(What's the story) morning glory? MRI findings in morning glory disc anomaly.

PURPOSE: Morning glory disc anomaly (MGDA) is a rare congenital ophthalmologic disorder. Historically it has been diagnosed fundoscopically, with little in the literature regarding its imaging findings. The purpose of this study is to further characterize the orbital and associated intracranial magnetic resonance imaging (MRI) findings of MGDA in our tertiary pediatric center. METHODS: A retrospective review was performed of fundoscopically-diagnosed cases of MGDA, that had been referred for MRI. All MRI studies were scrutinized for orbital and other intracranial abnormalities known to occur in association with MGDA. RESULTS: 18 of 19 cases of MGDA showed three characteristic MRI findings: funnel-shaped morphology of the posterior optic disc, abnormal soft tissue associated with the retrobulbar optic nerve, and effacement of adjacent subarachnoid spaces. The ipsilateral (intraorbital) optic nerve was larger in one patient and smaller in six. The ipsilateral optic chiasm was larger in two patients and smaller in one. CONCLUSION: This study represents a comprehensive radiological-led investigation into MGDA. It describes the most frequently-encountered MRI findings in MGDA and emphasizes the importance of MRI in this cohort, i.e., in distinguishing MGDA from other posterior globe abnormalities, in assessing the visual pathway, and in screening for associated intracranial abnormalities - skull base/cerebral, vascular, and facial. It hypothesizes neurocristopathy as an underlying cause of MGDA and its associations. Caliber abnormalities of the ipsilateral optic nerve and chiasm are a frequent finding in MGDA. Optic pathway enlargement should not be labeled "glioma". (239/250).

Overdose from Unintentional Fentanyl Use when Intending to Use a Non-opioid Substance: An Analysis of Medically Attended Opioid Overdose Events.

Fentanyl-mixed and substituted heroin is well-documented, but less is known about unintentional fentanyl use among people using stimulants. To determine the prevalence of and racial and ethnic disparities in unintentional fentanyl use among people experiencing a medically attended opioid overdose, we reviewed 448 suspected non-fatal overdose cases attended by a community paramedic overdose response team in San Francisco from June to September 2022. We applied a case definition for opioid overdose to paramedic records and abstracted data on intended substance use prior to overdose. Among events meeting case criteria with data on intended substance use, intentional opioid use was reported by 57.3%, 98.0% of whom intended to use fentanyl. No intentional opioid use was reported by 42.7%, with most intending to use stimulants (72.6%), including methamphetamine and cocaine. No intentional opioid use was reported by 58.5% of Black, 52.4% of Latinx, and 28.8% of White individuals (p = 0.021), and by 57.6% of women and 39.5% of men (p = 0.061). These findings suggest that unintentional fentanyl use among people without opioid tolerance may cause a significant proportion of opioid overdoses in San Francisco. While intentional fentanyl use might be underreported, the magnitude of self-reported unintentional use merits further investigation to confirm this phenomenon, explore mechanisms of use and disparities by race and ethnicity, and deploy targeted overdose prevention interventions.

A text message intervention aimed at nurturing peer outreach to help meet drinking limit goals: A remote pilot randomized trial in non-collegiate young adults.

OBJECTIVE: Scalable interventions attempting to nurture peer outreach to help young adults meet drinking limit goals remain under-developed. To address this gap, we developed ASPIRE, a text message intervention focused on coaching individuals to engage with close peers to assist them in meeting drinking limit goals. METHOD: Non-collegiate young adults who had reported one or more heavy drinking days in the preceding month and were at least contemplating change were recruited through social media. Participants were randomly assigned to one of three 6-week text message interventions: Control, Goal Support, or ASPIRE. All groups completed baseline assessments and received weekly text message assessments on Thursdays and Sundays. Control and ASPIRE groups were prompted to complete web-based outcome assessments at 6- and 12-weeks. RESULTS: We enrolled 92 young adults from 31 US states (65% female; 73% White). All groups had high text response rates but intervention usability was sub-optimal. Follow-up rates were 87% at 6-weeks and 79% at 12-weeks. Compared to Control, ASPIRE participants reported significantly more peer support and less peer pressure to drink. ASPIRE exhibited higher goal confidence compared to the Goal Support group. Using multiple imputation, there were no significant differences in drinking outcomes between groups. CONCLUSIONS: Preliminary findings from this pilot study suggest that a text message intervention focused on nurturing peer outreach to help meet drinking limit goals holds promise in altering peer support and pressure as well as boosting drinking limit goal confidence. Design improvements are needed to reduce alcohol consumption.

Prolonged Particulate Hexavalent Chromium Exposure Induces DNA Double-Strand Breaks and Inhibits Homologous Recombination Repair in Primary Rodent Lung Cells.

Hexavalent chromium [Cr(VI)] is a known lung carcinogen and a driving mechanism in human lung cells for Cr(VI)-induced lung cancer is chromosome instability, caused by prolonged Cr(VI) exposure inducing DNA double-strand breaks, while simultaneously inhibiting the repair of these breaks. In North Atlantic right whales, Cr(VI) induces breaks but does not inhibit repair. It is unclear if this repair inhibition is specific to human lung cells or occurs in other species, as it has only been considered in humans and North Atlantic right whales. We evaluated these outcomes in rodent cells, as rodents are an experimental model for metal-induced lung carcinogenesis. We used a guinea pig lung fibroblast cell line, JH4 Clone 1, and rat lung fibroblasts. Cells were exposed to two different particulate Cr(VI) compounds, ranging from 0 to 0.5 ug/cm2, for 24 or 120 h and assessed for cytotoxicity, DNA double-strand breaks, and DNA double-strand break repair. Both particulate Cr(VI) compounds induced a concentration-dependent increase in cytotoxicity and DNA double-strand breaks after acute and prolonged exposures. Notably, while the repair of Cr(VI)-induced DNA double-strand breaks increased after acute exposure, the repair of these breaks was inhibited after prolonged exposure. These results are consistent with outcomes in human lung cells indicating rodent cells respond like human cells, while whale cells have a markedly different response.

Biocompatibility of intraperitoneally implanted TEMPO-oxidized cellulose nanofiber hydrogels for antigen delivery in Atlantic salmon (Salmo salar L.) vaccines.

Disease outbreaks are a major impediment to aquaculture production, and vaccines are integral for disease management. Vaccines can be expensive, vary in effectiveness, and come with adjuvant-induced adverse effects, causing fish welfare issues and negative economic impacts. Three-dimensional biopolymer hydrogels are an appealing new technology for vaccine delivery in aquaculture, with the potential for controlled release of multiple immunomodulators and antigens simultaneously, action as local depots, and tunable surface properties. This research examined the intraperitoneal implantation of a cross-linked TEMPO cellulose nanofiber (TOCNF) hydrogel formulated with a Vibrio anguillarum bacterin in Atlantic salmon with macroscopic and microscopic monitoring to 600-degree days post-implantation. Results demonstrated a modified passive integrated transponder tagging (PITT) device allowed for implantation of the hydrogel. However, the Atlantic salmon implanted with TOCNF hydrogels exhibited a significant foreign body response (FBR) compared to sham-injected negative controls. The FBR was characterized by gross and microscopic external and visceral proliferative lesions, granulomas, adhesions, and fibrosis surrounding the hydrogel using Speilberg scoring of the peritoneum and histopathology of the body wall and coelom. Acutely, gross monitoring displayed rapid coagulation of blood in response to the implantation wound with development of fibrinous adhesions surrounding the hydrogel by 72 h post-implantation consistent with early stage FBR. While these results were undesirable for aquaculture vaccines, this work informs on the innate immune response to an implanted biopolymer hydrogel in Atlantic salmon and directs future research using cellulose nanomaterial formulations in Atlantic salmon for a new generation of aquaculture vaccine technology.

Young Adult Depression and Cannabis Use: Associations Before and After Recreational Legalization.

INTRODUCTION: The co-occurrence of depression with cannabis use worsens both mood and substance use disorder outcomes, with young adults particularly at risk of co-occurrence. This research investigates whether the association of state-level prevalence rates of young adult (age 18-25) depression and cannabis use in the U.S. changed following enactment of recreational (adult use) cannabis legalization between 2008 and 2019. METHODS: Annual, state prevalence data on past-year major depressive episode (hereafter, depression) and past-month cannabis use were extracted from the National Survey on Drug Use and Health (N=600 state-year observations). Moderated regression models tested whether the association of depression with cannabis use differed before versus after recreational legalization by comparing prevalence rates of depression and cannabis use in states that enacted recreational legalization to those that did not, while fixing state, year, and medical legalization effects. Data were accessed and analyzed in 2023. RESULTS: Prevalence rates of both depression and cannabis use increased throughout the study period. The positive statistical effect of depression on cannabis use more than doubled in magnitude after legalization (ß=0.564, 95% CI=0.291, 0.838) as compared to before (ß=0.229, 95% CI=0.049, 0.409), representing a significant change (ß=0.335, 95% CI=0.093, 0.577). CONCLUSIONS: These results suggest that the association between prevalence rates of young adult depression and cannabis use strengthened following recreational legalization in the U.S. This is potentially due to increases in cannabis accessibility and the acceptance of the health benefits of cannabis, which may enhance the use of cannabis as a coping mechanism among young adults with depression.

A low-cost, portable, dual-function readout device for amplification-based point-of-need diagnostics.

IMPORTANCE: The first critical step in timely disease management is rapid disease identification, which is ideally on-site detection. Of all the technologies available for disease identification, nucleic acid amplification-based diagnostics are often used due to their specificity, sensitivity, adaptability, and speed. However, the modules to interpret amplification results rapidly, reliably, and easily in resource-limited settings at point-of-need (PON) are in high demand. Therefore, we developed a portable, low-cost, and easy-to-perform device that can be used for amplification readout at PON to enable rapid yet reliable disease identification by users with minimal training.

Changing the diagnostic paradigm for sugarcane: development of a mill-based diagnostic for ratoon stunting disease in crude cane juice.

The availability of efficient diagnostic methods is crucial to monitor the incidence of crop diseases and implement effective management strategies. One of the most important elements in diagnostics, especially in large acreage crops, is the sampling strategy as hundreds of thousands of individual plants can grow in a single farm, making it difficult to assess disease incidence in field surveys. This problem is compounded when there are no external disease symptoms, as in the case for the ratoon stunting disease (RSD) in sugarcane. We have developed an alternative approach of disease surveillance by using the crude cane juice expressed at the sugar factory (mill). For this purpose, we optimized DNA extraction and amplification conditions for the bacterium Leifsonia xyli subsp xyli, the causal agent of RSD. The use of nucleic acid dipsticks and LAMP isothermal amplification allows to perform the assays at the mills, even in the absence of molecular biology laboratories. Our method has been validated using the qPCR industry standard and shows higher sensitivity. This approach circumvents sampling limitations, providing RSD incidence evaluation on commercial crops and facilitating disease mapping across growing regions. There is also potential is to extend the technology to other sugarcane diseases as well as other processed crops.

Testing Mechanisms of Change for Text Message-Delivered Cognitive Behavioral Therapy: Randomized Clinical Trial for Young Adult Depression.

BACKGROUND: Current psychiatric epidemiological evidence estimates that 17% of young adults (aged 18-25 years) experienced a major depressive episode in 2020, relative to 8.4% of all adults aged ≥26 years. Young adults with a major depressive episode in the past year are the least likely to receive treatment for depression compared with other age groups. OBJECTIVE: We conducted a randomized clinical trial following our initial 4-week SMS text message-delivered cognitive behavioral therapy (CBT-txt) for depression in young adults. We sought to test mechanisms of change for CBT-txt. METHODS: Based on participant feedback, outcome data, and the empirical literature, we increased the treatment dosage from 4-8 weeks and tested 3 mechanisms of change with 103 young adults in the United States. Participants were from 34 states, recruited from Facebook and Instagram and presenting with at least moderate depressive symptomatology. Web-based assessments occurred at baseline prior to randomization and at 1, 2, and 3 months after enrollment. The primary outcome, the severity of depressive symptoms, was assessed using the Beck Depression Inventory II. Behavioral activation, perseverative thinking, and cognitive distortions were measured as mechanisms of change. Participants were randomized to CBT-txt or a waitlist control condition. Those assigned to the CBT-txt intervention condition received 474 fully automated SMS text messages, delivered every other day over a 64-day period and averaging 14.8 (SD 2.4) SMS text messages per treatment day. Intervention texts are delivered via TextIt, a web-based automated SMS text messaging platform. RESULTS: Across all 3 months of the study, participants in the CBT-txt group showed significantly larger decreases in depressive symptoms than those in the control group (P<.001 at each follow-up), producing a medium-to-large effect size (Cohen d=0.76). Over half (25/47, 53%) of the treatment group moved into the "high-end functioning" category, representing no or minimal clinically significant depressive symptoms, compared with 15% (8/53) of the control condition. Mediation analysis showed that CBT-txt appeared to lead to greater increases in behavioral activation and greater decreases in cognitive distortions and perseverative thinking across the 3-month follow-up period, which were then associated with larger baseline to 3-month decreases in depression. The size of the indirect effects was substantial: 57%, 41%, and 50% of the CBT-txt effect on changes in depression were mediated by changes in behavioral activation, cognitive distortions, and perseverative thinking, respectively. Models including all 3 mediators simultaneously showed that 63% of the CBT-txt effect was mediated by the combined indirect effects. CONCLUSIONS: Results provide evidence for the efficacy of CBT-txt to reduce young adult depressive symptoms through hypothesized mechanisms. To the best of our knowledge, CBT-txt is unique in its SMS text message-delivered modality, the strong clinical evidence supporting efficacy and mechanisms of change. TRIAL REGISTRATION: ClinicalTrials.gov NCT05551702; https://clinicaltrials.gov/study/NCT05551702.

Effectiveness of Bundled Hyperpolypharmacy Deprescribing Compared With Usual Care Among Older Adults: A Randomized Clinical Trial.

Importance: Older patients using many prescription drugs (hyperpolypharmacy) may be at increased risk of adverse drug effects. Objective: To test the effectiveness and safety of a quality intervention intended to reduce hyperpolypharmacy. Design, Setting, and Participants: This randomized clinical trial allocated patients 76 years or older who used 10 or more prescription medications to a deprescribing intervention or to usual care (1:1 ratio) at an integrated health system with multiple preexisting deprescribing workflows. Data were collected from October 15, 2020, to July 29, 2022. Intervention: Physician-pharmacist collaborative drug therapy management, standard-of-care practice recommendations, shared decision-making, and deprescribing protocols administered by telephone over multiple cycles for a maximum of 180 days after allocation. Main Outcomes and Measures: Primary end points were change in the number of medications and in the prevalence of geriatric syndrome (falls, cognition, urinary incontinence, and pain) from 181 to 365 days after allocation compared with before randomization. Secondary outcomes were use of medical services and adverse drug withdrawal effects. Results: Of a random sample of 2860 patients selected for potential enrollment, 2470 (86.4%) remained eligible after physician authorization, with 1237 randomized to the intervention and 1233 to usual care. A total of 1062 intervention patients (85.9%) were reached and agreed to enroll. Demographic variables were balanced. The median age of the 2470 patients was 80 (range, 76-104) years, and 1273 (51.5%) were women. In terms of race and ethnicity, 185 patients (7.5%) were African American, 234 (9.5%) were Asian or Pacific Islander, 220 (8.9%) were Hispanic, 1574 (63.7%) were White (63.7%), and 257 (10.4%) were of other (including American Indian or Alaska Native, Native Hawaiian, or >1 race or ethnicity) or unknown race or ethnicity. During follow-up, both the intervention and usual care groups had slight reductions in the number of medications dispensed (mean changes, -0.4 [95% CI, -0.6 to -0.2] and -0.4 [95% CI, -0.6 to -0.3], respectively), with no difference between the groups (P = .71). There were no significant changes in the prevalence of a geriatric condition in the usual care and intervention groups at the end of follow-up and no difference between the groups (baseline prevalence: 47.7% [95% CI, 44.9%-50.5%] vs 42.9% [95% CI, 40.1%-45.7%], respectively; difference-in-differences, 1.0 [95% CI, -3.5 to 5.6]; P = .65). No differences in use of medical services or adverse drug withdrawal effects were observed. Conclusions and Relevance: In this randomized clinical trial from an integrated care setting with various preexisting deprescribing workflows, a bundled hyperpolypharmacy deprescribing intervention was not associated with reduction in medication dispensing, prevalence of geriatric syndrome, utilization of medical services, or adverse drug withdrawal effects. Additional research is needed in less integrated settings and in more targeted populations. Trial Registration: ClinicalTrials.gov Identifier: NCT05616689.

Treating Young Adult Depression With Text-Delivered Cognitive Behavioral Therapy: A Pilot Randomized Clinical Trial.

Young adults (ages 18 to 25) in the U.S. suffer from the highest rates of past-year major depressive episode and are the least likely to receive treatment compared to other age groups. As such, we examined the feasibility, acceptability, and efficacy of a text-message delivered cognitive behavioral therapy: CBT-txt with young adults. The study was a 2-month pilot RCT to test a 4-week intervention for depression that contained 197 text messages (average 12 texts every other day). The sample, recruited via Facebook and Instagram, was 102 U.S. young adults who presented with at least moderate depressive symptomatology. Assessments occurred at baseline prior to randomization and at 1 and 2 months post enrollment. The primary outcome, severity of depressive symptoms, was assessed using the Beck Depression Inventory II. Feasibility benchmarks were met and participants reported high levels of engagement with and acceptability of the intervention. Logistic regression indicated that treatment participants were three times as likely to have minimal or mild depression symptoms at 2 months compared to waitlist control participants. Latent change score modeling found that the strongest significant treatment effect appeared at the 1-month follow-up period, particularly for participants who began with severe depressive symptoms. Mediation analysis revealed significant indirect treatment effects of increases in behavioral activation on reducing depressive symptoms, suggesting a mechanism of change. Limitations were that the sample was relatively small and consisted of primarily women. These results provide initial evidence for the feasibility, acceptability, and efficacy of a text-delivered treatment for young adult depression.

Early detection of exon 1 huntingtin aggregation in zQ175 brains by molecular and histological approaches.

Huntingtin-lowering approaches that target huntingtin expression are a major focus for therapeutic intervention for Huntington's disease. When the cytosine, adenine and guanine repeat is expanded, the huntingtin pre-mRNA is alternatively processed to generate the full-length huntingtin and HTT1a transcripts. HTT1a encodes the aggregation-prone and highly pathogenic exon 1 huntingtin protein. In evaluating huntingtin-lowering approaches, understanding how the targeting strategy modulates levels of both transcripts and the huntingtin protein isoforms that they encode will be essential. Given the aggregation-propensity of exon 1 huntingtin, the impact of a given strategy on the levels and subcellular location of aggregated huntingtin will need to be determined. We have developed and applied sensitive molecular approaches to monitor the levels of aggregated and soluble huntingtin isoforms in tissue lysates. We have used these, in combination with immunohistochemistry, to map the appearance and accumulation of aggregated huntingtin throughout the CNS of zQ175 mice, a model of Huntington's disease frequently chosen for preclinical studies. Aggregation analyses were performed on tissues from zQ175 and wild-type mice at monthly intervals from 1 to 6 months of age. We developed three homogeneous time-resolved fluorescence assays to track the accumulation of aggregated huntingtin and showed that two of these were specific for the exon 1 huntingtin protein. Collectively, the homogeneous time-resolved fluorescence assays detected huntingtin aggregation in the 10 zQ175 CNS regions by 1-2 months of age. Immunohistochemistry with the polyclonal S830 anti-huntingtin antibody showed that nuclear huntingtin aggregation, in the form of a diffuse nuclear immunostain, could be visualized in the striatum, hippocampal CA1 region and layer IV of the somatosensory cortex by 2 months. That this diffuse nuclear immunostain represented aggregated huntingtin was confirmed by immunohistochemistry with a polyglutamine-specific antibody, which required formic acid antigen retrieval to expose its epitope. By 6 months of age, nuclear and cytoplasmic inclusions were widely distributed throughout the brain. Homogeneous time-resolved fluorescence analysis showed that the comparative levels of soluble exon 1 huntingtin between CNS regions correlated with those for huntingtin aggregation. We found that soluble exon 1 huntingtin levels decreased over the 6-month period, whilst those of soluble full-length mutant huntingtin remained unchanged, data that were confirmed for the cortex by immunoprecipitation and western blotting. These data support the hypothesis that exon 1 huntingtin initiates the aggregation process in knock-in mouse models and pave the way for a detailed analysis of huntingtin aggregation in response to huntingtin-lowering treatments.

Peer Network Counseling Effects on Substance Use: an Individual Participant Data Meta-Analysis Integrating Three Randomized Controlled Trials.

The current study describes an individual participant data meta-analysis (IPDMA) testing the efficacy of a peer-network counseling (PNC) intervention for preventing substance use escalation in adolescents and young adults. PNC has shown efficacy in reducing substance use among adolescents and young adults across small-scale randomized controlled trials (RCTs). Identifying expected large-scale effects and moderators is an important next step in guiding use of PNC in practice. To this end, we combine three small-scale RCTs to test PNC intervention effects on substance use change in a combined sample of 421 adolescents and young adults (50% intervention, 55% female, 69% Black/African-American, M age [SD] = 17.3 [2.2] years). Our approach combines latent change score modeling in a structural equation modeling (SEM) framework with study-level fixed effects to obtain (a) a more generalizable PNC effect than we could obtain with each constituent sample and (b) greater power and precision for individual-level moderation of treatment effects. We found that although PNC main effects on substance use outcomes (past 30-day cannabis, alcohol, tobacco, and drug use) were not significant, PNC effects were moderated by individual-level pre-intervention substance use frequency. PNC more strongly reduced drug use at the 1-month follow-up and cannabis use at the 3-month follow-up among participants who showed higher baseline use of these substances. Implications of our approach and findings for prevention researchers are discussed.

Recommendations for Identifying Valid Wear for Consumer-Level Wrist-Worn Activity Trackers and Acceptability of Extended Device Deployment in Children.

BACKGROUND: Self-reported physical activity is often inaccurate. Wearable devices utilizing multiple sensors are now widespread. The aim of this study was to determine acceptability of Fitbit Charge HR for children and their families, and to determine best practices for processing its objective data. METHODS: Data were collected via Fitbit Charge HR continuously over the course of 3 weeks. Questionnaires were given to each child and their parent/guardian to determine the perceived usability of the device. Patterns of data were evaluated and best practice inclusion criteria recommended. RESULTS: Best practices were established to extract, filter, and process data to evaluate device wear, r and establish minimum wear time to evaluate behavioral patterns. This resulted in usable data available from 137 (89%) of the sample. CONCLUSIONS: Activity trackers are highly acceptable in the target population and can provide objective data over longer periods of wear. Best practice inclusion protocols that reflect physical activity in youth are provided.

Magnetic resonance imaging patterns of paediatric brain infections: a pictorial review based on the Western Australian experience.

Paediatric brain infections are relatively uncommon, but it is important for radiologists to recognise the disease and provide accurate differential diagnoses. Magnetic resonance imaging (MRI) plays an important role in determining the most likely causative pathogen-either in the setting of an unwell child with acute infectious encephalitis, or in the evaluation of a child for sequela of prior infection. Image analysis can, however, be difficult since a particular pathogen can cause variable MRI findings across different geographic environments, and conversely, a particular appearance on MRI may be caused by a variety of pathogens. This educational review aims to identify some of the key MRI patterns seen in paediatric brain infections and present example cases encountered in Western Australia. Based on (i) the predominant type of signal abnormality (restricted diffusion versus T2 hyperintensity) and (ii) the distribution of signal abnormality throughout the brain, this review presents a framework of six key MRI patterns seen in paediatric brain infections, with an emphasis on acute infectious encephalitis. There is general utility to these MRI patterns-each suggestive of a group of likely diagnostic possibilities which can be calibrated according to institution and local environment. The pattern-based framework of this review can be easily transitioned into daily radiological practice, and we hope it facilitates the formation of accurate differential diagnoses in paediatric brain infections.

A Crowdsourcing Approach to Develop Machine Learning Models to Quantify Radiographic Joint Damage in Rheumatoid Arthritis.

Importance: An automated, accurate method is needed for unbiased assessment quantifying accrual of joint space narrowing and erosions on radiographic images of the hands and wrists, and feet for clinical trials, monitoring of joint damage over time, assisting rheumatologists with treatment decisions. Such a method has the potential to be directly integrated into electronic health records. Objectives: To design and implement an international crowdsourcing competition to catalyze the development of machine learning methods to quantify radiographic damage in rheumatoid arthritis (RA). Design, Setting, and Participants: This diagnostic/prognostic study describes the Rheumatoid Arthritis 2-Dialogue for Reverse Engineering Assessment and Methods (RA2-DREAM Challenge), which used existing radiographic images and expert-curated Sharp-van der Heijde (SvH) scores from 2 clinical studies (674 radiographic sets from 562 patients) for training (367 sets), leaderboard (119 sets), and final evaluation (188 sets). Challenge participants were tasked with developing methods to automatically quantify overall damage (subchallenge 1), joint space narrowing (subchallenge 2), and erosions (subchallenge 3). The challenge was finished on June 30, 2020. Main Outcomes and Measures: Scores derived from submitted algorithms were compared with the expert-curated SvH scores, and a baseline model was created for benchmark comparison. Performances were ranked using weighted root mean square error (RMSE). The performance and reproductivity of each algorithm was assessed using Bayes factor from bootstrapped data, and further evaluated with a postchallenge independent validation data set. Results: The RA2-DREAM Challenge received a total of 173 submissions from 26 participants or teams in 7 countries for the leaderboard round, and 13 submissions were included in the final evaluation. The weighted RMSEs metric showed that the winning algorithms produced scores that were very close to the expert-curated SvH scores. Top teams included Team Shirin for subchallenge 1 (weighted RMSE, 0.44), HYL-YFG (Hongyang Li and Yuanfang Guan) subchallenge 2 (weighted RMSE, 0.38), and Gold Therapy for subchallenge 3 (weighted RMSE, 0.43). Bootstrapping/Bayes factor approach and the postchallenge independent validation confirmed the reproducibility and the estimation concordance indices between final evaluation and postchallenge independent validation data set were 0.71 for subchallenge 1, 0.78 for subchallenge 2, and 0.82 for subchallenge 3. Conclusions and Relevance: The RA2-DREAM Challenge resulted in the development of algorithms that provide feasible, quick, and accurate methods to quantify joint damage in RA. Ultimately, these methods could help research studies on RA joint damage and may be integrated into electronic health records to help clinicians serve patients better by providing timely, reliable, and quantitative information for making treatment decisions to prevent further damage.

Further evidence for distinct traits associated with RBM10 missense variants.

A case of a missense RBM10 variant in an adult with mild to moderate intellectual disability.

Hirayama disease: the importance of flexion imaging.

Hirayama disease is a rare cervical myelopathy characterised by asymmetrical upper limb weakness and muscle atrophy in the forearm and hand. MRI of the cervical spine plays an essential role in diagnosis, however, the characteristic findings are often only seen when the patient is imaged with the neck in flexion. We present a case of a 15-year-old male who presented with left forearm and hand weakness with muscle wasting. An MRI of the cervical spine with the neck in a neutral position demonstrated atrophy of the spinal cord with intrinsic signal abnormality between C5 and C7. Further imaging with the patient's neck in flexion demonstrated the hallmark features of Hirayama disease. There was anterior displacement of the thecal sac and spinal cord, and an enlarged, crescent-shaped dorsal epidural space which enhanced following i.v. gadolinium administration. The atrophic segment of cord contacted the posterior vertebral bodies when the neck was in full flexion. This case highlights the importance of imaging patients suspected of having this entity with the neck in full flexion in order to make a diagnosis.

Predicting Self-Medication with Cannabis in Young Adults with Hazardous Cannabis Use.

Using cannabis to reduce psychological and physical distress, referred to as self-medication, is a significant risk factor for cannabis use disorder. To better understand this high-risk behavior, a sample of 290 young adults (ages 18-25; 45.6% female) were recruited from two U.S. universities in January and February of 2020 to complete a survey about their cannabis use and self-medication. Results: seventy-six percent endorsed using cannabis to reduce problems such as anxiety, sleep, depression, pain, loneliness, social discomfort, and concentration. When predicting reasons for self-medication with cannabis, logistic regression models showed that lower CUDIT-R scores, experiencing withdrawal, living in a state where cannabis was illegal, and being female were all associated with higher rates of self-medication. Withdrawal symptoms were tested to predict self-medication with cannabis, and only insomnia and loss of appetite were significant predictors. To further explore why young adults self-medicate, each of the original predictors were regressed on seven specified reasons for self-medication. Young adults experiencing withdrawal were more likely to self-medicate for pain. Participants living where cannabis is legal were less likely to self-medicate for anxiety and depression. Living where cannabis is illegal also significantly predicted self-medicating for social discomfort-though the overall model predicting social discomfort was statistically non-significant. Finally, female participants were more likely to self-medicate for anxiety. These results suggest widespread self-medication among young adults with likely CUD and underscore the complexity of their cannabis use. The findings have implications for understanding why young adults use cannabis in relation to psychological and physical distress and for accurately treating young adults with cannabis use disorder.

Responsiveness to mHealth Intervention for Cannabis Use in Young Adults Predicts Improved Outcomes.

Mobile health (mHealth) interventions have proliferated rapidly in part because of their advantages in reducing consumer and provider burden, but less attention has been paid to participant responsiveness to mHealth programs and how this may affect outcomes. This study adds to that literature by examining whether participant responsiveness to a text messaging-delivered intervention was predictive of treatment outcomes over baseline levels of the outcome. We analyzed data from a pilot-randomized controlled trial of a text messaging-intervention to treat young adults with cannabis use disorder (treatment arm, N = 47), examining three indicators of responsiveness (two behavioral: treatment completion and booster message participation; and one subjective: perceived helpfulness of treatment) on abstinence from cannabis use and use-related problems measured at 3-month follow-up. With the exception of completion, the indicators were positively correlated with each other. Each of the indicators was predictive of better treatment outcomes above and beyond baseline risk. Treatment completion and booster participation-measured via technical data captured during intervention administration-appeared to be stronger predictors of improved outcomes than self-reported perceived helpfulness. Results suggest that behavioral and subjective responsiveness measures appear to be valid indicators of treatment response to mHealth interventions for substance use. Responsiveness measured via technical data captured during intervention administration may be a stronger and more efficient strategy for monitoring continued engagement. We discuss implications of these findings for deploying mHealth interventions at scale and monitoring responsiveness.