Cost-utility of sirolimus in the treatment of vascular malformations.

Sirolimus is being increasingly employed to manage specific vascular anomalies. We performed an exploratory cost-utility analysis to evaluate sirolimus as a treatment for vascular malformations from the Australian healthcare system perspective. Over a one-year time horizon, sirolimus treatment was associated with an increased expenditure of AU$2832.80 and a gain of 0.08 quality-adjusted life years (QALYs) when compared to supportive care, resulting in an incremental cost-effectiveness ratio of AU$35,410/QALY. By most metrics, sirolimus would be considered a cost-effective treatment for vascular malformations.

A comparison of three methods for establishing an ACL reference length in vivo.

As anterior cruciate ligament (ACL) injuries are highly prevalent among active individuals, it is vital to better understand the loading conditions which lead to injury. One method for doing so is through measurement of dynamic, in vivo ACL strain. To measure strain, it is necessary to normalize elongation of the ACL to a 'reference length' which corresponds to the point at which the ligament transitions from being unloaded to carrying tension. The purpose of this study was to compare the length of the ACL in three different positions to evaluate their utility for establishing a reference (or zero-strain) length of the ACL. ACL reference length was determined using three different methods for each of ten healthy participants. Using magnetic resonance and biplanar radiographic imaging techniques, we measured the length of the ACL during supine resting, quiet standing, and anterior/posterior (AP) drawer testing. During the AP drawer testing, the slack-taut transition point was defined as the inflection point of the AP translation vs ACL elongation curve. There was good consistency between the three ACL length measurements (ICC=0.80). Differences in mean ACL length between the three methods were within 1 mm. While determining the precise zero-strain length of the ACL in vivo remains a challenge, the reference positions utilized in this study produce consistent measurements of ACL length. These findings are important because reliable measurements of in vivo ACL strain have the potential to serve as indicators of propensity for injury.

Outcomes of Patients with Myeloid Malignancies and Cardiovascular Disease Undergoing Allogeneic Stem Cell Transplantation.

INTRODUCTION/BACKGROUND: Reduced-intensity conditioning (RIC) and nonmyeloablative (NMA) regimens have enabled patients with cardiovascular disease (CVD) to undergo allogeneic stem cell transplantation (allo-HSCT). However, little is known about long-term outcomes, including cardiovascular (CV) complications. METHODS: We retrospectively studied 99 consecutive patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who underwent allo-HSCT between September 1, 2013, and November 30, 2020. Overall survival (OS), progression-free survival (PFS), nonrelapse mortality (NRM), cumulative incidence of relapse, and cumulative incidence of acute and chronic graft-versus-host disease (GvHD) were compared in patients with and without CV risk factors or disease. RESULTS: Preexisting CVD was present in 34 of 99 patients (34%). CVD patients more commonly had reduced-intensity conditioning (91% vs. 60%, p = 0.001) and unrelated donors (56% vs. 35%, p = 0.04). Early adverse cardiac events occurred more frequently in the CVD versus no-CVD group (38% vs. 14%), particularly arrhythmias (21% vs. 5%; p = 0.04). CVD patients tended to have poorer OS and PFS outcomes (HR = 1.98, [1.00, 3.92]; HR = 1.89, [0.96-3.72], respectively). OS rate at 1, 2, and 3 years for CVD versus no-CVD patients was 66% versus 72%, 55% versus 64%, and 46% versus 62%, respectively. Causes of death in the CVD and no-CVD groups were infections (53% vs. 28%), relapsed disease (32% vs. 52%), and CV events (10% vs. 3%). CONCLUSION: Based on these data, predictive models to identify patients with CVD with higher risk of post-allo-HSCT complications and mortality and strategies to mitigate these risks should be developed.

Clinical Features and Outcomes of Pediatric and Adult Patients Hospitalized for Coronavirus Disease 2019: A Comparison Across Age Strata.

Background: Coronavirus disease 2019 (COVID-19) continues to cause hospitalizations and severe disease in children and adults. Methods: This study compared the risk factors, symptoms, and outcomes of children and adults hospitalized for COVID-19 from March 2020 to May 2023 across age strata at 5 US sites participating in the Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence consortium. Eligible patients had an upper respiratory swab that tested positive for severe acute respiratory syndrome coronavirus 2 by nucleic acid amplification. Adjusted odds ratios (aOR) of clinical outcomes were determined for children versus adults, for pediatric age strata compared to adolescents (12-17 years), and for adult age strata compared to young adults (22-49 years). Results: Of 9101 patients in the Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence cohort, 1560 were hospitalized for COVID-19 as the primary reason. Compared to adults (22-105 years, n = 675), children (0-21 years, n = 885) were less commonly vaccinated (14.3% vs 34.5%), more commonly infected with the Omicron variant (49.5% vs 26.1%) and had fewer comorbidities (P < .001 for most comparisons), except for lung disease (P = .24). After adjusting for confounding variables, children had significantly lower odds of receiving supplemental oxygen (aOR, 0.57; 95% confidence interval, .35-.92) and death (aOR, 0.011; 95% confidence interval, <.01-.58) compa--red to adults. Among pediatric age strata, adolescents 12-17 years had the highest odds of receiving supplemental oxygen, high-flow oxygen, and ICU admission. Among adults, those 50-64 years had the highest odds of mechanical ventilation and ICU admission. Conclusions: Clinical outcomes of COVID-19 differed across pediatric and adult age strata. Adolescents experienced the most severe disease among children, whereas adults 50-64 years experienced the most severe disease among adults.

Artificial Intelligence Applications in Oral Cancer and Oral Dysplasia.

Oral squamous cell carcinoma (OSCC) is a highly unpredictable disease with devastating mortality rates that have not changed over the past decades, in the face of advancements in treatments and biomarkers, which have improved survival for other cancers. Delays in diagnosis are frequent, leading to more disfiguring treatments and poor outcomes for patients. The clinical challenge lies in identifying those patients at the highest risk of developing OSCC. Oral epithelial dysplasia (OED) is a precursor of OSCC with highly variable behavior across patients. There is no reliable clinical, pathological, histological, or molecular biomarker to determine individual risk in OED patients. Similarly, there are no robust biomarkers to predict treatment outcomes or mortality in OSCC patients. This review aims to highlight advancements in artificial intelligence (AI)-based methods to develop predictive biomarkers of OED transformation to OSCC or predictive biomarkers of OSCC mortality and treatment response. Biomarkers such as S100A7 demonstrate promising appraisal for the risk of malignant transformation of OED. Machine learning-enhanced multiplex immunohistochemistry workflows examine immune cell patterns and organization within the tumor immune microenvironment to generate outcome predictions in immunotherapy. Deep learning (DL) is an AI-based method using an extended neural network or related architecture with multiple "hidden" layers of simulated neurons to combine simple visual features into complex patterns. DL-based digital pathology is currently being developed to assess OED and OSCC outcomes. The integration of machine learning in epigenomics aims to examine the epigenetic modification of diseases and improve our ability to detect, classify, and predict outcomes associated with epigenetic marks. Collectively, these tools showcase promising advancements in discovery and technology, which may provide a potential solution to addressing the current limitations in predicting OED transformation and OSCC behavior, both of which are clinical challenges that must be addressed in order to improve OSCC survival.

An optical tweezer array of ultracold polyatomic molecules.

Polyatomic molecules have rich structural features that make them uniquely suited to applications in quantum information science1-3, quantum simulation4-6, ultracold chemistry7 and searches for physics beyond the standard model8-10. However, a key challenge is fully controlling both the internal quantum state and the motional degrees of freedom of the molecules. Here we demonstrate the creation of an optical tweezer array of individual polyatomic molecules, CaOH, with quantum control of their internal quantum state. The complex quantum structure of CaOH results in a non-trivial dependence of the molecules' behaviour on the tweezer light wavelength. We control this interaction and directly and non-destructively image individual molecules in the tweezer array with a fidelity greater than 90%. The molecules are manipulated at the single internal quantum state level, thus demonstrating coherent state control in a tweezer array. The platform demonstrated here will enable a variety of experiments using individual polyatomic molecules with arbitrary spatial arrangement.

Clinical outcomes of patients with acute myeloid leukemia and cardiovascular disease.

Incidence of both acute myeloid leukemia (AML) and cardiovascular disease (CVD) increases with age. We evaluated whether pre-existing CVD impacts clinical outcomes in AML. We retrospectively evaluated 291 consecutive adult AML patients treated at our institution, 2014-2020. Pretreatment comorbidities were identified by chart review. Outcomes included complete remission (CR) and CR with incomplete count recovery (CRi) rates, disease-free survival (DFS), overall survival (OS) and incidence of cardiovascular adverse events. CVD was present in 34% of patients at AML diagnosis. CVD patients had worse performance status (p=0.03) and more commonly had secondary AML (p=0.03) and received hypomethylating (HMA) agent-based therapy (72% vs 38%, p< 0.001). CVD (0.45 vs 0.71, p<0.001) and diabetes mellitus (HR= 0.24, 95% CI: 0.08 - 0.8, p= 0.01) were associated with lower probability of achieving CR/CRi. Accounting for age, performance status (PS), complex karyotype, secondary disease and treatment, CVD patients had shorter OS (HR=1.5, 95% CI: 1.1-2.2, p=0.002), with 1- and 3-year OS 44% vs 67% and 25% vs 40%, respectively, but there was no difference in cumulative incidence of relapse between patients with vs without CVD. Thus, CVD is an independent risk factor for lower response rate and shorter survival in AML patients.

Depression during the COVID-19 pandemic among older adults with stroke history: Findings from the Canadian Longitudinal Study on Aging.

OBJECTIVES: The COVID-19 pandemic and accompanying public health measures exacerbated many known risk factors for depression, while also increasing numerous health-related stressors for people with stroke history. Using a large longitudinal sample of older adults, the current study examined the prevalence of incident and recurrent depression among participants with stroke history, and also identified factors that were associated with depression during the pandemic among this population. METHODS: Data came from four waves of the Canadian Longitudinal Study on Aging's (CLSA) comprehensive cohort (n = 577 with stroke history; 46.1% female; 20.8% immigrants; mean age = 74.56 SD = 9.19). The outcome of interest was a positive screen for depression, based on the CES-D-10, collected during the 2020 CLSA COVID autumn questionnaire. Bivariate and multivariate logistic regression analyses were conducted to identify factors that were associated with depression. RESULTS: Approximately 1 in 2 (49.5%) participants with stroke history and a history of depression experienced a recurrence of depression early in the pandemic. Among those without a history of depression, approximately 1 in 7 (15.0%) developed depression for the first time during this period. The risk of depression was higher among immigrants, those who were lonely, those with functional limitations, and those who experienced COVID-19 related stressors, such as increased family issues, difficulty accessing healthcare, and becoming ill or having a loved one become ill or die during the pandemic. CONCLUSIONS: Interventions that target those with stroke history, both with and without a history of depression, are needed to buffer against the stressors of the COVID-19 pandemic and support the mental health of this population.

Detection and absolute quantification of Lactiplantibacillus plantarum ATCC 202195 by quantitative real-time PCR.

IMPORTANCE: When administered for seven consecutive days shortly after birth, the probiotic bacterium Lactiplantibacillus plantarum ATCC 202195 plus fructooligosaccharide (FOS) was reported to reduce sepsis and lower respiratory tract infection events during early infancy in a randomized trial in India. Since probiotic effects are often strain specific, strain-level detection and quantification by routine molecular methods enables the monitoring of safety outcomes, such as probiotic-associated bacteremia, and allows for the quality of probiotic interventions to be assessed and monitored (i.e., verify strain identity and enumerate). Despite the potential clinical applications of L. plantarum ATCC 202195, an assay to detect and quantify this strain has not previously been described. Herein, we report the design of primer and probe sequences to detect L. plantarum ATCC 202195 and the development and optimization of a real-time PCR assay to detect and quantify the strain with high specificity and high sensitivity.

Why Nonheme Iron Halogenases Do Not Fluorinate C-H Bonds: A Computational Investigation.

Selective halogenation is necessary for a range of fine chemical applications, including the development of therapeutic drugs. While synthetic processes to achieve C-H halogenation require harsh conditions, enzymes such as nonheme iron halogenases carry out some types of C-H halogenation, i.e., chlorination or bromination, with ease, while others, i.e., fluorination, have never been observed in natural or engineered nonheme iron enzymes. Using density functional theory and correlated wave function theory, we investigate the differences in structural and energetic preferences of the smaller fluoride and the larger chloride or bromide intermediates throughout the catalytic cycle. Although we find that the energetics of rate-limiting hydrogen atom transfer are not strongly impacted by fluoride substitution, the higher barriers observed during the radical rebound reaction for fluoride relative to chloride and bromide contribute to the difficulty of C-H fluorination. We also investigate the possibility of isomerization playing a role in differences in reaction selectivity, and our calculations reveal crucial differences in terms of isomer energetics of the key ferryl intermediate between fluoride and chloride/bromide intermediates. While formation of monodentate isomers believed to be involved in selective catalysis is shown for chloride and bromide intermediates, we find that formation of the fluoride monodentate intermediate is not possible in our calculations, which lack additional stabilizing interactions with the greater protein environment. Furthermore, the shorter Fe-F bonds are found to increase isomerization reaction barriers, suggesting that incorporation of residues that form a halogen bond with F and elongate Fe-F bonds could make selective C-H fluorination possible in nonheme iron halogenases. Our work highlights the differences between the fluoride and chloride/bromide intermediates and suggests potential steps toward engineering nonheme iron halogenases to enable selective C-H fluorination.

Depression during the COVID-19 pandemic among older Canadians with peptic ulcer disease: Analysis of the Canadian Longitudinal Study on Aging.

The COVID-19 pandemic and associated public health measures have exacerbated many known risk factors for depression that may be particularly concerning for individuals with chronic health conditions, such as peptic ulcer disease (PUD). In a large longitudinal sample of older adults with PUD, the current study examined the incidence of depression during the pandemic among those without a pre-pandemic history of depression (n = 689) and the recurrence of depression among those with a history of depression (n = 451). Data came from four waves of the Canadian Longitudinal Study on Aging (CLSA). Multivariate logistic regression analyses were conducted to identify factors associated with incident and recurrent depression. Among older adults with PUD and without a history of depression, approximately 1 in 8 (13.0%) developed depression for the first time during the COVID-19 pandemic. Among those with a history of depression, approximately 1 in 2 (46.6%) experienced depression during the pandemic. The risk of incident depression and recurrent depression was higher among those who were lonely, those with functional limitations, and those who experienced an increase in family conflict during the pandemic. The risk of incident depression only was higher among women, individuals whose income did not satisfy their basic needs, those who were themselves ill and/or those whose loved ones were ill or died during the pandemic, and those who had disruptions to healthcare access during the pandemic. The risk of recurrent depression only was higher among those with chronic pain and those who had difficulty accessing medication during the pandemic. Implications for interventions are discussed.

Modeled small airways lung deposition of two fixed-dose triple therapy combinations assessed with in silico functional respiratory imaging.

BACKGROUND: Small airways disease plays a key role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and is a major cause of obstruction; therefore, it is a critical pharmacotherapy target. This study evaluated lung deposition of two inhaled corticosteroid (ICS)/long-acting ß2-agonist/long-acting muscarinic antagonist single-inhaler triple therapies using in silico functional respiratory imaging (FRI). Deposition was assessed using real-world inhalation profiles simulating everyday use where optimal inhalation may be compromised. METHODS: Three-dimensional airway models were produced from 20 patients with moderate-to-very severe COPD. Total, central, and regional small airways deposition as a percentage of delivered dose of budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) 160/7.2/5 µg per actuation and fluticasone furoate/umeclidinium/vilanterol (FF/UM/VI) 100/62.5/25 µg were evaluated using in silico FRI based on in vitro aerodynamic particle size distributions of each device. Simulations were performed using multiple inhalation profiles of varying durations and flow rates representing patterns suited for a pressurized metered-dose inhaler or dry-powder inhaler (four for BGF, two for FF/UM/VI, with one common profile). For the common profile, deposition for BGF versus FF/UM/VI was compared post-hoc using paired t-tests. RESULTS: Across inhalation profiles, mean total lung deposition was consistently higher with BGF (47.0-54.1%) versus FF/UM/VI (20.8-22.7%) and for each treatment component, with greater deposition for BGF also seen in the central large airways. Mean regional small airways deposition was also greater across inhalation profiles with BGF (16.9-23.6%) versus FF/UM/VI (6.8-8.7%) and for each treatment component. For the common profile, total, central, and regional small airways deposition were significantly greater for BGF versus FF/UM/VI (nominal p < 0.001), overall and for treatment components; notably, regional small airways deposition of the ICS components was approximately five-fold greater with budesonide versus fluticasone furoate (16.1% vs. 3.3%). CONCLUSIONS: BGF was associated with greater total, central, and small airways deposition for all components versus FF/UM/VI. Importantly, using an identical inhalation profile, there was an approximately five-fold difference in small airways deposition for the ICS components, with only a small percentage of the ICS from FF/UM/VI reaching the small airways. Further research is needed to understand if the enhanced delivery of BGF translates to clinical benefits.

Pandemic-Induced Depression Among Older Adults with a History of Cancer During the COVID-19 Pandemic: Findings from the Canadian Longitudinal Study on Aging.

Purpose: The objectives of this study were to identify the prevalence of, and factors associated with, incident and recurrent depression in a sample of older adults with a history of cancer during the COVID-19 pandemic. Materials and Methods: Data were drawn from four waves of the Canadian Longitudinal Study on Aging Comprehensive Cohort (n=2486 with cancer). The outcome of interest was a positive screen for depression based on the CES-D-10 during the autumn of 2020. Results: Among older adults with cancer and no pre-pandemic history of depression (n=1765), 1 in 8 developed first onset depression during the pandemic. Among respondents with cancer and a history of depression (n=721), 1 in 2 experienced a recurrence of depression. The risk of both incident and recurrent depression was higher among those who were lonely, those with functional limitations, and those who experienced an increase in family conflict during the pandemic. The risk of incident depression only was higher among older women, those who did not engage in church or religious activities, those who experienced a loss of income during the pandemic, and those who became ill or had a loved one become ill or die during the pandemic. The risk of recurrent depression only was higher among those who felt isolated from others and those whose income did not satisfy their basic needs. Conclusion: Health care providers should continue to screen and provide mental health support to their cancer patients and those with a lifetime history of cancer, with consideration for those with the aforementioned vulnerabilities.

Breathless and Blue in the Canadian Longitudinal Study on Aging: Incident and Recurrent Depression Among Older Adults with COPD During the COVID-19 Pandemic.

Background and Objectives: The COVID-19 pandemic and related public health measures intensified risk factors for depression and concurrently heightened numerous health-related stressors for individuals with Chronic Obstructive Pulmonary Disease (COPD). Utilizing a comprehensive longitudinal sample of Canadian older adults, this study examined the incidence and recurrence of depression among older adults with COPD, and identified factors that were associated with depression during the pandemic among this population. Methods: Data came from four phases of the Canadian Longitudinal Study on Aging (CLSA) (n=875 with COPD). The primary outcome of interest was a positive screen for depression based on the CES-D-10, during autumn of 2020. Bivariate and multivariate logistic regression analyses were performed to identify factors that were associated with depression. Results: Approximately 1 in 6 (17%) respondents with COPD and no lifetime history of depression developed depression for the first time during the early stages of the pandemic. Approximately 1 in 2 (52%) participants with COPD and a history of depression experienced a recurrence of depressive symptoms during this period. Loneliness, functional limitations, and family conflict were associated with a higher risk of both incident and recurrent depression. The risk of incident depression only was higher among those who had difficulty accessing healthcare resources. The risk of recurrent depression only was higher among women, those with a post-secondary education, and those with more adverse childhood experiences. Conclusion: Screening and interventions aimed at individuals with COPD, both with and without a history of depression, are warranted to potentially mitigate the mental health impacts of the COVID-19 pandemic.

The SUPER reporting guideline suggested for reporting of surgical technique.

Background: Existing reporting guidelines pay insufficient attention to the detail and comprehensiveness reporting of surgical technique. The Surgical techniqUe rePorting chEcklist and standaRds (SUPER) aims to address this gap by defining reporting standards for surgical technique. The SUPER guideline intends to apply to articles that encompass surgical technique in any study design, surgical discipline, and stage of surgical innovation. Methods: Following the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network approach, 16 surgeons, journal editors, and methodologists reviewed existing reporting guidelines relating to surgical technique, reviewed papers from 15 top journals, and brainstormed to draft initial items for the SUPER. The initial items were revised through a three-round Delphi survey from 21 multidisciplinary Delphi panel experts from 13 countries and regions. The final SUPER items were formed after an online consensus meeting to resolve disagreements and a three-round wording refinement by all 16 SUPER working group members and five SUPER consultants. Results: The SUPER reporting guideline includes 22 items that are considered essential for good and informative surgical technique reporting. The items are divided into six sections: background, rationale, and objectives (items 1 to 5); preoperative preparations and requirements (items 6 to 9); surgical technique details (items 10 to 15); postoperative considerations and tasks (items 16 to 19); summary and prospect (items 20 and 21); and other information (item 22). Conclusions: The SUPER reporting guideline has the potential to guide detailed, comprehensive, and transparent surgical technique reporting for surgeons. It may also assist journal editors, peer reviewers, systematic reviewers, and guideline developers in the evaluation of surgical technique papers and help practitioners to better understand and reproduce surgical technique. Trial Registration: https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-other-study-designs/#SUPER.

The SUPER reporting guideline suggested for reporting of surgical technique: explanation and elaboration.

Background: Surgical technique plays an essential role in achieving good health outcomes. However, the quality of surgical technique reporting remains heterogeneous. Reporting checklists could help authors to describe the surgical technique more transparently and effectively, as well as to assist reviewers and editors evaluate it more informatively, and promote readers to better understand the technique. We previously developed SUPER (surgical technique reporting checklist and standards) to assist authors in reporting their research that contains surgical technique more transparently. However, further explanation and elaboration of each item are needed for better understanding and reporting practice. Methods: We searched surgical literature in PubMed, Google Scholar and journal websites published up to January 2023 to find multidiscipline examples in various article types for each SUPER item. Results: We explain the 22 items of the SUPER and provide rationales item by item alongside. We provide 69 examples from 53 literature that present optimal reporting of the 22 items. Article types of examples include pure surgical technique, and case reports, observational studies and clinical trials that contain surgical technique. Examples are multidisciplinary, including general surgery, orthopaedical surgery, cardiac surgery, thoracic surgery, gastrointestinal surgery, neurological surgery, oncogenic surgery, and emergency surgery etc. Conclusions: Along with SUPER article, this explanation and elaboration file can promote deeper understanding on the SUPER items. We hope that the article could further guide surgeons and researchers in reporting, and assist editors and peer reviewers in reviewing manuscripts related to surgical technique.

In vivo CRISPR/Cas9 screening identifies Pbrm1 as a regulator of myeloid leukemia development in mice.

CRISPR/Cas9 screening approaches are powerful tool for identifying in vivo cancer dependencies. Hematopoietic malignancies are genetically complex disorders in which the sequential acquisition of somatic mutations generates clonal diversity. Over time, additional cooperating mutations may drive disease progression. Using an in vivo pooled gene editing screen of epigenetic factors in primary murine hematopoietic stem and progenitor cells (HSPCs), we sought to uncover unrecognized genes that contribute to leukemia progression. We, first, modeled myeloid leukemia in mice by functionally abrogating both Tet2 and Tet3 in HSPCs, followed by transplantation. We, then, performed pooled CRISPR/Cas9 editing of genes encoding epigenetic factors and identified Pbrm1/Baf180, a subunit of the polybromo BRG1/BRM-associated factor SWItch/Sucrose Non-Fermenting chromatin-remodeling complex, as a negative driver of disease progression. We found that Pbrm1 loss promoted leukemogenesis with a significantly shortened latency. Pbrm1-deficient leukemia cells were less immunogenic and were characterized by attenuated interferon signaling and reduced major histocompatibility complex class II (MHC II) expression. We explored the potential relevance to human leukemia by assessing the involvement of PBRM1 in the control of interferon pathway components and found that PBRM1 binds to the promoters of a subset of these genes, most notably IRF1, which in turn regulates MHC II expression. Our findings revealed a novel role for Pbrm1 in leukemia progression. More generally, CRISPR/Cas9 screening coupled with phenotypic readouts in vivo has helped identify a pathway by which transcriptional control of interferon signaling influences leukemia cell interactions with the immune system.