***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:  Dizziness is common among older people and is associated with a cascade of debilitating symptoms, such as reduced quality of life, depression, and falls. The multifactorial aetiology of dizziness is a major barrier to establishing a clear diagnosis and offering effective therapeutic interventions. Only a few multidisciplinary interventions of dizziness have been conducted to date, all of a pilot nature and none tailoring the intervention to the specific causes of dizziness. Here, we aimed to test the hypothesis that a multidisciplinary dizziness assessment followed by a tailored multifaceted intervention would reduce dizziness handicap and self-reported dizziness as well as enhance balance and gait in people aged 50 years and over with dizziness symptoms.
We conducted a 6-month, single-blind, parallel-group randomized controlled trial in community-living people aged 50 years and over who reported dizziness in the past year. We excluded individuals currently receiving treatment for their dizziness, those with degenerative neurological conditions including cognitive impairment, those unable to walk 20 meters, and those identified at baseline assessment with conditions that required urgent treatment. Our team of geriatrician, vestibular neuroscientist, psychologist, exercise physiologist, study coordinator, and baseline assessor held case conferences fortnightly to discuss and recommend appropriate therapy (or therapies) for each participant, based on their multidisciplinary baseline assessments. A total of 305 men and women aged 50 to 92 years (mean [SD] age: 67.8 [8.3] years; 62% women) were randomly assigned to either usual care (control; n = 151) or to a tailored, multifaceted intervention (n = 154) comprising one or more of the following: a physiotherapist-led vestibular rehabilitation programme (35% [n = 54]), an 8-week internet-based cognitive-behavioural therapy (CBT) (19% [n = 29]), a 6-month Otago home-based exercise programme (24% [n = 37]), and/or medical management (40% [n = 62]). We were unable to identify a cause of dizziness in 71 participants (23% of total sample). Primary outcome measures comprised dizziness burden measured with the Dizziness Handicap Inventory (DHI) score, frequency of dizziness episodes recorded with monthly calendars over the 6-month follow-up, choice-stepping reaction time (CSRT), and gait variability. Data from 274 participants (90%; 137 per group) were included in the intention-to-treat analysis. At trial completion, the DHI scores in the intervention group (pre and post mean [SD]: 25.9 [19.2] and 20.4 [17.7], respectively) were significantly reduced compared with the control group (pre and post mean [SD]: 23.0 [15.8] and 21.8 [16.4]), when controlling for baseline scores (mean [95% CI] difference between groups [baseline adjusted]: −3.7 [−6.2 to −1.2]; p = 0.003). There were no significant between-group differences in dizziness episodes (relative risk [RR] [95% CI]: 0.87 [0.65 to 1.17]; p = 0.360), CSRT performance (mean [95% CI] difference between groups [baseline adjusted]: −15 [−40 to 10]; p = 0.246), and step-time variability during gait (mean [95% CI] difference between groups [baseline adjusted]: −0.001 [−0.002 to 0.001]; p = 0.497). No serious intervention-related adverse events occurred. Study limitations included the low initial dizziness severity of the participants and the only fair uptake of the falls clinic (medical management) and the CBT interventions.
A multifactorial tailored approach for treating dizziness was effective in reducing dizziness handicap in community-living people aged 50 years and older. No difference was seen on the other primary outcomes. Our findings therefore support the implementation of individualized, multifaceted evidence-based therapies to reduce self-perceived disability associated with dizziness in middle-aged and older people.
Australian New Zealand Clinical Trials Registry ACTRN12612000379819.


Output:

Dizziness is a frequent complaint amongst middle-aged and older people.
Dizziness can lead to poor health outcomes, including reduced quality of life, depression, and falls.
The increasingly multifactorial nature of dizziness with advancing age makes it difficult to objectively establish a diagnosis and offer effective interventions.
Although few multidisciplinary studies have been conducted, none to date have examined whether tailoring the intervention to the specific cause(s) of dizziness can improve dizziness in middle-aged and older community-dwellers.
We assessed 305 community-dwellers aged 50 years and above who reported dizziness in the past year on a range of questionnaires and tests of sensory and physical function, mental health, quality of life, and cardiovascular function, at baseline and 6 months.
We randomly assigned the participants to usual care (control; n = 151) or to a 6-month tailored, multifaceted intervention (n = 154) comprising one or more of the following: vestibular rehabilitation (35% [n = 54]), cognitive-behavioural therapy (CBT) for anxiety and depression (19% [n = 29]), a home-based exercise programme to train balance and lower-limb strength (24% [n = 37]), and/or medical management (40% [n = 62]).
We found that the multifactorial tailored intervention was effective in improving dizziness-related quality of life but did not affect balance, gait, or the frequency of dizziness episodes over 6 months.
Our pragmatic study findings suggest that prescribing middle-aged and older people with dizziness evidence-based therapies directly targeting their deficits is likely to reduce their dizziness handicap but might not improve their physical function.
Low-dizziness handicap on entry to the study and the inclusion of participants not currently receiving a dizziness treatment might partly explain the lack of intervention effect on balance and gait, as well as explain why we were unable to identify a cause of dizziness in 71 participants (23% of total sample).
We suggest that community-based dizziness clinics use existing healthcare services to implement tailored and multifaceted dizziness interventions based on multidisciplinary assessments.
