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1.
Qian Zhang Larry D. Mesner Gina M. Calabrese Naomi Dirckx Zhu Li Angela Verardo Qian Yang Robert J. Tower Marie-Claude Faugere Charles R. Farber Thomas L. Clemens 《The Journal of clinical investigation》2021,131(7)
Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass. 相似文献
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Angela Mauro Salvatore Mauro Roberto Rega Luigi Martemucci Rita Sottile 《Pediatric dermatology》2019,36(1):e34-e36
Henoch‐Schonlein purpura (HSP) is the most common systemic vasculitis in childhood. There is no consensus about the management for isolated cutaneous manifestations in HSP. We describe a case of HSP presenting with severe skin lesions that did not respond to standard therapy with corticosteroids. The 11‐year‐old child was treated with intravenous immunoglobulins, which induced rapid and persistent resolution of symptomatology. 相似文献
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Angela J. Jacques-Tiura Deborah A. Ellis April Idalski Carcone Sylvie Naar Kathryn Brogan Hartlieb Elizabeth K. Towner Thomas N. Templin K.-L. Catherine Jen 《The Journal of adolescent health》2019,64(3):355-361
Objective
Successful weight loss interventions for African-Americans adolescents are lacking. Cognitive-behavioral interventions seek to develop weight loss skills (e.g., counting calories, goal setting, managing one's environment). Little is known about how well adolescents implement such skills in their daily lives. Study aims were to (1) examine weight loss skills utilization at midpoint and end of a 6-month cognitive-behavioral/motivational interviewing weight loss sequential multiple assignment randomized trial (SMART), and (2) determine if greater skill utilization predicted weight loss at treatment end and 3 months post-treatment.Method
One hundred and eighty six African-Americans adolescents with obesity and their caregiver were first randomly assigned to complete 3 months of cognitive-behavioral and motivational interviewing family-based weight loss treatment in their home or in the research office (Phase 1). Nonresponders (i.e., those who lost < 3% of initial weight, n?=?161) were rerandomized to 3 months of continued skills training (n?=?83) or contingency management (n?=?78) for Phase 2; responders were allocated to 3 months of relapse prevention (n?=?20). Adolescents’ frequency of weight loss skills utilization was assessed via questionnaire at treatment midpoint and end.Results
Higher treatment attendance was associated with better skill utilization. Higher skill utilization was associated with more weight loss at treatment end, whereas higher baseline confidence was associated with more weight loss at follow-up.Conclusions
This study indicates the importance of attending weight loss intervention sessions to develop and strengthen weight loss skills in African-American adolescents with obesity, and strengthening confidence to use such skills for continued weight loss. 相似文献6.
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Thomas Asendorf Robin Henderson Heinz Schmidli Tim Friede 《Statistics in medicine》2019,38(9):1503-1528
In some diseases, such as multiple sclerosis, lesion counts obtained from magnetic resonance imaging (MRI) are used as markers of disease progression. This leads to longitudinal, and typically overdispersed, count data outcomes in clinical trials. Models for such data invariably include a number of nuisance parameters, which can be difficult to specify at the planning stage, leading to considerable uncertainty in sample size specification. Consequently, blinded sample size re-estimation procedures are used, allowing for an adjustment of the sample size within an ongoing trial by estimating relevant nuisance parameters at an interim point, without compromising trial integrity. To date, the methods available for re-estimation have required an assumption that the mean count is time-constant within patients. We propose a new modeling approach that maintains the advantages of established procedures but allows for general underlying and treatment-specific time trends in the mean response. A simulation study is conducted to assess the effectiveness of blinded sample size re-estimation methods over fixed designs. Sample sizes attained through blinded sample size re-estimation procedures are shown to maintain the desired study power without inflating the Type I error rate and the procedure is demonstrated on MRI data from a recent study in multiple sclerosis. 相似文献
9.
Sarah E. Henderson Shana A. Hall Jessica M. Callegari James A. Desjardins Sidney J. Segalowitz Karen L. Campbell 《Psychophysiology》2022,59(1):e13947
Recent work suggests that while voluntary episodic memory declines with age, involuntary episodic memory, which comes to mind spontaneously without intention, remains relatively intact. However, the neurophysiology underlying these differences has yet to be established. The current study used electroencephalography (EEG) to investigate voluntary and involuntary retrieval in older and younger adults. Participants first encoded sounds, half of which were paired with pictures, the other half unpaired. EEG was then recorded as they listened to the sounds, with participants in the involuntary group performing a sound localization cover task, and those in the voluntary group additionally attempting to recall the associated pictures. Participants later reported which sounds brought the paired picture to mind during the localization task. Reaction times on the localization task were slower for voluntary than involuntary retrieval and for paired than unpaired sounds, possibly reflecting increased attentional demands of voluntary retrieval and interference from reactivation of the associated pictures respectively. For the EEG analyses, young adults showed greater alpha event-related desynchronization (ERD) during voluntary than involuntary retrieval at frontal and occipital sites, while older adults showed pronounced alpha ERD regardless of intention. Additionally, older adults showed greater ERD for paired than unpaired sounds at occipital sites, likely reflecting visual reactivation of the associated pictures. Young adults did not show this alpha ERD memory effect. Taken together, these data suggest that involuntary memory is largely preserved with age, but this may be due to older adults' greater recruitment of top-down control even when demand for such control is limited. 相似文献
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