instruction:
In this task, you're given a paragraph and title from the research paper. Your task is to classify whether the given title is suitable or not for the research paper based on the given paragraph. Return "True" if title is proper according to paragraph else "False".
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Paragraph: Formalin-inactivated Japanese encephalitis virus (JEV) vaccines are widely available, but the effects of formalin inactivation on the antigenic structure of JEV and the profile of antibodies elicited after vaccination are not well understood. We used a panel of monoclonal antibodies (MAbs) to map the antigenic structure of live JEV virus, untreated control virus (UCV), formalin-inactivated commercial vaccine (FICV), and formalin-inactivated virus (FIV). The binding activity of T16 MAb against Nakayama-derived FICV and several strains of FIV was significantly lower compared to live virus and UCV. T16 MAb, a weakly neutralizing JEV serocomplex antibody, was found to inhibit JEV infection at the post-attachment step. The T16 epitope was mapped to amino acids 329, 331, and 389 within domain III (EDIII) of the envelope (E) glycoprotein. When we explored the effect of formalin inactivation on the immunogenicity of JEV, we found that Nakayama-derived FICV, FIV, and UCV all exhibited similar immunogenicity in a mouse model, inducing anti-JEV and anti-EDII 101/ 106/107 epitope-specific antibodies. However, the EDIII 329/331/389 epitope-specific IgG antibody and neutralizing antibody titers were significantly lower for FICV-immunized and FIV-immunized mouse serum than for UCV-immunized. Formalin inactivation seems to alter the antigenic structure of the E protein, which may reduce the potency of commercially available JEV vaccines. Virus inactivation by H 2 O 2 , but not by UV or by short-duration and higher temperature formalin treatment, is able to maintain the antigenic structure of the JEV E protein. Thus, an alternative inactivation method, such as H 2 O 2 , which is able to maintain the integrity of the E protein may be essential to improving the potency of inactivated JEV vaccines. We demonstrated that formalin inactivation of Japanese encephalitis virus (JEV) alters the antigenic structure of the JEV envelope glycoprotein (E), in particular an epitope in domain III, and that this reduces the ability of the inactivated vaccine to elicit protective neutralizing antibodies. Ours and others' previous studies have highlighted the importance of improving the immunogenicity of genotype III (GIII)-derived JEV vaccine in order to provide cross-protection against genotype I (GI) viruses, which are emerging and replacing GIII viruses in many JEV-endemic regions. Encouraging the wide use of live-attenuated or chimeric vaccines, such as SA14-14-2 or yellow-fever 17D/JEV vaccines, respectively, developing GI virus-derived inactivated or premembrane/E-containing, noninfectious virus-like particle (VLP) vaccines are two other possible ways to address this potential problem. In this exploratory study, we highlight an alternative inactivation method, such as H 2 O 2 treatment, which may improve the antigenic stability and immunogenicity of JEV. Japanese encephalitis virus (JEV), the most important etiological agent of viral encephalitis in Asian countries, causes regular outbreaks in eastern and southeastern Asia, India, and more recently in Australia [1,2]. Annually, 30,000 to 50,000 Japanese encephalitis (JE)-confirmed cases are reported in the JEV endemic areas, and 20% to 60% of symptomatic CNS infections are fatal [3-6]; 25% to 50% of symptomatic survivors have long-term neurological sequelae [7] . Asymptomatic JEV infection is about a thousand-fold higher than confirmed cases [8] [9] [10] . JEV is transmitted by virus-infected Culex mosquitos from inapparently infected viremic-amplifying hosts such as pigs or aquatic birds to symptomatic accidental hosts, such as horses and humans. Migratory birds have been implicated as the source of virus been introduced into new geographic regions, and associated with JE epidemics and replacement of genotype III (GIII)with genotype I (GI)-JEV from southeast Asia to east Asia [11, 12] . The genome of JEV consists of a~11-kb, positive-sense, single-stranded RNA, which is translated and processed by viral and host proteases to three structural proteins-capsid, precursor membrane/membrane protein (prM/M) and envelope glycoprotein (E)-and seven nonstructural proteins (NS)-NS1, 2A, 2B, 3, 4A, 4B and 5. The mature virion consists of 180 E proteins forming 90 homodimers and 180 processed M proteins. The immature virion is formed by 60 E and prM hetero-trimers [13, 14] . E protein is the most critical protein eliciting protective immunity in hosts after viral infection, offering critical protection in mice [15] and inducing protective antibodies in recovering humans [16] . The ectodomain of E protein can be separated into three structural domains: E domain I (EDI) to III (EDIII). The fusion peptide in EDII elicits group cross-reactive non-or low-neutralizing antibodies; EDIII, the receptor-binding domain, elicits potent type-specific neutralizing antibodies; and EDI, the center domain connecting EDII and EDIII, elicits complex cross-reactive high-or non-neutralizing antibodies after viral infection [16] [17] [18] . Vaccination remains the most effective strategy to control JE epidemics [19]. Live-attenuated and formalin-inactivated JEV vaccines are available for human use, but only live-attenuated vaccines are available for domestic animals, such as swine and horses. The first generation inactivated JEV vaccine, developed by BIKEN in Japan, was the mouse brain-derived, formalin-inactivated GIII Nakayama strain; manufacture of this vaccine has ceased since 2005 because of undesirable adverse effects [20] . Second generation tissue culture-derived, formalin-Formalin Inactivation Alters the Immunogenicity of JEV PLOS Neglected Tropical Diseases | 
 Title: Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III
answer:
False


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Paragraph: Objective: Tumor-treating fields are currently used to successfully treat various cancers; however, the specific pathways associated with its efficacy remain unknown in the immune responses. Here, we evaluated tumor-treating fields-mediated initiation of the macrophage-specific immune response. Materials and Methods: We subjected RAW 264.7 mouse macrophages to clinically relevant levels of tumor-treating fields (0.9 V/cm, 150 kHz) and evaluated alterations in cytokine expression and release, as well as cell viability. Additionally, we investigated the status of immunomodulatory pathways to determine their roles in tumor-treating fields-mediated immune activation. Results and Discussion: Our results indicated that tumor-treating fields treatment at 0.9 V/cm decreased cell viability and increased cytokine messenger RNA/protein levels, as well as levels of nitric oxide and reactive oxygen species, relative to controls. The levels of tumor necrosis factor a, interleukin 1b, and interleukin 6 were markedly increased in tumor-treating fields-treated RAW 264.7 cells cocultured with 4T1 murine mammary carcinoma cells compared with those in 4T1 or RAW 264.7 cells with or without tumor-treating fields treatment. Moreover, the viability of 4T1 cells treated with the conditioned medium of tumor-treating fields-stimulated RAW 264.7 cells decreased, indicating that macrophage activation by tumor-treating fields effectively killed the tumor cells. Moreover, tumor-treating fields treatment activated the nuclear factor kB and mitogen-activated protein kinase pathways involved in immunomodulatory signaling. Conclusion: These results provide critical insights into the mechanisms through which tumor-treating fields affect macrophagespecific immune responses and the efficacy of this method for cancer treatment. 
 Title: Tumor-Treating Fields Induce RAW264.7 Macrophage Activation Via NK-kB/MAPK Signaling Pathways
answer:
True


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Paragraph: The purpose of this subacute 22-day study was to evaluate methods for canine circulating immunoglobulins (IgM, IgG, and IgE) and select B-and T-lymphocyte populations (CD4-helpers, CD8-suppressors, pan-T and pan-B) for immunotoxicity testing using an organ system (concordance) approach. The challenge substance for immunoglobulin testing was repeated immunization with six-way distemper vaccination (DHLAPP), while the challenge substance for leukocyte subpopulations was treatment with cyclophosphamide. Immunoglobulin measurements were made by capture enzyme-linked immunosorbent assay (ELISA), and leukocyte immunophenotyping by fluorescein isothiocyanate/phycoerythrin conjugation (flow cytometry). A battery of parameters that would be used in a typical regulatory study were taken to aid interpretation of the data generated by these methods. Body weights, food consumption, clinical observations, complete clinical chemistry and urinalysis measurements were taken. Gross pathology and micropathology of sternal bone marrow, spleen, mesenteric and retropharyngeal lymph nodes, thymus, liver and kidney were completed. The ELISA method demonstrated acceptable intra-assay reproducibility for IgM, IgG and IgE, with values in good agreement as reported for radial immunodiffusion. The immunologic challenge demonstrated a biological trend of an increase in IgM that preceded an increase in IgG with no discernible trend in IgE response, and no abnormalities in lymphocyte subpopulations. Principle flow cytometry findings related to cyclophosphamide were that the relative percent of B cells decreased dramatically and progressively after compound administration; being statistically decreased in males on day 22 compared with day − 5. The relative percent CD4 and CD8 contribution increased, but the CD4/CD8 ratio remained relatively unchanged as total white blood cells decreased progressively. The increase in relative percent CD4 (males only) was statistically significant according to a two-sample t-test on days 17, 20 and 22 when compared with the pre-treatment day − 5. There was a relative percent increase in CD5-panT, but absolute numbers were dramatically decreased. We conclude that an organ system approach to assessment of the immune system which incorporates humoral antibody, enumeration of lymphocyte populations and pathologic evaluation of the lymphoreticular organs assists in the interpretation of an adverse toxicological response. The ELISA method for measurement of Igs detected the expected levels of IgG, IgM and IgE due to repeated vaccinations and to cyclophosphamide treatment. The flow cytometry method was acceptable for www.elsevier.com/locate/toxlet : S 0 3 7 8 -4 2 7 4 ( 0 0 ) 0 0 1 7 3 -9 R.D. Jones et al. / Toxicology Letters 115 (2000) 33-44 34 measuring select canine lymphocyte populations and detecting the expected decrease in B cells due to cyclophosphamide treatment. Both methods may be added to a testing battery for assessing immunotoxicity in canine regulatory studies. 
 Title: Capture ELISA and flow cytometry methods for toxicologic assessment following immunization and cyclophosphamide challenges in beagles
answer:

False