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".

Ex Input:
Paragraph: Metagenomics is currently the only generic method for pathogen detection. Starting from RNA allows the assessment of the whole sample community including RNA viruses. Here we present our modular concerted protocol for sample processing for diagnostic metagenomics analysis of human, animal, and food samples. The workflow does not rely on dedicated amplification steps at any stage in the process and, in contrast to published methods, libraries prepared accordingly will yield only minute amounts of unclassifiable reads. We confirmed the performance of the approach using a spectrum of pathogen/ matrix-combinations showing it has the potential to become a commonly usable analytical framework. Diagnostic metagenomics with high-throughput sequencing (HTS) techniques continuously gains importance for broad and swift identification of pathogens in human, animal, and food samples 1 . While for known pathogens, highly sensitive and specific diagnostic methods like real-time quantitative PCR (qPCR) are in routine use and deliver reliable results, the identification of unrecognized pathogens, meaning unexpected or newly emerging pathogens or pathogens that are only distantly related with known ones, can be very difficult. In this respect, metagenomics using HTS are much more promising than routine diagnostics. Unrecognized pathogens, especially newly emerging zoonoses, may cause serious infectious diseases, and a delay of medical treatment or development of vaccines might have fatal consequences for the affected patients and animal stocks. Such delays can be caused by performing numerous laborious screening tests until the potential pathogen is found instead of a single comprehensive screening test. Prominent cases of emerging infectious diseases caused by novel or varying viruses for instance are the discovery of the Middle East respiratory syndrome (MERS) coronavirus in 2012 2 , the tremendous Ebola outbreak in 2014 3 , the report on a novel zoonotic bornavirus 4 , or the detection of the new Schmallenberg virus 5 affecting domestic and wild ruminants. However, infectious diseases with clinical signs like high fever, diarrhoea, or encephalitis − often life-threatening − can be caused by very different infectious agents 6,7 , not only viruses. In such puzzling cases, a generic approach that works likewise successful and efficient for all pathogen groups, as sketched in Fig. 1 , is essential. In a number of review articles 1,8-12 , valuable considerations for this approach have been summarized. In addition to the overall workflow outlined in Fig. 1 , after metagenomic analysis, it is desirable to confirm the initial sequencing-based suspicion by other methods and in the ideal case by fulfilling the Henle-Loeffler-Koch postulates 13 as for example done in case of the Schmallenberg virus 5 . Metagenomics for generic pathogen detection, so-called diagnostic metagenomics, in its pure form is a broad and undirected approach to find gene sequences or sequence fragments of infectious agents within sequence data sets of the whole community of a sample generated by high-throughput sequencing. A crucial point when handling diagnostic sequencing approaches is to explicitly distinguish between i) high-throughput well-standardisable routine diagnostics for expected known pathogens and ii) diagnostic metagenomics for all including unrecognized pathogens. The first approach is easier to design based on the spectrum of known sequences, testing with specific oligonucleotide primers for pathogens of known identity 14,15 , known tropism, and maybe also of a known proportion within a sample. The latter one − used for unrecognized pathogens like in the case of Schmallenberg virus 5 − should be a generic approach that can ideally be applied to all samples and pathogens. This approach can indeed be developed and tested using samples of known origin and pathogen content. In case of an emergency, however, there might be no information about nature and proportion of the pathogen and only clinical data could be available, and the sample is a closed book. For these cases, metagenomics Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 
 Title: A Versatile Sample Processing Workflow for Metagenomic Pathogen Detection OPEN

Ex Output:
False


Ex Input:
Paragraph: Apelin is an inotropic and cardioprotective peptide that exhibits beneficial effects through activation of the APJ receptor in the pathology of cardiovascular diseases. Apelin induces the expression of angiotensin-converting enzyme 2 (ACE2) in failing hearts, thereby improving heart function in an angiotensin 1-7-dependent manner. Whether apelin antagonizes the over-activation of the renin-angiotensin system in the heart remains elusive. In this study we show that the detrimental effects of angiotensin II (Ang II) were exacerbated in the hearts of aged apelin-gene-deficient mice. Ang II-mediated cardiac dysfunction and hypertrophy were augmented in apelin knockout mice. The loss of apelin increased the ratio of angiotensin-converting enzyme (ACE) to ACE2 expression in the Ang II-stressed hearts, and Ang II-induced cardiac fibrosis was markedly enhanced in apelin knockout mice. mRNA expression of pro-fibrotic genes, such as transforming growth-factor beta (TGF-β) signaling, were significantly upregulated in apelin knockout hearts. Consistently, treatment with the ACE-inhibitor Captopril decreased cardiac contractility in apelin knockout mice. In vitro, apelin ameliorated Ang II-induced TGF-β expression in primary cardiomyocytes, accompanied with reduced hypertrophy. These results provide direct evidence that endogenous apelin plays a crucial role in suppressing Ang II-induced cardiac dysfunction and pathological remodeling. Int. J. Mol. Sci. 2019, 20, 239 2 of 12 dysfunctions [8, 10, 11] . By contrast, APJ was identified as a dual receptor to mediate cardiac hypertrophy [12, 13] via β-arrestin signaling [14, 15] . Thus, the precise role of endogenous apelin signaling in heart function remains elusive. Cardiac hypertrophy is an adaptive response to maintain cardiac function in the event of an increased workload, although prolonged cardiac hypertrophy can lead to heart failure via the ischemia of cardiomyocytes [16, 17] . In addition, cardiac fibrosis adversely increases tissue stiffness and impairs ventricular function. Consistently, cardiac hypertrophy and the development of fibrosis correlate with the deterioration of myocardial function in heart failure [18] [19] [20] . Thus, cardiac hypertrophy and fibrosis are key features of heart failure, and apelin's inotropic and protective roles in the heart are attractive as a potential therapeutic candidate for treating heart failure. Apelin has also been identified as a substrate for angiotensin-converting enzyme 2 (ACE2), which cleaves apelin with similar efficiency as its primary substrate angiotensin II (Ang II) [21] [22] [23] . ACE2 is a negative regulator of the renin-angiotensin system (RAS) that inactivates Ang II by converting it to angiotensin 1-7 (Ang 1-7) [21] [22] [23] , whereas angiotensin-converting enzyme 1 (or ACE1) activates RAS by converting Ang I to Ang II. ACE2 was also identified as a regulator of heart failure [24-26], diabetic nephropathy [27, 28] , acute lung failure [29, 30] , and the SARS (severe acute respiratory syndrome) coronavirus receptor [31, 32] . Apelin-APJ signaling has been shown to counteract the effects of Ang II on AT1R in defined physiological and pathophysiological settings. For instance, in hypertensive rat models, the continuous infusion of Ang II downregulates apelin and APJ expression [33] . We have shown that Apelin upregulates ACE2 expression. Apelin-induced ACE2 downregulates Ang II signaling while enhancing Ang 1-7-Mas receptor signaling in aged or failing hearts [34] . On the other hand, it has been suggested that the counter-balancing effects of the apelin-APJ axis on Ang II-AT1R signaling are mediated by receptor dimerization. The APJ receptor physically interacts with AT1 receptors, and exogenous apelin negatively regulates Ang II-AT1R signaling in in vitro cell culture systems and in an in vivo atherosclerosis model [35] . However, whether endogenous apelin counteracts the over-activation of RAS in the heart remains unexplored. In this study, we aimed to determine the effects of endogenous apelin on Ang II-induced pathology in the heart. We showed that Ang II-mediated cardiac dysfunction, hypertrophy, and fibrosis were augmented in apelin knockout (Apelin KO) mice. 
 Title: Loss of Apelin Augments Angiotensin II-Induced Cardiac Dysfunction and Pathological Remodeling

Ex Output:
True


Ex Input:
Paragraph: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced by the oxidative burst in activated macrophages and neutrophils cause oxidative stressimplicated diseases. Quercetin is flavonoid that occurs naturally in plants and is widely used as a nutritional supplement due to its antioxidant and anti-inflammatory properties. In this study, we investigated antioxidant activities and mechanisms of action in zymosan-induced macrophages of quercetin and quercetin-related flavonoids such as quercitrin, isoquercitrin, quercetin 3-O-β-(2′′-galloyl)rhamnopyranoside (QGR) and quercetin 3-O-β-(2′′-galloyl)glucopyranoside (QGG) as well as gallic acid, a building moiety of QGR and QGG. QGR and QGG exhibited stronger antioxidant activities compared with quercetin, whereas quercitrin, isoquercitrin and gallic acid exhibited weak-tono antioxidant activities, assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, superoxide production, superoxide scavenging, nitric oxide (NO) production, peroxynitrite (ONOO -) scavenging and myeloperoxidase (MPO) activity. Regarding mechanisms, the quercetincontaining flavonoids QGR and QGG differentially targeted compared with quercetin in the NF-κB signaling pathway that inhibited the DNA binding activity of the NF-κB complex without affecting the degradation and phosphorylation of IκBα and NF-κB phosphorylation. In addition, QGR and QGG inhibited CRE and activator protein (AP-1) transcriptional activity and JNK phosphorylation by inhibiting the cAMP/protein kinase A (PKA) and protein kinase C (PKC) signaling in a different manner than quercetin. Our results showed that although QGR and QGG exhibited stronger antioxidant activities than querce-tin in macrophages, their mechanisms of action in terms of the NF-κB, PKA and PKC signaling pathways were different. al., 
 Title: Relative Antioxidant Activities of Quercetin and Its Structurally Related Substances and Their Effects on NF-κB/CRE/AP-1 Signaling in Murine Macrophages

Ex Output:

False