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Small nucleolar RNAs (snoRNAs) are non-coding RNAs that function in ribosome and spliceosome biogenesis, primarily by guiding modifying enzymes to specific sites on ribosomal RNA (rRNA) and spliceosomal RNA (snRNA). However, many orphan snoRNAs remain uncharacterized, with unidentified or unvalidated targets, and studies on additional snoRNA-associated proteins are limited. We adapted an enhanced chimeric eCLIP approach to comprehensively profile snoRNA-target RNA interactions using both core and accessory snoRNA binding proteins as baits. Using core snoRNA binding proteins, we confirmed most annotated snoRNA-rRNA and snoRNA-snRNA interactions in mouse and human cell lines and called novel, high-confidence interactions for orphan snoRNAs. While some of these interactions result in chemical modification, others may have modification-independent functions. We then showed that snoRNA ribonucleoprotein complexes containing certain accessory proteins, like WDR43 and NOLC1, enriched for specific subsets of snoRNA-target RNA interactions with distinct roles in ribosome and spliceosome biogenesis. Notably, we discovered that SNORD89 guides 2'-O-methylation at two neighboring sites in U2 snRNA that are important for activating splicing, but also appear to ensure imperfect splicing for a subset of near-constitutive exons. Thus, chimeric eCLIP of snoRNA-associating proteins enables a comprehensive framework for studying snoRNA-target interactions in an RNA binding protein-dependent manner, revealing novel interactions and regulatory roles in RNA biogenesis., Competing Interests: Declaration of Interests ELVN is co-founder, member of the Board of Directors, on the SAB, equity holder, and paid consultant for Eclipse BioInnovations, on the SAB of RNAConnect, and is inventor of intellectual property owned by University of California San Diego. ELVN’s interests have been reviewed and approved by the Baylor College of Medicine in accordance with its conflict of interest policies.

Although the role of RNA binding proteins (RBPs) in extracellular RNA (exRNA) biology is well established, their exRNA cargo and distribution across biofluids are largely unknown. To address this gap, we extend the exRNA Atlas resource by mapping exRNAs carried by extracellular RBPs (exRBPs). This map was developed through an integrative analysis of ENCODE enhanced crosslinking and immunoprecipitation (eCLIP) data (150 RBPs) and human exRNA profiles (6,930 samples). Computational analysis and experimental validation identified exRBPs in plasma, serum, saliva, urine, cerebrospinal fluid, and cell-culture-conditioned medium. exRBPs carry exRNA transcripts from small non-coding RNA biotypes, including microRNA (miRNA), piRNA, tRNA, small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), Y RNA, and lncRNA, as well as protein-coding mRNA fragments. Computational deconvolution of exRBP RNA cargo reveals associations of exRBPs with extracellular vesicles, lipoproteins, and ribonucleoproteins across human biofluids. Overall, we mapped the distribution of exRBPs across human biofluids, presenting a resource for the community., Competing Interests: E.V.N. is co-founder, member of the Board of Directors, on the SAB, equity holder, and paid consultant for Eclipse BioInnovations. E.V.N.’s interests have been reviewed and approved by the Baylor College of Medicine in accordance with its conflict of interest policies., (© 2023 The Authors.)

Background: Fatal and non-fatal events associated with drug misuse are skyrocketing in most United States jurisdictions, including Indiana. Historically, the role of the judiciary is to arrest, impose sanctions and protect society from harm. Adults arrested for drug abuse in Indiana can be sentenced to 1 of 17 correctional facilities. As an alternative, they may be eligible to participate in a problem-solving court (PSC) programme that refers individuals to treatment as a pretrial diversionary strategy. The aim of the study is to determine which interventions offered by PSCs and correctional facilities impact morbidity and mortality. The study began in 2019 and will end in 2023; therefore, the results in this manuscript are preliminary., Methods: The study cohort included two populations arrested for drug misuse: (1) adults sentenced to Indianan correctional facilities (1 January 2018 to 30 June 2021) and (2) adults participating in an Indiana PSC programme (1 January 2018 to 30 June 2021). The study used a mixed-methods design that integrated qualitative interviews of deputy wardens, PSC team members and service providers with the following quantitative datasets: sentencing information, emergency department visits, inpatient hospitalization admissions, prescription drug monitoring programme data and death records. The individuals will be followed at 2-week, 4-week, 6-month and 1-year intervals post-release. Difference-in-difference and time-to-event analyses will identify impactful interventions. A model will be created to show the effect of impactful interventions in Indiana counties that do not have PSCs., Results: Findings are preliminary. There is variability amongst correctional facilities regarding programme eligibility, provided services and provision of medication-assisted treatment. All correctional facilities were severely impacted by the COVID-19 pandemic., Conclusion: It is anticipated that the adoption of impactful interventions will lower opioid-related morbidity and mortality rates., Competing Interests: Disclosure and potential conflicts of interest: None of the authors have any relevant conflicts of interest. None of the authors have any patents broadly relevant to the work. None of the authors has any relationships/conditions/circumstances that present a potential conflict of interest. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2021/11/dic.2021-8-1-COI.pdf, (Copyright © 2021 Van Nostrand E, Johnston A, Albert SM, Brown AL, Buchanich JM, Ray B, Roberts MS.)

Context: Leaders in public health have made great advances in workforce development over the past 30 years, while shifting from an emphasis based in training on individual, technical skills to a more holistic development approach, which boosts crosscutting skills. Efforts to increase public health workforce capabilities remain focused on workers as individuals, rather than the workforce as a collective unit., Program: Research has shown that a strategic adult learning approach can improve both individual capabilities and the collective performance of the workforce, which can be explained using social cognitive theory and the concept of collective efficacy, or the collective belief of workers in the ability of the group to succeed. We explain how a prior training program pushed us to explore this approach., Implementation: The proposed approach covers proposed implementation strategies to build collective efficacy as part of existing workforce development initiatives, with a focus on 5 key steps., Evaluation: Experience in fields as diverse as sports psychology and organizational development has shown that it is possible to evaluate changes in collective efficacy using measures that can be adopted in public health., Discussion: Adjusting existing public health workforce development initiatives to build collective efficacy can help link workforce self-confidence to performance. More actionable data are needed to determine the best methods for achieving those goals in the field of public health.

Background: The purpose of this study was to perform an interjurisdictional comparison of statutes and regulations (collectively laws) pertaining to the reporting of child dental neglect by dentists. Case law interpretation or enforcement of the laws was not included in this study., Methods: Child neglect laws were identified in 51 jurisdictions (50 states and the District of Columbia) by performing a Westlaw legal database search, conducting a systematic internet search, and engaging in direct communication with each jurisdiction. Laws on 2 domains relative to dentists were evaluated: protection from civil and criminal liability when reporting child neglect and sanctions for failing to report child neglect., Results: All jurisdictions have child neglect laws; however, only 8 specify failing to seek dental treatment as child neglect and none adopt the American Academy of Pediatric Dentistry's definition. Although all jurisdictions protect dental professionals who report child dental neglect in good faith, sanctions for failing to report neglect include imprisonment from 6 months (49%) through 5 years (2%) and fines from $1,000 (61%) through $10,000 (6%)., Conclusions: Although the laws vary across jurisdictions, dentists are protected when reporting child dental neglect but can be sanctioned for failing to report it., Practical Implications: Dentists may not be aware of the current sanctions or interjurisdictional differences. Becoming informed about these laws may incentivize dentists to establish reporting protocols for child dental neglect., (Copyright © 2020 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Volunteers who are deployed during times of disaster are critical public health system assets. These individuals share concerns about a variety of subjects with public health law implications, including whether they are entitled to employment benefits before, during, and after disaster response. We examined and analyzed state employment benefit laws pertaining to emergency response volunteers. We used the Emergency Law Inventory (ELI; https://legalinventory.pitt.edu )-an informatics tool developed at the University of Pittsburgh Graduate School of Public Health that contains more than 1300 statutory and regulatory provisions affecting volunteer activities-to access certain employment laws in 60 jurisdictions. Analyses of the laws revealed that fewer than half of the jurisdictions have laws that protect seniority, vacation time, sick time, or overtime privileges. Additionally, there is tremendous variance and lack of uniformity among the jurisdictions concerning employment status requirements, geographic constraints, time limitations, and economic impacts. Major disasters often necessitate interjurisdictional response. To facilitate effective deployment of volunteers, employment laws should be uniform across the states. Furthermore, limitations that impede volunteer responders should be eliminated.

Background: State policies pertaining to health care provider reporting of perinatal substance use have implications for provider screening and referral behavior, patients' care seeking and access to prenatal substance use disorder treatment, and pregnancy and birth outcomes., Objectives: This study sought to characterize specific provisions enacted in state statutes pertaining to mandates that health care providers report perinatal substance use, and to determine the proportion of births occurring in states with such laws., Methods: We conducted a systematic content analysis of statutes in all U.S. states that mentioned reporting by health care providers of substance use by pregnant women or infants exposed to substances in utero; inter-rater reliability was high. We calculated the number of states, and proportion of U.S. births occurring in states, with processes for mandatory reporting of perinatal substance use to authorities, and substance use disorder treatment provision for individuals who are reported., Results: Twenty states (corresponding with 31% of births) had laws requiring health care providers to report perinatal substance use to child protective authorities, and four states (18% of births) had laws requiring reporting only when a health care provider believed the substance use was associated with child maltreatment. About one-half of states (13) with any reporting law had a provision promoting substance use disorder treatment in the perinatal period., Conclusions: Findings inform the ongoing debate about how health policies may be used to reduce the population burden of perinatal substance use., (Copyright © 2016 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.)

Objective: Hurricane Sandy in the Rockaways, Queens, forced residents to evacuate and primary care providers to close or curtail operations. A large deficit in primary care access was apparent in the immediate aftermath of the storm. Our objective was to build a computational model to aid responders in planning to situate primary care services in a disaster-affected area., Methods: Using an agent-based modeling platform, HAZEL, we simulated the Rockaways population, its evacuation behavior, and primary care providers' availability in the aftermath of Hurricane Sandy. Data sources for this model included post-storm and community health surveys from New York City, a survey of the Rockaways primary care providers, and research literature. The model then tested geospatially specific interventions to address storm-related access deficits., Results: The model revealed that areas of high primary care access deficit were concentrated in the eastern part of the Rockaways. Placing mobile health clinics in the most populous census tracts reduced the access deficit significantly, whereas increasing providers' capacity by 50% reduced the deficit to a lesser degree., Conclusions: An agent-based model may be a useful tool to have in place so that policy makers can conduct scenario-based analyses to plan interventions optimally in the event of a disaster. (Disaster Med Public Health Preparedness. 2016;10:386-393).

During disaster response and recovery, legal issues often arise related to the provision of health care services to affected residents. Superstorm Sandy led to the evacuation of many hospitals and other health care facilities and compromised the ability of health care practitioners to provide necessary primary care. This article highlights the challenges and legal concerns faced by health care practitioners in the aftermath of Sandy, which included limitations in scope of practice, difficulties with credentialing, lack of portability of practitioner licenses, and concerns regarding volunteer immunity and liability. Governmental and nongovernmental entities employed various strategies to address these concerns; however, legal barriers remained that posed challenges throughout the Superstorm Sandy response and recovery period. We suggest future approaches to address these legal considerations, including policies and legislation, additional waivers of law, and planning and coordination among multiple levels of governmental and nongovernmental organizations. (Disaster Med Public Health Preparedness. 2016;10:518-524).

22q11.2 deletion syndrome (22q11DS) results from a hemizygous microdeletion on chromosome 22 and is characterized by extensive phenotypic variability. Penetrance of signs, including congenital heart, craniofacial, and neurobehavioral abnormalities, varies widely and is not well correlated with genotype. The three-dimensional structure of the genome may help explain some of this variability. The physical interaction profile of a given gene locus with other genetic elements, such as enhancers and co-regulated genes, contributes to its regulation. Thus, it is possible that regulatory interactions with elements outside the deletion region are disrupted in the disease state and modulate the resulting spectrum of symptoms. COMT, a gene within the commonly deleted ~3 Mb region has been implicated as a contributor to the neurological features frequently found in 22q11DS patients. We used this locus as bait in a 4C-seq experiment to investigate genome-wide interaction profiles in B lymphocyte and fibroblast cell lines derived from both 22q11DS and unaffected individuals. All normal B lymphocyte lines displayed local, conserved chromatin looping interactions with regions that are lost in atypical and distal deletions, which may mediate similarities between typical, atypical, and distal 22q11 deletion phenotypes. There are also distinct clusterings of cis interactions based on disease state. We identified regions of differential trans interactions present in normal, and lost in deletion-carrying, B lymphocyte cell lines. This data suggests that hemizygous chromosomal deletions such as 22q11DS can have widespread effects on chromatin organization, and may contribute to the inherent phenotypic variability.

Correct splice site recognition is critical in pre-mRNA splicing. We find that almost all of a diverse panel of exonic splicing silencer (ESS) elements alter splice site choice when placed between competing sites, consistently inhibiting use of intron-proximal 5' and 3' splice sites. Supporting a general role for ESSs in splice site definition, we found that ESSs are both abundant and highly conserved between alternative splice site pairs and that mutation of ESSs located between natural alternative splice site pairs consistently shifted splicing toward the intron-proximal site. Some exonic splicing enhancers (ESEs) promoted use of intron-proximal 5' splice sites, and tethering of hnRNP A1 and SF2/ASF proteins between competing splice sites mimicked the effects of ESS and ESE elements, respectively. Further, we observed that specific subsets of ESSs had distinct effects on a multifunctional intron retention reporter and that one of these subsets is likely preferred for regulation of endogenous intron retention events. Together, our findings provide a comprehensive picture of the functions of ESSs in the control of diverse types of splicing decisions.

Alternative pre-mRNA splicing affects a majority of human genes and plays important roles in development and disease. Alternative splicing (AS) events conserved since the divergence of human and mouse are likely of primary biological importance, but relatively few of such events are known. Here we describe sequence features that distinguish exons subject to evolutionarily conserved AS, which we call alternative conserved exons (ACEs), from other orthologous human/mouse exons and integrate these features into an exon classification algorithm, acescan. Genome-wide analysis of annotated orthologous human-mouse exon pairs identified approximately 2,000 predicted ACEs. Alternative splicing was verified in both human and mouse tissues by using an RT-PCR-sequencing protocol for 21 of 30 (70%) predicted ACEs tested, supporting the validity of a majority of acescan predictions. By contrast, AS was observed in mouse tissues for only 2 of 15 (13%) tested exons that had EST or cDNA evidence of AS in human but were not predicted ACEs, and AS was never observed for 11 negative control exons in human or mouse tissues. Predicted ACEs were much more likely to preserve the reading frame and less likely to disrupt protein domains than other AS events and were enriched in genes expressed in the brain and in genes involved in transcriptional regulation, RNA processing, and development. Our results also imply that the vast majority of AS events represented in the human EST database are not conserved in mouse.