Objective
This open‐label, 24‐week study was conducted to evaluate the safety and efficacy of abatacept in patients with refractory juvenile dermatomyositis (DM).
Methods
Ten patients ≥7 years of age ...with moderate disease activity were enrolled in a 24‐week study to examine the safety of subcutaneous abatacept and patient responses to the treatment. The primary endpoint was the International Myositis Assessment and Clinical Studies (IMACS) group Definition Of Improvement (DOI). Secondary endpoints included safety, changes in the core set activity measures (CSMs) of the IMACS group and the Pediatric Rheumatology International Trials Organization, and improvements in disease activity based on the American College of Rheumatology (ACR)/EULAR response criteria for juvenile DM. Radiologists blinded with regard to participant data assessed magnetic resonance images (MRIs) of patient thigh muscles. Interferon (IFN)–regulated gene score was performed on whole‐blood RNA samples using a NanoString assay, and cytokines were assessed using a Luminex assay.
Results
Five patients achieved DOI at week 12, and 9 patients achieved DOI at week 24, including 2 patients with minimal, 4 patients with moderate, and 3 patients with major improvement by the 2016 ACR/EULAR response criteria for juvenile DM when patients were assessed using the CSMs of the IMACS Group. Improvements from baseline were seen in all CSMs at weeks 12 and 24, except in muscle enzymes. Daily glucocorticoid doses decreased from a mean of 16.7 mg at baseline to 10.2 mg at week 24 (P = 0.002). Average MRI muscle edema scores decreased from a mean baseline score of 5.3 to 2.3 at week 24 (P = 0.01). Six patients had down‐trending IFN‐regulated gene scores and galectin‐9 expression at week 24. Decreases in IFN‐regulated gene scores and in levels of interferon‐γ‐inducible protein 10kDa, galectin‐9, and interleukin‐2 correlated with improvements in disease activity and in muscle edema shown on MRI. Eleven grade 2 or 3 treatment‐emergent adverse events were observed.
Conclusion
This open‐label study demonstrated that abatacept may be beneficial for patients with treatment‐refractory juvenile DM.
Copy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted to identify shared ...etiology among NDDs, but this is the first genome-wide CNV analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) at once. Using microarray (Affymetrix CytoScan HD), we genotyped 2,691 subjects diagnosed with an NDD (204 SCZ, 1,838 ASD, 427 ADHD and 222 OCD) and 1,769 family members, mainly parents. We identified rare CNVs, defined as those found in <0.1% of 10,851 population control samples. We found clinically relevant CNVs (broadly defined) in 284 (10.5%) of total subjects, including 22 (10.8%) among subjects with SCZ, 209 (11.4%) with ASD, 40 (9.4%) with ADHD, and 13 (5.6%) with OCD. Among all NDD subjects, we identified 17 (0.63%) with aneuploidies and 115 (4.3%) with known genomic disorder variants. We searched further for genes impacted by different CNVs in multiple disorders. Examples of NDD-associated genes linked across more than one disorder (listed in order of occurrence frequency) are
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, and long non-coding RNAs:
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. We demonstrated that CNVs impacting the same genes could potentially contribute to the etiology of multiple NDDs. The CNVs identified will serve as a useful resource for both research and diagnostic laboratories for prioritization of variants.
The COVID-19 pandemic created a complex psychological environment for persons in America. A total of 450 USA MTurk workers completed measures of: (a) basic demographic characteristics; (b) health ...risk factors for COVID-19; (c) perceived susceptibility variables related to COVID-19; (d) COVID-19 preventive health behaviors; and (e) distress, physical symptoms, and quality of life measures. The surveys were completed between April 9, 2020 and April 18, 2020. This recruitment period corresponded to the first 2–3 weeks of lockdown in most of the USA. Follow-up surveys were completed by 151 of the USA participants between June 19, 2020 and July 11, 2020 (approximately 2 months after the first measurement).
These data permit evaluation of relationships among demographic variables, COVID-19 stress and coping, COVID-19 preventive health behavior, and the role of mindfulness as a possible moderator of distress as well as a predictor of preventive health behavior. The availability of follow-up data permit longitudinal analyses that provide a stronger basis for causal inference.
Sensitive mutation detection by next-generation sequencing is critical for early cancer detection, monitoring minimal/measurable residual disease (MRD), and guiding precision oncology. Nevertheless, ...because of artifacts introduced during library preparation and sequencing, the detection of low-frequency variants at high specificity is problematic. Here, we present Espresso, an error suppression method that considers local sequence features to accurately detect single-nucleotide variants (SNVs). Compared to other advanced error suppression techniques, Espresso consistently demonstrated lower numbers of false-positive mutation calls and greater sensitivity. We demonstrated Espresso's superior performance in detecting MRD in the peripheral blood of patients with acute myeloid leukemia (AML) throughout their treatment course. Furthermore, we showed that accurate mutation calling in a small number of informative genomic loci might provide a cost-efficient strategy for pragmatic risk prediction of AML development in healthy individuals. More broadly, we aim for Espresso to aid with accurate mutation detection in many other research and clinical settings.
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