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  • 1
    Online Resource
    Online Resource
    Transstellar Journal Publications and Research Consultancy Private Limited ; 2020
    In:  International Journal of Mechanical and Production Engineering Research and Development Vol. 10, No. 3 ( 2020), p. 3073-3080
    In: International Journal of Mechanical and Production Engineering Research and Development, Transstellar Journal Publications and Research Consultancy Private Limited, Vol. 10, No. 3 ( 2020), p. 3073-3080
    Type of Medium: Online Resource
    ISSN: 2249-6890
    Language: English
    Publisher: Transstellar Journal Publications and Research Consultancy Private Limited
    Publication Date: 2020
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  • 2
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2010
    In:  Solar Physics Vol. 266, No. 2 ( 2010-10), p. 247-259
    In: Solar Physics, Springer Science and Business Media LLC, Vol. 266, No. 2 ( 2010-10), p. 247-259
    Type of Medium: Online Resource
    ISSN: 0038-0938 , 1573-093X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
    detail.hit.zdb_id: 2211848-2
    detail.hit.zdb_id: 1473830-2
    SSG: 16,12
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  • 3
    In: Life Science Alliance, Life Science Alliance, LLC, Vol. 5, No. 1 ( 2022-01), p. e202101211-
    Abstract: Metallocarboxypeptidases play critical roles in the development of mosquitoes and influence pathogen/parasite infection of the mosquito midgut. Here, we report the crystal structure of Aedes aegypti procarboxypeptidase B1 (PCPBAe1), characterized its substrate specificity and mechanism of binding to and inhibiting Dengue virus (DENV). We show that the activated PCPBAe1 (CPBAe1) hydrolyzes both Arg- and Lys-substrates, which is modulated by residues Asp 251 and Ser 239 . Notably, these residues are conserved in CPBs across mosquito species, possibly required for efficient digestion of basic dietary residues that are necessary for mosquito reproduction and development. Importantly, we characterized the interaction between PCPBAe1 and DENV envelope (E) protein, virus-like particles, and infectious virions. We identified residues Asp 18A , Glu 19A , Glu 85 , Arg 87 , and Arg 89 of PCPBAe1 are essential for interaction with DENV. PCPBAe1 maps to the dimeric interface of the E protein domains I/II (Lys 64 –Glu 84 , Val 238 –Val 252 , and Leu 278 –Leu 287 ). Overall, our studies provide general insights into how the substrate-binding property of mosquito carboxypeptidases could be targeted to potentially control mosquito populations or proposes a mechanism by which PCPBAe1 binds to and inhibits DENV.
    Type of Medium: Online Resource
    ISSN: 2575-1077
    Language: English
    Publisher: Life Science Alliance, LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2948687-7
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  • 4
    Online Resource
    Online Resource
    American Astronomical Society ; 2007
    In:  The Astrophysical Journal Vol. 657, No. 1 ( 2007-03), p. 592-599
    In: The Astrophysical Journal, American Astronomical Society, Vol. 657, No. 1 ( 2007-03), p. 592-599
    Type of Medium: Online Resource
    ISSN: 0004-637X , 1538-4357
    URL: Issue
    RVK:
    Language: English
    Publisher: American Astronomical Society
    Publication Date: 2007
    detail.hit.zdb_id: 2207648-7
    detail.hit.zdb_id: 1473835-1
    SSG: 16,12
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  • 5
    In: Pediatric Rheumatology, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2022-12)
    Abstract: To report baseline characteristics, patient reported outcomes and treatment of children with Juvenile Dermatomyositis (JDM) in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Methods Children newly diagnosed with JDM were enrolled in the CARRA Registry from 41 pediatric rheumatology centers. Baseline patient demographics, disease characteristics, assessments, patient reported outcome and treatments were recorded. Results In the first year, 119 JDM participants were enrolled. Most were female (63.4%), and white (72.3%) with a median diagnosis age 8.0 years (IQR 4.0–11.5), and median age of disease onset 7.0 years (IQR 3.5–7.5). They had characteristic rashes (92.4%), elevated muscle enzymes (83.2%), physician global score 4.0 (IQR 2.5–5.0) and manual muscle testing score 63.5 (IQR 51.0–75.0). Calcinosis (3.4%) and interstitial lung disease ( 〈  1%) were uncommon. Myositis specific antibodies were measured and reported in nearly half of participants enrolled where anti-MJ followed by Anti-p155/140 were most common (11/49 and 7/53 respectively). Childhood Health Assessment Questionnaire (CHAQ) results showed mild-moderate disability (median 0.750, IQR 0.030–1.875), as did patient/parent global assessments of disease activity (median 3, patient IQR: 1.75–5.25; parent IQR: 1–7). Patient Reported Outcomes Measurement Information System (PROMIS®) Pediatric Global Health 7 scores, Pain Interference, Physical Function scores for Mobility, and Upper Extremity Function were commonly worse than 95% of the general pediatric population. Conclusions In its inaugural year, 119 JDM patients were successfully enrolled in participapte in the New CARRA Registy. This registry will provide the necessary foundation to advance clinical research to improve outcomes using traditional measures and patient reported outcomes. With the CARRA biorepository, this infrastructure will enable future translational research. Together, these efforts may aid in future clinical trials, including comparative effectiveness trials.
    Type of Medium: Online Resource
    ISSN: 1546-0096
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2279468-2
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  • 6
    In: Rheumatology, Oxford University Press (OUP), Vol. 62, No. 2 ( 2023-02-01), p. 804-814
    Abstract: To describe 2-year trajectories of the clinical Juvenile Arthritis Disease Activity Score, 10 joints (cJADAS10) and associated baseline characteristics in patients with JIA. Methods JIA patients in the Childhood Arthritis and Rheumatology Research Alliance Registry enrolled within 3 months of diagnosis from 15 June 2015 to 6 December 2017 with at least two cJADAS10 scores and 24 months of follow-up were included. Latent growth curve models of cJADAS10 were analysed; a combination of Bayesian information criterion, posterior probabilities and clinical judgement was used to select model of best fit. Results Five trajectories were identified among the 746 included patients: High, Rapidly Decreasing (HRD) (n = 199, 26.7%); High, Slowly Decreasing (HSD) (n = 154, 20.6%); High, Increasing (HI) (n = 39, 5.2%); Moderate, Persistent (MP) (n = 218, 29.2%); and Moderate, Decreasing (MD) (n = 136, 18.2%). Most patients spent a significant portion of time at moderate to high disease activity levels. At baseline, HSD patients were more likely to be older, have a lower physician global assessment, normal inflammatory markers, longer time to first biologic, and have taken systemic steroids compared with HRD. Those with a HI trajectory were more likely to be ANA negative, have a longer time to first biologic, and less likely to be taking a conventional synthetic DMARD compared with HRD. MP patients were more likely to be older with lower household income, longer time to diagnosis, and markers of higher disease activity than those with a MD trajectory. Conclusions Five trajectories of JIA disease activity, and associated baseline variables, were identified.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474143-X
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  • 7
    In: Pediatric Rheumatology, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2021-12)
    Abstract: The impact of social determinants of health on children with polyarticular juvenile idiopathic arthritis (pJIA) is poorly understood. Prompt initiation of treatment for pJIA is important to prevent disease morbidity; however, a potential barrier to early treatment of pJIAs is delayed presentation to a pediatric rheumatologist. We examined the impact of community poverty level, a key social determinant of health, on time from patient reported symptom onset to first pediatric rheumatology visit among pJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Methods This is a cohort study of pJIA patients in the CARRA registry who lived in the United States from July 2015–February 2020. The primary exposure was community poverty level derived by geocoding patient addresses. The primary outcome was time to first rheumatology appointment. Kaplan-Meier analysis was performed to analyze time to first rheumatologist visit, stratified by community poverty and family income. Log-rank tests were used to identify differences between groups. Adjusted cox proportional-hazards models were used to determine the relationship between community poverty level and time from onset of disease symptoms to date first seen by rheumatologist. Results A total of 1684 patients with pJIA meeting study inclusion and exclusion criteria were identified. Median age of onset of pJIA was 7 years (IQR 3, 11), 79% were female, 17.6% identified as minority race and/or ethnicity, and 19% were from communities with ≥20% community poverty level. Kaplan-Meier analysis by community poverty level ( 〈  20% vs ≥20%) yielded no significant differences with time to initial presentation to a pediatric rheumatologist ( p  = 0.6). The Cox proportional hazards model showed that patients with ≥20% community poverty level were 19% less likely (adjusted HR 0.81, 95% CI 0.67–0.99, p  = 0.038) to be seen by a rheumatologist compared to patients with 〈  20% community poverty level, at the same time point, after adjusting for sex, race/ethnicity, insurance, education level, morning stiffness, RF status, and baseline CHAQ. Conclusion In this study of pJIA patients in the CARRA registry, increased community poverty level is associated with longer time to presentation to a pediatric rheumatologist after symptom onset.
    Type of Medium: Online Resource
    ISSN: 1546-0096
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2279468-2
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  • 8
    In: Pediatric Rheumatology, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2021-12)
    Abstract: We aimed to characterize etanercept (ETN) use in juvenile idiopathic arthritis (JIA) patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Methods The CARRA Registry is a convenience cohort of patients with paediatric onset rheumatic diseases, including JIA. JIA patients treated with ETN for whom the month and year of ETN initiation were available were included. Patterns of ETN and methotrexate (MTX) use were categorized as follows: combination therapy (ETN and MTX started concurrently), step-up therapy (MTX started first and ETN added later), switchers (MTX started and then stopped when or before ETN started), MTX add-on (ETN started first and MTX added later), and ETN only (no MTX use). Data were described using parametric and non-parametric statistics as appropriate. Results Two thousand thirty-two of the five thousand six hundred forty-one patients with JIA met inclusion criteria (74% female, median age at diagnosis 6.0 years [interquartile range 2.0, 11.0]. Most patients (66.9%) were treated with a non-biologic disease modifying anti-rheumatic drug (DMARD), primarily MTX, prior to ETN. There was significant variability in patterns of MTX use prior to starting ETN. Step-up therapy was the most common approach. Only 34.0% of persistent oligoarticular JIA patients continued treatment with a non-biologic DMARD 3 months or more after ETN initiation. ETN persistence overall was 66.3, 49.4, and 37.3% at 24, 36 and 48 months respectively. ETN persistence among spondyloarthritis patients (enthesitis related arthritis and psoriatic JIA) varied by MTX initiation pattern, with higher ETN persistence rates in those who initiated combination therapy (68.9%) and switchers/ETN only (73.3%) patients compared to step-up (65.4%) and MTX add-on (51.1%) therapy. Conclusion This study characterizes contemporary patterns of ETN use in the CARRA Registry. Treatment was largely in keeping with American College of Rheumatology guidelines.
    Type of Medium: Online Resource
    ISSN: 1546-0096
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2279468-2
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  • 9
    In: Pediatric Rheumatology, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2022-12)
    Abstract: Social determinants of health (SDH) greatly influence outcomes during the first year of treatment in rheumatoid arthritis, a disease similar to polyarticular juvenile idiopathic arthritis (pJIA). We investigated the correlation of community poverty level and other SDH with the persistence of moderate to severe disease activity and functional disability over the first year of treatment in pJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry. Methods In this cohort study, unadjusted and adjusted generalized linear mixed effects models analyzed the effect of community poverty and other SDH on disease activity, using the clinical Juvenile Arthritis Disease Activity Score-10, and disability, using the Child Health Assessment Questionnaire, measured at baseline, 6, and 12 months. Results One thousand six hundred eighty-four patients were identified. High community poverty (≥20% living below the federal poverty level) was associated with increased odds of functional disability (OR 1.82, 95% CI 1.28-2.60) but was not statistically significant after adjustment (aOR 1.23, 95% CI 0.81-1.86) and was not associated with increased disease activity. Non-white race/ethnicity was associated with higher disease activity (aOR 2.48, 95% CI: 1.41-4.36). Lower self-reported household income was associated with higher disease activity and persistent functional disability. Public insurance (aOR 1.56, 95% CI 1.06-2.29) and low family education (aOR 1.89, 95% CI 1.14-3.12) was associated with persistent functional disability. Conclusion High community poverty level was associated with persistent functional disability in unadjusted analysis but not with persistent moderate to high disease activity. Race/ethnicity and other SDH were associated with persistent disease activity and functional disability.
    Type of Medium: Online Resource
    ISSN: 1546-0096
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2279468-2
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  • 10
    In: Pediatric Rheumatology, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2022-11-25)
    Abstract: Children with juvenile idiopathic arthritis (JIA) who achieve a drug free remission often experience a flare of their disease requiring either intraarticular steroids (IAS) or systemic treatment with disease modifying anti-rheumatic drugs (DMARDs). IAS offer an opportunity to recapture disease control and avoid exposure to side effects from systemic immunosuppression. We examined a cohort of patients treated with IAS after drug free remission and report the probability of restarting systemic treatment within 12 months. Methods We analyzed a cohort of patients from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry who received IAS for a flare after a period of drug free remission. Historical factors and clinical characteristics and of the patients including data obtained at the time of treatment were analyzed. Results We identified 46 patients who met the inclusion criteria. Of those with follow up data available 49% had restarted systemic treatment 6 months after IAS injection and 70% had restarted systemic treatment at 12 months. The proportion of patients with prior use of a biologic DMARD was the only factor that differed between patients who restarted systemic treatment those who did not, both at 6 months (79% vs 35%, p   〈  0.01) and 12 months (81% vs 33%, p   〈  0.05). Conclusion While IAS are an option for all patients who flare after drug free remission, it may not prevent the need to restart systemic treatment. Prior use of a biologic DMARD may predict lack of success for IAS. Those who previously received methotrexate only, on the other hand, are excellent candidates for IAS.
    Type of Medium: Online Resource
    ISSN: 1546-0096
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2279468-2
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