in a state of stress, but their IFN response is complex and not completely understood. This study investigated the role of autocrine IFN in human chronic lymphocytic leukemia (CLL) cells. CLL cells were found to make low amounts of IFN via TANK-binding kinase 1 pathways, but p-STAT1 and -STAT2 proteins along with IFN-stimulated genes that reflect IFN activation were variably downregulated in cultured CLL cells by the neutralizing IFNAR1 Ab anifrolumab. Patients with CLL were segregated into two groups based on the response of their leukemia cells to anifrolumab. Samples associated with more aggressive clinical behavior indicated by unmutated IGHV genes along with high CD38 and p-Bruton’s tyrosine kinase expression exhibited responses to low amounts of IFN that were blocked by anifrolumab. Samples with more indolent behavior were unaffected by anifrolumab. Hypersensitivity to IFN was associated with higher expression of IFNAR1, MX1, STAT1, and STAT2 proteins and lower activity of negative regulatory tyrosine phosphatases. Autocrine IFN protected responsive CLL cells from stressful tissue culture environments and therapeutic drugs such as ibrutinib and venetoclax in vitro, in part by upregulating Mcl-1 expression. These findings suggest hypersensitivity to IFN may promote aggressive clinical behavior. Specific blockade of IFN signaling may improve outcomes for patients with CLL with higher-risk disease.
RNF186/EPHB2 Axis Is Essential in Regulating TNF Signaling for Colorectal Tumorigenesis in Colorectal Epithelial Cells
Authors: Zhang Huazhi , Cui Zhihui , Pan Ting , Hu Huijun , He Ruirui , Yi Ming , Sun Wanwei , Gao Ru , Wang Heping , Ma Xiaojian , Peng Qianwen , Feng Xiong , Liang Shuyan , Du Yanyun , Wang Chenhui 
Published: October 2022

Abstract
The receptor tyrosine kinase EPHB2 (EPH receptor B2) is highly expressed in many human cancer types, especially in gastrointestinal cancers, such as colorectal cancer. Several coding mutations of the EPHB2 gene have been identified in many cancer types, suggesting that EPHB2 plays a critical role in carcinogenesis. However, the exact functional mechanism of EPHB2 in carcinogenesis remains unknown. In this study, we find that EPHB2 is required for TNF-induced signaling activation and proinflammatory cytokine production in colorectal epithelial cells. Mechanistically, after TNF stimulation, EPHB2 is ubiquitinated by its E3 ligase RNF186. Then, ubiquitinated EPHB2 recruits and further phosphorylates TAB2 at nine tyrosine sites, which is a critical step for the binding between TAB2 and TAK1. Due to defects in TNF signaling in RNF186-knockout colorectal epithelial cells, the phenotype of colitis-propelled colorectal cancer model in RNF186-knockout mice is significantly reduced compared with that in wild-type control mice. Moreover, we find that a genetic mutation in EPHB2 identified in a family with colorectal cancer is a gain-of-function mutation that promoted TNF signaling activation compared with wild-type EPHB2. We provide evidence that the EPHB2-RNF186-TAB2-TAK1 signaling cascade plays an essential role in TNF-mediated signal transduction in colorectal epithelial cells and the carcinogenesis of colorectal cancer, which may provide potential targets for the treatment of colorectal cancer.
Cross-Regulation of F-Box Protein FBXL2 with T-bet and TNF-α during Acute and Chronic Lung Allograft Rejection
Authors: Das Antu , Wang Xingan , Wei Jianxin , Hoji Aki , Coon Tiffany A , Popescu Iulia , Brown Mark , Frizzell Sheila , Iasella Carlo J , Noda Kentaro , Sembrat John C , Devonshire Kaitlyn , Hannan Stefanie J , Snyder Mark E , Pilewski Joseph M , Sanchez Pablo G , Chandra Divay , Mallampalli Rama K , Alder Jonathan K , Chen Bill B , McDyer John F 
Published: October 2022

Abstract
Chronic lung allograft dysfunction is the major barrier to long-term survival in lung transplant recipients. Evidence supports type 1 alloimmunity as the predominant response in acute/chronic lung rejection, but the immunoregulatory mechanisms remain incompletely understood. We studied the combinatorial F-box E3 ligase system: F-box protein 3 (FBXO3; proinflammatory) and F-box and leucine-rich repeat protein 2 (FBXL2; anti-inflammatory and regulates TNFR-associated factor [TRAF] protein). Using the mouse orthotopic lung transplant model, we evaluated allografts from BALB/c → C57BL/6 (acute rejection; day 10) and found significant induction of FBXO3 and diminished FBXL2 protein along with elevated T-bet, IFN-γ, and TRAF proteins 1–5 compared with isografts. In the acute model, treatment with costimulation blockade (MR1/CTLA4-Ig) resulted in attenuated FBXO3, preserved FBXL2, and substantially reduced T-bet, IFN-γ, and TRAFs 1–5, consistent with a key role for type 1 alloimmunity. Immunohistochemistry revealed significant changes in the FBXO3/FBXL2 balance in airway epithelia and infiltrating mononuclear cells during rejection compared with isografts or costimulation blockade–treated allografts. In the chronic lung rejection model, DBA/2J/C57BL/6F1 &gt; DBA/2J (day 28), we observed persistently elevated FBXO3/FBXL2 balance and T-bet/IFN-γ protein and similar findings from lung transplant recipient lungs with chronic lung allograft dysfunction versus controls. We hypothesized that FBXL2 regulated T-bet and found FBXL2 was sufficient to polyubiquitinate T-bet and coimmunoprecipitated with T-bet on pulldown experiments and vice versa in Jurkat cells. Transfection with FBXL2 diminished T-bet protein in a dose-dependent manner in mouse lung epithelial cells. In testing type 1 cytokines, TNF-α was found to negatively regulate FBXL2 protein and mRNA levels. Together, our findings show the combinatorial E3 ligase FBXO3/FBXL2 system plays a role in the regulation of T-bet through FBXL2, with negative cross-regulation of TNF-α on FBXL2 during lung allograft rejection.
Sharks Provide Evidence for a Highly Complex TNFSF Repertoire in the Jawed Vertebrate Ancestor
Authors: Redmond Anthony K , Pettinello Rita , Bakke Fiona K , Dooley Helen 
Published: October 2022

Abstract
Cytokines of the TNF superfamily (TNFSF) control many immunological processes and are implicated in the etiology of many immune disorders and diseases. Despite their obvious biological importance, the TNFSF repertoires of many species remain poorly characterized. In this study, we perform detailed bioinformatic, phylogenetic, and syntenic analyses of five cartilaginous fish genomes to identify their TNFSF repertoires. Strikingly, we find that shark genomes harbor ∼30 TNFSF genes, more than any other vertebrate examined to date and substantially more than humans. This is due to better retention of the ancestral jawed vertebrate TNFSF repertoire than any other jawed vertebrate lineage, combined with lineage-specific gene family expansions. All human TNFSFs appear in shark genomes, except for lymphotoxin-α (LTA; TNFSF1) and TNF (TNFSF2), and CD70 (TNFSF7) and 4-1BBL (TNFSF9), which diverged by tandem duplications early in tetrapod and mammalian evolution, respectively. Although lacking one-to-one LTA and TNF orthologs, sharks have evolved lineage-specific clusters of LTA/TNF co-orthologs. Other key findings include the presence of two BAFF (TNFSF13B) genes along with orthologs of APRIL (TNFSF13) and BALM (TNFSF13C) in sharks, and that all cartilaginous fish genomes harbor an ∼400-million-year-old cluster of multiple FASLG (TNFSF6) orthologs. Finally, sharks have retained seven ancestral jawed vertebrate TNFSF genes lost in humans. Taken together, our data indicate that the jawed vertebrate ancestor possessed a much larger and diverse TNFSF repertoire than previously hypothesized and oppose the idea that the cartilaginous fish immune system is “primitive” compared with that of mammals.
A finTRIM Family Protein Acquires RNA-Binding Activity and E3 Ligase Activity to Shape the IFN Response in Fish
Authors: Qu Zi-Ling , Li Yi-Lin , Gong Xiu-Ying , Zhao Xiang , Sun Hao-Yu , Dan Cheng , Gui Jian-Fang , Zhang Yi-Bing 
Published: October 2022

Abstract
Tripartite motif (TRIM) family proteins have come forth as important modulators of innate signaling dependent on of E3 ligase activity. Recently, several human TRIM proteins have been identified as unorthodox RNA-binding proteins by RNA interactome analyses; however, their targets and functions remain largely unknown. FTRCA1 is a crucian carp (Carassius auratus)–specific finTRIM (fish novel TRIM) member and negatively regulates the IFN antiviral response by targeting two retinoic acid–inducible gene-I (RIG-I)–like receptor (RLR) pathway molecules, that is, TANK-binding kinase 1 (TBK1) and IFN regulatory factor 7 (IRF7). In this study, we identify FTRCA1 as an RNA-binding E3 ligase and characterize the contribution of its RNA-binding activity and E3 ligase activity to fish IFN response. Besides targeting TBK1 and IRF7, FTRCA1 downregulates fish IFN response also by targeting stimulator of IFN response cGAMP interactor 1 (STING1). E3 ligase activity is required for full inhibition on the TBK1- and IRF7-mediated IFN response, but partial inhibition on the STING1-mediated IFN response. However, FTRCA1 has a general binding potential to mRNAs in vitro, it selectively binds STING1 and IRF7 mRNAs in vivo to attenuate mRNA levels, and it directly interacts with TBK1 protein to target protein degradation for downregulating the IFN response. Our results present an interesting example of a fish species–specific finTRIM protein that has acquired RNA-binding activity and E3 ligase activity to fine-tune fish IFN response.
Peribronchial Inflammation Resulting from Regulatory T Cell Deficiency Damages the Respiratory Epithelium and Disturbs Barrier Function
Authors: Jonckheere Anne-Charlotte , Steelant Brecht , Seys Sven F , Cremer Jonathan , Dilissen Ellen , Boon Louis , Liston Adrian , Schrijvers Rik , Breynaert Christine , Vanoirbeek Jeroen A J , Ceuppens Jan L , Bullens Dominique M A 
Published: October 2022

Abstract
Regulatory T cells (Tregs) that express the transcription factor Foxp3 have a critical role in limiting inflammatory processes and tissue damage. Whether Tregs are functional in maintaining epithelial barriers and in control of tight junction expression has not yet been explored. In this study, we investigated the effect of Treg deficiency on the airway epithelial barrier in an experimental murine model in which diphtheria toxin was repeatedly injected in Foxp3-diphtheria toxin receptor (DTR) mice to deplete Tregs. This resulted in spontaneous peribronchial inflammation and led to a systemic and local increase of IL-4, IL-5, CCL3, IFN-γ, and IL-10 and a local (lung) increase of IL-6 and IL-33 and decreased amphiregulin levels. Moreover, Treg depletion increased airway permeability and decreased epithelial tight junction (protein and mRNA) expression. CTLA4-Ig treatment of Treg-depleted mice almost completely prevented barrier dysfunction together with suppression of lung inflammation and cytokine secretion. Treatment with anti–IL-4 partly reversed the effects of Treg depletion on tight junction expression, whereas neutralization of IL-6 of IFN-γ had either no effect or only a limited effect. We conclude that Tregs are essential to protect the epithelial barrier at the level of tight junctions by restricting spontaneous T cell activation and uncontrolled secretion of cytokines, in particular IL-4, in the bronchi.
Pengembangan Sistem Monitoring Jaringan KomputerMenggunakan Dude
Authors: Tenriawaru Andi , Subardin Subardin , Nurkaeani Nurkaeani 
Published: October 2022

Perkembangan teknologi informasi pada saat sekarang ini para administrator jaringan dituntut untuk bekerja dengan cepat, handal dan professional ketika terjadi masalah pada lalu lintas (traffic) infrastruktur jaringan yang ditanganinya. Sementara itu disisi lain para administrator jaringan tidak selamanya berada di kantor untuk memonitoring unjuk kerja dan lalu lintas infrastruktur jaringan. Masalah yang terjadi pada operasional jaringan akan mengakibatkan kerugian yang tidak kecil, terutama pada instansi-instansi yang memanfaatkan teknologi jaringan. Berdasarkan referensi monitoring jaringan menggunakan aplikasi whireshark digunakan memantau atau melihat pada kualitas jaringan. Oleh karena itu, Hal tersebut membuat peneliti tertarik mengambil judul “Pengembangan Sistem Monitoring Jaringan Komputer Menggunakan Dude”. Pada penelitian ini sistem monitoring agar bekerja atau berfungsi untuk mendeteksi pada jaringan. Sebuah sistem monitoring melakukan proses pengumpulan data mengenai dirinya sendiri dan melakukan analisis terhadap data-data yang dimiliki data yang dikumpulkan pada umumnya merupakan data yang real-time, baik data yang diperoleh dari sistem yang hard real-time maupun sistem yang soft real-time. Observasi awal penelitian sampai pada tahap proses pengujian dapat disimpulkan. Kecepatan troughput yaitu 62 bits/s dan packet loss yaitu Dengan hasil pengukuran troughput dan packet loss sesuai dengan kategori tiphon termasuk kategori bagus. Dengan adanya pengembangan monitoring jaringan menggunakan aplikasi the dude memperkecil kemungkinan kesalahan dan mempermudah kepada putugas/operator di saat ada koneksi internet komputer yang down/terputus.
Redesigning the College of Education Curriculum to meet the Learner Centered Approach Needs of the Pre-service teacher for Effective Implementation of the Standard Based Curriculum in Ghana
Authors: Yekple Sampson, L.K , Kumi John-Newton , Kumah Maxwell, S. 
Published: October 2022

Purpose: There is the need for the training of Pre-Service Teachers (PST) to appreciate and exhibit Learner Centered Approach (LCA) in the teaching and learning process. As we celebrate the preparedness of the college of education tutors to impart this knowledge to the PST, the space to deliver is faced with challenges. This paper aims at exploring how tutors are implementing the practices in LCA in colleges of education in their lesson delivery. It also aims at populating the challenges associated with the implementing the approach. The paper in addition, aims at highlighting the possible practices that can support Pre-Service Teachers to appreciate the use LCA in facilitating concepts in the classroom.
Methodology: This current qualitative research adopted exploratory and descriptive design. Qualitative data was collected through interview. Three Colleges of Education (CoE) in VOLTI zone were purposively sampled for the study.
Result: From the interview results, it was found that, college curriculum on academic content is focusing much of its attention on academic content than practicum. The mode of assessment is also making the impartation of LCA to the pre-service teacher seemingly untenable. The college tutors are functionally equipped to impart the methodology of LCA to the pre-service teacher, however the use of the LCA does not support them co cover much curriculum content. Tutors struggle to complete the semester’s curriculum hence a deviation from the low usage of the LCA. It is also noted that, quizzes and End of Semester examination assessment items do not reflect practicum. The observation results supportively confirm that tutors have difficulty of integrating LCA in the teaching of content related courses due to their apparent focus on examination.
Unique Contribution to Theory, Policy and Practice: It is therefore concluded that, the current practice of promoting LCA without appropriate forms of assessment to sustain its practice demotivates both tutors and students to engage in such classroom practices. We therefore recommend that, the B.Ed program is reorganized to include more practicum to prepare functional PST in towards the facilitation of the Standard based Curriculum.
A storm-centered multivariate modeling of extreme precipitation frequency based on atmospheric water balance
Authors: Liu Yuan , Wright Daniel B. 
Published: October 2022

Abstract. Conventional rainfall frequency analysis faces several limitations. These include difficulty incorporating relevant atmospheric variables beyond precipitation and limited ability to depict the frequency of rainfall over large areas that is relevant for flooding. This study proposes a storm-based model of extreme precipitation frequency based on the atmospheric water balance equation. We developed a storm tracking and regional characterization (STARCH) method to identify precipitation systems in space and time from hourly ERA5 precipitation fields over the contiguous United States from 1951 to 2020. Extreme “storm catalogs” were created by selecting annual maximum storms with specific areas and durations over a chosen region. The annual maximum storm precipitation was then modeled via multivariate distributions of atmospheric water balance components using vine copula models. We applied this approach to estimate precipitation average recurrence intervals for storm areas from 5000 to 100 000 km2 and durations from 2 to 72 h in the Mississippi Basin and its five major subbasins. The estimated precipitation distributions show a good fit to the reference data from the original storm catalogs and are close to the estimates from conventional univariate GEV distributions. Our approach explicitly represents the contributions of water balance components in extreme precipitation. Of these, water vapor flux convergence is the main contributor, while precipitable water and a mass residual term can also be important, particularly for short durations and small storm footprints. We also found that ERA5 shows relatively good water balance closure for extreme storms, with a mass residual on average 10 % of precipitation. The approach can incorporate nonstationarities in water balance components and their dependence structures and can benefit from further advancements in reanalysis products and storm tracking techniques.
ГИПЕРТРОФИЯЛЫҚ КАРДИОМИОПАТИЯ – КӨП ҚЫРЛЫ МӘСЕЛЕНІҢ ҚАЗІРГІ ЖАҒДАЙЫ
Authors: ЖАКАЕВ М.А. , НУРБАЙ Ж.Н. , ТУЛЕУТАЕВ Р.М. , КОДАСБАЕВ А.Т. 
Published: October 2022

Сложнейшая проблема современной кардиохирургии – гипертрофическая кардиомиопатия. На основании анализа крупных, преимущественно англоязычных, исследований по изучению гипертрофической кардиомиопатии, представлены данные по эпидемиологии, рассмотрены достижения генетики и морфологии, освещены современные возможности диагностики и лечения этого заболевания. Разобраны спорные механизмы развития обструкции выходного тракта левого желудочка. Подчеркнуты недостатки диагностических критериев и лечебных подходов, влияющих на прогноз естественного течения заболевания, исходы медикаментозного и инвазивных методов лечения. Озвучены значимые проблемы и вопросы, решение которых позволит пересмотреть существующие абстрактные парадигмы диагностики и лечения для достижения наилучших клинических результатов.
Бұл шолу мақала заманауи кардиохирургияның ең күрделі мәселесі – гипертрофиялық кардиомиопатияға арналған. Бұл мақалада жан-жақты ауқымды, негізінен ағылшын тілінде жүргізілген кешенді талдау негізінде гипертрофиялық кардиомиопатияны зерттеу бойынша талдаулар, эпидемиологиялық деректер, генетика және морфологияның жетістіктері, сондай-ақ осы ауруды диагностикалау мен емдеудің заманауи мүмкіндіктері көрсетілген. Сол қарынша шығу жолы тарылуының дамуындағы даулы механизмдер талданады. Аурудың табиғи ағымының болжамына әсер ететін диагностикалық критерийлер мен терапиялық тәсілдердің кемшіліктері, емдеудің медикаментозды және инвазивті әдістерінің нәтижелері атап өтіледі. Ең жақсы клиникалық нәтижелерге қол жеткізу үшін қолданыстағы диагностика мен емдеудің абстрактілі парадигмаларын қайта қарауға мүмкіндік беретін өзекті мәселелер мен сұрақтар айтылады
Hypertrophic cardiomyopathy isa sophisticated problem of modern cardiac surgery.. This review based on a comprehensive analysis of large, predominantly English-language, studies ofhypertrophic cardiomyopathy. The review also presents epidemiologic data , considers the achievements of genetics and morphology, and highlights modern possibilities for diagnosing and treating the disease. Controversial mechanisms of left ventricular outflow tract obstruction are considered. The shortcomings of diagnostic criteria and therapeutic approaches influencing the prognosis of the natural course of the disease, outcomes of medical and invasive treatment methods are highlighted. Mentioned significant problems and questions solution of which will make it possible to revise the existing abstract paradigms of diagnosis and treatment in order to achieve the best clinical results.
Literacy and Preservation in “The Death and Burial of Cock Robin”
Authors: Lewis Molly B. 
Published: October 2022

Abstract
This article considers an 1850 publication of the children’s nursery rhyme “The Death and Burial of Cock Robin” and accompanying illustrations by Harrison Weir. The publication serves as educational material, guiding Victorian children through the process of losing a loved one while providing a window into preservation culture in mid-nineteenth-century Britain. Weir’s illustrations, reflecting popular taxidermy tableaux, nuance this pedagogical project by drawing on the growing naturalist preoccupation of the nineteenth century and attendant preservation culture. The preservation and commodification of animal bodies was also closely tied to education for both children and adults, as they provided windows into other experiences of an ever-widening world. Unlike other depictions of the rhyme, Weir’s unique illustrations focus on animals in nature rather than as material for human drama. This emphasis reflects the period’s shifting attitudes toward the natural world in light of industrialization. Children’s fluency with the natural world was beginning to experience fissures. Thus, the Cock Robin nursery rhyme served as an education in both burial roles and seeing, recognizing, and naming the natural world. Its reflection of commodification culture, however, makes it a poor educational tool today, even while our need for such material continues to grow.
Assessment of the Relationship between Drug Compliance and Depression among Patients with Diabetes Mellitus
Authors: Hamzah Israa Hussein , Saeed Noor Al-Huda A. A. H. , Al-Kadmy Israa M. 
Published: October 2022

Diabetes and depression are highly prevalent conditions and have significant impact on health outcomes. We aimed to assess the relationship between diabetes and depression among patients. Methods: 200 patients diagnosed with diabetes attending diabetes clinics were invited to participate in this study. Results: In this study most of the participants belong to the age group of 61- 70 years, 140 participants are female. Study results indicated that 64 (32%) participants have 6 to 10 years of illness, 49 (24.5%) participants are on treatment for 6 to 10 years of duration, 199 (99.5%) participants are taking oral drugs twice a day, 97 (48.5%) participants have hypertension, 137 (68.5%) participants had no family history of diabetes mellitus and 179 (89.5%) participants do not have any complication currently In this study, 137(68.5%) participants did not forget to take medication,177 (88.5%) participants did not stop medication when symptoms are under control,163(81.5%) participants felt convenient to take medication and 172 (86%) participants did not feel difficulty in remembering to take medication. 96 (48%) patients with diabetes mellitus had high adherence, 74 (37%) participants had moderate adherence and 30 (15%) participants had low adherence. Conclusion: The current study demonstrates slight correlation between depression and diabetes particularly complications.