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| 1 | 3D assessment of intervertebral disc degeneration in zebrafish identifies changes in bone density that prime disc disease显示文摘Back pain is a common condition with a high social impact and represents a global health burden.Intervertebral disc disease(IVDD)is one of the major causes of back pain;no therapeutics are currently available to reverse this disease.The impact of bone mineral density(BMD)on IVDD has been controversial,with some studies suggesting osteoporosis as causative for IVDD and others suggesting it as protective for IVDD.Functional studies to evaluate the influence of genetic components of BMD in IVDD could highlight opportunities for drug development and repurposing.By taking a holistic 3D approach,we established an aging zebrafish model for spontaneous IVDD.Increased BMD in aging,detected by automated computational analysis,is caused by bone deformities at the endplates.However,aged zebrafish spines showed changes in bone morphology,microstructure,mineral heterogeneity,and increased fragility that resembled osteoporosis.Elements of the discs recapitulated IVDD symptoms found in humans:the intervertebral ligament(equivalent to the annulus fibrosus)showed disorganized collagen fibers and herniation,while the disc center(nucleus pulposus equivalent)showed dehydration and cellular abnormalities.We manipulated BMD in young zebrafish by mutating sp7 and cathepsin K,leading to low and high BMD,respectively.Remarkably,we detected IVDD in both groups,demonstrating that low BMD does not protect against IVDD,and we found a strong correlation between high BMD and IVDD.Deep learning was applied to high-resolution synchrotron\iCJ image data to analyze osteocyte 3D lacunar distribution and morphology,revealing a role of sp7 in controlling the osteocyte lacunar 3D profile.Our findings suggest potential avenues through which bone quality can be targeted to identify beneficial therapeutics for IVDD. | Erika Kague Francesco Turci Elis Newman Yushi Yang Kate Robson Brown Mona S.Aglan Ghada A.Otaify Sarnia A.Temtamy Victor L.Ruiz-Perez Stephen Cross C.Patrick Royall P.Eckhard Witten Chrissy L.Hammond | 2021 | Bone Research2021，9，4： | 2 |
| 2 | Computed tomography evaluation of the inner ear as a diagnostic,counseling and management strategy in patients with congenital sensorineural hearing impairment显示文摘 | CROSS N C STEPHENS S D G FRANCIS M | 1999 | Clin Otolaryngol1999，24，： | 1 |
| 3 | A Relational View of Information Seeking and Learningin Social Networks 显示文摘 | Borgatti Stephen P Cross Rob | 2003 | Management Science2003，49，4： | 1 |
| 4 | A diet containing myristoleic plus palmitoleic acids elevates plasma cholesterol in young growing swine显示文摘 | Dana R. Smith Darrell A. Knabe H. Russell Cross Stephen B. Smith | 1996 | Lipids1996，，8： | 1 |
| 5 | Safety of thrombolysis in association with cardiopulmonary resuscitation显示文摘 | Stephen J Cross Shiang Lee John MR | 1991 | Br Med J1991，303，： | 1 |
| 6 | Computed tomography evaluation of the inner ear as a diagnostic,counseling and management strategy in patients with congenital sensorineural hearing impairment显示文摘 | CROSS N C STEPHENS S D G FRANCIS M | 1999 | Clin Otolaryngol1999，24，： | 1 |
| 7 | Effects of social stressors on cardiovascular reactivity in black and white women显示文摘 | Stephen J. Lepore Tracey A. Revenson Sarah L. Weinberger Peter Weston Pasquale G. Frisina Rommel Robertson Minerva Mentor Portillo Hollie Jones William Cross | 2006 | Annals of Behavioral Medicine2006，，2： | 1 |
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| 9 | Insularity and Accessibility: the Small Island Communities of Western Ireland 显示文摘 | Michael Cross Stephen Nutley | 1999 | Journal of Rural Studies1999，15，3： | 1 |
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