• Systems neuroscience: Foraging through serotonin's tangled web

  Yemini, Eviatar (2023-07-24)

  Serotonin signaling is conserved in regulating animal behaviors. A new paper decodes the nonlinear effects of all serotonin receptor combinations on foraging behaviors. The authors introduce a brain-wide multiscale method to dissect receptor dynamics, receptor effects on neural activity, and resulting behavioral changes.
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  The prospective outcome of the monkeypox outbreak in 2022 and characterization of monkeypox disease immunobiology

  Qudus, Muhammad Suhaib; Cui, Xianghua; Tian, Mingfu; Afaq, Uzair; Sajid, Muhammad; Qureshi, Sonia; Liu, Siyu; Ma, June; Wang, Guolei; Faraz, Muhammad; et al. (2023-07-18)

  A new threat to global health re-emerged with monkeypox's advent in early 2022. As of November 10, 2022, nearly 80,000 confirmed cases had been reported worldwide, with most of them coming from places where the disease is not common. There were 53 fatalities, with 40 occurring in areas that had never before recorded monkeypox and the remaining 13 appearing in the regions that had previously reported the disease. Preliminary genetic data suggest that the 2022 monkeypox virus is part of the West African clade; the virus can be transmitted from person to person through direct interaction with lesions during sexual activity. It is still unknown if monkeypox can be transmitted via sexual contact or, more particularly, through infected body fluids. This most recent epidemic's reservoir host, or principal carrier, is still a mystery. Rodents found in Africa can be the possible intermediate host. Instead, the CDC has confirmed that there are currently no particular treatments for monkeypox virus infection in 2022; however, antivirals already in the market that are successful against smallpox may mitigate the spread of monkeypox. To protect against the disease, the JYNNEOS (Imvamune or Imvanex) smallpox vaccine can be given. The spread of monkeypox can be slowed through measures such as post-exposure immunization, contact tracing, and improved case diagnosis and isolation. Final Thoughts: The latest monkeypox epidemic is a new hazard during the COVID-19 epidemic. The prevailing condition of the monkeypox epidemic along with coinfection with COVID-19 could pose a serious condition for clinicians that could lead to the global epidemic community in the form of coinfection.
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  NIDM-Terms: community-based terminology management for improved neuroimaging dataset descriptions and query

  Queder, Nazek; Tien, Vivian B; Abraham, Sanu Ann; Urchs, Sebastian Georg Wenzel; Helmer, Karl G; Chaplin, Derek; van Erp, Theo G M; Kennedy, David N; Poline, Jean-Baptiste; Grethe, Jeffrey S; et al. (2023-07-18)

  The biomedical research community is motivated to share and reuse data from studies and projects by funding agencies and publishers. Effectively combining and reusing neuroimaging data from publicly available datasets, requires the capability to query across datasets in order to identify cohorts that match both neuroimaging and clinical/behavioral data criteria. Critical barriers to operationalizing such queries include, in part, the broad use of undefined study variables with limited or no annotations that make it difficult to understand the data available without significant interaction with the original authors. Using the Brain Imaging Data Structure (BIDS) to organize neuroimaging data has made querying across studies for specific image types possible at scale. However, in BIDS, beyond file naming and tightly controlled imaging directory structures, there are very few constraints on ancillary variable naming/meaning or experiment-specific metadata. In this work, we present NIDM-Terms, a set of user-friendly terminology management tools and associated software to better manage individual lab terminologies and help with annotating BIDS datasets. Using these tools to annotate BIDS data with a Neuroimaging Data Model (NIDM) semantic web representation, enables queries across datasets to identify cohorts with specific neuroimaging and clinical/behavioral measurements. This manuscript describes the overall informatics structures and demonstrates the use of tools to annotate BIDS datasets to perform integrated cross-cohort queries.
• A System for Rapidly Yet Rigorously Evaluating the Quality of Randomized Controlled Trials

  Smith, Eric G; Grigorian, Hannah L (2023-07-01)

  This tutorial describes a system for rapidly yet rigorously assessing the quality of randomized controlled trials (RCTs). The system has 7 criteria, represented by the acronym "BIS FOES." The BIS FOES system directs readers to assess RCTs based on the following 7 criteria: the RCT's use (or not) of effective (1) Blinding; the RCT's use (or not) of (2) Intent-to-Treat Analysis; the RCT's (3) Size and other information reflecting the effectiveness of randomization; the amount of sample lost during (4) Follow-up; the (5) Outcomes examined by the RCT (specifically, the outcome measures used by the RCT), the (6) Efects reported (ie, the statistical and clinical significance of the RCT's primary, secondary, and safety findings), and any (7) Special Considerations (ie, additional strengths, limitations, or notable features of the RCT). The first 6 criteria are of basic importance to the assessment of every RCT, whereas the Special Considerations criteria allows the system to be expanded to include virtually any other important aspect of the RCT. This tutorial explains the importance of these criteria and how to assess them. This tutorial also describes how many BIS FOES criteria can be initially assessed from the RCT Abstract while also directing readers to specific locations in the RCT article where additional important information can be found. We hope that the BIS FOES system will help healthcare trainees, but also potentially clinicians, researchers, and the general public, rapidly and thoroughly assess RCTs.
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  Feasibility of a Career Development Intervention for Veterans in Vocational Rehabilitation: Protocol for a Pilot Randomized Controlled Trial

  Stevenson, Brian; Teravainen, Taina; Kathawalla, Ummul Kiram; Singer, Margo; Wilkins, Sarah; Mueller, Lisa; Kelly, Megan; Ellison, Marsha; Shirk, Steven D; Bakken, Shana; et al. (2023-06-30)

  Background: Veterans with psychiatric disorders want additional career development services to support their recovery and pursuit of meaningful employment. However, no career counseling programs have been designed for this specific population. We developed the Purposeful Pathways intervention to fill this need. Objective: This study protocol aims to (1) evaluate the feasibility and acceptability of the Purposeful Pathways intervention for veterans living with psychiatric disorders and (2) explore preliminary clinical outcome data. Methods: A total of 50 veterans who are participating in transitional work vocational rehabilitation services at a Veterans Affairs hospital will be randomized to either treatment as usual or the augmented treatment condition (treatment as usual plus Purposeful Pathways). Feasibility will be assessed via recruitment rates, clinician fidelity to treatment, retention rates, and acceptability of randomization procedures. Acceptability will be assessed via client satisfaction at treatment termination using quantitative and qualitative data collection. Preliminary clinical and vocational outcomes will be assessed at baseline, 6 weeks, 12 weeks (treatment termination), and a 3-month follow-up via quantitative measures assessing vocational functioning, vocational process, and mental and physical functioning. Results: This pilot randomized controlled trial is beginning recruitment in June 2023 and is expected to continue through November 2025. Data collection is expected to be completed by February 2026, with full data analysis completed by March 2026. Conclusions: Findings from this study will provide information on the feasibility and acceptability of the Purposeful Pathways intervention, as well as secondary outcomes related to vocational functioning, vocational process, and mental and physical functioning. Trial registration: ClinicalTrials.gov NCT04698967; https://clinicaltrials.gov/ct2/show/NCT04698967. International registered report identifier (irrid): PRR1-10.2196/47986.
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  The CERV protein of Cer1, a C. elegans LTR retrotransposon, is required for nuclear export of viral genomic RNA and can form giant nuclear rods

  Sun, Bing; Kim, Haram; Mello, Craig C; Priess, James R (2023-06-29)

  Retroviruses and closely related LTR retrotransposons export full-length, unspliced genomic RNA (gRNA) for packaging into virions and to serve as the mRNA encoding GAG and POL polyproteins. Because gRNA often includes splice acceptor and donor sequences used to splice viral mRNAs, retroelements must overcome host mechanisms that retain intron-containing RNAs in the nucleus. Here we examine gRNA expression in Cer1, an LTR retrotransposon in C. elegans which somehow avoids silencing and is highly expressed in germ cells. Newly exported Cer1 gRNA associates rapidly with the Cer1 GAG protein, which has structural similarity with retroviral GAG proteins. gRNA export requires CERV (C. elegans regulator of viral expression), a novel protein encoded by a spliced Cer1 mRNA. CERV phosphorylation at S214 is essential for gRNA export, and phosphorylated CERV colocalizes with nuclear gRNA at presumptive sites of transcription. By electron microscopy, tagged CERV proteins surround clusters of distinct, linear fibrils that likely represent gRNA molecules. Single fibrils, or groups of aligned fibrils, also localize near nuclear pores. During the C. elegans self-fertile period, when hermaphrodites fertilize oocytes with their own sperm, CERV concentrates in two nuclear foci that are coincident with gRNA. However, as hermaphrodites cease self-fertilization, and can only produce cross-progeny, CERV undergoes a remarkable transition to form giant nuclear rods or cylinders that can be up to 5 microns in length. We propose a novel mechanism of rod formation, in which stage-specific changes in the nucleolus induce CERV to localize to the nucleolar periphery in flattened streaks of protein and gRNA; these streaks then roll up into cylinders. The rods are a widespread feature of Cer1 in wild strains of C. elegans, but their function is not known and might be limited to cross-progeny. We speculate that the adaptive strategy Cer1 uses for the identical self-progeny of a host hermaphrodite might differ for heterozygous cross-progeny sired by males. For example, mating introduces male chromosomes which can have different, or no, Cer1 elements.
• Beyond diversity and inclusion: Developing a research agenda for anti-racism in emergency medicine education

  Ordonez, Edgardo; Bradby, Cassandra; Carey, Jennifer; Gupta, Sanjey; Hiller, Katherine M; Miller, Danielle; Pierce, Ava; Wiesendanger, Kathryn; Moffett, Shannon (2023-06-27)

  Background: Addressing racism in emergency medicine education is vital for providing optimal training and assessment of physicians in the specialty, developing physicians with the skills necessary to advocate for their patients, and recruiting and retaining a diverse group of physicians. To form a prioritized research agenda, the Society of Academic Emergency Medicine (SAEM) conducted a consensus conference at the annual meeting in May 2022 on addressing racism in emergency medicine, which included a subgroup on education. Methods: The education workgroup worked on summarizing the current literature on addressing racism in emergency medicine education, identifying critical knowledge gaps, and creating a consensus-driven research agenda for addressing racism in emergency medicine education. We used a nominal group technique and modified Delphi to develop priority questions for research. We then distributed a pre-conference survey to conference registrants to rate priority areas for research. During the consensus conference, group leaders provided an overview and background describing the rationale for the preliminary research question list. Attendees were then involved in discussions to help modify and develop research questions. Results: Nineteen questions were initially selected by the education workgroup as potential areas for research. The education workgroup's next round of consensus building resulted in a consensus of ten questions to be included in the pre-conference survey. No questions in the pre-conference survey reached consensus. After robust discussion and voting by workgroup members and attendees at the consensus conference, six questions were determined to be priority research areas. Conclusions: We believe recognizing and addressing racism in emergency medicine education is imperative. Critical gaps in curriculum design, assessment, bias training, allyship, and the learning environment negatively impact training programs. These gaps must be prioritized for research as they can have adverse effects on recruitment, the ability to promote a safe learning environment, patient care, and patient outcomes.
• From inequity to access: Evidence-based institutional practices to enhance care for individuals with disabilities

  Rotoli, Jason; Poffenberger, Cori; Backster, Anika; Sapp, Richard; Modi, Payal; Stehman, Christine R; Mirus, Carl; Johnson, Luke; Siegelman, Jeffrey N; Coates, Wendy C (2023-06-27)

  People with disabilities experience barriers to care in all facets of health care, from engaging with the provider in a clinical setting (attitudinal and communication barriers) to navigating a large institution in a complex health care environment (organizational and environmental barriers), culminating in significant health care disparities. Institutional policy, culture, and physical layout may be inadvertently fostering ableism, which can perpetuate health care inaccessibility and health disparities in the disability community. Here, we present evidence-based interventions at the provider and institutional levels to accommodate patients with hearing, vision, and intellectual disabilities. Institutional barriers can be met with strategies of universal design (i.e., accessible exam rooms and emergency alerts), maximizing electronic medical record accessibility/visibility, and institutional policy development to recognize and reduce discrimination. Barriers at the provider level can be met with dedicated training on care of patients with disabilities and implicit bias training specific to the surrounding patient demographics. Such efforts are crucial to ensuring equitable access to quality care for these patients.
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  Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder

  Bauer, Michael; Glenn, Tasha; Achtyes, Eric D; Alda, Martin; Agaoglu, Esen; Altınbaş, Kürsat; Andreassen, Ole A; Angelopoulos, Elias; Ardau, Raffaella; Aydin, Memduha; et al. (2023-06-22)

  Background: Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample. Methods: Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001. Results: The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger. Conclusion: UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.
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  On the Q statistic with constant weights in meta-analysis of binary outcomes

  Kulinskaya, Elena; Hoaglin, David C (2023-06-21)

  Background: Cochran's Q statistic is routinely used for testing heterogeneity in meta-analysis. Its expected value (under an incorrect null distribution) is part of several popular estimators of the between-study variance, [Formula: see text]. Those applications generally do not account for use of the studies' estimated variances in the inverse-variance weights that define Q (more explicitly, [Formula: see text]). Importantly, those weights make approximating the distribution of [Formula: see text] rather complicated. Methods: As an alternative, we are investigating a Q statistic, [Formula: see text], whose constant weights use only the studies' arm-level sample sizes. For log-odds-ratio (LOR), log-relative-risk (LRR), and risk difference (RD) as the measures of effect, we study, by simulation, approximations to distributions of [Formula: see text] and [Formula: see text], as the basis for tests of heterogeneity. Results: The results show that: for LOR and LRR, a two-moment gamma approximation to the distribution of [Formula: see text] works well for small sample sizes, and an approximation based on an algorithm of Farebrother is recommended for larger sample sizes. For RD, the Farebrother approximation works very well, even for small sample sizes. For [Formula: see text], the standard chi-square approximation provides levels that are much too low for LOR and LRR and too high for RD. The Kulinskaya et al. (Res Synth Methods 2:254-70, 2011) approximation for RD and the Kulinskaya and Dollinger (BMC Med Res Methodol 15:49, 2015) approximation for LOR work well for [Formula: see text] but have some convergence issues for very small sample sizes combined with small probabilities. Conclusions: The performance of the standard [Formula: see text] approximation is inadequate for all three binary effect measures. Instead, we recommend a test of heterogeneity based on [Formula: see text] and provide practical guidelines for choosing an appropriate test at the .05 level for all three effect measures.
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  Relaxed targeting rules help PIWI proteins silence transposons

  Gainetdinov, Ildar; Vega-Badillo, Joel; Cecchini, Katharine; Bagci, Ayca; Colpan, Cansu; De, Dipayan; Bailey, Shannon; Arif, Amena; Wu, Pei-Hsuan; MacRae, Ian J; et al. (2023-06-21)

  In eukaryotes, small RNA guides, such as small interfering RNAs and microRNAs, direct AGO-clade Argonaute proteins to regulate gene expression and defend the genome against external threats. Only animals make a second clade of Argonaute proteins: PIWI proteins. PIWI proteins use PIWI-interacting RNAs (piRNAs) to repress complementary transposon transcripts1,2. In theory, transposons could evade silencing through target site mutations that reduce piRNA complementarity. Here we report that, unlike AGO proteins, PIWI proteins efficiently cleave transcripts that are only partially paired to their piRNA guides. Examination of target binding and cleavage by mouse and sponge PIWI proteins revealed that PIWI slicing tolerates mismatches to any target nucleotide, including those flanking the scissile phosphate. Even canonical seed pairing is dispensable for PIWI binding or cleavage, unlike plant and animal AGOs, which require uninterrupted target pairing from the seed to the nucleotides past the scissile bond3,4. PIWI proteins are therefore better equipped than AGO proteins to target newly acquired or rapidly diverging endogenous transposons without recourse to new small RNA guides. Conversely, the minimum requirements for PIWI slicing are sufficient to avoid inadvertent silencing of host RNAs. Our results demonstrate the biological advantage of PIWI over AGO proteins in defending the genome against transposons and suggest an explanation for why the piRNA pathway was retained in animal evolution.
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  Wnt signaling preserves progenitor cell multipotency during adipose tissue development

  Yang Loureiro, Zinger; Joyce, Shannon; DeSouza, Tiffany; Solivan-Rivera, Javier; Desai, Anand; Skritakis, Pantos; Yang, Qin; Ziegler, Rachel; Zhong, Denise; Nguyen, Tammy T; et al. (2023-06-19)

  Mesenchymal stem/progenitor cells are essential for tissue development and repair throughout life, but how they are maintained under chronic differentiation pressure is not known. Using single-cell transcriptomics of human progenitor cells we find that adipose differentiation stimuli elicit two cellular trajectories: one toward mature adipocytes and another toward a pool of non-differentiated cells that maintain progenitor characteristics. These cells are induced by transient Wnt pathway activation and express numerous extracellular matrix genes and are therefore named structural Wnt-regulated adipose tissue cells. We find that the genetic signature of structural Wnt-regulated adipose tissue cells is present in adult human adipose tissue and adipose tissue developed from human progenitor cells in mice. Our results suggest a mechanism whereby adipose differentiation occurs concurrently with the maintenance of a mesenchymal progenitor cell pool, ensuring tissue development, repair and appropriate metabolic control over the lifetime.
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  Asymmetric trichotomous partitioning overcomes dataset limitations in building machine learning models for predicting siRNA efficacy

  Monopoli, Kathryn R; Korkin, Dmitry; Khvorova, Anastasia (2023-06-14)

  Chemically modified small interfering RNAs (siRNAs) are promising therapeutics guiding sequence-specific silencing of disease genes. Identifying chemically modified siRNA sequences that effectively silence target genes remains challenging. Such determinations necessitate computational algorithms. Machine learning is a powerful predictive approach for tackling biological problems but typically requires datasets significantly larger than most available siRNA datasets. Here, we describe a framework applying machine learning to a small dataset (356 modified sequences) for siRNA efficacy prediction. To overcome noise and biological limitations in siRNA datasets, we apply a trichotomous, two-threshold, partitioning approach, producing several combinations of classification threshold pairs. We then test the effects of different thresholds on random forest machine learning model performance using a novel evaluation metric accounting for class imbalances. We identify thresholds yielding a model with high predictive power, outperforming a linear model generated from the same data, that was predictive upon experimental evaluation. Using a novel model feature extraction method, we observe target site base importances and base preferences consistent with our current understanding of the siRNA-mediated silencing mechanism, with the random forest providing higher resolution than the linear model. This framework applies to any classification challenge involving small biological datasets, providing an opportunity to develop high-performing design algorithms for oligonucleotide therapies.
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  Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals

  Hinojosa, Cecilia A; Liew, Amanda; An, Xinming; Stevens, Jennifer S; Basu, Archana; van Rooij, Sanne J H; House, Stacey L; Beaudoin, Francesca L; Zeng, Donglin; Neylan, Thomas C; et al. (2023-06-13)

  Background: Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians. Methods: In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance. Results: Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12. Conclusions: Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.
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  Template-jumping prime editing enables large insertion and exon rewriting in vivo

  Zheng, Chunwei; Liu, Bin; Dong, Xiaolong; Gaston, Nicholas; Sontheimer, Erik J; Xue, Wen (2023-06-08)

  Targeted insertion of large DNA fragments holds promise for genome engineering and gene therapy. Prime editing (PE) effectively inserts short (<50 bp) sequences. Employing paired prime editing guide RNAs (pegRNAs) has enabled PE to better mediate relatively large insertions in vitro, but the efficiency of larger insertions (>400 bp) remains low and in vivo application has not been demonstrated. Inspired by the efficient genomic insertion mechanism of retrotransposons, we develop a template-jumping (TJ) PE approach for the insertion of large DNA fragments using a single pegRNA. TJ-pegRNA harbors the insertion sequence as well as two primer binding sites (PBSs), with one PBS matching a nicking sgRNA site. TJ-PE precisely inserts 200 bp and 500 bp fragments with up to 50.5 and 11.4% efficiency, respectively, and enables GFP (~800 bp) insertion and expression in cells. We transcribe split circular TJ-petRNA in vitro via a permuted group I catalytic intron for non-viral delivery in cells. Finally, we demonstrate that TJ-PE can rewrite an exon in the liver of tyrosinemia I mice to reverse the disease phenotype. TJ-PE has the potential to insert large DNA fragments without double-stranded DNA breaks and facilitate mutation hotspot exon rewriting in vivo.
• Learning Probabilistic Piecewise Rigid Atlases of Model Organisms via Generative Deep Networks

  Nejatbakhsh, Amin; Dey, Neel; Venkatachalam, Vivek; Yemini, Eviatar; Paninski, Liam; Varol, Erdem (2023-06-08)

  Atlases are crucial to imaging statistics as they enable the standardization of inter-subject and inter-population analyses. While existing atlas estimation methods based on fluid/elastic/diffusion registration yield high-quality results for the human brain, these deformation models do not extend to a variety of other challenging areas of neuroscience such as the anatomy of C. elegans worms and fruit flies. To this end, this work presents a general probabilistic deep network-based framework for atlas estimation and registration which can flexibly incorporate various deformation models and levels of keypoint supervision that can be applied to a wide class of model organisms. Of particular relevance, it also develops a deformable piecewise rigid atlas model which is regularized to preserve inter-observation distances between neighbors. These modeling considerations are shown to improve atlas construction and key-point alignment across a diversity of datasets with small sample sizes including neuron positions in C. elegans hermaphrodites, fluorescence microscopy of male C. elegans, and images of fruit fly wings. Code is accessible at https://github.com/amin-nejat/Deformable-Atlas.
• Labor and Delivery Clinician Perspectives on Impact of Traumatic Clinical Experiences and Need for Systemic Supports

  Xu, Lulu; Masters, Grace A; Moore Simas, Tiffany A; Bergman, Aaron L; Byatt, Nancy (2023-06-06)

  Objectives: Few studies have elucidated the impact of work-related trauma on labor and delivery clinician or considered whether it may be a cause of burnout. This study aims to elicit labor and delivery clinician perspectives on the impact of exposure to traumatic births on their professional quality of life. Methods: Labor and delivery clinicians (physicians, midwives, nurse practitioners, and nurses; n = 165) were recruited to complete an online questionnaire on experiences with traumatic births. The questionnaire contained measures from the Maslach Burnout Inventory and the professional quality of life scale version 5. Some participants completed an optional free-text prompt to recommend ways to support clinicians after traumatic births (n = 115). Others opted into a semi-structured phone interview (n = 8). Qualitative data was analyzed using a modified grounded theory approach. Results: Self-reported adequate institutional support for clinicians after a traumatic birth was positively correlated with compassion satisfaction (r = 0.21, p < 0.01) and negatively correlated with secondary traumatic stress (r = - 0.27, p < 0.01), and burnout (r = - 0.26, p < 0.01). Qualitative themes included lack of system-wide and leadership support, lack of access to mental health resources, and suboptimal workplace culture as contributors toward secondary traumatic stress and burnout. Participants recommended proactive leadership, consistent debriefing protocols, trauma education, and improved access to counseling. Conclusions for practice: Multi-level barriers prevented labor and delivery clinicians from accessing needed mental health support after exposure to traumatic births. Proactive investment in healthcare system supports for clinicians may improve clinician professional quality of life.
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  Effectiveness of using a patient education mobile application to improve the quality of bowel preparation: a randomised controlled trial

  Dao, Hang Viet; Dao, Quan Viet; Lam, Hoa Ngoc; Hoang, Long Bao; Nguyen, Van Thi; Nguyen, Thuy Thi; Vu, Dat Quoc; Pokorny, Christopher S; Nguyen, Hoa Lan; Allison, Jeroan J.; et al. (2023-06-05)

  Aims: To determine the effectiveness of a mobile application (app) in improving the quality of bowel preparation for colonoscopy. Method: An endoscopist-blinded randomised controlled trial enrolled patients who were undergoing a colonoscopy on the same day of bowel preparation. The intervention used a Vietnamese mobile app that provides instructions on bowel preparation while patients in the comparison group received conventional instructions. Outcomes included the Boston Bowel Preparation Scale (BBPS) to assess the quality of bowel preparation and the polyp detection rate (PDR) and adenoma detection rate (ADR). Results: The study recruited 515 patients (256 in the intervention group). The median age was 42 years, 50.9% were females, 69.1% high school graduates and higher, and 45.2% from urban area. Patients in the intervention group had higher adherence to instructions (60.9% vs 52.4%, p=0.05) and longer length of taking laxatives (mean difference 0.17 hours, 95% CI 0.06 to 0.27). The intervention did not reduce the risk of poor bowel cleansing (total BBPS<6) in both overall (7.4% vs 7.7%; risk ratio 0.96, 95% CI 0.53 to 1.76) and subgroup analysis. PDR and ADR were similar between the two groups. Conclusions: The mobile app providing instructions on proper bowel preparation improved the practice during bowel preparation but did not improve the quality of bowel cleansing or PDR.
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  Using Simulation-Based Learning with Standardized Patients (SP) in an Implicit Bias Mitigation Clinician Training Program

  Tjia, Jennifer; Pugnaire, Michele; Calista, Joanne; Eisdorfer, Ethan; Hale, Janet; Terrien, Jill; Valdman, Olga; Potts, Stacy; Garcia, Maria; Yazdani, Majid; et al. (2023-06-05)

  Objectives: To describe the development and refinement of an implicit bias recognition and management training program for clinical trainees. Methods: In the context of an NIH-funded clinical trial to address healthcare disparities in hypertension management, research and education faculty at an academic medical center used a participatory action research approach to engage local community members to develop and refine a "knowledge, awareness, and skill-building" bias recognition and mitigation program. The program targeted medical residents and Doctor of Nursing Practice students. The content of the two-session training included: didactics about healthcare disparities, racism and implicit bias; implicit association test (IAT) administration to raise awareness of personal implicit bias; skill building for bias-mitigating communication; and case scenarios for skill practice in simulation-based encounters with standardized patients (SPs) from the local community. Results: The initial trial year enrolled n = 65 interprofessional participants. Community partners and SPs who engaged throughout the design and implementation process reported overall positive experiences, but SPs expressed need for greater faculty support during in-person debriefings following simulation encounters to balance power dynamics. Initial year trainee participants reported discomfort with intensive sequencing of in-person didactics, IATs, and SP simulations in each of the two training sessions. In response, authors refined the training program to separate didactic sessions from IAT administration and SP simulations, and to increase safe space, and trainee and SP empowerment. The final program includes more interactive discussions focused on identity, race and ethnicity, and strategies to address local health system challenges related to structural racism. Conclusion: It is possible to develop and implement a bias awareness and mitigation skills training program that uses simulation-based learning with SPs, and to engage with local community members to tailor the content to address the experience of local patient populations. Further research is needed to measure the success and impact of replicating this approach elsewhere.
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  Visualizing everything, everywhere, all at once: Cryo-EM and the new field of structureomics

  Lucas, Bronwyn A (2023-06-04)

  Twenty years ago, the release of the first draft of the human genome sequence instigated a paradigm shift in genomics and molecular biology. Arguably, structural biology is entering an analogous era, with availability of an experimentally determined or predicted molecular model for almost every protein-coding gene from many genomes-producing a reference "structureome". Structural predictions require experimental validation and not all proteins conform to a single structure, making any reference structureome necessarily incomplete. Despite these limitations, a reference structureome can be used to characterize cell state in more detail than by quantifying sequence or expression levels alone. Cryogenic electron microscopy (cryo-EM) is a method that can generate atomic resolution views of molecules and cells frozen in place. In this perspective I consider how emerging cryo-EM methods are contributing to the new field of structureomics.

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