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The goal of a diagnostic test is to provide information on the probability of disease. In this article, we review the principles of diagnostic test characteristics, including sensitivity, specificity, positive and negative predictive value, receiver operating characteristics curves, likelihood ratios, and interval likelihood ratios. We illustrate how interval likelihood ratios optimize the information that can be obtained from test results that can take on >2 values, how they are reflected in the slope of the receiver operating characteristics curve, and how they can be easily calculated from published data.

Temperature measurement plays a central role in determining pediatric patients' disease risk and management. However, current pediatric temperature thresholds may be outdated and not applicable to children.To characterize pediatric temperature norms and variation by patient characteristics, time of measurement, and thermometer route.In this cross-sectional study, we analyzed 134,641 well-child visits occurring between 2014-2019 at primary care clinics that routinely measured temperature. We performed bivariate and multivariable quantile regressions with clustered standard errors to determine temperature percentiles and variation by age, sex, time of measurement, and thermometer route. We performed sensitivity analyses: 1) using a cohort that excluded visits with infectious diagnoses that could explain temperature aberrations and 2) including clinic as a fixed effect.The median rectal temperature for visits of infants ≤12 months old was 37.2˚C, which was 0.4˚C higher than the median axillary temperature. The median axillary temperature for children 1-18 years old was 36.7˚C, which was 0.1˚C lower than the median values of all other routes. The 99th percentile for rectal temperatures in infants was 37.8˚C and the 99.9th percentile for axillary temperatures in children was 38.5˚C. Adjusted analyses did not demonstrate clinically significant variation in temperature by sex, age, or time of measurement.These updated temperature norms can serve as reference values in clinical practice and should be considered in the context of thermometer route used and the clinical condition being evaluated. Variations in temperature values by sex, age, and time of measurement were not clinically significant.

Surface fully functionalized one-dimensional nanowire was designed for the highly sensitive and specific detection of H2S under visible light.

A facile “chemical scissor” strategy is first proposed to rationally design a dangling bond for COF materials, which remarkably promotes their gas sensing performance.

Pancreatic neuroendocrine tumors (P-NETs) are highly heterogeneous with wide spectrum of biological behaviors and growth patterns. Here, we aimed to assess the impact of tumor grading on P-NETs prognosis and survival outcomes.Patients with P-NET were recruited to determine correlations between grades and clinicopathological factors, survival outcomes and prognostic factors.A total of 152 patients with P-NETs were enrolled. G1 P-NET were associated with significantly lower rates of perineural invasion, lymphovascular invasion, lymph node involvement and distant metastasis. The pancreatic head was the most common location of P-NETs. The 1-year, 5-year and 10-year overall survival rates of the patients were 94.4%, 89.1% and 78.8%, respectively. Majority of pancreatic neuroendocrine carcinoma (P-NEC) were unresectable (90.9%), and P-NECs patients had poor survival rates (1-year, 20% and no 5-year). Male sex, tumor size ≥2.5 cm, perineural invasion, lymph node invasion, metastasis, and advanced stage were significantly associated with poorer survival outcomes. Tumor grade and sex were independent survival predictors. Moreover, tumor grade was the most powerful prognostic factor.Tumor grade, sex, perineural invasion, tumor size, lymph node involvement, metastasis, and stage are survival predictors for patients with P-NETs. Tumor grade is the most powerful independent prognostic factor.

This paper addresses the issues of static output feedback [Formula: see text] control for switched linear parameter-varying (LPV) time-delay systems using multiple parameter-dependent Lyapunov functions. First, a parameter and state-dependent switching strategy with dwell time is designed and a sufficient condition ensuring the stability of the unforced switched LPV time-delay systems is established with the aid of the switching law. Then, the piecewise parameter-dependent controller is designed, such that the closed-loop system is asymptotically stable and satisfies an [Formula: see text] performance index. Finally, two examples are provided to show the effectiveness of the results.

We sought to evaluate the utility and validity of ICU-free days and ventilator-free days as candidate outcomes for OHCA trials.We conducted a secondary analysis of the Pragmatic Airway Resuscitation Trial. We determined ICU-free (days alive and out of ICU during the first 30 days) and ventilator-free days (days alive and without mechanical ventilation). We determined ICU-free and ventilator-free day distributions and correlations with Modified Rankin Scale (MRS). We tested associations with trial interventions (laryngeal tube (LT), endotracheal intubation (ETI)) using continuous (t-test), non-parametric (Wilcoxon Rank-Sum test - WRS), count (negative binomial - NB) and survival models (Cox proportional hazards (CPH) and competing risks regression (CRR)). We conducted bootstrapped simulations to estimate statistical power.ICU-free days was skewed; median 0 days (IQR 0, 0), survivors only 24 (18, 27). Ventilator-free days was skewed; median 0 (IQR 0, 0) days, survivors only 27 (IQR 23, 28). ICU-free and ventilator-free days correlated with MRS (Spearman's ρ = -0.95 and -0.97). LT was associated with higher ICU-free days using t-test (p = 0.001), WRS (p = 0.003), CPH (p = 0.02) and CRR (p = 0.04), but not NB (p = 0.13). LT was associated with higher ventilator-free days using t-test (p = 0.001), WRS (p = 0.001) and CRR (p = 0.03), but not NB (p = 0.13) or CPH (p = 0.13). Simulations suggested that t-test and WRS would have had the greatest power to detect the observed ICU- and ventilator-free days differences.ICU-free and ventilator-free days correlated with MRS and differentiated trial interventions. ICU-free and ventilator-free days may have utility in the design of OHCA trials.

This paper concentrates on the state observer–based event-triggered control problem for a class of switched linear systems with external disturbance and transmission delay. It is assumed that the controller can only access the transmitted information of the state observer at each delayed event-triggered instant with a waiting time. First, by adopting the multiple Lyapunov–Krasovskii functional method, some sufficient conditions are derived for the establishment of the state observer, the input-to-state stability (ISS) and the globally uniformly exponential stability (GUES) of the switched linear systems under adjacent mode-dependent average dwell time (AMDADT) scheme. Then, we propose a state observer-based event-triggered sampling mechanism with waiting time and design an observer-based state feedback controller for the considered switched systems. Under the proposed event-triggered mechanism, the Zeno behavior can be easily excluded in all sampling processes. Finally, a numerical example is included to validate the proposed theory.

Benzodiazepines like midazolam were generally considered one of the possible causes affecting postoperative cognitive recovery. As a new kind of rapid-effect benzodiazepine, remimazolam tosylate was widely used in clinical anesthesia for its pharmacological advantage, but few studies reported its effects on cognitive function in the elderly. Here, we aimed to research the effects of remimazolam tosylate on cognitive function in aged mice and its underlying biological mechanisms. We measured the memory function of aged mice immediately and one month after intraperitoneal injection of remimazolam tosylate compared to the saline control. The brain metabolism level was detected by Positron Emission Tomography/Computed tomography (PET/CT). Compared with the control, we observed a decrease in memory ability， as well as an increase in tau phosphorylation level and a decrease in phosphatase level in the short term; however, one month later, contrary to the previous results, we observed better memory and brain metabolism and lower tau phosphorylation levels in the experimental group compared to the control. Therefore, we concluded that remimazolam tosylate did not cause long-term damage to the cognitive function of aged mice and even delayed the decline of memory function in the aging process to some extent.

Background and Purpose: The aim of this study was to investigate the association between daytime napping frequency and the incidence of essential hypertension or stroke as well as to validate causality in this relationship via Mendelian randomization (MR). Methods: We conducted Cox regression analysis on 358 451 participants free of hypertension or stroke from UK Biobank. To validate the results of the observational analysis, we conducted a 2-sample MR for daytime napping frequency (123 single-nucleotide polymorphisms) with essential hypertension in FinnGen Biobank, stroke, and ischemic stroke in MEGASTROKE consortium and performed a corresponding 1-sample MR on the UK Biobank data. Results: Compared with never napping, usually napping was associated with a higher risk of essential hypertension (hazard ratio, 1.12 [95% CI, 1.08–1.17]), stroke (hazard ratio, 1.24 [95% CI, 1.10–1.39], and ischemic stroke (hazard ratio, 1.20 [95% CI, 1.05–1.36]) in our prospective observational analysis. Both the 1-sample and 2-sample MR results indicated that increased daytime napping frequency was likely to be a potential causal risk factor for essential hypertension in FinnGEN (odds ratio, 1.43 [95% CI, 1.06–1.92]) and UK Biobank (odds ratio, 1.40 [95% CI, 1.28–1.58]). The 2-sample MR results supported the potential causal effect of nap frequency on ischemic stroke in MEGASTROKE (odds ratio, 1.29 [95% CI, 1.04–1.62]). Conclusions: Prospective observational and MR analyses provided evidence that increased daytime nap frequency may represent a potential causal risk factor for essential hypertension. The potential causal association of increased nap frequency with ischemic stroke was supported by 2-sample MR and prospective observational results.

To examine the hypothesis that longer distance from home-to-hospital is associated with worse outcomes among hospitalizations for community-acquired sepsis.A secondary analysis of data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) prospective cohort of 30,239 white and Black US adults greater than or equal to 45 years old was conducted. Self-reported hospitalizations for serious infection between 2003 and 2012 fulfilling 2/4 systemic inflammatory response syndrome criteria were included. Estimated driving distance was derived from geocoded data and evaluated continuously and as quartiles of very close, close, far, very far (3.1, 3.1-5.8, 5.9-11.5, and11.5 miles respectively). The primary outcome was 30-day mortality while the secondary outcome was sequential organ failure assessment (SOFA) score on arrival.Of the 912 hospitalizations for community-acquired sepsis had adequate data for analysis. The median (interquartile range) estimated driving distance was 5.8 miles (3.1,11.7), and 54 (5.9%) experienced the primary outcome. Compared to living very close, participants living very far had a mortality odds ratio of 1.30 (95% CI 0.64,2.62) and presenting SOFA score difference of 0.33 (95% CI -0.03,0.68).Among a national sample of community-acquired sepsis hospitalizations, there was no significant association between home-to-hospital distance and either 30-day mortality or SOFA score on hospital presentation.

Barrett’s oesophagus (BE) is the precursor of oesophageal adenocarcinoma, which has become the most common type of oesophageal cancer in many Western populations. Existing evidence on diet and risk of BE predominantly comes from case–control studies, which are subject to recall bias in measurement of diet. We aimed to investigate the potential effect of diet, including macronutrients, carotenoids, food groups, specific food items, beverages and dietary scores, on risk of BE in over 20 000 participants of the Melbourne Collaborative Cohort Study. Diet at baseline (1990–1994) was measured using a food frequency questionnaire. The outcome was BE diagnosed between baseline and follow-up (2007–2010). Logistic regression models were used to estimate OR and 95 % CI for diet in relation to risk of BE. Intakes of leafy vegetables and fruit were inversely associated with risk of BE (highest v. lowest quartile: OR = 0·59; CI: 0·38, 0·94; P-trend = 0·02 and OR = 0·58; CI: 0·37, 0·93; P-trend = 0·02 respectively), as were dietary fibre and carotenoids. Stronger associations were observed for food than the nutrients found in them. Positive associations were observed for discretionary food (OR = 1·54; CI: 0·97, 2·44; P-trend = 0·04) and total fat intake (OR per 10 g/d = 1·11; CI: 1·00, 1·23), the association for fat was less robust in sensitivity analyses. No association was observed for meat, protein, dairy products or diet scores. Diet is a potential modifiable risk factor for BE. Public health and clinical guidelines that incorporate dietary recommendations could contribute to reduction in risk of BE and, thereby, oesophageal adenocarcinoma.

Pulmonary hypertension (PAH) is a proliferative disease of pulmonary blood vessels, but the pathogenesis of pulmonary hypertension is still unclear. This article explores the role of tumor necrosis factor-α (TNF-α), tissue factor (TF), and coagulation function (CF) in the pathogenesis of PAH. PAH is often accompanied by vascular intima injury and muscular arterial media thickening. Coupled with the wide application of nanotargeted drugs in recent years, a targeted nanocarrier encapsulating sildenafil was prepared in this study. The particle size, PDI, zeta potential, drug loading, and encapsulation efficiency were 194.32 ± 17.31 nm , 0.28 ± 0.02 , − 6.34 ± 0.33 , 24.61%, and 70.52%. The monocrotaline PAH rat model was constructed, and it was found that the levels of TNF-α, TF, and CF in the peripheral blood of PAH rats were abnormally increased. 30 PAH rats were randomly divided into 5 groups and injected with saline (NS group), sildenafil (sildenafil group), target the nanoempty carrier (TNC-E group), ordinary nanocarrier encapsulated sildenafil (CNC-sildenafil group), and targeted nanocarrier encapsulate sildenafil (TNC-sildenafil group). Compared with the NS group, the mean pulmonary artery pressure in the TNC-sildenafil group was lower ( P < 0.05 ). Compared with the normal rat group, the pulmonary small blood vessel media thickness, TNF-α level, TF level, and the area of myocardial cells were increased in the NS group, sildenafil group, TNC-E group, and CNC-sildenafil group ( P < 0.05 ). Compared with the NS group, the pulmonary small blood vessel media thickness, myocardial cell area, and the levels of TNF-α and TF in the TNC-sildenafil group were reduced ( P < 0.05 ). Targeting nanocarrier encapsulation of sildenafil can obviously reduce the average pulmonary artery pressure in rats with pulmonary hypertension, improve pulmonary vascular media proliferation and myocardial hypertrophy, and restore the levels of TNF-α, TF, and CF to a normal state.

Introduction: Thoracic trauma is the second leading cause of death after traumatic brain injury in children presenting with blunt chest trauma, which represents 80% of thoracic trauma in children. We hypothesized that older children undergo more clinical and surgical changes in management than younger children screened for intrathoracic injury at a single, urban, pediatric Level I trauma center. Methods: In this retrospective observational study, we determined the frequencies and types of lesions diagnosed only by chest computed tomography (CCT) and resulting changes of clinical and surgical management among different age groups in a pediatric cohort examined for blunt trauma with chest radiograph and CCT. We used logistic regression to quantify variations in CCT diagnoses and changes in clinical and surgical management across age groups. For each age category, we determined the odds ratio for diagnosis made only on CCT and subsequent changes in all clinical management and, specifically, surgical management. We performed the test of trend to determine the relationship across age with changes in management resulting from additional diagnoses made by CCT. Results: We analyzed data on 1,235 patients screened for intrathoracic injury. We found the following overall clinical management and surgical management changes, respectively, per age group: 0-2 years, 5/128 (3.9) and 0/128 (0.0); 3-6 years, 11/212 (5.2) and 1/212 (0.5); 7-10 years, 16/175 (9.1) and 2/175 (1.1); 11-13 years, 17/188 (9.0) and 3/188 (1.6); 14-17 years, 58/532 (10.9) and 25/532 (4.7). There were no observed surgical management changes in the 0-2 age group and, thus, no estimated odds ratio could be calculated. The adjusted odds ratios for the occurrence of surgical change in management (14-17 age group as reference) was 0.1 (0.0-0.9) for 3-6 years, 0.3 (0.1-1.3) for 7-10 years, and 0.3 (0.1- 1.1) for 11-13 years. The trend of odds ratios across ages showed that with every subsequent year of life there was a 10% increase in management change and a 30% increase in surgical management change. Conclusion: Chest computed tomography plays a limited role in younger children and seldom significantly changes management albeit making additional diagnoses.

Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive and has poor prognosis. There are few biomarkers to inform treatment decisions, and collecting tumour samples for testing is challenging.Circulating tumour cells (CTCs) from patients with PDAC liquid biopsies were expanded ex vivo to form CTC-derived organoid cultures, using a laboratory-developed biomimetic cell culture system. CTC-derived organoids were tested for sensitivity to a PDAC panel of nine drugs, with tests conducted in triplicate, and a weighted cytotoxicity score (CTS) was calculated from the results. Clinical response to treatment in patients was evaluated using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 criteria at the time of blood sampling and 3 months later. The correlation between CTS and clinical response was then assessed.A total of 41 liquid biopsies (87.8% from patients with Stage 4 disease) were collected from 31 patients. The CTC-derived organoid expansion was achieved in 3 weeks, with 87.8% culture efficiency. CTC-derived organoid cultures were positive for EpCAM staining and negative for CD45 staining in the surface marker analysis. All patients had received a median of two lines of treatment prior to enrolment and prospective utility analysis indicated significant correlation of CTS with clinical treatment response. Two representative case studies are also presented to illustrate the relevant clinical contexts.CTCs were expanded from patients with PDAC liquid biopsies with a high success rate. Drug sensitivity profiles from CTC-derived organoid cultures correlated meaningfully with treatment response. Further studies are warranted to validate the predictive potential for this approach.

A core-shell molecularly imprinted polymer nanoparticle with biological enzyme functional characteristics was developed by oxidative polymerization of template protein and polydopamine on the surface of protease-copper phosphate hybrid nanoflowers by molecular imprinting technology and enzyme immobilization technology. The obtained molecularly imprinted polymer showed specific binding characteristics with the template protein. It recognized and enriched the target molecules through the surface molecularly imprinted sites of the shell structure. In addition, the bound target molecules were further degraded into fragments by nanozymes with biological enzyme characteristics in the core. In this study, molecular imprinting technology and biotechnology were combined to obtain bifunctional molecularly imprinted polymer nanoparticles that can not only enrich template molecules but also degrade them into fragments. Herein, we selected interleukin 6 (IL-6), the target molecule of cytokine release syndrome (CRS), as a template molecule, and reported a molecularly imprinted polymer with degrading enzyme properties that can rapidly reduce IL-6 levels in vivo, including a molecularly imprinted layer that can recognize and bind IL-6 and nanozymes that can degrade IL-6 and deactivate it. It is used to clear the excessive secretion of IL-6 in CRS and reduce the level of IL-6 in the body to achieve the purpose of adjuvant treatment of CRS.

We present a measurement of the Cabibbo-Kobayashi-Maskawa unitarity triangle angle ϕ 3 (also known as γ) using a model-independent Dalitz plot analysis of B + → D ( K S 0 $$ {K}_S^0 $$ h + h − )h +, where D is either a D 0 or D ¯ $$ \overline{D} $$ 0 meson and h is either a π or K. This is the first measurement that simultaneously uses Belle and Belle II data, combining samples corresponding to integrated luminosities of 711 fb −1 and 128 fb −1, respectively. All data were accumulated from energy-asymmetric e + e − collisions at a centre-of-mass energy corresponding to the mass of the Υ(4S) resonance. We measure ϕ 3 = (78.4 ± 11.4 ± 0.5 ± 1.0)°, where the first uncertainty is statistical, the second is the experimental systematic uncertainty and the third is from the uncertainties on external measurements of the D-decay strong-phase parameters.

Study objective While often prioritized in the resuscitation of patients with out-of-hospital cardiac arrest, the optimal timing of advanced airway insertion is unknown. We evaluated the association between the timing of advanced airway (laryngeal tube and endotracheal intubation) insertion attempt and survival to hospital discharge in adult out-of-hospital cardiac arrest. Methods We performed a secondary analysis of the Pragmatic Airway Resuscitation Trial (PART), a clinical trial comparing the effects of laryngeal tube and endotracheal intubation on outcomes after adult out-of-hospital cardiac arrest. We stratified the cohort by randomized airway strategy (laryngeal tube or endotracheal intubation). Within each subset, we defined a time-dependent propensity score using patients, arrest, and emergency medical services systems characteristics. Using the propensity score, we matched each patient receiving an initial attempt of laryngeal tube or endotracheal intubation with a patient at risk of receiving laryngeal tube or endotracheal intubation attempt within the same minute. Results Of 2,146 eligible patients, 1,091 (50.8%) and 1,055 (49.2%) were assigned to initial laryngeal tube and endotracheal intubation strategies, respectively. In the propensity score-matched cohort, timing of laryngeal tube insertion attempt was not associated with survival to hospital discharge: 0 to lesser than 5 minutes (risk ratio [RR]=1.35, 95% confidence interval [CI] 0.53 to 3.44); 5 to lesser than10 minutes (RR=1.07, 95% CI 0.66 to 1.73); 10 to lesser than 15 minutes (RR=1.17, 95% CI 0.60 to 2.31); or 15 to lesser than 20 minutes (RR=2.09, 95% CI 0.35 to 12.47) after advanced life support arrival. Timing of endotracheal intubation attempt was also not associated with survival: 0 to lesser than 5 minutes (RR=0.50, 95% CI 0.05 to 4.87); 5 to lesser than10 minutes (RR=1.20, 95% CI 0.51 to 2.81); 10 to lesser than15 minutes (RR=1.03, 95% CI 0.49 to 2.14); 15 to lesser than 20 minutes (RR=0.85, 95% CI 0.30 to 2.42); or more than/equal to 20 minutes (RR=0.71, 95% CI 0.07 to 7.14). Conclusion In the PART, timing of advanced airway insertion attempt was not associated with survival to hospital discharge.

Acute myeloid leukemia (AML) patients refractory to induction therapy or relapsed within 1 year have poor outcomes. Autocrine production of hepatocyte growth factor by myeloid blasts drives leukemogenesis in preclinical models. A phase Ib trial evaluated ficlatuzumab, a first-in-class anti-HGF antibody, in combination with cytarabine in this high-risk population. Dose-limiting toxicities were not observed, and 20 mg/kg was established as the recommended phase II dose. The most frequent treatment-related adverse event was febrile neutropenia. Among 17 evaluable patients, the overall response rate was 53%, all complete remissions. Phospho-proteomic mass cytometry showed potent on-target suppression of p-MET after ficlatuzumab treatment and that attenuation of p-S6 was associated with clinical response. Multiplexed single-cell RNA sequencing using prospectively acquired patient specimens identified IFN response genes as adverse predictive factors. The ficlatuzumab and cytarabine combination is well tolerated, with favorable efficacy. High-dimensional analyses at single-cell resolution represent promising approaches for identifying biomarkers of response and mechanisms of resistance in prospective clinical studies.Significance:This study demonstrates a favorable safety profile and promising clinical activity of ficlatuzumab and cytarabine in high-risk AML, thus supporting further investigation of this combination in a randomized trial. It also shows the utility of a novel application using multiplexed single-cell analyses to detect on-target activity and identify biomarkers of response.This article is highlighted in the In This Issue feature, p. 403

Supplementary Data from Inhibition of MET Signaling with Ficlatuzumab in Combination with Chemotherapy in Refractory AML: Clinical Outcomes and High-Dimensional Analysis

Supplementary Table 1. The shRNA and sgRNA Oligonucleotide Sequences Supplementary Table 2. 5'-and 3' RACE Primers Supplementary Table 3. qPCR Primers Supplementary Table 4. Hypoxia-induced lncRNAs in TNBC cells. Supplementary Table 5. Abundance of hypoxia-induced lncRNAs in both MDA-MB-231 and SUM159 cells. Supplementary Figure 1. The nucleotide sequence alignment of lncIHAT. Supplementary Figure 2. LncIHAT promotes TNBC growth and metastasis in mice. Supplementary Figure 3. LncIHATis required for expression of PDK1 and ITGA6 in TNBC cells. Supplementary Figure 4 .LncIHAT overexpression has no effect on PDK1 and ITGA6 expression. Supplementary Figure 5. Time-dependent induction of lncIHAT and PDK1 by hypoxia in TNBC cells. Supplementary Figure 6. PDK1 and ITGA6 mediate the effect of lncIHAT on TNBC cell growth in vitro.

International audience; Epilepsy is a complex disease that requires various approaches for its study. In this short review, we discuss the contribution of theoretical and computational models. The review presents theoretical frameworks that underlie the understanding of certain seizure properties and their classification based on their dynamical properties at the onset and offset of seizures. Dynamical system tools are valuable resources in the study of seizures. By analyzing the complex, dynamic behavior of seizures, these tools can provide insights into seizure mechanisms and offer a framework for their classification. Additionally, computational models have high potential for clinical applications, as they can be used to develop more accurate diagnostic and personalized medicine tools. We discuss various modeling approaches that span different scales and levels, while also questioning the neurocentric view, and emphasize the importance of considering glial cells. Finally, we explore the epistemic value provided by this type of approach.

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Emerging studies indicate that DNA damage in cancer cells triggers antitumor immunity, but its intrinsic regulatory mechanism in breast cancer cells remains poorly understood. Here, we show that ZMYND8 is upregulated and inhibits micronucleus formation and DNA damage in breast cancer cells. Loss of ZMYND8 triggered activation of the DNA sensor cyclic guanosine monophosphate-adenosine monophosphate synthase in micronuclei, leading to further activation of the downstream signaling effectors stimulator of IFN genes and NF-κB, but not TANK-binding kinase 1 and IFN regulatory factor 3, thereby inducing the expression of IFNβ and IFN-stimulated genes (ISG) in breast cancer cells in vitro and tumors in vivo. ZMYND8 knockout (KO) in breast cancer cells promoted infiltration of CD4+ and CD8+ T cells, leading to tumor inhibition in syngeneic mouse models, which was significantly attenuated by treatment of anti-CD4/CD8–depleting antibodies or anti-IFNAR1 antibody and in immunodeficient Rag1 KO mice. In human breast tumors, ZMYND8 was negatively correlated with ISGs, CD4, CD8A, CD8B, and the tumor-lymphocyte infiltration phenotype. Collectively, these findings demonstrate that maintenance of genome stability by ZMYND8 causes breast cancer cells to evade cytotoxic T-lymphocyte surveillance, which leads to tumor growth.Significance:These findings show that ZMYND8 is a new negative and intrinsic regulator of the innate immune response in breast tumor cells, and ZMYND8 may be a possible target for antitumor immunotherapy.

XLSX file - 66K, List of the differentially expressed probes for the analysis Epithelioid MPM vs. Sarcomatoid MPM.