Evaluating the feasibility and acceptability of a co-designed physical activity intervention for rural middle schoolers: a pilot study.

BACKGROUND: Lack of physical activity is a concern for children across diverse backgrounds, particularly affecting those in rural areas who face distinct challenges compared to their urban counterparts. Community-derived interventions are needed that consider the unique context and additional physical activity barriers in under-resourced rural settings. Therefore, a prospective pre-post pilot/feasibility study of Hoosier Sport was conducted over 8-weeks with 6th and 7th grade children in a low-socioeconomic rural middle school setting. The primary objective of the present study was to assess trial- and intervention-related feasibility indicators; and the secondary objective was to collect preliminary assessment data for physical activity levels, fitness, psychological needs satisfaction, and knowledge of physical activity and nutrition among participating youth. METHODS: This prospective 8-week pilot/feasibility study took place in the rural Midwestern United States where twenty-four middle school students participated in a mixed-methods pre-post intervention during physical education classes. The intervention included elements like sport-based youth development, individualized goal setting, physical activity monitoring, pedometer usage, and health education. Data were collected at baseline (T1) and post-intervention (T3), with intermediate measures during the intervention (T2). Qualitative data were integrated through semi-structured interviews. Analytical methods encompassed descriptive statistics, correlations, repeated measures ANOVA, and thematic analysis. RESULTS: Key findings indicate robust feasibility, with intervention-related scores (FIM, AIM, and IAM) consistently surpassing the "good" threshold and 100% retention and recruitment success. Additionally, participants showed significant physical performance improvement, shifting from the 25th to the 50th percentile in the 6-minute walk test (p < 0.05). Autonomy and competence remained high, reflecting positive perceptions of program practicality. Nutrition knowledge, initially low, significantly improved at post-intervention (p < 0.01), highlighting the efficacy of targeted nutritional education in Hoosier Sport. CONCLUSIONS: This study pioneers a community-engaged model for physical activity intervention in under-resourced rural settings. Positive participant feedback, coupled with improvements in physical fitness and psychosocial factors, highlights the potential of the co-design approach. The findings offer valuable insights and a practical template for future community-based research, signaling the promising impact of such interventions on holistic well-being. This research lays the foundation for subsequent phases of the ORBIT model, emphasizing collaborative, community-driven approaches to address the complex issue of declining physical activity levels among adolescents.

Fecal incontinence is not associated with UTI: A contemporary case-control study.

INTRODUCTION: Urinary tract infections (UTIs) are a leading cause of infection in adults. The most common cause is gastrointestinal bacteria ascending the urethra into the bladder. Studies showing fecal incontinence (FI) is a risk factor for UTI have been limited to nursing home populations. Healthy patients with recurrent UTI, especially women, often receive counseling, suggesting improper personal hygiene contributes to UTIs. This advice can be stigmatizing. Given UTI prevalence, it is important to elucidate risk factors for improved diagnosis, treatment, and patient education. Our objective was to perform a hospital-centered, retrospective case-control analysis to assess the effect of FI on UTI development in ambulatory patients. METHODS: Patients (n = 3035) with a diagnosis of FI were identified from a single institution and propensity score-matched with screening colonoscopy patients (n = 3035) from 2018 to 2021. Patients were matched on age, sex, race, ethnicity, body mass index, and comorbidities, for example, diabetes, vesicoureteral reflux, and urinary incontinence. The association between FI and UTI was tested using Pearson's χ2 test. RESULTS: Median age was 64 years with more females than males (73.81% vs. 71.20% female for case/control, p = 0.02). Patients with FI were more often to have concurrent urinary incontinence (18.62% vs. 10.25% for case/control, p < 0.001), as well as specifically urgency incontinence (13.28% vs. 11.57% for case/control, p = 0.04). There was no significant difference in the incidence of UTI between patients with FI and those presenting for screening colonoscopy (p = 0.44). CONCLUSION: FI was not associated with an increased number of UTIs. Based on our results, current stigmatizing beliefs regarding the association between FI and UTI should be reevaluated.

Obesity-associated microbiomes instigate visceral adipose tissue inflammation by recruitment of distinct neutrophils.

Neutrophils are increasingly implicated in chronic inflammation and metabolic disorders. Here, we show that visceral adipose tissue (VAT) from individuals with obesity contains more neutrophils than in those without obesity and is associated with a distinct bacterial community. Exploring the mechanism, we gavaged microbiome-depleted mice with stool from patients with and without obesity during high-fat or normal diet administration. Only mice receiving high-fat diet and stool from subjects with obesity show enrichment of VAT neutrophils, suggesting donor microbiome and recipient diet determine VAT neutrophilia. A rise in pro-inflammatory CD4+ Th1 cells and a drop in immunoregulatory T cells in VAT only follows if there is a transient spike in neutrophils. Human VAT neutrophils exhibit a distinct gene expression pattern that is found in different human tissues, including tumors. VAT neutrophils and bacteria may be a novel therapeutic target for treating inflammatory-driven complications of obesity, including insulin resistance and colon cancer.

The Capicua C1 Domain is Required for Full Activity of the CIC::DUX4 Fusion Oncoprotein.

Rearrangements between genes can yield neomorphic fusions that drive oncogenesis. Fusion oncogenes are made up of fractional segments of the partner genes that comprise them, with each partner potentially contributing some of its own function to the nascent fusion oncoprotein. Clinically, fusion oncoproteins driving one diagnostic entity are typically clustered into a single molecular subset and are often treated a similar fashion. However, knowledge of where specific fusion breakpoints occur in partner genes, and the resulting retention of functional domains in the fusion, is an important determinant of fusion oncoprotein activity and may differ between patients. This study investigates this phenomena through the example of CIC::DUX4, a fusion between the transcriptional repressor capicua (CIC) and the double homeobox 4 gene (DUX4), which drives an aggressive subset of undifferentiated round cell sarcoma. Using a harmonized dataset of over 100 patient fusion breakpoints from the literature, we show that most bona fide CIC::DUX4 fusions retain the C1 domain, which is known to contribute to DNA binding by wild type CIC. Mechanistically, deletion or mutation of the C1 domain reduces, but does not eliminate, activation of CIC target genes by CIC::DUX4. We also find that expression of C1-deleted CIC::DUX4 is capable of exerting intermediate transformation-related phenotypes compared with those imparted by full-length CIC::DUX4, but was not sufficient for tumorigenesis in a subcutaneous mouse model. In summary, our results suggest a supercharging role for the C1 domain in the activity of CIC::DUX4.

Does Family Functioning Matter? Understanding the Relationship Between Family Interactions and Depressive Symptoms for Caregivers of Cancer Patients.

BACKGROUND: Caregivers of cancer patients are at increased risk of depression and other health challenges. There is limited understanding of the role of the caregiver's own family members in promoting or discouraging mental wellbeing. Family functioning conceptualizes how family members interact to promote a positive family environment and has the potential to impact caregiver mental health. The purpose of this study is to assess the association between family interactions and depressive symptoms among family caregivers of cancer patients. METHODS: Secondary analysis of baseline data from an NIH-funded randomized control trial of family caregivers of cancer patients recruited from academic palliative care clinics at three sites (2 Midwest, 1 East). We tested for an association between caregiver responses to the Family Quality of Life in Dementia-Family Interactions Subscale and Patient-Reported Outcomes Measurement Information System Depression Short Form 8A using a block-wise approach to linear modeling. RESULTS: A total of 246 caregivers were included in analysis; caregivers were mostly White (82%), not Hispanic or Latina/o (96%), and female (65%), with an average age of 55 years. Overall, participants had high family interactions (mean 57.7, sd 11.7) and an average depressive symptom burden (t-score 52.4, SD 8.57). Family interactions was significantly negatively associated with depressive symptoms (b = -.163, se = .057) when accounting for relevant covariates. CONCLUSION: Family caregivers with more positive family interactions are likely to have fewer depressive symptoms, suggesting family functioning may play a key role in bolstering family caregiver mental health and wellbeing.

Loneliness, psychological distress, and the moderating effect of positive aspects of caregiving among cancer caregivers.

PURPOSE: Family caregivers of patients with cancer often experience both loneliness and symptoms of psychological distress, such as anxiety and depression. The purpose of this study was to evaluate the associations between loneliness and anxiety and loneliness and depression among family caregivers of patients with cancer and to investigate whether positive aspects of caregiving can have a moderating effect on these relationships. METHODS: We conducted a cross-sectional exploratory study using baseline data from an ongoing multisite clinical trial. Multiple linear regression models were used to analyze the relationships between loneliness and psychological distress symptoms and the moderating effect of positive aspects of caregiving. Psychological distress outcomes were measured using PROMIS Short Forms (8a) for Anxiety and Depression. RESULTS: We identified a significant association between loneliness and symptoms of both anxiety and depression. Positive aspects of caregiving did not significantly moderate the relationship between loneliness and depression or loneliness and anxiety. CONCLUSION: The results of this study shed new light on the relationship between loneliness and symptoms of psychological distress experienced by family caregivers of cancer patients, providing a better understanding of the impact that recognition of positive aspects of caregiving has on the association between loneliness and psychological distress symptoms. Our findings emphasize the importance of targeting family caregiver loneliness in order to reduce psychological distress among family caregivers of cancer patients.

Association of biliary distention with a diagnosis of acute cholecystitis.

BACKGROUND: Gallbladder distention has been described in radiology literature but its value on point-of-care ultrasound (PoCUS) performed by emergency physicians is unclear. We sought to determine the test characteristics of gallbladder distention on PoCUS for cholecystitis (acute or chronic), and secondarily whether distention was associated with an obstructing stone-in-neck (SIN), acute cholecystitis on subsequent pathology report, and longer cholecystectomy operative times. METHODS: This was a dual-site retrospective cohort study of all Emergency Department (ED) patients that underwent diagnostic biliary PoCUS and were subsequently admitted from 11/1/2020 to 10/31/2022. Patients with pregnancy, liver failure, ascites, hepatobiliary cancer, prior cholecystectomy, or known cholecystitis were excluded. Gallbladder distention was defined as a width ≥4 cm or a length ≥10 cm. Saved ultrasound images were reviewed by three independent reviewers who obtained measurements during the review. Test characteristics, Cohen's kappa (κ), and strength of association between distention and our variables (acute cholecystitis on pathology report and SIN on PoCUS) were calculated using a Chi Square analysis, where intervention (cholecystectomy, percutaneous cholecystostomy, or intravenous antibiotics) was used as the reference standard for AC. A one-tail two sample t-test was calculated for mean operative times. RESULTS: Of 280 admitted patients who underwent ED biliary PoCUS, 53 were excluded, and 227 were analyzed. Of the 227 patients, 113 (49.8%) had cholecystitis according to our reference standard, and 68 (30.0%) had distention on PoCUS: 32 distended by both width and length, 16 distended by width alone, and 20 distended by length alone. Agreement between investigators was substantial for width (κ 0.630) and length (κ 0.676). Distention was 85.09% (95% CI 77.20-91.07%) specific and 45.1% (95% CI 35.8-54.8%) sensitive for cholecystitis. There was an association between distention and SIN; odds ratio (OR) 2.76 (95% CI 1.54-4.97). Distention of both length and width was associated with acute over chronic cholecystitis; OR 4.32 (95% CI 1.42-13.14). Among patients with acute cholecystitis, mean operative times were 114 min in patients with distention and 89 min in patients without distention (p = 0.03). CONCLUSION: Gallbladder distention on PoCUS was specific for cholecystitis (acute or chronic), and associated with SIN, acute cholecystitis on subsequent pathology report, and longer cholecystectomy operative times. Measurement of gallbladder dimensions as part of the assessment of cholecystitis may be advantageous.

Comparison of Work Relative Value Units Assigned to Urological and Gynecological Surgical Procedures.

INTRODUCTION: We sought to determine if work relative value unit differences exist between analogous, sex-specific procedures. METHODS: Representatives from the AUA and the American College of Obstetricians and Gynecologists independently reviewed the entire procedural code set and identified sex-specific procedures that had an analogous procedure in the opposite sex. These pairs were then evaluated and compared using current American Medical Association Relative Value Scale Update Committee methodology. Comparable code pair values were then examined to determine any systemic bias in the work relative value units assigned between the procedures. Mean differences and 95% confidence intervals were used to determine any differences in procedure or physician time values. The methodology used considered global period, intraservice time, total time, hospital days, postoperative office visits, and the date of the committee review. RESULTS: Of the 10 directly analogous code pairs reviewed, 7 of the female procedures had higher work relative value unit differences (range 0.29-6.47), and 3 of the male procedures had higher work relative value unit differences (range 1.23-2.34). There was no statistical difference between the code pair work relative value units. The work relative value unit per minute of intraservice time and total time were not statistically different. CONCLUSIONS: In this study, we compared operative procedures performed in women with clinically comparable operative procedures performed in men that had similar surgical approaches, global periods, and valuation methodologies. Overall, no statistical differences in work relative value units were demonstrated.

The dynamic response of human lungs due to underwater shock wave exposure.

Since the 19th century, underwater explosions have posed a significant threat to service members. While there have been attempts to establish injury criteria for the most vulnerable organs, namely the lungs, existing criteria are highly variable due to insufficient human data and the corresponding inability to understand the underlying injury mechanisms. This study presents an experimental characterization of isolated human lung dynamics during simulated exposure to underwater shock waves. We found that the large acoustic impedance at the surface of the lung severely attenuated transmission of the shock wave into the lungs. However, the shock wave initiated large bulk pressure-volume cycles that are distinct from the response of the solid organs under similar loading. These pressure-volume cycles are due to compression of the contained gas, which we modeled with the Rayleigh-Plesset equation. The extent of these lung dynamics was dependent on physical confinement, which in real underwater blast conditions is influenced by factors such as rib cage properties and donned equipment. Findings demonstrate a potential causal mechanism for implosion injuries, which has significant implications for the understanding of primary blast lung injury due to underwater blast exposures.

Closed-loop automated drug infusion regulator: A clinically translatable, closed-loop drug delivery system for personalized drug dosing.

BACKGROUND: Dosing of chemotherapies is often calculated according to the weight and/or height of the patient or equations derived from these, such as body surface area (BSA). Such calculations fail to capture intra- and interindividual pharmacokinetic variation, which can lead to order of magnitude variations in systemic chemotherapy levels and thus under- or overdosing of patients. METHODS: We designed and developed a closed-loop drug delivery system that can dynamically adjust its infusion rate to the patient to reach and maintain the drug's target concentration, regardless of a patient's pharmacokinetics (PK). FINDINGS: We demonstrate that closed-loop automated drug infusion regulator (CLAUDIA) can control the concentration of 5-fluorouracil (5-FU) in rabbits according to a range of concentration-time profiles (which could be useful in chronomodulated chemotherapy) and over a range of PK conditions that mimic the PK variability observed clinically. In one set of experiments, BSA-based dosing resulted in a concentration 7 times above the target range, while CLAUDIA keeps the concentration of 5-FU in or near the targeted range. Further, we demonstrate that CLAUDIA is cost effective compared to BSA-based dosing. CONCLUSIONS: We anticipate that CLAUDIA could be rapidly translated to the clinic to enable physicians to control the plasma concentration of chemotherapy in their patients. FUNDING: This work was supported by MIT's Karl van Tassel (1925) Career Development Professorship and Department of Mechanical Engineering and the Bridge Project, a partnership between the Koch Institute for Integrative Cancer Research at MIT and the Dana-Farber/Harvard Cancer Center.

Telomere dysfunction alters intestinal stem cell dynamics to promote cancer.

Telomere dynamics are linked to aging hallmarks, and age-associated telomere loss fuels the development of epithelial cancers. In Apc-mutant mice, the onset of DNA damage associated with telomere dysfunction has been shown to accelerate adenoma initiation via unknown mechanisms. Here, we observed that Apc-mutant mice engineered to experience telomere dysfunction show accelerated adenoma formation resulting from augmented cell competition and clonal expansion. Mechanistically, telomere dysfunction induces the repression of EZH2, resulting in the derepression of Wnt antagonists, which causes the differentiation of adjacent stem cells and a relative growth advantage to Apc-deficient telomere dysfunctional cells. Correspondingly, in this mouse model, GSK3ß inhibition countered the actions of Wnt antagonists on intestinal stem cells, resulting in impaired adenoma formation of telomere dysfunctional Apc-mutant cells. Thus, telomere dysfunction contributes to cancer initiation through altered stem cell dynamics, identifying an interception strategy for human APC-mutant cancers with shortened telomeres.

Exercise-induced ß2-adrenergic Receptor Activation Enhances the Antileukemic Activity of Expanded γδ T-Cells via DNAM-1 Upregulation and PVR/Nectin-2 Recognition.

Exercise mobilizes cytotoxic lymphocytes to blood which may allow superior cell products to be harvested and manufactured for cancer therapy. Gamma-Delta (γδ) T-cells have shown promise for treating solid tumors, but there is a need to increase their potency against hematologic malignancies. Here, we show that human γδ T-cells mobilized to blood in response to just 20 minutes of graded exercise have surface phenotypes and transcriptomic profiles associated with cytotoxicity, adhesion, migration, and cytokine signaling. Following 14 days ex vivo expansion with zoledronic acid and IL2, exercise mobilized γδ T-cells had surface phenotypes and transcriptomic profiles associated with enhanced effector functions and demonstrated superior cytotoxic activity against multiple hematologic tumors in vitro and in vivo in leukemia-bearing xenogeneic mice. Infusing humans with the ß1+ß2-agonist isoproterenol and administering ß1 or ß1+ß2 antagonists prior to exercise revealed these effects to be ß2-adrenergic receptor (AR) dependent. Antibody blocking of DNAM-1 on expanded γδ T-cells, as well as the DNAM-1 ligands PVR and Nectin-2 on leukemic targets, abolished the enhanced antileukemic effects of exercise. These findings provide a mechanistic link between exercise, ß2-AR activation, and the manufacture of superior γδ T-cell products for adoptive cell therapy against hematologic malignancies. SIGNIFICANCE: Exercise mobilizes effector γδ T-cells to blood via ß2-adrenergic signaling which allows for generation of a potent expanded γδ T-cell product that is highly cytotoxic against hematologic malignancies.

Preeclampsia With Posterior Reversible Encephalopathy Syndrome at 19 Weeks Gestation Resulting in Intrauterine Fetal Demise.

Posterior reversible encephalopathy syndrome (PRES) can be defined as a clinical syndrome of headache, seizures, visual disturbance, altered mental status, and characteristic magnetic resonance imaging (MRI) findings of vasogenic edema in the posterior subcortical parietal-occipital white matter. There are numerous potential inciting factors, including immunosuppression, renal disease, malignancy, cytotoxic medications, hypertension, preeclampsia, and eclampsia. In this paper, we present the case of a 21-year-old female at 19 weeks gestation presenting with symptoms consistent with preeclampsia with severe features and PRES. She was transferred to our facility after initial stabilization. She had an atypical course of preeclampsia prior to 20 weeks gestation, PRES lacking seizure activity, and ultimately her case resulted in intrauterine fetal demise (IUFD) at 20 weeks and six days gestation. As indicated by its name, PRES is considered a fully reversible syndrome, and the patient recovered after stabilization of her hypertensive disorder and delivery of the fetus. This case illustrates the importance of prompt recognition and treatment of hypertensive disorders in pregnant patients and the possibility of complications that can result in significant morbidity and mortality for both the mother and fetus.

Histologic Distribution of Lung and Bronchus Tumors: A Population-Based Study in the Upper Peninsula of Michigan.

INTRODUCTION: Lung cancer remains the leading cause of cancer-related mortality in the United States, with cigarette smoking recognized as the most important modifiable risk factor. The distinct smoking rates and occupational landscape in the Upper Peninsula of Michigan underscore the necessity of investigating the multifactorial influences on the prevalence and distribution of lung and bronchus cancer within this population. METHODS: This study, conducted from January 2012 to December 2022, included 1035 patients diagnosed with lung or bronchus tumors who were first seen and/or received the first course of treatment at Upper Peninsula Health Systems (UPHS) - Marquette, the largest hospital system in the Upper Peninsula of Michigan and one of only two radiation oncology treatment centers in the Upper Peninsula. RESULTS: This study demonstrated that the histologic trend of lung and bronchus cancers in a sample of 1035 patients in the Upper Peninsula of Michigan closely resembles that of national averages. Participants with a lifetime history of smoking made up 943 (91.1%) cases of patients diagnosed with lung or bronchus cancers in this study. Lifetime non-smokers only made up 53 (5.1%) cases of patients diagnosed with lung or bronchus cancers. The median age at diagnosis of participants in this study was 70 years. CONCLUSION: Our study provides significant insights into the histologic distribution of lung and bronchus cancers within the Upper Peninsula of Michigan, addressing a notable gap in the current literature for this rural and medically underserved population. The histologic distribution of lung and bronchus cancers in this region aligns with national trends. Furthermore, the distinct rates of cigarette smoking in the Upper Peninsula emphasize the critical role of smoking cessation efforts in reducing the burden of lung and bronchus cancers in this region.

A Molecular Framework for Delirium.

Over 2.6 million adults over the age of 65 develop delirium each year in the United States (US). Delirium is associated with a significant increase in mortality and the US health care costs associated with delirium are estimated at over $164 billion annually. Despite the prevalence of the condition, the molecular pathophysiology of delirium remains unexplained, limiting the development of pharmacotherapies. Delirious patients can be identified by prominent impairments in attention and working memory (WM), two cognitive domains that localize to the dorsolateral prefrontal cortex (dlPFC). The dlPFC is also a key site for Alzheimer's disease (AD) pathology, and given the high risk of delirium in AD patients, suggests that efforts at understanding delirium might focus on the dlPFC as a final common endpoint for cognitive changes. Preclinical studies of the dlPFC reproduce many of the pharmacological observations made of delirious patients, including sensitivity to anticholinergics and an 'inverted U' pattern of dependence on monoaminergic input, with diminished performance outside a narrow range of signaling. Medications like guanfacine, which influence the dlPFC in the context of attention-deficit/hyperactivity disorder (ADHD), have emerged as therapies for delirium and motivate a detailed understanding of the influence of α-2 agonists on WM. In this review, I will discuss the neural circuitry and molecular mechanisms underlying WM and the function of the dlPFC. Localizing the cognitive deficits that are commonly seen in delirious patients may help identify new molecular targets for this highly prevalent disease.

A population-based study of COVID-19 mortality risk in US cancer patients.

BACKGROUND: In this study, we provide the largest analysis to date of a US-based cancer cohort to characterize death from COVID-19. METHODS: A total of 4,020,669 patients across 15 subtypes living with cancer in 2020 and included in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database were abstracted. We investigated prognostic factors for death due to COVID-19 using a cox proportional hazards model and calculated hazard ratios (HRs). Standardized mortality ratios (SMRs) were calculated using observed mortality counts from SEER and expected mortality based on U.S. mortality rates. RESULTS: 291,323 patients died, with 14,821 (5.1%) deaths attributed to COVID-19 infection. The COVID-19 disease-specific mortality rate was 11.81/10,000-persons years, and SMR of COVID-19 was 2.30 (95% CI: 2.26-2.34, p < .0001). COVID-19 ranked as the second leading cause of death following ischemic heart disease (5.2%) among 26 non-cancer causes of death. Patients who are older (80+ vs < =49 years old: HR 21.47, 95% CI: 19.34-23.83), male (vs female: HR 1.46, 95% CI: 1.40-1.51), unmarried (vs married: HR 1.47, 95% CI: 1.42-1.53), and Hispanic or Non-Hispanic African American (vs Non-Hispanic White: HR 2.04, 95% CI: 1.94-2.14 and HR 2.03, 95% CI: 1.94-2.14, respectively) were at greatest risk of COVID-19 mortality. CONCLUSIONS AND RELEVANCE: We observed that people living with cancer are at two times greater risk of dying from COVID-19 compared to the general US population. This work may be used by physicians and public health officials in the creation of survivorship programs that mitigate the risk of COVID-19 mortality.

Induction of Viral Mimicry Upon Loss of DHX9 and ADAR1 in Breast Cancer Cells.

Detection of viral double-stranded RNA (dsRNA) is an important component of innate immunity. However, many endogenous RNAs containing double-stranded regions can be misrecognized and activate innate immunity. The IFN-inducible ADAR1-p150 suppresses dsRNA sensing, an essential function for adenosine deaminase acting on RNA 1 (ADAR1) in many cancers, including breast. Although ADAR1-p150 has been well established in this role, the functions of the constitutively expressed ADAR1-p110 isoform are less understood. We used proximity labeling to identify putative ADAR1-p110-interacting proteins in breast cancer cell lines. Of the proteins identified, the RNA helicase DHX9 was of particular interest. Knockdown of DHX9 in ADAR1-dependent cell lines caused cell death and activation of the dsRNA sensor PKR. In ADAR1-independent cell lines, combined knockdown of DHX9 and ADAR1, but neither alone, caused activation of multiple dsRNA sensing pathways leading to a viral mimicry phenotype. Together, these results reveal an important role for DHX9 in suppressing dsRNA sensing by multiple pathways. SIGNIFICANCE: These findings implicate DHX9 as a suppressor of dsRNA sensing. In some cell lines, loss of DHX9 alone is sufficient to cause activation of dsRNA sensing pathways, while in other cell lines DHX9 functions redundantly with ADAR1 to suppress pathway activation.