TASK DEFINITION: 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".
PROBLEM: Paragraph: Human rhinovirus 3C protease (HRV 3C pro ) is known to be a promising target for development of therapeutic agents against the common cold because of the importance of the protease in viral replication as well as its expression in a large number of serotypes. To explore non-peptidic inhibitors of HRV 3C pro , a series of novel heteroaromatic esters was synthesized and evaluated for inhibitory activity against HRV 3C pro , to determine the structure-activity relationships. The most potent inhibitor, 7, with a 5-bromopyridinyl group, had an IC 50 value of 80 nM. In addition, the binding mode of a novel analog, 19, with the 4hydroxyquinolinone moiety, was explored by molecular docking, suggesting a new interaction in the S1 pocket. Ó 2009 Elsevier Ltd. All rights reserved. Picornaviruses include important human pathogens such as human rhinovirus (HRV), enterovirus (EV), coxsackievirus (CV), poliovirus (PV), and hepatitis A virus (HAV). HRVs are the single major cause of the common cold in populations of all ages. 1,2 Although rhinovirus infection is self-limiting, complications still occur in patients with asthma, congestive heart failure, bronchiectasis, and cystic fibrosis. 1 To date, no agent has been approved by the FDA for treatment of rhinovirus infection. In addition, the large number (>100) of known HRV serotypes makes vaccine development difficult. 3 Clinical treatments are directed toward relief of the most prominent symptoms of each clinical syndrome. Previous work on anti-rhinoviral therapeutic agents focused principally on capsid-binding anti-picornaviral compounds 4 and HRV 3C protease (3C pro ) inhibitors. 5, 6 HRV 3C pro is essential for virus replication, specifically catalyzing the cleavage of glutamine-glycine peptide bonds in a 230 kDa viral polyprotein produced by cellular translation of the viral RNA genome. HRV 3C pro belongs to the cysteine protease family, showing structural similarity to trypsin proteases, but sharing minimal homology with common mammalian enzymes. 7,8 Because of the importance of the enzyme in viral replication, and the high conservation of enzyme active site components in all known HRV serotypes, potent and selective HRV 3C pro inhibitors could be potential broad-spectrum anti-rhinoviral therapeutic agents. [9] [10] [11] As part of an effort to develop HRV 3C pro inhibitors, peptidomimetic approaches have been widely employed based on active site structure and cleavage specificity. To date, one peptidomimetic analog, rupintrivir (AG7088) (1), shown in Figure 1 , is the only HRV 3C Pro inhibitor that has advanced to the stage of human clinical trials. Phase II clinical trials of rupintrivir showed that intranasal delivery reduced the mean total daily symptom score by 33%. 12 Recently, several efforts to develop orally bioavailable anti-rhinoviral agents have been reported; these include a rupintrivir analog, 2, 13 with an improved pharmacokinetic profile, and the non-peptidic inhibitors 3 and 4. 14-16 The crystal structure of severe acute respiratory syndrome (SARS) coronavirus 3C-like protease (3CL pro ) 17 revealed a high similarity of active site architecture to that of HRV 3C pro , suggesting that picornavirus 3C pro and SARS 3CL pro inhibitors should cross-react. In fact, SARS 3CL pro inhibitors were developed by modifying rupintrivir 18 and common inhibitors with IC 50 values in the micromolar range were recently identified for both picornavirus 3C pro and coronavirus 3CL pro using high-throughput screening. 19,20 The pyridinyl thiophene ester 5 was discovered by screening a small molecule library (50,000 molecules) and has significant inhibitory activity against both HAV 3C pro and SARS 3CL pro (IC 50 = 0.5 lM). 19, 21 Further work on a series of heteroaromatic esters resulted in the discovery of the most potent ester 6, inhibiting SARS 3CL pro with an IC 50 of 30 nM and an antiviral activity (EC 50 value) of 6.9 lM. 22 Another analog, 7, also showed potent inhibition of HAV 3C pro with an IC 50 of 53 nM. 23 Studies on the inhibitory and molecular docking mechanisms of heteroaromatic esters have shown that the 5-halopyridine moiety is crucial in binding to the S1 pocket, because both 3C pro and 3CL pro show high specificity for Gln as the P1 residue. 23 0960-894X/$ -see front matter Ó 
 Title: Structure-activity relationships of heteroaromatic esters as human rhinovirus 3C protease inhibitors

SOLUTION: True

PROBLEM: Paragraph: Background: The purpose of this study is to determine the incidence and significance of hypouricemia in patients with severe acute respiratory syndrome (SARS). Pulmonary lesions in patients with SARS are thought to result from proinflammatory cytokine dysregulation. Acute renal failure has been reported in patients with SARS, but whether cytokines can injure renal tubules is unknown. Methods: Sixty patients diagnosed with SARS in Taiwan in April 2003 were studied. Patients were identified as hypouricemic when their serum uric acid (UA) level was less than 2.5 mg/dL (<149 mol/L) within 15 days after fever onset. Urine UA and creatinine levels were available for 43 patients; the serum cytokines interleukin-6 (IL-6), IL-8, and tumor necrosis factor-␣ (TNF-␣) were measured in 16 patients. Results: Sixteen patients (26.7%) had hypouricemia (UA, 1.68 ؎ 0.52 mg/dL [100 ؎ 31 mol/L]). No differences in age, sex, symptoms, vital signs, hemogram, or other biochemistry data existed between the hypouricemic and normouricemic groups. Fractional excretion (FE) of UA (FE UA ) in 12 hypouricemic patients was 39.6% ؎ 23.4%, significantly greater than that of 31 normouricemic patients (16.4% ؎ 11.4%; P < 0.0001). After adjustments for age and sex, high FE UA was significantly associated with the lowest blood oxygenation (P ‫؍‬ 0.001; r ‫؍‬ ؊0.624). The number of catastrophic outcomes (endotracheal intubation and/or death) adjusted for older age and sex showed that hypouremic patients had an odds ratio of 10.57 (confidence interval, 2.33 to 47.98; P ‫؍‬ 0.002). Kaplan-Meier curves for catastrophic outcome-free results showed significant differences between patients with normouricemia or hypouricemia (P ‫؍‬ 0.01). Serum IL-8 levels correlated significantly with FE UA (P < 0.001; r ‫؍‬ 0.785) and inversely with serum UA level (P ‫؍‬ 0.044; r ‫؍‬ ؊0.509); neither IL-6 nor TNF-␣ level showed such correlations. Conclusion: One fourth of patients with SARS developed hypouricemia, which might result from a defect in renal UA handling and was associated with a high serum IL-8 level. Renal hypouricemia is an ominous sign in patients with SARS. Am J Kidney Dis 45:88 -95. 
 Title: Renal Hypouricemia Is an Ominous Sign in Patients With Severe Acute Respiratory Syndrome

SOLUTION: True

PROBLEM: Paragraph: We present a unique and informative instance of respiratory syncytial virus (RSV) infection associated with antiphospholipid syndrome (APS), and discuss this case in the context of the literature addressing the immunopathogenesis of APS associated with diverse infections. We describe the case of a 43-yearold man with no significant past medical history who presented with the acute onset of fever, hemoptysis, and extensive bullous, ecchymotic lesions in both lower extremities. Punch biopsy of the lesion demonstrated thrombotic vasculopathy. Further evaluation revealed serum antiphospholipid antibodies as well as a positive RSV PCR in a nasal swab specimen. Clinical manifestations, positive laboratory and pathological findings were strongly suggestive of APS associated with a recent RSV infection. When an infectious etiology is considered for APS, RSV should also be included in the differential diagnosis. 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). We present what, to our knowledge, is the first reported case of antiphospholipid syndrome (APS) associated with Respiratory Syncytial Virus (RSV) infection. APS is a disorder characterized by vascular thrombosis, or pregnancy-related morbidity, in the presence of antiphospholipid (aPL) antibodies [1]. APS is classified as either primary or secondary, and secondary APS is associated with autoimmune disease, infection, medication or malignancy [2] . RSV is a common causative agent of acute viral upper and lower respiratory tract infection throughout all age groups. Despite the common occurrence of RSV respiratory infections, an association or possible causal relationship between RSV and APS has not to our knowledge been discussed previously. We report a case where progressive, extensive ecchymoses appeared to be the initial manifestation of APS occurring in temporal association with, and seemingly triggered by, a recent episode of RSV infection. A 43-year-old male with no significant past medical history presented during the month of December with a 4-day history of fever (maximum temperature 38.8 C), shaking chills, hemoptysis and worsening dyspnea. He had experienced intermittent night sweats, pain and swelling of both wrists and ankle joints over the last several months. He also reported a 10 kg weight loss during this time, but never sought medical attention. He had noted a painful ecchymotic lesion on his left calf one day prior to the admission. Over the subsequent 24 h, the patient developed similar lesions on his abdomen, back, right upper arm and right calf. The patient's 3 year old son had recently had a respiratory illness. On physical examination, the patient had a temperature of 35.3 C, blood pressure of 117/75 mmHg, pulse rate of 112 beats/ min, respiratory rate of 29 breaths/min, and an oxygen saturation of 96% on room air. There were bilateral lung wheezes, and multiple painful ecchymosis with several hemorrhagic bullae over his trunk and extremities (Fig. 1) . CBC on admission showed WBC 9000/mm3 (87% neutrophils) and Hemoglobin 13.4 g/dL, and comprehensive metabolic panel including electrolytes, liver and renal function was all within normal range. The significant laboratory data included high lactate dehydrogenase of 799 IU/L, erythrocyte sedimentation rate of 81 mm/h, and C-reactive protein level of 38.5 mg/dL. The Xray and computed tomography (CT) of the * Corresponding author. Present address: Azumabashi 1-23-30, River Pier Azumabashi Room 2707, Sumida-ku, 
 Title: Case report Fulminant ecchymosis as the initial manifestation of antiphospholipid syndrome (APS) triggered by respiratory syncytial virus (RSV) infection: A case report and review of the literature

SOLUTION:
False