TASK DEFINITION: Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: Recently, it has been shown that exposure to welding fumes containing both zinc and copper leads to asymptomatic systemic inflammation in humans as shown by an increase of blood C-reactive protein. In the present study, it was investigated which metal is responsible for this effect.', 'Fifteen healthy male subjects were exposed under controlled conditions to welding fumes containing either zinc, or copper, or copper and zinc.', 'For each exposure blood C-reactive protein increased.

SOLUTION: Does single and Combined Exposure to Zinc- and Copper-Containing Welding Fumes lead to Asymptomatic Systemic Inflammation?

PROBLEM: Precise long-term assessment of movement and physical function following Achilles tendon rupture is required for the development and evaluation of treatment, including different regimens of physical therapy.', 'To assess intermediate-term (<10 years by conventional thinking) objective measures of physical function following Achilles tendon rupture treated nonsurgically and to compare these with self-reported measures of physical function.', 'Cross-sectional study; Level of evidence, 3.', 'Two to 5 years after Achilles tendon rupture, 9 women and 43 men (mean age, 49.2 years; range, 26-68 years) were assessed by physical examination, performance of 1-legged jumps, and 3-dimensional gait analysis (including calculation of muscle work). Self-reported scores for foot function (Achilles tendon rupture score) and level of physical activity were collected. Twenty age- and sex-matched controls were assessed in the same manner.', 'Physical examination of patients with the knee extended revealed 11.1° of dorsiflexion on the injured side and 9.2° on the uninjured side (P = .020), indicating gastrocnemius muscle lengthening. The 1-legged jump distance was shorter on the injured side (89.5 vs 96.2 cm; P < .001). Gait analysis showed higher peak dorsiflexion (14.3° vs 13.3°; P = .016) and lower concentric (positive) plantar flexor work (16.6 vs 19.9 J/kg; P = .001) in the ankle on the uninjured side. At the same time, eccentric (negative) dorsiflexor work was higher on the injured side (13.2 vs 11.9 J/kg; P = .010). Self-perceived foot function and physical activity were lower in patients than in healthy controls (mean Achilles tendon rupture score, 78.6 and 99.8, respectively).

SOLUTION: Does three-Dimensional Gait Analysis Following Achilles Tendon Rupture With Nonsurgical Treatment reveal Long-Term Deficiencies in Muscle Strength and Function?

PROBLEM: Detection of drug-induced pro-arrhythmic risk is a primary concern for pharmaceutical companies and regulators. Increased risk is linked to prolongation of the QT interval on the body surface ECG. Recent studies have shown that multiple ion channel interactions can be required to predict changes in ventricular repolarisation and therefore QT intervals. In this study we attempt to predict the result of the human clinical Thorough QT (TQT) study, using multiple ion channel screening which is available early in drug development.', "Ion current reduction was measured, in the presence of marketed drugs which have had a TQT study, for channels encoded by hERG, CaV1.2, NaV1.5, KCNQ1/MinK, and Kv4.3/KChIP2.2. The screen was performed on two platforms - IonWorks Quattro (all 5 channels, 34 compounds), and IonWorks Barracuda (hERG & CaV1.2, 26 compounds). Concentration-effect curves were fitted to the resulting data, and used to calculate a percentage reduction in each current at a given concentration. Action potential simulations were then performed using the ten Tusscher and Panfilov (2006), Grandi et al. (2010) and O'Hara et al. (2011) human ventricular action potential models, pacing at 1Hz and running to steady state, for a range of concentrations.", 'We compared simulated action potential duration predictions with the QT prolongation observed in the TQT studies. At the estimated concentrations, simulations tended to underestimate any observed QT prolongation. When considering a wider range of concentrations, and conventional patch clamp rather than screening data for hERG, prolongation of ≥5ms was predicted with up to 79% sensitivity and 100% specificity.

SOLUTION:
Does prediction of Thorough QT study result using action potential simulations based on ion channel screens?