***TASK***
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:  Low socioeconomic position (SEP) is recognized as a risk factor for worse health outcomes. How socioeconomic factors influence end-of-life care, and the magnitude of their effect, is not understood. This review aimed to synthesise and quantify the associations between measures of SEP and use of healthcare in the last year of life.
MEDLINE, EMBASE, PsycINFO, CINAHL, and ASSIA databases were searched without language restrictions from inception to 1 February 2019. We included empirical observational studies from high-income countries reporting an association between SEP (e.g., income, education, occupation, private medical insurance status, housing tenure, housing quality, or area-based deprivation) and place of death, plus use of acute care, specialist and nonspecialist end-of-life care, advance care planning, and quality of care in the last year of life. Methodological quality was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS). The overall strength and direction of associations was summarised, and where sufficient comparable data were available, adjusted odds ratios (ORs) were pooled and dose-response meta-regression performed.
A total of 209 studies were included (mean NOS quality score of 4.8); 112 high- to medium-quality observational studies were used in the meta-synthesis and meta-analysis (53.5% from North America, 31.0% from Europe, 8.5% from Australia, and 7.0% from Asia). Compared to people living in the least deprived neighbourhoods, people living in the most deprived neighbourhoods were more likely to die in hospital versus home (OR 1.30, 95% CI 1.23–1.38, p < 0.001), to receive acute hospital-based care in the last 3 months of life (OR 1.16, 95% CI 1.08–1.25, p < 0.001), and to not receive specialist palliative care (OR 1.13, 95% CI 1.07–1.19, p < 0.001). For every quintile increase in area deprivation, hospital versus home death was more likely (OR 1.07, 95% CI 1.05–1.08, p < 0.001), and not receiving specialist palliative care was more likely (OR 1.03, 95% CI 1.02–1.05, p < 0.001). Compared to the most educated (qualifications or years of education completed), the least educated people were more likely to not receive specialist palliative care (OR 1.26, 95% CI 1.07–1.49, p = 0.005).
The observational nature of the studies included and the focus on high-income countries limit the conclusions of this review.
In high-income countries, low SEP is a risk factor for hospital death as well as other indicators of potentially poor-quality end-of-life care, with evidence of a dose response indicating that inequality persists across the social stratum. These findings should stimulate widespread efforts to reduce socioeconomic inequality towards the end of life.


Output:

Social inequality in health is a global phenomenon; people with lower socioeconomic position (SEP) experience earlier onset of disease and have reduced life expectancy.
Studies have identified low SEP as a risk factor for worse care at the end of life, and several socioeconomic factors have been identified as determinants of care towards the end of life.
Despite growing recognition, no empirical synthesis of evidence exists to support efforts to reduce socioeconomic inequality at the end of life.
We carried out a systematic review of studies that reported an association between a measure of SEP (including income, education, occupation, private medical insurance status, housing tenure, housing quality, or area-based deprivation) and healthcare received by adults in their last year of life (including place of death, use of acute care, use of specialist palliative care, use of nonspecialist end-of-life care, use of advance care planning, or quality of care) in high-income countries.
A total of 209 studies were included in the review; we found consistent evidence that low SEP increases the odds of hospital versus home death and of using acute care services in the last 3 months of life and reduces the odds of using specialist palliative care in the last year of life.
We also found that measurement of SEP in this field is dominated by measures of area deprivation and education, and justification for choice of SEP measure(s) is often inadequately described.
We have found consistent evidence of socioeconomic inequality in the care received by people towards the end of life, in that people with lower SEP are more likely to experience worse care.
We must now make further efforts to reduce this inequality.
We recommend the following: that all research on care received towards the end of life should attempt to account for SEP, end-of-life care interventions should be analysed for their different effects across the social strata, and the planning and provision of end-of-life care services should consider SEP in local populations.
