Objective. Patients with rheumatic diseases such as rheumatoid arthritis (RA) and lupus have increased risk of infection and are treated with medications that may increase this risk yet are also hypothesized to help treat COVID-19. We set out to understand how the COVID-19 pandemic has impacted the lives of these patients in the United States.Methods. Participants in a US-wide longitudinal observational registry responded to a supplemental COVID-19 questionnaire by e-mail on March 25, 2020, about their symptoms, COVID-19 testing, health care changes, and related experiences during the prior 2 weeks. Analysis compared responses by diagnosis, disease activity, and new onset of symptoms. Qualitative analysis was conducted on optional free-text comment fields.Results. Of the 7061 participants invited to participate, 530 responded, with RA as the most frequent diagnosis (61%). Eleven participants met COVID-19 screening criteria, of whom two sought testing unsuccessfully. Six others sought testing, three of whom were successful, and all test results were negative. Not quite half of participants (42%) reported a change to their care in the prior 2 weeks. Qualitative analysis revealed four key themes: emotions in response to the pandemic, perceptions of risks from immunosuppressive medications, protective measures to reduce risk of COVID-19 infection, and disruptions in accessing rheumatic disease medications, including hydroxychloroquine.Conclusion. After 2 weeks, many participants with rheumatic diseases already had important changes to their health care, with many altering medications without professional consultation or because of hydroxychloroquine shortage. As evidence accumulates on the effectiveness of potential COVID-19 treatments, effort is needed to safeguard access to established treatments for rheumatic diseases.

BackgroundThe rhesus macaque (Macaca mulatta) is a key species for advancing biomedical research. Like all draft mammalian genomes, the draft rhesus assembly (rheMac2) has gaps, sequencing errors and misassemblies that have prevented automated annotation pipelines from functioning correctly. Another rhesus macaque assembly, CR_1.0, is also available but is substantially more fragmented than rheMac2 with smaller contigs and scaffolds. Annotations for these two assemblies are limited in completeness and accuracy. High quality assembly and annotation files are required for a wide range of studies including expression, genetic and evolutionary analyses.ResultsWe report a new de novo assembly of the rhesus macaque genome (MacaM) that incorporates both the original Sanger sequences used to assemble rheMac2 and new Illumina sequences from the same animal. MacaM has a weighted average (N50) contig size of 64 kilobases, more than twice the size of the rheMac2 assembly and almost five times the size of the CR_1.0 assembly. The MacaM chromosome assembly incorporates information from previously unutilized mapping data and preliminary annotation of scaffolds. Independent assessment of the assemblies using Ion Torrent read alignments indicates that MacaM is more complete and accurate than rheMac2 and CR_1.0. We assembled messenger RNA sequences from several rhesus tissues into transcripts which allowed us to identify a total of 11,712 complete proteins representing 9,524 distinct genes. Using a combination of our assembled rhesus macaque transcripts and human transcripts, we annotated 18,757 transcripts and 16,050 genes with complete coding sequences in the MacaM assembly. Further, we demonstrate that the new annotations provide greatly improved accuracy as compared to the current annotations of rheMac2. Finally, we show that the MacaM genome provides an accurate resource for alignment of reads produced by RNA sequence expression studies.ConclusionsThe MacaM assembly and annotation files provide a substantially more complete and accurate representation of the rhesus macaque genome than rheMac2 or CR_1.0 and will serve as an important resource for investigators conducting next-generation sequencing studies with nonhuman primates.ReviewersThis article was reviewed by Dr. Lutz Walter, Dr. Soojin Yi and Dr. Kateryna Makova.

Glioblastoma (GBM) is the most common and the deadliest type of primary brain tumor, with a median survival time of only 15 months despite aggressive treatment. Although most patients have an extremely poor prognosis, a relatively small number of patients survive far beyond the median survival time. Investigation of these exceptional responders has sparked a great deal of interest and is becoming an important focus in the field of cancer research. To investigate the molecular differences between typical and exceptional responders in GBM, comparative analyses of somatic mutations, copy number, methylation, and gene expression datasets from The Cancer Genome Atlas were performed, and the results of these analyses were integrated via gene ontology and pathway analyses to assess the functional significance of the differential aberrations. Less severe copy number loss of CDKN2A, lower expression of CXCL8, and FLG mutations are all associated with an exceptional response. Typical responders are characterized by upregulation of NF-κB signaling and of pro-inflammatory cytokines, while exceptional responders are characterized by upregulation of Alzheimer’s and Parkinson’s disease pathways as well as of genes involved in synaptic transmission. The upregulated pathways and processes in typical responders are consistently associated with more aggressive tumor phenotypes, while those in the exceptional responders suggest a retained ability in tumor cells to undergo cell death in response to treatment. With the upcoming launch of the National Cancer Institute’s Exceptional Responders Initiative, similar studies with much larger sample sizes will likely become possible, hopefully providing even more insight into the molecular differences between typical and exceptional responders.

Objective To understand medication, lifestyle, and clinical care changes of persons with rheumatoid arthritis (RA) during the first months (March 2020 through May 2020) of the COVID‐19 pandemic in the US. Methods Data were collected from adults with RA participating in FORWARD, The National Databank for Rheumatic Diseases observational registry, who answered COVID‐19 web‐based surveys in May 2020 and previously provided baseline characteristics and medication use prior to the US COVID‐19 pandemic. We compared medication changes by disease‐modifying antirheumatic drug (DMARD) exposure in logistic models that were adjusted for age, sex, comorbidities including pulmonary and cardiovascular diseases, education level, health insurance status, RA disease activity, fatigue, and polysymptomatic distress. Results Of 734 respondents, 221 (30%) reported medication changes. Among respondents who experienced a medication change, i.e., “medication changers/changers,” glucocorticoids (GCs) were more commonly used compared to respondents who did not experience a medication change (“non‐changers”) (33% versus 18%). Non‐hydroxychloroquine conventional DMARDs were less commonly used in changers compared to non‐changers pre–COVID‐19 (49% versus 62%), and changers reported more economic hardship during the COVID‐19 pandemic compared to non‐changers (23% versus 15%). While JAK inhibitor use was associated with the likelihood of a medication change, with an odds ratio (OR) of 1.9 (95% confidence interval [95% CI] 1.0, 3.4), only pre‐COVID GC use remained a strong predictor for medication change in multivariable models (OR 3.0 [95% CI 1.9, 4.9]). Change in care was observed to have a significant association with pulmonary disease (OR 2.9 [95% CI 1.3, 6.5]), worse RA disease activity (OR 1.1 [95% CI 1.0, 1.1]), and GC use (OR 1.6 [95% CI 1.0, 2.5]). While the incidence of medication changes was the same before and after the American College of Rheumatology (ACR) guidance for the management of rheumatic disease in adult patients during the COVID‐19 pandemic were first published in April 2020, self‐imposed changes in medication were approximately twice as likely before publication of the guidelines, and physician‐guided changes were more likely after publication. Conclusion Persons with RA in the US made substantial medication changes during the first three months of the COVID‐19 pandemic, and changes among persons with RA after publication of the ACR guidance in April 2020 were made with increased physician guidance.

Objective. Despite advances in treatments and outcomes among patients with rheumatic diseases, there is an unmet need in pain management. Cannabis has emerged as a potential opioid-sparing alternative, with arthritic pain as a commonly cited reason for medicinal cannabis use. However, little is known, and we set out to understand patterns of cannabis use in a US-wide rheumatic disease population.Methods. The study included participants in FORWARD, The National Databank for Rheumatic Diseases. Participants were asked in 2014 and 2019 about their past and current cannabis use. Demographic characteristics, patient-reported outcomes, medications, comorbidities, and diagnoses were compared between cannabis users and non-users with t-tests, chi-square tests, logistic regression, and geographic assessment.Results. Among 11,006 respondents, cannabis use increased from 6.3% in 2014 to 18.4% in 2019, with the greatest prevalence of use in states where cannabis use was legalized. Most users (74% and 62% in 2014 and 2019, respectively) reported that cannabis was effective in the relief of arthritis symptoms. Cannabis users were more likely to be taking weak opioids (odds ratio 1.2 [95% confidence interval 1.0, 1.5], P = 0.03), to have a history of smoking tobacco (odds ratio 1.7 [95% confidence interval 1.5, 2.1], P < 0.001), and had worse measures on all assessed patient-reported outcomes.Conclusion. Reported cannabis use in this cohort increased significantly between 2014 and 2019. Characteristics of users suggest that those who try cannabis are feeling worse symptomatically, and their pain management needs may not be adequately addressed by other therapies. The association between cannabis, opioids, and patientreported outcomes highlight areas for future work.