TASK DEFINITION: In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
PROBLEM: The Pneumonia Etiology Research for Child Health (PERCH) project is the largest multicountry etiology study of childhood pneumonia since the Board on Science and Technology in International Development studies of the 1980s. However, it is not the only recent or ongoing pneumonia etiology study, and even with seven sites, it cannot capture all epidemiologic settings in the developing world. Funding providers, researchers and policymakers rely on the best available evidence to strategically plan programs, new research directions and interventions. We aimed to describe the current landscape of recent pneumonia etiology studies in children under 5 years of age in the developed and developing world, as ascertained by a literature review of relevant studies with data since the year 2000 and a survey of researchers in the field of childhood pneumonia. We collected information on the study population, study design, case definitions, laboratory samples and methods and identified pathogens. A literature review identified 88 studies with child pneumonia etiology results. As of June 2010, our survey of researchers identified an additional 65 ongoing and recently completed child pneumonia etiology studies. This demonstrates the broad existing context into which the PERCH study must be placed. However, the landscape analysis also reveals a multiplicity of case definitions, levels of clinician involvement, facility types, specimen collection, and laboratory techniques. It reinforces the need for the standardization of methods and analyses for present and future pneumonia etiology studies in order to optimize their cumulative potential to accurately describe the microbial causes of childhood pneumonia. Each year, approximately 1.6 million children die from pneumonia [1]. The Pneumonia Etiology Research for Child Health (PERCH) study is the largest multisite study of childhood pneumonia since the Board of Science and Technology for International Development (BOSTID) studies were done in the 1980s [2] . The goal of PERCH is to identify the expected etiologies of pneumonia in 2015, a time when the burden of the major causes of bacterial pneumonia in the developing world, Streptococcus pneumoniae and Haemophilus influenzae type b (Hib), will likely be significantly reduced by widespread introduction and use of conjugate vaccines. Moreover, PERCH capitalizes upon new molecular diagnostic techniques that were not available 2 decades ago when the BOSTID studies were carried out. Another salient difference between PERCH and the BOSTID studies is that the 7 sites participating in PERCH will follow a highly standardized protocol, which includes standardization of enrollment criteria, specimen collection, and laboratory testing. Although PERCH is the largest multicountry, childhood pneumonia etiology study in developing countries that has been conducted in the past 2 decades, it is not the only contemporary pneumonia etiology study, and cannot capture the entire complexity of all epidemiologic settings. In recent years, many developed and developing country sites have initiated pneumonia studies that provide etiology data. These studies will

SOLUTION: A Literature Review and Survey of Childhood Pneumonia Etiology Studies: 2000-2010

PROBLEM: There are currently no non-human primate models with fully defined major histocompatibility complex (MHC) class II genetics. We recently showed that 6 common MHC haplotypes account for essentially all MHC diversity in cynomolgus macaques (Macaca fascicularis) from the island of Mauritius. Here we employ cDNA cloning and sequencing to comprehensively characterize full length MHC class II alleles expressed at the Mafa-DPA, -DPB, -DQA, -DQB, -DRA, and -DRB loci on the 6 common haplotypes. We describe 34 full-length MHC class II alleles, 12 of which are completely novel. Polymorphism was evident at all six loci, including DPA which is considered monomorphic in rhesus macaques. Similar to other old world monkeys, Mauritian cynomolgus macaques (MCM) share MHC class II allelic lineages with humans at the DQ and DR loci, but not at the DP loci. Additionally, we identified extensive sharing of MHC class II alleles between MCM and other non-human primates. The characterization of these full length expressed MHC class II alleles will enable researchers to generate MHC class II transferent cell lines and tetramers that can be used to explore CD4+ T-lymphocyte responses in MCM.

SOLUTION: Comprehensive characterization of MHC class II haplotypes in Mauritian cynomolgus macaques

PROBLEM: Interferon-stimulated genes (ISGs) are a group of gene products that coordinately combat pathogen invasions, in particular viral infections. Transcription of ISGs occurs rapidly upon pathogen invasion, and this is classically provoked via activation of the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway, mainly by interferons (IFNs). However, a plethora of recent studies have reported a variety of non-canonical mechanisms regulating ISG transcription. These new studies are extremely important for understanding the quantitative and temporal differences in ISG transcription under specific circumstances. Because these canonical and non-canonical regulatory mechanisms are essential for defining the nature of host defense and associated detrimental proinflammatory effects, we comprehensively review the state of this rapidly evolving field and the clinical implications of recently acquired knowledge in this respect. IFN-mediated innate immune response forms a forward line of cell-autonomous defense against pathogens. Virus invasion (e.g., the presence of single-stranded RNA in endosomes or cytosolic double-stranded RNA) triggers the host cells to recognize the infection through pattern recognition receptors (PRRs), that in turn mediate the production of IFNs [1]. The thusreleased IFN molecules bind to cell-surface receptors and initiate signal transduction prominently involving the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway. This activates the transcription of hundreds of so-called ISGs that are the effectors of cell-autonomous antiviral defense. Representative and well-studied ISG members with specific or broad antiviral activities include RIG-I, MDA5, MX2, IRF1, IRF3, IRF7, IRF9, IFITM3, ISG15, and OASL [2]. ISGs act at different stages of the viral life cycle, from entry, replication, assembly to release. This leads to a remarkable antiviral state that provides adequate cellular immunity against positive-, negative-, and double-stranded RNA viruses, DNA viruses, and even intracellular bacteria and parasites. Although the JAK-STAT pathway plays key roles in regulating ISG transcription, a far more complex cell signaling network with both canonical and non-canonical mechanisms is involved [3] . The signaling strength, kinetics, and specificity of regulatory pathways on ISG transcription are modulated at various levels by distinct mechanisms operating in conjunction. Understanding the different mechanisms of ISG transcription and how their modes of action relate to clinically used antiviral medications will provide new insights into virus-host interactions and novel avenues for antiviral drug development. Therefore, we aim to comprehensively review the classical and non-classical mechanisms regulating ISG transcription with emphasis on their clinical implications. Transcriptional regulation of ISGs defines the state of host anti-pathogen defense. In light of the recently identified regulatory elements and mechanisms of the IFN-JAK-STAT pathway, new insights have been gained into this classical cascade in regulating ISG transcription. A variety of non-canonical mechanisms have been recently revealed that coordinately regulate ISG transcription. With regards to the adverse effects of IFNs in clinic, ISG-based antiviral strategy could be the next promising frontier in drug discovery.

SOLUTION:
Transcriptional Regulation of Antiviral Interferon-Stimulated Genes