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the task is to simplify the input abstract of a biomedical literature

***INPUT***
the input is the abstract of a biomedical literature

***OUTPUT***
the output is the simplified abstract for the input abstract of a biomedical literature
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Input: Functionally analogous enzymes are those that catalyze similar reactions on similar substrates but do not share common ancestry, providing a window on the different structural strategies nature has used to evolve required catalysts. Identification and use of this information to improve reaction classification and computational annotation of enzymes newly discovered in the genome projects would benefit from systematic determination of reaction similarities. Here, we quantified similarity in bond changes for overall reactions and catalytic mechanisms for 95 pairs of functionally analogous enzymes (non-homologous enzymes with identical first three numbers of their EC codes) from the MACiE database. Similarity of overall reactions was computed by comparing the sets of bond changes in the transformations from substrates to products. For similarity of mechanisms, sets of bond changes occurring in each mechanistic step were compared; these similarities were then used to guide global and local alignments of mechanistic steps. Using this metric, only 44% of pairs of functionally analogous enzymes in the dataset had significantly similar overall reactions. For these enzymes, convergence to the same mechanism occurred in 33% of cases, with most pairs having at least one identical mechanistic step. Using our metric, overall reaction similarity serves as an upper bound for mechanistic similarity in functional analogs. For example, the four carbon-oxygen lyases acting on phosphates (EC 4.2.3) show neither significant overall reaction similarity nor significant mechanistic similarity. By contrast, the three carboxylic-ester hydrolases (EC 3.1.1) catalyze overall reactions with identical bond changes and have converged to almost identical mechanisms. The large proportion of enzyme pairs that do not show significant overall reaction similarity (56%) suggests that at least for the functionally analogous enzymes studied here, more stringent criteria could be used to refine definitions of EC sub-subclasses for improved discrimination in their classification of enzyme reactions. The results also indicate that mechanistic convergence of reaction steps is widespread, suggesting that quantitative measurement of mechanistic similarity can inform approaches for functional annotation.
Output:  When species evolve, their genes duplicate and diverge to allow for adaptation of their functional repertoires to the changing environment. In this scenario, unrelated genes can convergently evolve to produce proteins with the same molecular function, termed “functionally analogous.” A quantitative determination of the reaction similarities among functionally analogous enzymes could provide insight about the different structural solutions nature has used to evolve similar catalysts. Bond changes between substrates and products, and between successive reaction intermediates, were used to compare the reactions catalyzed and the mechanisms of catalysis for 95 pairs of functionally analogous enzymes. Less than half of the reactions catalyzed by unrelated enzymes, but defined as similar by the Enzyme Commission (EC) classification, are similar in terms of bond changes, suggesting that this classification often fails to capture quantitative differences between many enzyme reactions. Furthermore, we addressed for the first time whether the chemical mechanisms by which similar overall reactions are achieved in functional analogs are also similar. We conclude that convergence of reaction is often accompanied by convergence of chemical mechanism. These results will be useful for classifying enzymes, guiding functional annotation of newly determined enzyme sequences and structures and for informing the engineering of enzymes with new functions.

Input:  During December 2013, the first locally transmitted chikungunya virus (CHIKV) infections in the Americas were reported in the Caribbean. Although CHIKV infection is rarely fatal, risk for severe disease increases with age and medical comorbidities. Herein we describe characteristics of Veterans Health Administration (VHA) patients with CHIKV infection and, among those with infections diagnosed in Puerto Rico, investigated risk factors for hospitalization.
We queried VHA’s national electronic medical records to identify patients with CHIKV testing during 2014. Demographics, clinical history, laboratory results, and outcomes were abstracted. We investigated risk factors for hospitalization among patients with laboratory-confirmed CHIKV infection in Puerto Rico.
We identified 180 laboratory-confirmed CHIKV infections; 148 (82.2%) were diagnosed in Puerto Rico, and 32 (17.8%) were diagnosed among returning travelers elsewhere in the United States. In Puerto Rico, where more patients were hospitalized (55.4% versus 20.0%) and died (4.1% versus 0%), risk for hospitalization increased with age (relative risk [RR]/each 10-year increase, 1.19; 95% confidence interval [CI], 1.06–1.32) and, adjusted for age, increased among patients with congestive heart failure (RR, 1.58; 95% CI, 1.25–1.99), chronic kidney disease (RR, 1.52; 95% CI, 1.19–1.94), diabetes mellitus (RR, 1.39; 95% CI, 1.06–1.84), or chronic lung disease (RR, 1.37; 95% CI, 1.03–1.82).
CHIKV infection is an emerging problem among Veterans residing in or visiting areas with CHIKV transmission. Although overall mortality rates are low, clinicians in affected areas should be aware that older patients and patients with comorbidities may be at increased risk for severe disease.


Output:

Infection with mosquito-borne chikungunya virus causes fever and severe diffuse joint pain—an illness known as chikungunya fever, or "that which bends up." Epidemics of chikungunya fever have occurred in Asia, Africa, and Europe. Not until December 2013 were there reports of chikungunya virus infection occurring in the Americas. Since then, it has involved most countries in the Western Hemisphere with >1.1 million cases reported by the end of 2014. Previous data from the Réunion Island outbreak demonstrated that older patients and patients with certain chronic medical conditions may have a higher risk of severe disease. The Veterans Health Administration is the largest health care system in the United States and has facilities in U.S. territories, including Puerto Rico, which has been heavily affected by this epidemic. Among Veterans in Puerto Rico, we investigated risk factors for severe disease and described all chikungunya-associated deaths. Risk for hospitalization increased with age, and for patients of the same age, was increased among those with congestive heart failure, chronic kidney disease, diabetes, or chronic lung disease. Further work is needed to determine whether prevention strategies targeted to those who may be at greatest risk for severe disease could help decrease morbidity and mortality among these populations.
