***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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Output:

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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:  Falls are a leading reason for older people presenting to the emergency department (ED), and many experience further falls. Little evidence exists to guide secondary prevention in this population. This randomised controlled trial (RCT) investigated whether a 6-month telephone-based patient-centred program—RESPOND—had an effect on falls and fall injuries in older people presenting to the ED after a fall.
Community-dwelling people aged 60–90 years presenting to the ED with a fall and planned for discharge home within 72 hours were recruited from two EDs in Australia. Participants were enrolled if they could walk without hands-on assistance, use a telephone, and were free of cognitive impairment (Mini-Mental State Examination > 23). Recruitment occurred between 1 April 2014 and 29 June 2015. Participants were randomised to receive either RESPOND (intervention) or usual care (control). RESPOND comprised (1) home-based risk assessment; (2) 6 months telephone-based education, coaching, goal setting, and support for evidence-based risk factor management; and (3) linkages to existing services. Primary outcomes were falls and fall injuries in the 12-month follow-up. Secondary outcomes included ED presentations, hospital admissions, fractures, death, falls risk, falls efficacy, and quality of life. Assessors blind to group allocation collected outcome data via postal calendars, telephone follow-up, and hospital records. There were 430 people in the primary outcome analysis—217 randomised to RESPOND and 213 to control. The mean age of participants was 73 years; 55% were female. Falls per person-year were 1.15 in the RESPOND group and 1.83 in the control (incidence rate ratio [IRR] 0.65 [95% CI 0.43–0.99]; P = 0.042). There was no significant difference in fall injuries (IRR 0.81 [0.51–1.29]; P = 0.374). The rate of fractures was significantly lower in the RESPOND group compared with the control (0.05 versus 0.12; IRR 0.37 [95% CI 0.15–0.91]; P = 0.03), but there were no significant differences in other secondary outcomes between groups: ED presentations, hospitalisations or falls risk, falls efficacy, and quality of life. There were two deaths in the RESPOND group and one in the control group. No adverse events or unintended harm were reported. Limitations of this study were the high number of dropouts (n = 93); possible underreporting of falls, fall injuries, and hospitalisations across both groups; and the relatively small number of fracture events.
In this study, providing a telephone-based, patient-centred falls prevention program reduced falls but not fall injuries, in older people presenting to the ED with a fall. Among secondary outcomes, only fractures reduced. Adopting patient-centred strategies into routine clinical practice for falls prevention could offer an opportunity to improve outcomes and reduce falls in patients attending the ED.
Australian New Zealand Clinical Trials Registry (ACTRN12614000336684).


Output:

Falls are a leading reason that older adults present to emergency departments (EDs).
There is systematic review evidence for interventions to reduce falls in older people living in the community.
When similar interventions are applied to those presenting to the ED with a fall, there is a lack of effectiveness.
A randomised-controlled trial was undertaken to investigate whether a 6-month telephone-based patient-centred program—RESPOND—reduced falls and fall injuries in older people presenting to the ED after a fall.
RESPOND is a patient-centred falls prevention program developed specifically for community-dwelling older people presenting to the ED with a fall. It consists of a home-based risk assessment; 6 months telephone-based education, coaching, goal setting, and support for evidence-based risk factor management; and linkages to existing services.
RESPOND had an effect on falls and fractures but not fall injuries.
Our study provides evidence for a telephone-based, patient-centred falls prevention program to reduce falls and fractures in older people presenting to the ED with a fall.
This approach may empower and support older people to participate in falls prevention activities.
