The bacterial cytoplasm has glass-like properties and is fluidized by metabolic activity.

The physical nature of the bacterial cytoplasm is poorly understood even though it determines cytoplasmic dynamics and hence cellular physiology and behavior. Through single-particle tracking of protein filaments, plasmids, storage granules, and foreign particles of different sizes, we find that the bacterial cytoplasm displays properties that are characteristic of glass-forming liquids and changes from liquid-like to solid-like in a component size-dependent fashion. As a result, the motion of cytoplasmic components becomes disproportionally constrained with increasing size. Remarkably, cellular metabolism fluidizes the cytoplasm, allowing larger components to escape their local environment and explore larger regions of the cytoplasm. Consequently, cytoplasmic fluidity and dynamics dramatically change as cells shift between metabolically active and dormant states in response to fluctuating environments. Our findings provide insight into bacterial dormancy and have broad implications to our understanding of bacterial physiology, as the glassy behavior of the cytoplasm impacts all intracellular processes involving large components.

Lineage regulators direct BMP and Wnt pathways to cell-specific programs during differentiation and regeneration.

BMP and Wnt signaling pathways control essential cellular responses through activation of the transcription factors SMAD (BMP) and TCF (Wnt). Here, we show that regeneration of hematopoietic lineages following acute injury depends on the activation of each of these signaling pathways to induce expression of key blood genes. Both SMAD1 and TCF7L2 co-occupy sites with master regulators adjacent to hematopoietic genes. In addition, both SMAD1 and TCF7L2 follow the binding of the predominant lineage regulator during differentiation from multipotent hematopoietic progenitor cells to erythroid cells. Furthermore, induction of the myeloid lineage regulator C/EBPα in erythroid cells shifts binding of SMAD1 to sites newly occupied by C/EBPα, whereas expression of the erythroid regulator GATA1 directs SMAD1 loss on nonerythroid targets. We conclude that the regenerative response mediated by BMP and Wnt signaling pathways is coupled with the lineage master regulators to control the gene programs defining cellular identity.

Identifying topologically associating domains using differential kernels.

Chromatin is a polymer complex of DNA and proteins that regulates gene expression. The three-dimensional (3D) structure and organization of chromatin controls DNA transcription and replication. High-throughput chromatin conformation capture techniques generate Hi-C maps that can provide insight into the 3D structure of chromatin. Hi-C maps can be represented as a symmetric matrix [Formula: see text], where each element represents the average contact probability or number of contacts between chromatin loci i and j. Previous studies have detected topologically associating domains (TADs), or self-interacting regions in [Formula: see text] within which the contact probability is greater than that outside the region. Many algorithms have been developed to identify TADs within Hi-C maps. However, most TAD identification algorithms are unable to identify nested or overlapping TADs and for a given Hi-C map there is significant variation in the location and number of TADs identified by different methods. We develop a novel method to identify TADs, KerTAD, using a kernel-based technique from computer vision and image processing that is able to accurately identify nested and overlapping TADs. We benchmark this method against state-of-the-art TAD identification methods on both synthetic and experimental data sets. We find that the new method consistently has higher true positive rates (TPR) and lower false discovery rates (FDR) than all tested methods for both synthetic and manually annotated experimental Hi-C maps. The TPR for KerTAD is also largely insensitive to increasing noise and sparsity, in contrast to the other methods. We also find that KerTAD is consistent in the number and size of TADs identified across replicate experimental Hi-C maps for several organisms. Thus, KerTAD will improve automated TAD identification and enable researchers to better correlate changes in TADs to biological phenomena, such as enhancer-promoter interactions and disease states.

The role of prescription opioid and cannabis supply policies on opioid overdose deaths.

Mandatory prescription drug monitoring programs and cannabis legalization have been hypothesized to reduce overdose deaths. We examined associations between prescription monitoring programs with access mandates ("must-query PDMPs"), legalization of medical and recreational cannabis supply, and opioid overdose deaths in United States counties in 2013-2020. Using data on overdose deaths from the National Vital Statistics System, we fit Bayesian spatiotemporal models to estimate risk differences and 95% credible intervals (CrI) in county-level opioid overdose deaths associated with enactment of these state policies. Must-query PDMPs were independently associated with on average 0.8 (95% CrI: 0.5, 1.0) additional opioid-involved overdose deaths per 100,000 person-years. Legal cannabis supply was not independently associated with opioid overdose deaths in this time period. Must-query PDMPs enacted in the presence of legal (medical or recreational) cannabis supply were associated with 0.7 (95% CrI: 0.4, 0.9) more opioid-involved deaths, relative to must-query PDMPs without any legal cannabis supply. In a time when overdoses are driven mostly by non-prescribed opioids, stricter opioid prescribing policies and more expansive cannabis legalization were not associated with reduced overdose death rates.

BET-bromodomain and EZH2 inhibitor-treated chronic GVHD mice have blunted germinal centers with distinct transcriptomes.

Despite advances in the field, chronic graft-versus-host-disease (cGVHD) remains a leading cause of morbidity and mortality following allogenic hematopoietic stem cell transplant. Because treatment options remain limited, we tested efficacy of anticancer, chromatin-modifying enzyme inhibitors in a clinically relevant murine model of cGVHD with bronchiolitis obliterans (BO). We observed that the novel enhancer of zeste homolog 2 (EZH2) inhibitor JQ5 and the BET-bromodomain inhibitor JQ1 each improved pulmonary function; impaired the germinal center (GC) reaction, a prerequisite in cGVHD/BO pathogenesis; and JQ5 reduced EZH2-mediated H3K27me3 in donor T cells. Using conditional EZH2 knockout donor cells, we demonstrated that EZH2 is obligatory for the initiation of cGVHD/BO. In a sclerodermatous cGVHD model, JQ5 reduced the severity of cutaneous lesions. To determine how the 2 drugs could lead to the same physiological improvements while targeting unique epigenetic processes, we analyzed the transcriptomes of splenic GCB cells (GCBs) from transplanted mice treated with either drug. Multiple inflammatory and signaling pathways enriched in cGVHD/BO GCBs were reduced by each drug. GCBs from JQ5- but not JQ1-treated mice were enriched for proproliferative pathways also seen in GCBs from bone marrow-only transplanted mice, likely reflecting their underlying biology in the unperturbed state. In conjunction with in vivo data, these insights led us to conclude that epigenetic targeting of the GC is a viable clinical approach for the treatment of cGVHD, and that the EZH2 inhibitor JQ5 and the BET-bromodomain inhibitor JQ1 demonstrated clinical potential for EZH2i and BETi in patients with cGVHD/BO.

Identifying and Linking Patients At Risk for MASLD with Advanced Fibrosis to Care in Primary Care.

BACKGROUND AND AIMS: Severity of fibrosis is the driver of liver-related outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD), and non-invasive testing such as fibrosis-4 (FIB-4) score is utilized for risk stratification. We aimed to determine if primary care patients at risk for MASLD and advanced fibrosis were evaluated with subsequent testing. A secondary aim was to determine if at-risk patients with normal aminotransferases had advanced fibrosis. METHODS: Primary care patients at increased risk for MASLD with advanced fibrosis (n = 91,914) were identified using previously established criteria. Patients with known alternative/concomitant etiology of liver disease or cirrhosis were excluded. The study cohort included patients with calculated FIB-4 score in 2020 (n = 52,006), and stratified into low, indeterminate, and high likelihood of advanced fibrosis. Among those at indeterminate/high risk, rates of subsequent testing were measured. RESULTS: Risk stratification with FIB-4 characterized 77% (n = 40,026) as low risk, 17% (n = 8847) as indeterminate, and 6% (n = 3133) as high risk. Among indeterminate/high-risk patients (n = 11,980), 78.7% (n = 9433) had aminotransferases within normal limits, 0.95% (n = 114) had elastography, and 8.2% (n = 984) were referred for subspecialty evaluation. CONCLUSION: In this cohort of primary care patients at risk for MASLD with fibrosis, the FIB-4 score identified a substantial proportion of indeterminate/high-risk patients, the majority of which had normal aminotransferase levels. Low rates of subsequent testing were observed. These data suggest that a majority of patients at increased risk for liver-related outcomes remain unrecognized and highlight opportunities to facilitate their identification.

A Positive Psychology Intervention in Allogeneic Hematopoietic Stem Cell Transplantation Survivors (PATH): A Pilot Randomized Clinical Trial.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) survivors experience significant psychological distress and low levels of positive psychological well-being, which can undermine patient-reported outcomes (PROs), such as quality of life (QoL). Hence, we conducted a pilot randomized clinical trial to assess the feasibility and preliminary efficacy of a telephone-delivered positive psychology intervention (Positive Affect for the Transplantation of Hematopoietic stem cells intervention [PATH]) for improving well-being in HSCT survivors. METHODS: HSCT survivors who were 100 days post-HSCT for hematologic malignancy at an academic institution were randomly assigned to either PATH or usual care. PATH, delivered by a behavioral health expert, entailed 9 weekly phone sessions on gratitude, personal strengths, and meaning. We defined feasibility a priori as >60% of eligible participants enrolling in the study and >75% of PATH participants completing ≥6 of 9 sessions. At baseline and 9 and 18 weeks, patients self-reported gratitude, positive affect, life satisfaction, optimism, anxiety, depression, posttraumatic stress disorder (PTSD), QoL, physical function, and fatigue. We used repeated measures regression models and estimates of effect size (Cohen's d) to explore the preliminary effects of PATH on outcomes. RESULTS: We enrolled 68.6% (72/105) of eligible patients (mean age, 57 years; 50% female). Of those randomized to PATH, 91% completed all sessions and reported positive psychology exercises as easy to complete and subjectively useful. Compared with usual care, PATH participants reported greater improvements in gratitude (ß = 1.38; d = 0.32), anxiety (ß = -1.43; d = -0.40), and physical function (ß = 2.15; d = 0.23) at 9 weeks and gratitude (ß = 0.97; d = 0.22), positive affect (ß = 2.02; d = 0.27), life satisfaction (ß = 1.82; d = 0.24), optimism (ß = 2.70; d = 0.49), anxiety (ß = -1.62; d = -0.46), depression (ß = -1.04; d = -0.33), PTSD (ß = -2.50; d = -0.29), QoL (ß = 7.70; d = 0.41), physical function (ß = 5.21; d = 0.56), and fatigue (ß = -2.54; d = -0.33) at 18 weeks. CONCLUSIONS: PATH is feasible, with promising signals for improving psychological well-being, QoL, physical function, and fatigue in HSCT survivors. Future multisite trials that investigate PATH's efficacy are needed to establish its effects on PROs in this population.

Effects of older age on visual and self-motion sensory cue integration in navigation.

Older adults demonstrate impairments in navigation that cannot be explained by general cognitive and motor declines. Previous work has shown that older adults may combine sensory cues during navigation differently than younger adults, though this work has largely been done in dark environments where sensory integration may differ from full-cue environments. Here, we test whether aging adults optimally combine cues from two sensory systems critical for navigation: vision (landmarks) and body-based self-motion cues. Participants completed a homing (triangle completion) task using immersive virtual reality to offer the ability to navigate in a well-lit environment including visibility of the ground plane. An optimal model, based on principles of maximum-likelihood estimation, predicts that precision in homing should increase with multisensory information in a manner consistent with each individual sensory cue's perceived reliability (measured by variability). We found that well-aging adults (with normal or corrected-to-normal sensory acuity and active lifestyles) were more variable and less accurate than younger adults during navigation. Both older and younger adults relied more on their visual systems than a maximum likelihood estimation model would suggest. Overall, younger adults' visual weighting matched the model's predictions whereas older adults showed sub-optimal sensory weighting. In addition, high inter-individual differences were seen in both younger and older adults. These results suggest that older adults do not optimally weight each sensory system when combined during navigation, and that older adults may benefit from interventions that help them recalibrate the combination of visual and self-motion cues for navigation.

Starvation induces shrinkage of the bacterial cytoplasm.

Environmental fluctuations are a common challenge for single-celled organisms; enteric bacteria such as Escherichia coli experience dramatic changes in nutrient availability, pH, and temperature during their journey into and out of the host. While the effects of altered nutrient availability on gene expression and protein synthesis are well known, their impacts on cytoplasmic dynamics and cell morphology have been largely overlooked. Here, we discover that depletion of utilizable nutrients results in shrinkage of E. coli's inner membrane from the cell wall. Shrinkage was accompanied by an ∼17% reduction in cytoplasmic volume and a concurrent increase in periplasmic volume. Inner membrane retraction after sudden starvation occurred almost exclusively at the new cell pole. This phenomenon was distinct from turgor-mediated plasmolysis and independent of new transcription, translation, or canonical starvation-sensing pathways. Cytoplasmic dry-mass density increased during shrinkage, suggesting that it is driven primarily by loss of water. Shrinkage was reversible: upon a shift to nutrient-rich medium, expansion started almost immediately at a rate dependent on carbon source quality. A robust entry into and recovery from shrinkage required the Tol-Pal system, highlighting the importance of envelope coupling during shrinkage and recovery. Klebsiella pneumoniae also exhibited shrinkage when shifted to carbon-free conditions, suggesting a conserved phenomenon. These findings demonstrate that even when Gram-negative bacterial growth is arrested, cell morphology and physiology are still dynamic.

A Qualitative Analysis of the Impact of Preoperative Mindfulness-Based Stress Reduction on Total Knee Arthroplasty Surgical Experiences.

We qualitatively explored the impact of preoperative mindfulness-based stress reduction (MBSR) on total knee arthroplasty (TKA) experiences. Participants (n = 10) who received MBSR prior to TKA participated in semi-structured interviews concerning their experiences with MBSR and its perceived impact on surgery. We analyzed interviews according to reflexive thematic analysis, and coded data into three main themes: 1) Impact of MBSR on surgery experiences; 2) Contributors to change; and 3) Motivations for participation. Participants noted they were able to relax, feel more confident, and cope more effectively during the preoperative period, and that others in their lives noticed positive changes following their participation in MBSR. Participants' openness to mindfulness and health-related beliefs and may have contributed to the positive impacts they experienced from MBSR. Participants described being motivated to participate in MBSR to help them prepare for their surgery and to learn new coping strategies. Participants described a strong level of commitment to the intervention. With further research, integration of MBSR into prehabilitation for TKA may be appropriate.

Pathogenic Gene Variants Identified in Patients Presenting With Perthes or Perthes-like Hip Disorder.

AIMS: Legg-Calve-Perthes disease (LCPD) is a diagnosis of exclusion. Various conditions, such as skeletal dysplasias, can closely mimic LCPD and these must be ruled out to provide appropriate treatment, prognosis, and counseling. Traditionally, genetic testing has not been readily available in pediatric orthopaedic practice. Furthermore, the clinical value of genetic testing patients with LCPD is unclear. With the advance of next-generation sequencing (NGS) technology, genetic testing has become clinically available as a lab test. The purposes of this study were to assess the clinical utility of genetic testing in select patients with LCPD and to determine the patient characteristics of those who tested positive for skeletal dysplasia. METHODS: This is an IRB-approved, retrospective study of 63 consecutive patients who presented with Perthes-like symptoms and/or x-ray findings and who had genetic testing. The reason(s) for genetic testing included bilateral hip disease, family history of LCPD, short stature, suspected skeletal dysplasia, atypical radiographic findings, and/or combinations of these reasons. RESULTS: Of the 63 patients, 19 patients (30%) were found to have a pathogenic gene variant. In 8 of the 19, a variety of skeletal dysplasia was diagnosed. The remaining 11 patients were found to be carriers of autosomal recessive disorders. All 19 patients were referred for genetic counseling. Of the 8 patients found to have skeletal dysplasia, 3 had bilateral disease, 3 were <10 percentile in height, 1 had a family history of "LCPD," and 3 had atypical x-ray findings. In addition to the pathogenic variants, numerous genetic variants of unknown significance were found with 2 gene variants showing exactly the same variant found in 2 unrelated patients. CONCLUSIONS: With 30% of the patients showing pathogenic results, genetic testing of select patients with Perthes-like disease is valuable in detecting an underlying genetic disorder or a carrier status of a genetic disorder.

Does Screening Ultrasound Timing in Developmental Dysplasia of the Hip Need to be Adjusted for Moderate Preterm and Near-term Infants: A Prospective Study.

INTRODUCTION: An initial screening ultrasound is essential for patients at higher risk of developmental dysplasia of the hip (DDH) due to breech presentation or a family history of DDH. The American Academy of Pediatrics recommends screening ultrasounds to be performed after 6 weeks of age to reduce the rate of false positives. However, there is limited evidence regarding whether these screening ultrasounds need to be adjusted for gestational age in prematurity. The purpose of this study was to evaluate the influence of moderate preterm and near-term births on screening hip ultrasounds for high-risk DDH populations. METHODS: We identified all prospectively enrolled patients in a single-center database referred for screening hip ultrasound for DDH. We included those hips referred for risk factors of DDH, including breech presentation, family history of DDH, or hip click, and excluded those with known dysplasia or referral for hip instability. Each ultrasound was measured by a pediatric radiologist to determine the alpha angle and femoral head coverage. Patients were classified as "premature" if born at <37 weeks gestation or "full term" if born at ≥37 weeks gestation. All patients underwent screening hip ultrasound between 5 and 8 weeks of age. Sonographic markers of dysplasia and the incidences of abnormal ultrasound and Pavlik harness treatment were compared between cohorts. Significance was set at P <0.05. RESULTS: A total of 244 hips in 122 patients were included, 58 hips in the premature cohort and 186 hips in the full-term cohort. The premature cohort had a significantly decreased gestational age compared with the full-term cohort (35.4 ± 1.1 vs 38.5 ± 1.1 wk, respectively, P < 0.001). However, there was no difference between premature and full-term cohorts in sex distribution (69% vs 75%, females, P = 0.39), unadjusted age at the time of ultrasound (6.6 ± 0.7 vs 6.8±0.7 wk, respectively, P = 0.07), or referral reason ( P = 0.14). On hip ultrasound, there was no difference between premature and full-term cohorts with respect to alpha angle (62.6 ± 3.3 vs 62.2 ± 5.3 degrees, P = 0.41), femoral head coverage (54.9 ± 6.3 vs 55.1 ± 10.6, P = 0.19), rate of abnormal ultrasound (18.3% vs 20.7%, respectively, P = 0.68), or the rate of Pavlik harness treatment (0% vs 5.3%, respectively, P = 0.12). DISCUSSION: There was no significant difference in alpha angle or femoral head coverage between premature and full-term patients at 5 to 8 weeks of unadjusted age. This preliminary data suggests that screening ultrasounds can be performed without adjusting for prematurity. LEVEL OF EVIDENCE: Level II, prognostic study.

Perceived control moderates the internalized stigma model of seeking mental health services in distressed older adults.

Older adults are especially unlikely to seek mental health services, and internalized stigma is a key reason why. However, little research has investigated which older adults are particularly likely to have stigma influence help-seeking. To address this, we tested whether perceived control (PC) moderates an internalized stigma model in which public stigma is internalized as self-stigma, which negatively predicts help-seeking attitudes and help-seeking intentions. We employed moderated mediation analysis of cross-sectional, secondary data from 348 psychologically distressed Canadian adults aged 65 years and older. Participants completed an online survey that included measures of public stigma of help-seeking, self-stigma of help-seeking, help-seeking attitudes, conditional help-seeking intentions, psychological distress, and PC. PC emerged as a moderator of the internalized stigma model. Those lower in PC were more likely to have public stigma negatively predict help-seeking intentions through the serial mediation of (a) self-stigma and (b) help-seeking attitudes. Further, those lower in PC were more likely to have public stigma internalized as self-stigma and more likely to have negative help-seeking attitudes predict lower help-seeking intentions. Finally, those lower in PC also had lower help-seeking intentions in the face of low levels of self-stigma. These results contribute to a nuanced understanding of which older adults are unlikely to seek help. Identifying PC as a moderator of the internalized stigma model suggests that interventions that enhance PC should protect against public stigma's internalization and improve help-seeking behaviors for older adults who need such help. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Contribution of Lower-Body Kinematics to Pitching and Hitting Performance in Baseball: Utilizing the OpenBiomechanics Project.

As markerless motion capture systems become more affordable than ever, it is becoming far easier to collect and analyze kinematic data on baseballers. To ensure this data can be used impactfully, coaches and practitioners should possess a good understanding of specific technique characteristics that are associated with enhanced performance in pitchers and hitters. This study used the open-source data provided by Driveline Baseball's OpenBiomechanics Project to evaluate the contribution of lower-body kinematics to pitch velocity and bat speed. In addition to correlational analyses to examine the association between discrete kinematic variables and performance, statistical nonparametric mapping was used to compare slow and fast velocity groups across the entirety of pitching and hitting motions from peak knee height to ball release/contact. It was found that rotation of the trail leg and extension of the lead knee were both associated with performance in pitchers and hitters. Consequently, coaches and practitioners should ensure that individuals possess an adequate level of strength and flexibility to facilitate optimal movement of the trail hip and lead knee during pitching and hitting movements. If deficiencies exist, then training programs should be designed to address these issues and eventually bring about an improvement in performance.

Development, feasibility, and acceptability of a process based intervention to decrease internalized ageism.

A lifetime of exposure to ageism may be internalized in older adults, and these ageist beliefs that are directed inwards can have severe consequences. However, research on reducing internalized ageism is scarce. To address this, we designed and implemented a six-week online process-based intervention to reduce internalized ageism and to assess its feasibility. The intervention utilized a process-based therapy approach targeting psychological, behavioral, and physiological pathways through which internalized ageism negatively impacts health, as specified by stereotype embodiment theory. Intervention components included education, acceptance and commitment therapy techniques, and attributional retraining. A total of 81 older adult participants participated in the feasibility study. Most participants rated each session and the overall program as very useful after each session (average program usefulness rating of 4.54/5). Participants also attributed a wide range of novel behaviors to this intervention and stated that they felt it changed their perspectives on ageism and/or internalized ageism. Results from this study provide a promising foundation from which to advance research on interventions that address internalized ageism - a problem that has severe consequences on the health and well-being of growing numbers of older adults globally.

Reimagine Aging: A Process-Based Intervention to Decrease Internalized Ageism.

OBJECTIVES: Exposure to ageism may be internalized in older adults, and this can have severe consequences. However, little research has addressed reducing internalized ageism. Thus, Reimagine Aging, a 6-week process-based intervention to reduce internalized ageism, was designed and implemented, using education, acceptance and commitment therapy, and attributional retraining to target theoretically based mechanisms of change. METHODS: Seventy-two older adults (M = 70.4 years, SD = 6.4 years) participated in Reimagine Aging, consented to participate in this robust single-sample pilot study, and provided valid data. Participants completed questionnaires prior to, immediately following, and 2 months after the intervention. RESULTS: Participants' self-perceptions of aging (ηp2=0.37, p < .001) and perceptions of older adults (ηp2=0.27, p < .001) became significantly more positive, associated with large effect sizes. Furthermore, these positive gains were mediated by increases in psychological flexibility, mindfulness, and perceived control. DISCUSSION: This study provides initial support for this process-based intervention targeting a reduction of internalized ageism. CLINICAL IMPLICATIONS: This program has the potential to reduce the negative impact internalized ageism has on the health of older adults. Furthermore, it provides novel insights into intervention targets and tools that may be useful in achieving this reduction.

Utility of Machine Learning to Detect Cytomegalovirus in Digital Hematoxylin and Eosin-Stained Slides.

Rapid and accurate cytomegalovirus (CMV) identification in immunosuppressed or immunocompromised patients presenting with diarrhea is essential for therapeutic management. Due to viral latency, however, the gold standard for CMV diagnosis remains to identify viral cytopathic inclusions on routine hematoxylin and eosin (H&E)-stained tissue sections. Therefore, biopsies may be taken and "rushed" for pathology evaluation. Here, we propose the use of artificial intelligence to detect CMV inclusions on routine H&E-stained whole-slide images to aid pathologists in evaluating these cases. Fifty-eight representative H&E slides from 30 cases with CMV inclusions were identified and scanned. The resulting whole-slide images were manually annotated for CMV inclusions and tiled into 300 × 300 pixel patches. Patches containing annotations were labeled "positive," and these tiles were oversampled with image augmentation to account for class imbalance. The remaining patches were labeled "negative." Data were then divided into training, validation, and holdout sets. Multiple deep learning models were provided with training data, and their performance was analyzed. All tested models showed excellent performance. The highest performance was seen using the EfficientNetV2BO model, which had a test (holdout) accuracy of 99.93%, precision of 100.0%, recall (sensitivity) of 99.85%, and area under the curve of 0.9998. Of 518,941 images in the holdout set, there were only 346 false negatives and 2 false positives. This shows proof of concept for the use of digital tools to assist pathologists in screening "rush" biopsies for CMV infection. Given the high precision, cases screened as "positive" can be quickly confirmed by a pathologist, reducing missed CMV inclusions and improving the confidence of preliminary results. Additionally, this may reduce the need for immunohistochemistry in limited tissue samples, reducing associated costs and turnaround time.

Prescribing Syringes to People Who Inject Drugs: Advancing Harm Reduction in Primary Care.

Access to new syringes can reduce the risk of HIV and hepatitis C transmission, skin and soft tissue infections, and infectious endocarditis for people who inject drugs (PWID). Syringe service programs (SSPs) and other harm reduction programs are a good source of syringes. However, they are sometimes not accessible due to limited hours, geographic barriers, and other factors. In this perspective, we argue that when PWID faces barriers to syringes physicians and other providers should prescribe, and pharmacists should dispense, syringes to decrease health risks associated with syringe re-use. This strategy is endorsed by professional organizations and is legally permissible in most states. Such prescribing has numerous benefits, including insurance coverage of the cost of syringes and the sense of legitimacy conveyed by a prescription. We discuss these benefits as well as the legality of prescribing and dispensing syringes and address practical considerations such as type of syringe, quantity, and relevant diagnostic codes, if required. In the face of an unprecedented overdose crisis with many associated health harms, we also make the case for advocacy to change state and federal laws to make access to prescribed syringes uniform, smooth, and universal as part of a suite of harm reduction efforts.

Effects of Opioid Prescribing Cap Laws on Opioid and Other Pain Treatments Among Persons with Chronic Pain.

BACKGROUND: Many states have adopted laws that limit the amount or duration of opioid prescriptions. These limits often focus on prescriptions for acute pain, but there may be unintended consequences for those diagnosed with chronic pain, including reduced opioid prescribing without substitution of appropriate non-opioid treatments. OBJECTIVE: To evaluate the effects of state opioid prescribing cap laws on opioid and non-opioid treatment among those diagnosed with chronic pain. DESIGN: We used a difference-in-differences approach that accounts for staggered policy adoption. Treated states included 32 states that implemented a prescribing cap law between 2017 and 2019. POPULATION: A total of 480,856 adults in the USA who were continuously enrolled in medical and pharmacy coverage from 2013 to 2019 and diagnosed with a chronic pain condition between 2013 and 2016. MAIN MEASURES: Among individuals with chronic pain in each state: proportion with at least one opioid prescription and with prescriptions of a specific duration or dose, average number of opioid prescriptions, average opioid prescription duration and dose, proportion with at least one non-opioid chronic pain prescription, average number of such prescriptions, proportion with at least one chronic pain procedure, and average number of such procedures. KEY RESULTS: State laws limiting opioid prescriptions were not associated with changes in opioid prescribing, non-opioid medication prescribing, or non-opioid chronic pain procedures among patients with chronic pain diagnoses. CONCLUSIONS: These findings do not support an association between state opioid prescribing cap laws and changes in the treatment of chronic non-cancer pain.

Knowledge-guided analysis of "omics" data using the KnowEnG cloud platform.

We present Knowledge Engine for Genomics (KnowEnG), a free-to-use computational system for analysis of genomics data sets, designed to accelerate biomedical discovery. It includes tools for popular bioinformatics tasks such as gene prioritization, sample clustering, gene set analysis, and expression signature analysis. The system specializes in "knowledge-guided" data mining and machine learning algorithms, in which user-provided data are analyzed in light of prior information about genes, aggregated from numerous knowledge bases and encoded in a massive "Knowledge Network." KnowEnG adheres to "FAIR" principles (findable, accessible, interoperable, and reuseable): its tools are easily portable to diverse computing environments, run on the cloud for scalable and cost-effective execution, and are interoperable with other computing platforms. The analysis tools are made available through multiple access modes, including a web portal with specialized visualization modules. We demonstrate the KnowEnG system's potential value in democratization of advanced tools for the modern genomics era through several case studies that use its tools to recreate and expand upon the published analysis of cancer data sets.