Journal articles: 'IFML4'

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Lunova, Mariia, Jan Kubovciak, Barbora Smolková, Mariia Uzhytchak, Kyra Michalova, Alexandr Dejneka, Pavel Strnad, Oleg Lunov, and Milan Jirsa. "Expression of Interferons Lambda 3 and 4 Induces Identical Response in Human Liver Cell Lines Depending Exclusively on Canonical Signaling." International Journal of Molecular Sciences 22, no. 5 (March 4, 2021): 2560. http://dx.doi.org/10.3390/ijms22052560.

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Lambda interferons mediate antiviral immunity by inducing interferon-stimulated genes (ISGs) in epithelial tissues. A common variant rs368234815TT/∆G creating functional gene from an IFNL4 pseudogene is associated with the expression of major ISGs in the liver but impaired clearance of hepatitis C. To explain this, we compared Halo-tagged and non-tagged IFNL3 and IFNL4 signaling in liver-derived cell lines. Transfection with non-tagged IFNL3, non-tagged IFNL4 and Halo-tagged IFNL4 led to a similar degree of JAK-STAT activation and ISG induction; however, the response to transfection with Halo-tagged IFNL3 was lower and delayed. Transfection with non-tagged IFNL3 or IFNL4 induced no transcriptome change in the cells lacking either IL10R2 or IFNLR1 receptor subunits. Cytosolic overexpression of signal peptide-lacking IFNL3 or IFNL4 in wild type cells did not interfere with JAK-STAT signaling triggered by interferons in the medium. Finally, expression profile changes induced by transfection with non-tagged IFNL3 and IFNL4 were highly similar. These data do not support the hypothesis about IFNL4-specific non-canonical signaling and point out that functional studies conducted with tagged interferons should be interpreted with caution.

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Miyamura, Tatsuo, Tatsuo Kanda, Shingo Nakamoto, Makoto Arai, Masato Nakamura, Shuang Wu, Xia Jiang, et al. "IFNL4 ss469415590 Variant Is Associated with Treatment Response in Japanese HCV Genotype 1 Infected Individuals Treated with IFN-Including Regimens." International Journal of Hepatology 2014 (2014): 1–6. http://dx.doi.org/10.1155/2014/723868.

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Aim. Eradication of hepatitis C virus (HCV) is still challenging even if interferon- (IFN-) free regimens with direct-acting antiviral agents (DAAs) for HCV-infected individuals are available in clinical practice. IFNL4 is a newly described protein, associated with human antiviral defenses. We investigated whether IFNL4 ss469415590 variant has an effect on the prediction of treatment response in HCV-infected patients treated with IFN-including regimens.Patients and Methods. In all, 185 patients infected with HCV genotype 1 treated with peg-IFN plus ribavirin, with or without telaprevir, were genotyped for IFNL4 ss469415590. We retrospectively investigated whether the role of IFNL4 ss469415590 variant and other factors could predict sustained virological response (SVR) in Japanese patients infected with HCV genotype 1.Results. There were 65.7%, 31.5%, and 2.8% patients in the IFNL4 ss469415590 TT/TT, TT/-G, and -G/-G groups, respectively. SVR rates were 82.1% or 49.3% in patients treated with peg-IFN plus ribavirin with or without telaprevir, respectively. IFNL4 ss469415590 variant and HCV viral loads or IFNL4 ss469415590 variant and early virological response were better predictors of SVR in patients treated with peg-IFN plus ribavirin with or without telaprevir, respectively.Conclusion. In the era of DAAs, measurement of IFNL4 ss469415590 variant could help the prediction of SVR in Japanese HCV genotype 1 infected individuals treated with IFN-including regimens.

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Sy, Aminata, Leanne McCabe, Emma Hudson, Azim M. Ansari, Vincent Pedergnana, Shang-Kuan Lin, S. Santana, et al. "Utility of a buccal swab point-of-care test for the IFNL4 genotype in the era of direct acting antivirals for hepatitis C virus." PLOS ONE 18, no. 1 (January 23, 2023): e0280551. http://dx.doi.org/10.1371/journal.pone.0280551.

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Background The CC genotype of the IFNL4 gene is known to be associated with increased Hepatitis C (HCV) cure rates with interferon-based therapy and may contribute to cure with direct acting antivirals. The Genedrive® IFNL4 is a CE marked Point of Care (PoC) molecular diagnostic test, designed for in vitro diagnostic use to provide rapid, real-time detection of IFNL4 genotype status for SNP rs12979860. Methods 120 Participants were consented to a substudy comparing IFNL4 genotyping results from a buccal swab analysed on the Genedrive® platform with results generated using the Affymetix UK Biobank array considered to be the gold standard. Results Buccal swabs were taken from 120 participants for PoC IFNL4 testing and a whole blood sample for genetic sequencing. Whole blood genotyping vs. buccal swab PoC testing identified 40 (33%), 65 (54%), and 15 (13%) had CC, CT and TT IFNL4 genotype respectively. The Buccal swab PoC identified 38 (32%) CC, 64 (53%) CT and 18 (15%) TT IFNL4 genotype respectively. The sensitivity and specificity of the buccal swab test to detect CC vs non-CC was 90% (95% CI 76–97%) and 98% (95% CI 91–100%) respectively. Conclusions The buccal swab test was better at correctly identifying non-CC genotypes than CC genotypes. The high specificity of the Genedrive® assay prevents CT/TT genotypes being mistaken for CC, and could avoid patients being identified as potentially ‘good responders’ to interferon-based therapy.

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Sorrentino, Leonardo, Valentina Silvestri, Giuseppe Oliveto, Mirko Scordio, Federica Frasca, Matteo Fracella, Camilla Bitossi, et al. "Distribution of Interferon Lambda 4 Single Nucleotide Polymorphism rs11322783 Genotypes in Patients with COVID-19." Microorganisms 10, no. 2 (February 4, 2022): 363. http://dx.doi.org/10.3390/microorganisms10020363.

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Type III interferons (IFN-III), also known as IFN-Lambda, have a pivotal role during SARS-CoV-2 infection. IFN-Lambda response among individuals is heterogeneous and its association with COVID-19 symptoms severity needs to be further clarified. We analyzed the genotype frequencies of IFNL4 single nucleotide polymorphism (SNP) rs11322783 in patients with COVID-19 (n = 128), in comparison with a validated data set of European healthy controls (n = 14152). The IFNL4 SNP was also analyzed according to the haematological and clinical parameters of patients with COVID-19. The distributions of IFNL4 genotypes among SARS-CoV-2 positive patients [TT/TT 41.4% (n = 53), TT/ΔG 47.7% (n = 61) and ΔG/ΔG 10.9% (n = 14)] and healthy controls were comparable. Different levels of white blood cells (p = 0.036) and neutrophils (p = 0.042) were found in the IFNL4 different genotypes in patients with COVID-19; the ΔG/ΔG genotype was more represented in the groups with low white blood cells and neutrophils. There were no differences in major inflammation parameters (C-reactive protein, D-dimer, Albumin, and Lactate-dehydrogenase (LDH)] and survival rate according to the IFNL4 genotypes. In conclusion, although patients with COVID-19 did not exhibit a different distribution of the IFNL4 SNP, the ΔG/ΔG genotype was associated with a lower count of immune cell populations. These findings need to be confirmed in larger groups of patients with COVID-19 and the role of IFNL4 SNP needs to be also investigated in other respiratory viral infections.

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SEVENSTER, MERLIJN. "DECIDABILITY OF INDEPENDENCE-FRIENDLY MODAL LOGIC." Review of Symbolic Logic 3, no. 3 (July 13, 2010): 415–41. http://dx.doi.org/10.1017/s1755020310000146.

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In this paper we consider an independence-friendly modal logic, IFML. It follows from results in the literature that qua expressive power, IFML is a fragment of second-order existential logic, $\Sigma _1^1$, that cannot be translated into first-order logic. It is also known that IFML lacks the tree structure property. We show that IFML has the ‘truncated structure property’, a weaker version of the tree structure property, and that its satisfiability problem is solvable in 2NEXP. This implies that this paper reveals a new decidable fragment of $\Sigma _1^1$. We also show that IFML becomes undecidable if we add the identity symbol to its vocabulary by means of a reduction from the tiling problem.

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Barlogie, Bart, Michel Attal, John Crowley, Frits van Rhee, Jackie Szymonifka, Philippe Moreau, Brian G. M. Durie, and Jean-Luc Harousseau. "Long-Term Follow-Up of Autotransplantation Trials for Multiple Myeloma: Update of Protocols Conducted by the Intergroupe Francophone du Myelome, Southwest Oncology Group, and University of Arkansas for Medical Sciences." Journal of Clinical Oncology 28, no. 7 (March 1, 2010): 1209–14. http://dx.doi.org/10.1200/jco.2009.25.6081.

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Purpose The purpose of this study was to update outcomes of autotransplantation trials for myeloma conducted by the Intergroupe Francophone du Myelome (IFM), the Southwest Oncology Group, and the University of Arkansas for Medical Sciences (Total Therapy [TT]). Methods IFM90 (N = 194), IFM04 (N = 402), IFM9902 (N = 692), IFM9904 (N = 197), S9321 (N = 817), TT1 (N = 231), TT2 (N = 668), and TT3 (N = 303) were updated, and results were compared with original reports. Results Superior survival with single transplantation versus standard therapy in IFM90 was confirmed (P = .004), and a trend in favor of tandem versus single transplantation was maintained in IFM94 (P = .08). S9321 data were validated, with comparable survival in single transplantation and standard treatment arms (P = .35). A survival benefit from thalidomide maintenance in IFM9902 was not confirmed (P = .39) but emerged for the thalidomide arm of TT2 (P = .04). On multivariate analysis, survival was superior in TT2, TT3, and IFM9902 (all P < .001); tandem transplantations were superior to both single transplantations and standard therapies (P < .001), as were tandem transplantations with added thalidomide versus trials without thalidomide (P < .001). Postrelapse survival (PRS) was superior when initial event-free survival (EFS) exceeded 1280 days and when tandem transplantations had been administered, whereas PRS was shorter when EFS lasted 803 days or less and when trials had included thalidomide and bortezomib. Conclusion These long-term follow-up data of transplantation trials provide a crucial framework of reference for outcome reporting of novel agent–based trials reportedly exhibiting remarkable short-term efficacy approaching high-dose therapy results.

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Huschka, Henriette, and Sabine Mihm. "Hepatic IFNL4 Gene Activation in Hepatocellular Carcinoma Patients with Regard to Etiology." International Journal of Molecular Sciences 22, no. 15 (July 21, 2021): 7803. http://dx.doi.org/10.3390/ijms22157803.

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Hepatocellular carcinoma (HCC) is a malignancy with a leading lethality. The etiology is quite diverse, ranging from viral infections to metabolic disorders or intoxications, and associates with specific somatic mutational patterns and specific host immunological phenotypes. Particularly, hepatitis C virus (HCV)-infected liver is featured by an activation of interferon (IFN)-stimulated genes (ISGs; IFN signature), which we suppose is driven by type III IFNL4. Taking advantage of the TCGA collection of HCC patients of various different etiologies, this study aimed at validating our previous findings on hepatic IFNL4 gene activation in HCV infection in an independent and larger cohort of patients with advanced liver disease. In a cohort of n = 377 cases, the entirety of the sequencing data was used to assess the IFNL genotypes, and the cases were stratified for etiology. The number of IFNL4 transcripts within nonmalignant and malignant tissues was found to be more abundant in patients with HCV or HCV/HBV infections when compared to other risk factors. Moreover, in patients with HCV infection as a risk factor, a close, positive relationship was found between ISG activation and the number of functional IFNL4 transcripts. Data on this independent TCGA sample support the concept of an IFNL4-dependent HCV-driven activation of hepatic ISGs. In addition to that, they add to the understanding of etiology-related host immunological phenotypes in HCC.

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Jenkins, Frank J., Tsion Z. Minas, Wei Tang, Tiffany H. Dorsey, and Stefan Ambs. "Abstract LB162: Human herpesvirus 8 infection is associated with prostate cancer among IFNL4-ΔG carriers." Cancer Research 82, no. 12_Supplement (June 15, 2022): LB162. http://dx.doi.org/10.1158/1538-7445.am2022-lb162.

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Abstract Background: Chronic inflammation as seen with chronic infections, has been proposed as a risk factor for prostate cancer. Numerous studies failed to identify a specific microbial agent associated with prostate cancer risk. We have previously reported that human herpesvirus 8 (HHV-8) is associated with increased prostate cancer risk in Tobago; a population that is 97% of African ancestry. This association was not found in several studies of US men, who were predominately of European American ancestry. It is unclear if the discrepancies between US and Tobago men are due to differences in HHV-8 seroprevalence rates or ancestry-related genetics. Previous studies have reported that the dinucleotide germline variant, rs368234815-ΔG, in the IFNL4 gene encoding interferon λ4 is more prevalent among individuals of African ancestry and impairs viral clearance. In this study, we investigated whether the association of HHV-8 with prostate cancer is IFNL4-ΔG-dependent. Methods: We investigated the association of HHV-8 seropositivity with prostate cancer in 728 IFNL4-ΔG-genotyped cases and 813 genotyped population-based control men from the NCI-Maryland Prostate Cancer Case-Control study. Associations between HHV-8 and prostate cancer were assessed in multivariable unconditional logistic regression models. We calculated adjusted odds ratios (OR) and stratified the analysis into men harboring the IFNL4-ΔG-variant and non-carriers (ΔG/ΔG or ΔG/TT vs. TT/TT). Results: HHV-8 seropositivity was higher in cases than controls (OR 1.76; 95%CI: 1.20 - 2.59). The association of HHV-8 seropositivity with prostate cancer was restricted to carriers of the ΔG allele (OR 2.19: 95%CI: 1.38 - 3.48). HHV-8 seropositivity did not associate with prostate cancer among TT/TT genotype carriers (OR 1.03: 95%CI: 0.51 - 2.11). Further stratification by race/ethnicity showed that HHV-8 is associated with prostate cancer exclusively among carriers of the ΔG allele in both European American (OR 2.59; 95%CI: 1.20 - 5.56) and African American men (OR 1.96; 95%CI: 1.08 - 3.56). Conclusions: HHV-8 seropositivity is associated with increased odds of prostate cancer in men harboring the IFNL4 rs368234815-ΔG variant. Impact: The study establishes IFNL4-ΔG as a candidate prostate cancer risk factor in men with an HHV-8 infection. This gene-environment association of IFNL4-ΔG with prostate cancer should be further evaluated using prospective study designs. Citation Format: Frank J. Jenkins, Tsion Z. Minas, Wei Tang, Tiffany H. Dorsey, Stefan Ambs. Human herpesvirus 8 infection is associated with prostate cancer among IFNL4-ΔG carriers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB162.

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Gadalla, Shahinaz M., Tao Wang, Olusegun Onabajo, Youjin Wang, Michael D. Haagenson, Jennifer A. Sees, Stephen R. Spellman, Hormuzd A. Katki, Stephanie J. Lee, and Ludmila Prokunina-Olsson. "Donor IFNL4 Genotype Is Associated with Transplant-Related Mortality after Unrelated Donor Myeloablative Hematopoietic Cell Transplantation in Patients with Acute Leukemia." Blood 132, Supplement 1 (November 29, 2018): 968. http://dx.doi.org/10.1182/blood-2018-99-111391.

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Abstract Introduction. Interferon Lambda 4 gene (IFNL4) encodes IFN-λ4 protein, a new member of the type-III interferon family. IFNL4 genotype (rs368234815-dG allele), defines the genetic ability to produce IFN-λ4 and has been associated with reduced clearance of hepatitis C virus (HCV) infection. Given antiviral activity and immune modulation properties of IFN-λ4, we hypothesized that IFNL4 genotype of recipient and/or donor may modulate post-transplant survival outcomes, possibly through control of viral infections, and/or alloreactivity. Methods. From the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we randomly selected 627 patients who received unrelated hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML, N=449) or acute lymphocytic leukemia (ALL, N=178). The patients had to match the following criteria: 1) HCT between 2004 and 2012, 2) available pre-HCT blood sample for the donor and recipient, 3) 8/8 HLA matching, and 3) myeloablative conditioning. IFNL4 genotyping was completed for 619 donors and 522 recipients using a custom-designed TaqMan assay for rs368234815. Multivariable Cox proportional hazard models were used for statistical analyses. Follow-up ended in November 2017. Results. Median age at HCT was 40 years (range=<1-68). Most patients (66%, N=411) were in first complete remission, had a Karnofsky Performance Score (KPS) between 90-100% (70%, N=436), and received peripheral blood stem cell grafts (70%, N=439). The median post-HCT follow-up was 68 months (range=5-122). Donor IFNL4 genotype was associated with risk of transplant-related mortality (TRM); with 5 years probabilities=19%, 27%, and 30% for donor TT/TT (n=286), TT/dG (n=267), and dG/dG (n=64) genotypes, respectively, p=0.02. The results remained significant in multivariable analysis (p=0.002); compared with patients receiving HCT from donors with TT/TT genotype, with the HR=1.59 (95% CI=1.13-2.23, p=0.007) for TT/dG donors and HR=1.95 (95% CI=1.18-3.23, p=0.009) for dG/dG donors. The data suggested that donor IFNL4 genotype may also predict risk of disease-free survival (DFS; HR=1.43, 95% CI=1.02-2.00, p=0.03), and overall survival (OS; HR=1.40 (95% CI=0.98-1.99, p=0.06) for donor dG/dG genotype (Table1). No association between recipient genotype and any survival outcome was observed (p>0.05 for OS, DFS, and TRM) Conclusions. Donor IFNL4 genotype is associated with risk of transplant-related mortality in patients with acute leukemia. The data suggest that avoiding donors with dG/dG genotype will improve HCT outcomes without limiting the potential donor pool. A validation study is needed; if confirmed, IFNL4 genotype may provide an added value to donor selection criteria. Disclosures Lee: Onyx: Research Funding; Kadmon: Research Funding; Amgen: Consultancy, Research Funding; Mallinckrodt: Honoraria; Incyte: Consultancy; Pfizer: Consultancy; Takeda: Research Funding.

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Wakil, Karzan, and Dayang N. A. Jawawi. "Extensibility Interaction Flow Modeling Language Metamodels to Develop New Web Application Concerns." Kurdistan Journal of Applied Research 2, no. 3 (August 27, 2017): 172–77. http://dx.doi.org/10.24017/science.2017.3.23.

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Web engineering is a systematic approach to develop web applications, and numerous web engineering methods have been proposed. These methods were extended through defining new models by using different mechanisms to capture the web application concepts. Due to the complexity rising of web applications, the web engineering methods cannot provide web solutions anymore. Even though Interaction Flow Modeling Language (IFML) is recently proposed as a new method for developing web applications, it has limitations. Therefore these methods need to be improved. In this paper, we present the ability of IFML extensibility to support new concerns from web applications. Moreover, we extend IFML through UML mechanisms to support new concerns from the context to the user interface. The new IFML solves the lack of context web application through defining a new model and becomes a new direction to develop concerns modern web applications.

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Hong, MeeAe, Johannes Schwerk, Chrissie Lim, Alison Kell, Abigail Jarret, Joseph Pangallo, Yueh-Ming Loo, et al. "Interferon lambda 4 expression is suppressed by the host during viral infection." Journal of Experimental Medicine 213, no. 12 (October 31, 2016): 2539–52. http://dx.doi.org/10.1084/jem.20160437.

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Interferon (IFN) lambdas are critical antiviral effectors in hepatic and mucosal infections. Although IFNλ1, IFNλ2, and IFNλ3 act antiviral, genetic association studies have shown that expression of the recently discovered IFNL4 is detrimental to hepatitis C virus (HCV) infection through a yet unknown mechanism. Intriguingly, human IFNL4 harbors a genetic variant that introduces a premature stop codon. We performed a molecular and biochemical characterization of IFNλ4 to determine its role and regulation of expression. We found that IFNλ4 exhibits similar antiviral activity to IFNλ3 without negatively affecting antiviral IFN activity or cell survival. We show that humans deploy several mechanisms to limit expression of functional IFNλ4 through noncoding splice variants and nonfunctional protein isoforms. Furthermore, protein-coding IFNL4 mRNA are not loaded onto polyribosomes and lack a strong polyadenylation signal, resulting in poor translation efficiency. This study provides mechanistic evidence that humans suppress IFNλ4 expression, suggesting that immune function is dependent on other IFNL family members.

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Gui, Jinsong, Yao Liu, Xiaoheng Deng, and Bin Liu. "Network Capacity Optimization for Cellular-Assisted Vehicular Systems by Online Learning-Based mmWave Beam Selection." Wireless Communications and Mobile Computing 2021 (March 20, 2021): 1–26. http://dx.doi.org/10.1155/2021/8876186.

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Directional communication is helpful to improve the performance of millimeter Wave (mmWave) links. However, the dynamic nature of vehicular scenarios raises the complexity of directional mmWave vehicular communications. Also, a mmWave link is susceptible to blockages. Therefore, a mmWave vehicular communication system requires high environmental adaptability and context-awareness. Due to inadequate context information and insufficient beam settings in the existing related algorithm, it is difficult to pick out the set of beams with more reasonable widths and directions, which hinders the further promotion of network capacity in vehicular networks. Therefore, we propose an improved fast machine learning (IFML) algorithm to overcome this shortcoming. In order to improve network capacity while suppressing the additional beam search overhead, a partitioned search method is designed in the IFML. Also, in order to be robust to occasional fluctuations and timely adapt to significant changes in communication environments, the IFML adopts a flexible beam performance update approach based on adjustable weight coefficient. The simulation results show that the IFML significantly outperforms the existing related algorithm in terms of aggregate received data after a certain number of online learning time periods.

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Jäger, Roland, Elisabeth Fuchs, Edith Bogner, Jelena D. Milosevic Feenstra, Kurt Krejcy, Christoph Klade, Michael Zoerer, Heinz Gisslinger, and Robert Kralovics. "Germline Genetic Factors Affecting Interferon Alpha Therapy in Polycythemia Vera." Blood 134, Supplement_1 (November 13, 2019): 1685. http://dx.doi.org/10.1182/blood-2019-130139.

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Introduction: Interferon alpha (IFNa) based therapies can induce sustained hematological and molecular responses (HR/MR) in Polycythemia Vera (PV) and other Myeloproliferative Neoplasms (MPN), however, not all patients respond sufficiently. While previous studies suggest that disease driving somatic mutations and genomic aberrations do not predict response to IFNa, the role of common germline polymorphisms remains elusive. We addressed the effect of germline genetic factors on PV therapy with Ropeginterferon alfa-2b (Ropeg), a novel monopegylated IFNa. We performed genome-wide association studies (GWAS) as an unbiased approach, and additionally evaluated a previously reported influence of polymorphisms at the IFNL4 locus in a large PV patient cohort. Methods: Genomic DNA was isolated from whole blood of PV patients (n=115) on Ropeg therapy, who provided consent within the PROUD-PV (NCT01949805) and CONTI-PV (NCT02218047) study programs. Patients were genotyped for >900k tagging single nucleotide polymorphisms (SNPs) across the genome on the Affymetrix SNP 6.0 array platform. Additional IFNL4 SNPs were typed using an amplicon-based next generation sequencing approach. Association analyses were performed using the PLINK toolset. JAK2-V617F mutant allele burden was quantified using a qPCR-based assay (ipsogen MutaQuant, Qiagen). MR was measured based on changes in mutant allele burden upon therapy as defined by the European LeukemiaNet (ELN) criteria. Results: To test for potential associations between germline genetic variation and response to IFNa therapy, we performed GWAS for MR data upon 12 months (M), 18M, 24M and 30M and 36M follow-up on Ropeg treatment. Genome-wide tagging SNPs were tested both for association in a case-control setup applying chi-square statistics as well as for quantitative trait association, using peripheral blood JAK2-V617F mutational burden changes from baseline as continuous variables. After Bonferroni correction for multiple testing, none of those analyses revealed a statistically significant association, suggesting the absence of strong germline predisposition factors for MR. Germline variation at the interferon-lambda (IFNL) locus was previously reported to strongly influence viral clearance during IFNa therapy of Hepatitis C (reviewed in Wack et al., Nat Immunol, 2015). While the same variants were recently reported to also affect HR during IFNa treatment in an MPN patient cohort (Lindgren et al., EJH, 2018), their potential impact on MR as surrogate marker for the size of the malignant MPN clone has not yet been evaluated. Upon testing for MR in our PV cohort, in a case-control setup we observed a statistically significant association only upon 36M follow-up (p=0.02; OR=2.51; 95%CI=[1.14-5.62]; Figure 1a). Notably, testing for change of JAK2-V617F mutational burden under Ropeg treatment as quantitative trait, we found the association to be present at formal statistical significance at all stages during follow-up (Figure 1a). For the Hepatitis C association, it is now widely acknowledged that a diplotype of two coding variants covers most of the causality, where rs368234815_TT disrupts the open reading frame (no IFNL4) while rs117648444_G results in the impaired IFNL4-S70 in contrast to the fully functional IFNL4-P70, the latter paradoxically impacting negatively on viral clearance (Terczynska-Dyla et al., Nat Commun, 2014). Similarly, in our PV cohort genotyping and phasing of this diplotype revealed a significant influence on MR in carriers of the fully functional IFNL4-P70 (p=0.01; Figure 1b; shown are patients at 36M follow-up (n=70)). Conclusions: The absence of a strong germline predisposition factor for Ropeg treatment response in our cohort implies that any PV patient may be eligible for Ropeg therapy independently of their genetic makeup. While the IFNL4 diplotype is of potential use for patient stratification, it remains to be investigated whether increase of treatment duration and/or dose adjustments can overcome the adverse effect of functional IFNL4 on Ropeg therapy. Longitudinal monitoring of JAK2-V617F mutational burden under Ropeg treatment in conjunction with determination of the IFNL4 germline genetic status may allow for optimizing patient management. Disclosures Krejcy: AOP Orphan Pharmaceuticals AG: Employment. Klade:AOP Orphan Pharmaceuticals AG: Employment. Zoerer:AOP Orphan Pharmaceuticals AG: Employment. Gisslinger:Janssen-Cilag: Honoraria; Roche Austria GmbH: Consultancy; Novartis Pharma GmbH: Consultancy, Honoraria, Research Funding; Myelopro GmbH: Consultancy; Celgene GmbH: Honoraria; Pharma Essentia: Other: Personal fees; AOP Orphan Pharmaceuticals: Consultancy, Honoraria, Research Funding. Kralovics:Novartis: Honoraria; AOP Orphan Pharmaceuticals AG: Honoraria, Other: Advisory board; Pharma Essentia: Honoraria; Qiagen: Honoraria; MyeloPro Diagnostics and Research: Equity Ownership.

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Kokura, Yoji, and Ryo Momosaki. "Prevalence of Malnutrition Assessed by the GLIM Criteria and Association with Activities of Daily Living in Older Residents in an Integrated Facility for Medical and Long-Term Care." Nutrients 14, no. 17 (September 4, 2022): 3656. http://dx.doi.org/10.3390/nu14173656.

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Malnutrition is associated with poor functional outcomes in residents in long-term care facilities. The integrated facility for medical and long-term care (IFMLC) is a new Japanese long-term care facility where medical services can be provided. This study aimed to investigate the prevalence of malnutrition diagnosed based on the Global Leadership Initiative on Malnutrition (GLIM) criteria and its association with activities of daily living (ADL) in older residents in IFMLC. In this cross-sectional study of older residents, we diagnosed mild and severe malnutrition using the GLIM criteria and assessed ADLs using the Barthel index (BI). Multivariate regression analysis was used to investigate the relationship between BI score and GLIM-defined malnutrition. A total of 117 older residents (84 women; median age, 88 years) were analyzed in this study. The prevalence values of mild and severe malnutrition were 29% and 18%, respectively. Multivariate analyses for the BI score after adjusting for potential confounders showed that mild and severe malnutrition were independently associated with BI score (B = −6.113, p < 0.046; B = −8.411, p = 0.015, respectively). GLIM-defined malnutrition is negatively associated with ADLs in older residents in IFMLC.

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Prokunina-Olsson, Ludmila, Robert D. Morrison, Adeola Obajemu, Almahamoudou Mahamar, Sungduk Kim, Oumar Attaher, Oscar Florez-Vargas, et al. "IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children." Genes & Immunity 22, no. 1 (April 13, 2021): 44–55. http://dx.doi.org/10.1038/s41435-021-00127-7.

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AbstractGenetic polymorphisms within the IFNL3/IFNL4 genomic region, which encodes type III interferons, have been strongly associated with clearance of hepatitis C virus. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. In a cohort of 914 Malian children, we genotyped functional variants IFNL4-rs368234815, IFNL4-rs117648444, and IFNL3-rs4803217 and analyzed episodes of malaria, gastrointestinal, and respiratory infections recorded at 30,626 clinic visits from birth up to 5 years of age. Compared to children with the rs368234815-TT/TT genotype (IFN-λ4-Null), rs368234815-dG allele was most strongly associated with an earlier time-to-first episode of gastrointestinal infections (p = 0.003). The risk of experiencing an infection episode during the follow-up was also significantly increased with rs368234815-dG allele, with OR = 1.53, 95%CI (1.13–2.07), p = 0.005 for gastrointestinal infections and OR = 1.30, 95%CI (1.02–1.65), p = 0.033 for malaria. All the associations for the moderately linked rs4803217 (r2 = 0.78 in this set) were weaker and lost significance after adjusting for rs368234815. We also analyzed all outcomes in relation to IFN-λ4-P70S groups. Our results implicate IFN-λ4 and not IFN-λ3 as the primary functional cause of genetic associations with increased overall risk and younger age at first clinical episodes but not with recurrence or intensity of several common pediatric infections.

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Emmanuel, Benjamin, Samer S. El-Kamary, Laurence S. Magder, Kristen A. Stafford, Man E. Charurat, Cheryl Chairez, Mary McLaughlin, et al. "Metabolic Changes in Chronic Hepatitis C Patients Who Carry IFNL4-ΔG and Achieve Sustained Virologic Response With Direct-Acting Antiviral Therapy." Journal of Infectious Diseases 221, no. 1 (August 26, 2019): 102–9. http://dx.doi.org/10.1093/infdis/jiz435.

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Abstract Background Clearance of hepatitis C virus (HCV) results in rapid changes in metabolic parameters early in direct-acting antiviral (DAA) therapy. Long-term changes after sustained virologic response (SVR) remain unknown. Methods We investigated longitudinal changes in metabolic and inflammatory outcomes in chronic hepatitis C (CHC) patients: low-density lipoprotein (LDL), high-density lipoprotein, triglycerides, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) using a general linear model for repeated measurements at 5 clinical time points and by human immunodeficiency virus (HIV) coinfection and IFNL4 genotype. Results The mean LDL increased markedly during DAA therapy (pre-DAA, 86.6 to DAA, 107.4 mg/dL; P < .0001), but then it decreased to 97.7 mg/dL by post-SVR year 1 (P < .001 compared with DAA; P = .0013 compared with SVR). In patients who carry the IFNL4-ΔG allele, mean LDL increased during treatment, then decreased at post-SVR year 1; however, in patients with TT/TT, genotype did not change during and after DAA treatment. The mean ALT and AST normalized rapidly between pre-DAA and DAA, whereas only mean ALT continued to decrease until post-SVR. Metabolic and inflammatory outcomes were similar by HIV-coinfection status. Conclusions Changes in LDL among CHC patients who achieved SVR differed by IFNL4 genotype, which implicates the interferon-λ4 protein in metabolic changes observed in HCV-infected patients.

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Duy Thong, Vo, Srunthron Akkarathamrongsin, Anchalee Avihingsanon, Apiradee Theamboonlers, Yong Poovorawan, and Pisit Tangkijvanich. "The Correlation between Hepatitis C Core Antigen and Hepatitis C Virus RNA Levels with Respect to Human Immunodeficiency Virus Status, Hepatitis C Virus Genotype and Interferon-Lambda-4 Polymorphism." Intervirology 58, no. 2 (2015): 73–79. http://dx.doi.org/10.1159/000370070.

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Objectives: Serum hepatitis C virus (HCV) core antigen (HCVcAg) concentrations correlate with HCV RNA levels in HCV monoinfected patients. Data in HCV/HIV coinfected patients are still limited. We aim to compare the use of HCVcAg measurement with respect to HIV status, HCV genotypes, interferon-lambda-4 (IFNL4) polymorphism and clinical parameters. Methods: We analyzed an untreated cohort of 104 patients with HCV monoinfection and 85 patients with HCV/HIV coinfection. Serum HCVcAg was measured by a commercial chemiluminescent microparticle immunoassay. The presence of IFNL4 polymorphism ss469415590 was identified by real-time PCR. Results: log10 HCVcAg levels were significantly correlated with corresponding log10 HCV RNA levels (r = 0.889, p < 0.001), but not with ALT levels and liver stiffness. The correlation between HCV RNA and HCVcAg was particularly high in coinfected patients and those with high viremia. Mean log10 HCVcAg concentration was significantly higher in coinfected patients than in monoinfected patients. Patients harboring the TT/TT genotype of ss469415590 had significantly higher levels of log10 HCVcAg than those with the non-TT/TT genotype. HCVcAg levels were similar across HCV genotypes. Conclusions: HCVcAg concentrations had an excellent correlation with HCV RNA levels, particularly in HCV/HIV-coinfected individuals and might be associated with IFNL4 polymorphism. HCVcAg testing could be used as an alternative to HCV RNA assays in resource-limited settings.

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Jiang, Joy J., Michelle Z. Fang, Sarah S. Jackson, and Thomas R. O'Brien. "CCR5-Δ32 and IFNL4-ΔG/TT." Clinical Therapeutics 41, no. 12 (December 2019): 2658–59. http://dx.doi.org/10.1016/j.clinthera.2019.10.004.

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Fang, Michelle Z., Sarah S. Jackson, and Thomas R. O'Brien. "IFNL4: Notable variants and associated phenotypes,." Gene 730 (March 2020): 144289. http://dx.doi.org/10.1016/j.gene.2019.144289.

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Gotti, Sara, and Samir Mbarki. "IFVM Bridge: A Model Driven IFML Execution." International Journal of Online and Biomedical Engineering (iJOE) 15, no. 04 (February 27, 2019): 111. http://dx.doi.org/10.3991/ijoe.v15i04.9707.

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Graphical user interfaces (GUIs) present a powerful part of software systems that allows a simplified assimilation and manipulation by users throw visual objects such as text, image and button. however, with the increasing complexity of GUIs and the diversity of their interaction mode required by users to access information anywhere and anytime, the need for designing efficient and more adaptive user interfaces has become a necessity. Therefore, UIs researchers have attempted to address these issues by designing user interfaces at a high level of abstraction to separate GUI’s specification from its implementation. Besides, the OMG (Object Management Group) adopted the Interaction Flow Modeling Language (IFML) as a standard in March 2013 for this purpose. In this paper, we present a new model driven development approach to efficiently execute the abstract representation of software’s front-end with focus on navigation between the views. We introduce a IFML virtual machine IFVM which executes user interfaces by passing from IFML models to be translated into an intermediate bytecode representation proposed as the instruction set of IFVM virtual machine.

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Cao, Rong Kai, and Xiaoyan Liu. "IFML-Based Web Application Modeling." Procedia Computer Science 166 (2020): 129–33. http://dx.doi.org/10.1016/j.procs.2020.02.034.

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Onabajo, Olusegun O., Fang Wang, Rouf Banday, and Ludmila Prokunina-Olsson. "Tumor transcriptome analysis and immune infiltrate profiling suggests a role for the IFNL3/IFNL4 genomic locus in liver cancer." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 178.8. http://dx.doi.org/10.4049/jimmunol.200.supp.178.8.

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Abstract HCV infection and cirrhosis are among the strongest risk factors for developing liver cancer. Impaired HCV clearance is strongly associated with a dG allele of a genetic variant, rs368234815-TT/dG; this allele creates an open reading frame for interferon lambda 4 (IFNL4). The dG allele has also been linked to reduced risk of cirrhosis. Despite strong association of HCV and cirrhosis with liver cancer, no link between rs368234815-TT/dG and liver cancer has been reported. To evaluate potential association of rs368234815-TT/dG with liver cancer, we explored resources of The Cancer Genome Atlas (TCGA). We used a genetic variant rs12980275-A/G located downstream of IFNL3 gene as a TCGA-genotyped proxy for rs368234815-TT/dG. Using multivariate statistical models, we observed that liver cancer patients homozygous for rs12980275-G allele (corresponds to rs368234815-dG allele) had less cirrhosis but reduced survival. Tumor transcriptome analysis showed association of rs12980275-G allele with immunosuppressed tumor microenvironment in non-cirrhotic patients. By deconvoluting tumor infiltrating immune cell signatures, we observed lower levels of CD8+ and follicular helper T cells, but increased M1 macrophages in non-cirrhotic patients with rs12980275-G allele. Transcriptome analysis also identified metallothioneins (MTs), which are involved in removal of reactive oxygen species in the liver, to be differentially expressed according to rs12980275 genotypes. Using hepatoma cell lines, we show that MTs are induced by IFNL4. Our results suggest an association of IFNL3/IFNL4 locus with both an immunosuppressed tumor microenvironment in liver cancer, and increased expression of MTs which could contribute to reduced fibrosis.

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Grzegorzewska, Alicja E. "Genetic Polymorphisms within Interferon-λ Region and Interferon-λ3 in the Human Pathophysiology: Their Contribution to Outcome, Treatment, and Prevention of Infections with Hepatotropic Viruses." Current Medicinal Chemistry 26, no. 25 (October 16, 2019): 4832–51. http://dx.doi.org/10.2174/0929867325666180719121142.

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: Genetic polymorphisms within the interferon λ (IFN-λ) chromosomal region, mainly rs12979860 of IFN-λ4 gene (IFNL4), are known as associated with spontaneous hepatitis C virus (HCV) resolution and sustained viral response to therapy with pegylated interferon- α and ribavirin. Strong linkage disequilibrium of IFNL4 rs12979860 with IFNL4 rs368234815, which is casually associated with HCV spontaneous and therapeutical eradication, at least partially explains favorable HCV outcomes attributed to major homozygosity in rs12979860. Effects of IFN-based antiviral treatment are associated with pretreatment expression of the IFN-λ1 receptor, expression of hepatic IFN-stimulated genes, production of IFN- λ4, and preactivation of the JAK-STAT signaling. Nowadays direct-acting antivirals (DAAs) became a potent tool in the treatment of hepatitis C, but IFN-λs are still under investigation as potential antivirals and might be an option in HCV infection (DAA resistance, recurrent viremia, adverse effects). : Patients with altered immunocompetence are especially prone to infections. In uremic subjects, polymorphisms within the IFN-λ chromosomal region associate with spontaneous HCV clearance, similarly like in the non-uremic population. Circulating IFN-λ3 shows a positive correlation with plasma titers of antibodies to surface antigen of hepatitis B virus (anti-HBs), which are crucial for protection against hepatitis B virus. More efficient anti-HBs production in the presence of higher IFN-λ3 levels might occur due to IFN-λ3-induced regulation of indoleamine 2,3-dioxygenase (IDO) expression. IFN-stimulated response element is a part of IDO gene promoter. It is worth further investigation whether IDO gene, circulating IDO, genetic polymorphisms within the IFN-λ region, and circulating IFN-λ3 act in concordance in immunological response to hepatotropic viruses.

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Onabajo, Olusegun O., Fang Wang, Mei-Hsuan Lee, Oscar Florez-Vargas, Adeola Obajemu, Mauro A. Castro, Joselin Vargas, et al. "Intracellular expression of IFN-λ4 leads to ER stress, enhanced IRF1 signaling and decreased proliferation in hepatic cells that might protect HCV+ patients from liver cirrhosis." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 225.17. http://dx.doi.org/10.4049/jimmunol.204.supp.225.17.

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Abstract Several genetic variants in the human IFNL3/IFNL4 locus have been associated with reduced hepatic fibrosis despite poor clearance of HCV infection. We expanded this analysis to cirrhosis, a more advanced stage of fibrosis. In 2931 individuals with chronic HCV, the IFNL4 genotype that generates IFN-λ4 was associated with protection from cirrhosis (OR=0.65, p=0.012, adjusted for age and sex). The IFNL4 genotype affects the production of IFN-λ4 and, additionally, may affect expression levels of IFN-λ3, making it difficult to delineate the individual contribution of these IFNs. To address this, we established HepG2-based cell models engineered to inducibly express either IFN-λ3 or IFN-λ4. Using RNA-seq based expression profile generated in these hepatic cell lines, we explored the global transcriptome of liver tumors (n=373) from The Cancer Genome Atlas to identify transcription factor networks affected by these IFNs in the liver. Several networks, including IRF1, were upregulated by IFN-λ4 more strongly than by IFN-λ3. Intracellular expression of IFN-λ4 but not of IFN-λ3 also led to potent IRF1-dependent antiproliferative effects. Live cell imaging revealed that IFN-λ4 was poorly secreted, mainly accumulated in lysosomes, and caused apoptosis, suggesting increased ER-stress via the misfolded protein response. Knockdown of DNA damage-inducible transcript 3 (DDIT3), an ER-stress response effector, significantly attenuated the antiproliferative effects of IFN-λ4. This novel interplay of enhanced IRF1 signaling coupled with intracellular accumulation and induction of ER stress by IFN-λ4 may have complex consequences on liver homeostasis during chronic HCV infection but also mediate anti-cirrhotic phenotypes.

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Ansari, M. Azim, Emanuele Marchi, Narayan Ramamurthy, Dominik Aschenbrenner, Sophie Morgan, Carl-Philipp Hackstein, Shang-Kuan Lin, et al. "In vivo negative regulation of SARS-CoV-2 receptor, ACE2, by interferons and its genetic control." Wellcome Open Research 6 (March 3, 2021): 47. http://dx.doi.org/10.12688/wellcomeopenres.16559.1.

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Background: Angiotensin I converting enzyme 2 (ACE2) is a receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and differences in its expression may affect susceptibility to infection. Methods: We performed a genome-wide expression quantitative trait loci (eQTL) analysis using hepatitis C virus-infected liver tissue from 190 individuals. Results: We discovered that polymorphism in a type III interferon gene (IFNL4), which eliminates IFN-λ4 production, is associated with a two-fold increase in ACE2 RNA expression. Conversely, among genes negatively correlated with ACE2 expression, IFN-signalling pathways were highly enriched and ACE2 was downregulated after IFN-α treatment. Negative correlation was also found in the gastrointestinal tract where inflammation driven IFN-stimulated genes were negatively correlated with ACE2 expression and in lung tissue from a murine model of SARS-CoV-1 infection suggesting conserved regulation of ACE2 across tissue and species. Conclusions: We conclude that ACE2 is likely a negatively-regulated interferon-stimulated gene (ISG) and carriage of IFNL4 gene alleles which modulates ISGs expression in viral infection may play a role in SARS-CoV-2 pathogenesis with implications for therapeutic interventions.

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Suryanto, Steven Putera, Timothy John Pattiasina, and Anggya Soetarmono. "Perancangan dan Pengembangan Toko Online dengan Metode Interaction Flow Modeling Language (Studi Kasus Toko Winata)." Teknika 6, no. 1 (November 30, 2017): 7–18. http://dx.doi.org/10.34148/teknika.v6i1.60.

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Penjualan produk dan interaksi dengan konsumen adalah proses yang sering dilakukan di usaha/toko yang bergerak di bidang penjualan. Proses penjualan biasanya dilakukan secara langsung dan bertatap muka dengan konsumen. Persoalan penjualan secara langsung berkaitan dengan ruang lingkup dan waktu yang terbatas. Pada penelitian ini penulis merancang dan mengembangkan toko online dengan studi kasus Toko Winata dan menggunakan metode Interaction Flow Modeling Language (IFML). Fungsi dari metode IFML adalah membantu mempermudah komunikasi desain interaksi dengan pemangku kepentingan non-teknis. Fokus penelitian ini adalah pada tampilan antar muka yang menarik, kemudahan penggunaan, serta penyampaian informasi produk kepada konsumen dengan memanfaatkan website sebagai salah satu layanan secara online. Penelitian ini akan membahas mengenai penjualan produk dan interaksi dengan konsumen secara online. Dengan adanya toko online ini diharapkan dapat memberikan peningkatan pendapatan pada Toko Winata dan keuntungan berupa ruang lingkup yang lebih luas dan waktu yang banyak sehingga dapat menjawab persoalan penjualan secara langsung.

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Sajji, Abir, Yassine Rhazali, and Youssef Hadi. "A methodology for transforming BPMN to IFML into MDA." Bulletin of Electrical Engineering and Informatics 11, no. 5 (October 1, 2022): 2773–82. http://dx.doi.org/10.11591/eei.v11i5.3973.

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Responding to rising information system complexity and the high expense of technological migration, model driven architecture (MDA) was created. As a result, the OMG advocates raising the abstraction level to overcome technological limitations. MDA seeks to describe the functional and performance requirements of an application on a platform independently. Using the MDA approach, the business process model and notation (BPMN), and interaction flow modeling language (IFML) standards, we represent a methodology that allows transforming semi-automatically from the computation independent model (CIM) level to the platform independent model (PIM) level; to achieve this a collection of unique rules for transforming in a semi-automatic manner from CIM to PIM were developed. At the CIM level, we create models of business process using the notation standard BPMN, and IFML is used to adapt PIM models with web-oriented graphical user interfaces (GUI). To properly demonstrate the transformation procedure from CIM to PIM models a case study of the order management process was presented.

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Ochi, Hidenori, Daiki Miki, C. Nelson Hayes, Hiromi Abe, Yasufumi Hayashida, Michiaki Kubo, and Kazuaki Chayama. "IFNL4/IL-28B haplotype structure and its impact on susceptibility to hepatitis C virus and treatment response in the Japanese population." Journal of General Virology 95, no. 6 (June 1, 2014): 1297–306. http://dx.doi.org/10.1099/vir.0.060103-0.

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A new type III interferon, IFN lambda 4 (IFNL4), and its single-nucleotide polymorphism (SNP) ss469415590 causing a frame shift have been recently reported strongly to affect antiviral therapy for chronic hepatitis C virus (HCV) infection in African and Caucasian populations compared to previously reported IL-28B SNPs rs12979860 and rs8099917. To compare the predictability for treatment outcome among those polymorphisms, we estimated haplotype structure of IFNL4/IL-28B consisting of the three SNPs in 4630 Japanese chronic hepatitis C patients and 1122 healthy controls and then compared their impact on response to pegylated-IFN (PEG-IFN) plus ribavirin (RBV) combined therapy in 903 HCV-1b-infected patients. A total of five haplotypes were identified, although two major haplotypes accounted for >99 % of the variation. The SNPs were tightly linked but not in absolute linkage disequilibrium. We could not find any difference in the predictive impact of any of these three SNPs with regard to susceptibility to HCV and treatment response. However, patients with favourable rs8099917 TT, linked to unfavourable genotypes of ss469415590 and rs12979860, showed poor initial viral response compared with those with all favourable genotypes (P = 0.0022). These findings suggest that, in part, ss469415590 and rs12979860 may have better predictive impact on response to PEG-IFN plus RBV therapy in the Japanese population, especially in patients with any of the minor haplotypes consisting of these SNPs.

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Kucherenko, A. M., V. M. Pampukha, and L. A. Livshits. "Study on the IFNL4 gene ss469415590 variant in Ukrainian population." Biopolymers and Cell 30, no. 5 (September 28, 2014): 400–402. http://dx.doi.org/10.7124/bc.0008b8.

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Amanzada, Ahmad, Waltraut Kopp, Ulrich Spengler, Giuliano Ramadori, and Sabine Mihm. "Interferon-λ4 (IFNL4) Transcript Expression in Human Liver Tissue Samples." PLoS ONE 8, no. 12 (December 20, 2013): e84026. http://dx.doi.org/10.1371/journal.pone.0084026.

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O’Brien, T. R., J. Feld, and R. Pfeiffer. "Gender and IFNL4 rs12979860 Genotype Predict Response to Ledipasvir/Sofosbuvir." Journal of Hepatology 64, no. 2 (2016): S828. http://dx.doi.org/10.1016/s0168-8278(16)01620-2.

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Ray, Katrina. "New gene IFNL4 is associated with impaired clearance of HCV." Nature Reviews Gastroenterology & Hepatology 10, no. 2 (January 22, 2013): 63. http://dx.doi.org/10.1038/nrgastro.2013.7.

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Zheng, Kexi, Yunsong Shen, Xueshan Xia, Yuzhu Song, and A.-Mei Zhang. "Genetic polymorphisms in the IFNL4, MxA, and MxB genes were associated with biochemical index of chronic HBV patients from Yunnan, China." PeerJ 10 (April 28, 2022): e13353. http://dx.doi.org/10.7717/peerj.13353.

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Hepatitis B virus (HBV) infection causes Hepatitis B, which is one of the most common causes of hepatocellular carcinoma (HCC). The single nucleotide polymorphisms (SNPs) of the host immune genes could impact HBV infection, viral clearance, and treatment effect. However, the contradictory roles of several studies suggest further analysis of various populations. The whole blood and biochemical indexes of 448 HBV patients and matched controls were collected from the Yunnan population to investigate the genetic roles of IFNL4 and the downstream genes (MxA and MxB). The genotypes, alleles, and haplotypes frequencies of the seven SNPs (rs11322783, rs117648444, rs2071430, rs17000900, rs9982944, rs408825, and rs2838029) from the HBV patients and controls were analyzed. However, no association was identified between the SNPs and HBV infection. Then, biochemical index levels were evaluated among the HBV patients with different genotypes of the seven SNPs. The results indicated that the liver function index levels (including alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), and albumin (ALB)) were influenced by the genotypes of the SNPs in HBV patients. Moreover, when the HBV patients were divided into HBsAg-positive and -negative groups, the association between the SNP genotypes and the biochemical indexes still existed. In addition, although the genetic polymorphisms in the IFNL4, MxA, and MxB genes were not significantly associated with HBV infection in the Yunnan population, these genes could indirectly influence disease progression by associating with the biochemical index levels of Yunnan HBV patients.

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Pan, Minxue, Yifei Lu, Yu Pei, Tian Zhang, Juan Zhai, and Xuandong Li. "Effective testing of Android apps using extended IFML models." Journal of Systems and Software 159 (January 2020): 110433. http://dx.doi.org/10.1016/j.jss.2019.110433.

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Tu, Hengjia, and Junrong Bao. "IFNL4, ACE1, PKR, IFNG, MBL2 genetic polymorphisms and severe COVID-19." Medicine 101, no. 21 (May 27, 2022): e29405. http://dx.doi.org/10.1097/md.0000000000029405.

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Fernández-Carrillo, Carlos, Mairene Coto-Llerena, Patricia González, Gonzalo Crespo, Laura Mensa, Noelia Caro-Pérez, Martina Gambato, Miquel Navasa, Xavier Forns, and Sofía Pérez-del-Pulgar. "IFNL4 polymorphism predicts response to hepatitis C treatment after liver transplantation." Journal of Clinical Virology 61, no. 2 (October 2014): 282–85. http://dx.doi.org/10.1016/j.jcv.2014.07.015.

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Rodriguez-Echeverria, Roberto, Juan C. Preciado, Álvaro Rubio-Largo, José M. Conejero, and Álvaro E. Prieto. "A Pattern-Based Development Approach for Interaction Flow Modeling Language." Scientific Programming 2019 (April 14, 2019): 1–15. http://dx.doi.org/10.1155/2019/7904353.

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Development and deployment technologies for data-intensive web applications have considerably evolved in the last years. Domain-specific frameworks or model-driven web engineering approaches are examples of these technologies. They have made possible to face implicit problems of these systems such as quick evolving business rules or severe time-to-market requirements. Both approaches propose the automation of redundant development tasks as the key factor for their success. The implementation of CRUD operations is a clear example of repetitive and recurrent task that may be automated. However, although web application frameworks have provided mechanisms to automate the implementation of CRUD operations, model-driven web engineering approaches have generally ignored them, so automation has not been properly faced yet. This paper presents a pattern-based development approach for the Interaction Flow Modeling Language as a way to finally automate repetitive specification tasks. Our approach is illustrated by defining and applying IFML patterns for CRUD operations. Additionally, a supporting tool, which enables automation, is shown. The suitability of our approach and the utility of its tool have been evaluated by its application into several real projects developed by a software company specialized in model-driven web application development. The results obtained present evidence of a significant productivity improvement obtained by the automation of the IFML specification of CRUD operations.

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Real, Luis M., Rocío Herrero, Antonio Rivero-Juárez, Ángela Camacho, Juan Macías, Sandra Vic, Vincent Soriano, et al. "IFNL4 rs368234815 polymorphism is associated with innate resistance to HIV-1 infection." AIDS 29, no. 14 (September 2015): 1895–97. http://dx.doi.org/10.1097/qad.0000000000000773.

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Galmozzi, E., F. Facchetti, R. Perbellini, and A. Aghemo. "High-resolution melting assay for genotyping of IFNL4-associated dinucleotide variant rs368234815." Clinical Microbiology and Infection 20, no. 11 (November 2014): O936—O938. http://dx.doi.org/10.1111/1469-0691.12637.

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Westervelt, Peter. "IFNL4 and donor selection for matched unrelated donor haematopoietic stem-cell transplantation." Lancet Haematology 7, no. 10 (October 2020): e698-e699. http://dx.doi.org/10.1016/s2352-3026(20)30287-8.

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Farid, Saadia, Laila Rashed, and Samya Sweilam. "Interferon Lambda 4 Gene (IFNL4) Linked to Hepatitis C Virus Clearance, Treatment." Egyptian Journal of Hospital Medicine 67, no. 2 (April 2017): 635–44. http://dx.doi.org/10.12816/0037815.

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Nguyen, Hieu Trung, Linh Thi Nhut Tran, Hung Huu Nguyen, and Chuong Hoang Nguyen. "Molecular typing protocol of ss469415590 in IFNL4 gene in relation to the clearance of hepatitis C virus." Science and Technology Development Journal - Natural Sciences 1, T1 (March 31, 2017): 17–25. http://dx.doi.org/10.32508/stdjns.v1it1.431.

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We built a molecular typing protocol of the ss469415590 SNP in the IFNL4 gene based on the real-time PCR technique with two Taqman probes which are specific for each allele of ss469415590. The protocol includes: (1) DNA extraction from whole blood; (2) DNA amplification in real-time PCR reactions with the primer pair of ss469415590_IFNL4_F - ss469415590_IFNL4_R and two speific Taqman probes ss469415590_IFNL4_FAM for the G allele and ss469415590_IFNL4_VIC for the TT allele. The typing protocol was evaluated on 95 clinical DNA samples. The allele frequencies were calculated as 93 % for the TT allele and 7 % for the G allele. The comparison of the typing protocol to the sequencing method revealed 100 % identical results.

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Yigitbas, Enes, Ivan Jovanovikj, Kai Biermeier, Stefan Sauer, and Gregor Engels. "Integrated model-driven development of self-adaptive user interfaces." Software and Systems Modeling 19, no. 5 (January 27, 2020): 1057–81. http://dx.doi.org/10.1007/s10270-020-00777-7.

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Abstract Modern user interfaces (UIs) are increasingly expected to be plastic, in the sense that they retain a constant level of usability, even when subjected to context changes at runtime. Self-adaptive user interfaces (SAUIs) have been promoted as a solution for context variability due to their ability to automatically adapt to the context-of-use at runtime. The development of SAUIs is a challenging and complex task as additional aspects like context management and UI adaptation have to be covered. In classical model-driven UI development approaches, these aspects are not fully integrated and hence introduce additional complexity as they represent crosscutting concerns. In this paper, we present an integrated model-driven development approach where a classical model-driven development of UIs is coupled with a model-driven development of context-of-use and UI adaptation rules. We base our approach on the core UI modeling language IFML and introduce new modeling languages for context-of-use (ContextML) and UI adaptation rules (AdaptML). The generated UI code, based on the IFML model, is coupled with the context and adaptation services, generated from the ContextML and AdaptML model, respectively. The integration of the generated artifacts, namely UI code, context, and adaptation services in an overall rule-based execution environment, enables runtime UI adaptation. The benefit of our approach is demonstrated by two case studies, showing the development of SAUIs for different application scenarios and a usability study which has been conducted to analyze end-user satisfaction of SAUIs.

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Decuyper, C. M., L. E. Claps, and Eleodoro Del Valle. "Primer reporte de Ceroplastes grandis (Hemiptera: Coccidae) en plantas ornamentales de Duranta erecta var. lemon L. (Verbenaceae) en la provincia de Entre Ríos, Argentina." AgriScientia 37, no. 2 (December 30, 2020): 53–58. http://dx.doi.org/10.31047/1668.298x.v37.n2.27419.

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Se realizó un relevamiento de cochinillas blandas pertenecientes al género Ceroplastes Gray, asociadas a Duranta erecta var. lemon L. en la ciudad de Paraná, Entre Ríos, Argentina. Estos insectos afectan el crecimiento de las plantas, provocando su decaimiento y disminuyendo su valor ornamental. Se realizaron preparaciones microscópicas y se identificó a la especie Ceroplastes grandis Hempel (Hemiptera: Coccomorpha: Coccidae) en la totalidad de las plantas relevadas. Las preparaciones microscópicas fueron depositadas en la Colección de Coccomorpha del Instituto Fundación Miguel Lillo –IFML- (Tucumán, Argentina). Se reporta por primera vez en Argentina la asociación de C. grandis y plantas de D. erecta var. lemon.

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Galmozzi, Enrico, and Roberta D’Ambrosio. "Nonalcoholic fatty liver disease: is the IFNL4 rs368234815 variant protective from liver damage?" HepatoBiliary Surgery and Nutrition 7, no. 3 (June 2018): 209–11. http://dx.doi.org/10.21037/hbsn.2018.03.06.

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O’Brien, Thomas R., Ruth M. Pfeiffer, Ashley Paquin, Krystle A. Lang Kuhs, Sabrina Chen, Herbert L. Bonkovsky, Brian R. Edlin, et al. "Comparison of functional variants in IFNL4 and IFNL3 for association with HCV clearance." Journal of Hepatology 63, no. 5 (November 2015): 1103–10. http://dx.doi.org/10.1016/j.jhep.2015.06.035.

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Hamdani, Maryum, Wasi Haider Butt, Muhammad Waseem Anwar, Imran Ahsan, Farooque Azam, and Mudassar Adeel Ahmed. "A Novel Framework to Automatically Generate IFML Models From Plain Text Requirements." IEEE Access 7 (2019): 183489–513. http://dx.doi.org/10.1109/access.2019.2959813.

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Kucherenko, A. M., V. M. Pampukha, K. Yu Romanchuk, S. Yu Chernushyn, I. A. Bobrova, L. V. Moroz, and L. A. Livshits. "IFNL4 polymorphism as a predictor of chronic hepatitis C treatment efficiency in Ukrainian patients." Cytology and Genetics 50, no. 5 (September 2016): 330–33. http://dx.doi.org/10.3103/s0095452716050066.

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Jaimes-Bernal, Claudia, Norma Rallón, José M. Benito, Mohamed Omar, María Amparo Gómez-Vidal, Francisco José Márquez, Beatriz Sánchez-Arcas, et al. "A Knockout IFNL4 Variant Is Associated With Protection From Sexually Transmitted HIV-1 Infection." Journal of Infectious Diseases 219, no. 5 (October 5, 2018): 772–76. http://dx.doi.org/10.1093/infdis/jiy584.

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Shridhar Gulati, Rachna, Thakshani Wimalanathan, Solveig Norheim Andersen, Kjetil Isaksen, Martin Lagging, Håvard Midgard, Amir Moghaddam, and Olav Dalgard. "The relationship between IFNL4 genotype and the rate of fibrosis in hepatitis C patients." Scandinavian Journal of Gastroenterology 54, no. 9 (September 2, 2019): 1172–75. http://dx.doi.org/10.1080/00365521.2019.1643403.

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Journal articles on the topic 'IFML4'

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