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  • 1
    In: Journal of Bone and Mineral Research, Wiley, Vol. 35, No. 2 ( 2020-02), p. 382-395
    Abstract: Periodontitis is a bacterially induced chronic inflammatory condition of the oral cavity where tooth‐supporting tissues including alveolar bone are destructed. Previously, we have shown that the adaptor protein SH3‐domain binding protein 2 (SH3BP2) plays a critical role in inflammatory response and osteoclastogenesis of myeloid lineage cells through spleen tyrosine kinase (SYK). In this study, we show that SH3BP2 is a novel regulator for alveolar bone resorption in periodontitis. Micro‐CT analysis of SH3BP2‐deficient ( Sh3bp2 −/− ) mice challenged with ligature‐induced periodontitis revealed that Sh3bp2 −/− mice develop decreased alveolar bone loss (male 14.9% ± 10.2%; female 19.0% ± 6.0%) compared with wild‐type control mice (male 25.3% ± 5.8%; female 30.8% ± 5.8%). Lack of SH3BP2 did not change the inflammatory cytokine expression and osteoclast induction. Conditional knockout of SH3BP2 and SYK in myeloid lineage cells with LysM‐Cre mice recapitulated the reduced bone loss without affecting both inflammatory cytokine expression and osteoclast induction, suggesting that the SH3BP2‐SYK axis plays a key role in regulating alveolar bone loss by mechanisms that regulate the bone‐resorbing function of osteoclasts rather than differentiation. Administration of a new SYK inhibitor GS‐9973 before or after periodontitis induction reduced bone resorption without affecting inflammatory reaction in gingival tissues. In vitro, GS‐9973 treatment of bone marrow–derived M‐CSF‐dependent macrophages suppressed tartrate‐resistant acid phosphatase (TRAP)‐positive osteoclast formation with decreased mineral resorption capacity even when GS‐9973 was added after RANKL stimulation. Thus, the data suggest that SH3BP2‐SYK is a novel signaling axis for regulating alveolar bone loss in periodontitis and that SYK can be a potential therapeutic target to suppress alveolar bone resorption in periodontal diseases. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.
    Type of Medium: Online Resource
    ISSN: 0884-0431 , 1523-4681
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2008867-X
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  • 2
    In: Journal of Shoulder and Elbow Surgery, Elsevier BV, Vol. 30, No. 7 ( 2021-07), p. e430-e431
    Type of Medium: Online Resource
    ISSN: 1058-2746
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2046901-9
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  • 3
    In: Journal of Shoulder and Elbow Surgery, Elsevier BV, Vol. 30, No. 7 ( 2021-07), p. e430-
    Type of Medium: Online Resource
    ISSN: 1058-2746
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2046901-9
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  • 4
    In: Seminars in Arthroplasty: JSES, Elsevier BV, Vol. 30, No. 1 ( 2020-05), p. 28-34
    Type of Medium: Online Resource
    ISSN: 1045-4527
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2260910-6
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  • 5
    In: Arthroscopy: The Journal of Arthroscopic & Related Surgery, Elsevier BV, Vol. 37, No. 3 ( 2021-03), p. 964-971
    Type of Medium: Online Resource
    ISSN: 0749-8063
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 1491233-8
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  • 6
    In: JBMR Plus, Wiley, Vol. 4, No. 6 ( 2020-06)
    Abstract: Cherubism (OMIM#118400) is a craniofacial disorder characterized by destructive jaw expansion. Gain‐of‐function mutations in SH3‐domain binding protein 2 (SH3BP2) are responsible for this rare disorder. We have previously shown that homozygous knock‐in (KI) mice ( Sh3bp2 KI/KI ) recapitulate human cherubism by developing inflammatory lesions in the jaw. However, it remains unknown why heterozygous KI mice ( Sh3bp2 KI/+ ) do not recapitulate the excessive jawbone destruction in human cherubism, even though all mutations are heterozygous in humans. We hypothesized that Sh3bp2 KI/+ mice need to be challenged for developing exacerbated jawbone destruction and that bacterial stimulation in the oral cavity may be involved in the mechanism. In this study, we applied a ligature‐induced periodontitis model to Sh3bp2 KI/+ mice to induce inflammatory alveolar bone destruction. Ligature placement induced alveolar bone resorption with gingival inflammation. Quantification of alveolar bone volume revealed that Sh3bp2 KI/+ mice developed more severe bone loss (male: 43.0% ± 10.6%, female: 42.6% ± 10.4%) compared with Sh3bp2 +/+ mice (male: 25.8% ± 4.0%, female: 30.9% ± 6.5%). Measurement of bone loss by the cement‐enamel junction–alveolar bone crest distance showed no difference between Sh3bp2 KI/+ and Sh3bp2 +/+ mice. The number of osteoclasts on the alveolar bone surface was higher in male Sh3bp2 KI/+ mice, but not in females, compared with Sh3bp2 +/+ mice. In contrast, inflammatory cytokine levels in gingiva were comparable between Sh3bp2 KI/+ and Sh3bp2 +/+ mice with ligatures. Genetic deletion of the spleen tyrosine kinase in myeloid cells and antibiotic treatment suppressed alveolar bone loss in Sh3bp2 KI/+ mice, suggesting that increased osteoclast differentiation and function mediated by SYK and accumulation of oral bacteria are responsible for the increased alveolar bone loss in Sh3bp2 KI/+ mice with ligature‐induced periodontitis. High amounts of oral bacterial load caused by insufficient oral hygiene could be a trigger for the initiation of jawbone destruction in human cherubism. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
    Type of Medium: Online Resource
    ISSN: 2473-4039 , 2473-4039
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2905710-3
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  • 7
    In: Seminars in Arthroplasty: JSES, Elsevier BV, Vol. 30, No. 2 ( 2020-07), p. 154-161
    Type of Medium: Online Resource
    ISSN: 1045-4527
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2260910-6
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  • 8
    In: JMIR Mental Health, JMIR Publications Inc., Vol. 8, No. 8 ( 2021-8-10), p. e27589-
    Abstract: Although effective mental health treatments exist, the ability to match individuals to optimal treatments is poor, and timely assessment of response is difficult. One reason for these challenges is the lack of objective measurement of psychiatric symptoms. Sensors and active tasks recorded by smartphones provide a low-burden, low-cost, and scalable way to capture real-world data from patients that could augment clinical decision-making and move the field of mental health closer to measurement-based care. Objective This study tests the feasibility of a fully remote study on individuals with self-reported depression using an Android-based smartphone app to collect subjective and objective measures associated with depression severity. The goals of this pilot study are to develop an engaging user interface for high task adherence through user-centered design; test the quality of collected data from passive sensors; start building clinically relevant behavioral measures (features) from passive sensors and active inputs; and preliminarily explore connections between these features and depression severity. Methods A total of 600 participants were asked to download the study app to join this fully remote, observational 12-week study. The app passively collected 20 sensor data streams (eg, ambient audio level, location, and inertial measurement units), and participants were asked to complete daily survey tasks, weekly voice diaries, and the clinically validated Patient Health Questionnaire (PHQ-9) self-survey. Pairwise correlations between derived behavioral features (eg, weekly minutes spent at home) and PHQ-9 were computed. Using these behavioral features, we also constructed an elastic net penalized multivariate logistic regression model predicting depressed versus nondepressed PHQ-9 scores (ie, dichotomized PHQ-9). Results A total of 415 individuals logged into the app. Over the course of the 12-week study, these participants completed 83.35% (4151/4980) of the PHQ-9s. Applying data sufficiency rules for minimally necessary daily and weekly data resulted in 3779 participant-weeks of data across 384 participants. Using a subset of 34 behavioral features, we found that 11 features showed a significant (P 〈 .001 Benjamini-Hochberg adjusted) Spearman correlation with weekly PHQ-9, including voice diary–derived word sentiment and ambient audio levels. Restricting the data to those cases in which all 34 behavioral features were present, we had available 1013 participant-weeks from 186 participants. The logistic regression model predicting depression status resulted in a 10-fold cross-validated mean area under the curve of 0.656 (SD 0.079). Conclusions This study finds a strong proof of concept for the use of a smartphone-based assessment of depression outcomes. Behavioral features derived from passive sensors and active tasks show promising correlations with a validated clinical measure of depression (PHQ-9). Future work is needed to increase scale that may permit the construction of more complex (eg, nonlinear) predictive models and better handle data missingness.
    Type of Medium: Online Resource
    ISSN: 2368-7959
    Language: English
    Publisher: JMIR Publications Inc.
    Publication Date: 2021
    detail.hit.zdb_id: 2798262-2
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  • 9
    Online Resource
    Online Resource
    SAGE Publications ; 2020
    In:  Orthopaedic Journal of Sports Medicine Vol. 8, No. 7_suppl6 ( 2020-07-01), p. 2325967120S0048-
    In: Orthopaedic Journal of Sports Medicine, SAGE Publications, Vol. 8, No. 7_suppl6 ( 2020-07-01), p. 2325967120S0048-
    Abstract: The Patient-Reported Outcomes Measurement Information System (PROMIS) is emerging as a valid and efficient means of collecting patient outcomes in patients with meniscal tears. Our purpose was to examine the role of pre-operative PROMIS computer adaptive test (CAT) scores in predicting post-operative PROMIS CAT scores, as well as the minimal clinically important difference (MCID) following meniscectomy. We hypothesize that pre-operative PROMIS CAT scores will directly impact both post-operative PROMIS CAT scores and likelihood of achieving MCID. Methods: Patients undergoing arthroscopic meniscectomy that completed PROMIS CAT forms for physical function (PROMIS-PF), pain interference (PROMIS-PI), and depression (PROMIS-D) were utilized. MCID was calculated according to the distribution methodology, and receiver operating characteristics (ROC) were utilized to determine if pre-operative scores were predictive of post-operative outcomes. Preoperative cutoffs were used to predict which patients would likely meet MCID, using 90% specificity. Results: A total of 135 patients met our inclusion criteria. PROMIS-PF, PROMIS-PI, and PROMIS-D improved 3 months after surgery (p 〈 0.01). 62% of the entire cohort met MCID for PROMIS-PF, while 68% met MCID for PROMIS-PI, and 41% met MCID for PROMIS-D. Individuals with PROMIS-PF scores below 34.9 yielded an 82% probability of achieving MCID, while PROMIS-PI scores above 67.5 yielded an 86% probability of achieving MCID and a cutoff of 58.9 for PROMIS-D yielded a 60% probability of achieving MCID, with 90% specificity. Conclusions: Significant portions of patients undergoing meniscectomy achieve MCID in PROMIS-PF, PROMIS-PI, and PROMIS-D, at the 3-month time point. In particular, patients with PROMIS-PF scores of 〈 34.9 are far more likely to achieve MCID for physical function.
    Type of Medium: Online Resource
    ISSN: 2325-9671 , 2325-9671
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
    detail.hit.zdb_id: 2706251-X
    SSG: 31
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  • 10
    Online Resource
    Online Resource
    SAGE Publications ; 2021
    In:  Orthopaedic Journal of Sports Medicine Vol. 9, No. 1 ( 2021-01-01), p. 232596712097019-
    In: Orthopaedic Journal of Sports Medicine, SAGE Publications, Vol. 9, No. 1 ( 2021-01-01), p. 232596712097019-
    Abstract: Multiple studies have demonstrated the National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS) to be a responsive and efficient measure for patients undergoing orthopaedic surgery. While these studies were rigorous in their protocol and methodology, no efforts in recent literature have been made to identify if these reference scores apply to elite athletes. Purpose/Hypothesis: The purpose of this study was to determine whether there is a difference in the baseline scores of elite athletes versus the general population. We hypothesized that athletes’ PROMIS upper extremity general function (PROMIS-UE) and general physical function (PROMIS-PF) scores would vary substantially from the mean health state of the general population. We further hypothesized that these scores would be affected by specific sport and level of competition Study Design: Cross-sectional study; Level of evidence, 3. Methods: Three PROMIS computer adaptive test (CAT) domains were administered to elite athlete (≥18 years) volunteers (either in person or through email). An elite athlete was defined as one participating in sports at the collegiate level or higher. Test domains included PROMIS-PF, PROMIS-UE, and pain interference (PROMIS-PI). PROMIS domain t scores were defined and assessed against NIH reference values to identify significant differences. Distribution analysis was conducted using histograms and normality assessments. Domains were also subject to correlation analysis. Finally, subgroup analysis was conducted for all athlete characteristics to identify any factors associated with variance. Results: In total, 196 elite athletes (mean age, 21.1 years; range, 18.0-36.7 years) completed all 3 PROMIS-CAT forms. Overall, the mean scores were 56.0 ± 6.4, 58.1 ± 7.7, and 47.1 ± 7.3 for PROMIS-UE, PROMIS-PF, and PROMIS-PI, respectively. Distribution analysis showed nonnormal distribution for all 3 PROMIS domains (Kolmogorov-Smirnov test, P 〈 .001). Similarly, in all 3 PROMIS domains the athletes displayed more disparate scores than the NIH-reported reference values (1-way sign test, P 〈 .001). Only the presence of pain and sport played showed association with variance in PROMIS domain scores ( P 〈 .001 and P = .003, respectively). Conclusion: Elite athletes displayed more disparate reference scores than the NIH-reported average of 50 for PROMIS-UE, PROMIS-PF, and PROMIS-PI. Furthermore, these forms were sensitive to varying levels of sport among collegiate athletes.
    Type of Medium: Online Resource
    ISSN: 2325-9671 , 2325-9671
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
    detail.hit.zdb_id: 2706251-X
    SSG: 31
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