Given a passage with a context and an answer, 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.

[Q]: Context: Aggrecanase cleavage at the 392Glu-393Ala bond in the interglobular domain (IGD) of aggrecan, releasing N-terminal 393ARGS fragments, is an early key event in arthritis and joint injuries. Here, we use a quantitative immunoassay of aggrecan ARGS neoepitope fragments in human synovial fluid to determine if this cleavage-site specific method better identifies joint pathology than previously available less specific aggrecan assays.', 'Synovial fluid (SF) from 26 people with healthy knees (reference) and 269 patients were analyzed in a cross-sectional study. Patient groups were acute inflammatory arthritis, acute knee injury, chronic knee injury and knee osteoarthritis (OA). Aggrecan ARGS fragments were assayed by ELISA using the monoclonal antibody OA-1. Total aggrecan content was analyzed by an ELISA using the monoclonal antibody 1-F21, and sulfated glycosaminoglycan by Alcian blue precipitation.', 'Aggrecan ARGS fragment concentrations in all groups differed from the reference group (P < 0.001). The acute inflammatory arthritis group had the highest median level, 177-fold greater than that of the reference group. Median levels (in pmol ARGS/ml SF) were: reference 0.5, acute inflammatory arthritis 88.5, acute knee injury 53.9, chronic knee injury 0.5 and OA 4.6. In contrast, aggrecan and sulfated glycosaminoglycan concentrations varied much less between groups, and only acute inflammatory arthritis and acute knee injury were found to have a two-fold increase in median levels compared to the reference.
Answer: Levels of aggrecan ARGS fragments in human synovial fluid are increased in human arthritis, OA and after knee injury, likely reflecting an enhanced cleavage at the 392Glu-393Ala bond in the IGD by aggrecanase. An assay that specifically quantified these fragments better distinguished samples from joints with pathology than assays monitoring aggrecan or glycosaminoglycan concentrations. The newly developed ARGS fragment assay can be used to monitor aggrecanase activity in human joint disease and experimental models.
[A]: Is synovial fluid level of aggrecan ARGS fragments a more sensitive marker of joint disease than glycosaminoglycan or aggrecan levels : a cross-sectional study?


[Q]: Context: Facial dog bite injuries pose a significant public health problem.', 'Seventy-five consecutive patients (45 males, 30 females) treated solely by plastic surgery service for facial dog bite injuries at a Level I trauma center in the Denver Metro area between 2006 and 2012 were retrospectively reviewed. The following information were recorded: breed, relationship of patient to dog, location and number of wounds, the duration between injury and surgical repair and dog bite incident, type of repair, and antibiotic prophylaxis. Primary end points measured were wound infection, the need for revision surgery, and patient satisfaction.', 'Ninety-eight wounds in the head and neck region were repaired (46 children; mean age, 6.8 years) and (29 adults; mean age, 47.3 years). Twelve different breeds were identified. There was no significant association between the type of dog breed and the number of bite injuries. The duration between injury and repair ranged from 4 hours to 72 hours (mean [SD], 13.7 [10.9] hours). The majority of bite wounds (76 of 98) involved the cheek, lip, nose, and chin region. Direct repair was the most common surgical approach (60 of 98 wounds) (p < 0.05). There was no statistically significant association between wounds needing reconstruction versus direct repair according to dog breed (p = 0.25). Ten wounds required grafting. Twenty-five wounds were managed by one-stage or two-stage flaps. Only three patients (3.06 %) underwent replantation/revascularization of amputated partial lip (n = 2) and of cheek (n = 1). There was one postoperative infection. Data from five-point Likert scale were available for fifty-two patients. Forty patients were satisfied (5) with the outcome, while five patients were somewhat satisfied (4), and seven were neutral.
Answer: Availability of the plastic surgery service at a Level I trauma center is vital for the optimal treatment of facial dog bite injuries. Direct repair and reconstruction of facial dog bite injuries at the earliest opportunity resulted in good outcomes as evidenced by the satisfaction survey data and low complication rate.
[A]: Do retrospective analysis of facial dog bite injuries at a Level I trauma center in the Denver metro area?


[Q]: Context: Cardiac function is dependent on the coordinate activities of membrane ion channels, transporters, pumps, and hormone receptors to tune the membrane electrochemical gradient dynamically in response to acute and chronic stress. Although our knowledge of membrane proteins has rapidly advanced during the past decade, our understanding of the subcellular pathways governing the trafficking and localization of integral membrane proteins is limited and essentially unstudied in vivo. In the heart, to our knowledge, there are no in vivo mechanistic studies that directly link endosome-based machinery with cardiac physiology.', 'To define the in vivo roles of endosome-based cellular machinery for cardiac membrane protein trafficking, myocyte excitability, and cardiac physiology.', 'We identify the endosome-based Eps15 homology domain 3 (EHD3) pathway as essential for cardiac physiology. EHD3-deficient hearts display structural and functional defects including bradycardia and rate variability, conduction block, and blunted response to adrenergic stimulation. Mechanistically, EHD3 is critical for membrane protein trafficking, because EHD3-deficient myocytes display reduced expression/localization of Na/Ca exchanger and L-type Ca channel type 1.2 with a parallel reduction in Na/Ca exchanger-mediated membrane current and Cav1.2-mediated membrane current. Functionally, EHD3-deficient myocytes show increased sarcoplasmic reticulum [Ca], increased spark frequency, and reduced expression/localization of ankyrin-B, a binding partner for EHD3 and Na/Ca exchanger. Finally, we show that in vivo EHD3-deficient defects are attributable to cardiac-specific roles of EHD3 because mice with cardiac-selective EHD3 deficiency demonstrate both structural and electric phenotypes.
Answer: These data provide new insight into the critical role of endosome-based pathways in membrane protein targeting and cardiac physiology. EHD3 is a critical component of protein trafficking in heart and is essential for the proper membrane targeting of select cellular proteins that maintain excitability.
[A]:
Does eHD3-dependent endosome pathway regulate cardiac membrane excitability and physiology?