What are the barriers towards cervical cancer screening for vulnerable women? A qualitative comparative analysis of stakeholder perspectives in seven European countries.

OBJECTIVES: The aim of this study was to map and compare stakeholders' perceptions of barriers towards cervical cancer screening for vulnerable women in seven European countries. DESIGN: In Collaborative User Boards, stakeholders were invited to participate to identify barriers towards participation in cervical cancer screening. SETTING: The study is nested in the European Union-funded project CBIG-SCREEN which aims to tackle inequity in cervical cancer screening for vulnerable women (www.cbig-screen.eu). Data collection took place in Bulgaria, Denmark, Estonia, France, Italy, Portugal and Romania. PARTICIPANTS: Participants represented micro-level stakeholders covering representatives of users, that is, vulnerable women, meso-level stakeholders covering healthcare professionals and social workers, and macro-level stakeholders covering programme managers and decision-makers. METHODS: Across the seven countries, 25 meetings in Collaborative User Boards with a duration of 2 hours took place between October 2021 and June 2022. The meetings were video recorded or audio recorded, transcribed and translated into English for a qualitative framework analysis. RESULTS: 120 participants took part in the Collaborative User Boards. Context-specific barriers were related to different healthcare systems and characteristics of vulnerable populations. In Romania and Bulgaria, the lack of a continuous screening effort and lack of ways to identify eligible women were identified as barriers for all women rather than being specific for women in vulnerable situations. The participants in Denmark, Estonia, France, Italy and Portugal identified providers' lack of cultural and social sensitivity towards vulnerable women as barriers. In all countries, vulnerable women's fear, shame and lack of priority to preventive healthcare were identified as psychological barriers. CONCLUSION: The study provides an overview of stakeholders' perceived barriers towards vulnerable women's cervical cancer screening participation in seven European countries. The organisation of healthcare systems and the maturity of screening programmes differ between countries, while vulnerable women's psychological barriers had several similarities.

First Insights on the Bioaccessibility and Absorption of Anthocyanins from Edible Flowers: Wild Pansy, Cosmos, and Cornflower.

Edible flowers are regaining interest among both the scientific community and the general population, not only for their appealing sensorial characteristics but also from the growing evidence about their health benefits. Among edible flowers, those that contain anthocyanins are among the most consumed worldwide. However, little is known regarding the bioaccessibility and absorption of their bioactive compounds upon ingestion. The aim of this work was to explore, for the first time, the behavior of anthocyanin-rich extracts from selected edible flowers under different food processing conditions and after ingestion using simulated digestions, as well as their absorption at the intestinal level. Overall, the results showed that the monoglucoside and rutinoside anthocyanin extracts were less stable under different pH, temperature, and time conditions as well as different digestive processes in the gastrointestinal tract. There was a prominent decrease in the free anthocyanin content after the intestinal phase, which was more pronounced for the rutinoside anthocyanin extract (78.41% decrease from the oral phase). In contrast, diglucoside and rutinoside anthocyanin extracts showed the highest absorption efficiencies at the intestinal level, of approximately 5% after 4 h of experiment. Altogether, the current results emphasize the influence of anthocyanins' structural arrangement on both their chemical stability as well as their intestinal absorption. These results bring the first insights about the bioaccessibility and absorption of anthocyanins from wild pansy, cosmos, and cornflower and the potential outcomes of such alternative food sources.

Reuse of lime sludge from immediate one-step lime precipitation process as a coagulant (aid) in slaughterhouse wastewater treatment.

The circularity of wastewater treatment subproducts is on the worldwide agenda. In this way, this work aims to evaluate alternatives for the reuse of sludge from slaughterhouse wastewater treatment. Wetted sludges produced in the immediate one-step lime precipitation process were applied directly or first calcined, as a coagulant or coagulant aid, in the absence or presence of Ca(OH)2, to slaughterhouse wastewaters with different characteristics. For the best sludge reuse, successive reuses of the sludge were carried out and the characteristics of treated slaughterhouse wastewater were evaluated after each reuse. Results showed a great similarity between slaughterhouse and treated slaughterhouse wastewaters using wetted and calcined sludges as a coagulant for highly contaminated slaughterhouse wastewater. In addition, a great similarity was also observed between the calcined and the wetted sludges, both as a coagulant aid, for all the slaughterhouse wastewaters tested. However, the latter consumed more hydrated lime, more volume of sludge sedimented, and higher concentrations phosphorus and organic matter in the treated wastewater. Calcined sludge as a coagulant aid guaranteed the best slaughterhouse wastewater quality for almost of the tested paramenters (≥94% for absorbances at 254 nm and 410 nm, E. coli, turbidity, and phosphorus, chemical oxygen demand between 3 and 91%, and total Kjeldahl nitrogen between 3 and 62%) independently of the wastewater characteristics. Calcined sludge as a coagulant aid can be three times reused for the tested parameters and slaughterhouse wastewater characteristics without significantly decreasing the quality. The successive sludge reused saves the hydrated lime dose applied (up to 28.4%) and the sedimented sludge volume (up to 24.7%), and can be a solution to stabilize sludge due to the pH increase (sludge pH = 12).

Immune Response to SARS-CoV-2 Vaccination in Cancer Patients: A Prospective Study.

Introduction Cancer patients on active treatment are at increased risk of developing coronavirus disease 2019 (COVID-19), making effective immunization of the utmost importance. However, the effectiveness of vaccination in this population is still unclear. This study aims to evaluate the response against COVID-19 in a cohort of patients with active cancer under immunosuppressive therapy. Methods This was a prospective, cross-sectional, single-center study that included patients with cancer under immunosuppressive therapy vaccinated against COVID-19 between April and September 2021. Exclusion criteria were: previous known severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, single-dose vaccine or incomplete vaccination scheme. Immunoglobulin G (IgG) anti-SARS-CoV-2 antibody levels were assessed using 35.2 binding antibody units (BAU)/mL as the positive cut-off. Assessments were performed 14-31 days after the first and second dose and three months after the second dose. Results A total of 103 patients were included. The median age was 60 years. Most patients were being treated for gastrointestinal cancer (n=38, 36.9%), breast cancer (n=33, 32%) or head and neck cancer (n=18, 17.5%). At evaluation, 72 patients (69.9%) were being treated with palliative intent. The majority were being treated with chemotherapy (CT) alone (57.3%). At the first assessment, levels of circulating SARS-CoV-2 IgG consistent with seroconversion were present in 49 patients (47.6%). At the time of the second assessment, 91% (n=100) achieved seroconversion. Three months after the second dose, 83% (n=70) maintained levels of circulating SARS-CoV-2 IgG consistent with seroconversion. In this study, no SARS-CoV-2 infection was reported in the study population. Conclusions Our findings suggest that this group of patients had a satisfactory COVID-19 immunization response. Although promising, this study should be replicated on a wider scale in order to validate these findings.

The role of spirituality in people with amyotrophic lateral sclerosis and their caregivers: Scoping review.

BACKGROUND: There are few studies evaluating the role of spirituality and the role of spiritually integrated interventions in people with amyotrophic lateral sclerosis (PALS) and their caregivers. OBJECTIVES: A scoping review was conducted to examine the nature and breadth of peer-reviewed literature on the role of spirituality, interventions integrating spirituality, and outcomes for PALS and their caregivers. METHODS: A literature review was performed, following the methods from the Joanna Briggs Institute Reviewers, based on all articles published between January 2006 and April 2022, identified in the CINAHL Complete, MEDLINE Complete, MedicLatina, Psychology and Behavioral Sciences Collection, and SPORTDiscus with full-text databases using key terms. Extracted data included research aims, study design, population and characteristics, theme description, and measures or type of intervention. RESULTS: A total of 18 articles were included in this study: 14 qualitative, 3 quantitative, and 1 protocol of a quantitative study. Eight studies were based in Europe. The search identified different main themes related to spirituality for caregivers and patients, 2 spiritual measure scales, and one intervention. However, many studies were limited in sample size, generalizability, and transferability and used less sophisticated research designs. SIGNIFICANCE OF THE RESULTS: This scoping review illustrates the importance given to spirituality by caregivers and PALS and reveals a very heterogeneous response. Thus, experimental studies in the area of spirituality are needed to systematically explore the impact of spiritual interventions, and the results of these studies could advance practice and policy by enhancing the quality of life for PALS and their caregivers.

Valorization of Brewery Waste through Polyhydroxyalkanoates Production Supported by a Metabolic Specialized Microbiome.

Raw brewers' spent grain (BSG), a by-product of beer production and produced at a large scale, presents a composition that has been shown to have potential as feedstock for several biological processes, such as polyhydroxyalkanoates (PHAs) production. Although the high interest in the PHA production from waste, the bioconversion of BSG into PHA using microbial mixed cultures (MMC) has not yet been explored. This study explored the feasibility to produce PHA from BSG through the enrichment of a mixed microbial culture in PHA-storing organisms. The increase in organic loading rate (OLR) was shown to have only a slight influence on the process performance, although a high selectivity in PHA-storing microorganisms accumulation was reached. The culture was enriched on various PHA-storing microorganisms, such as bacteria belonging to the Meganema, Carnobacterium, Leucobacter, and Paracocccus genera. The enrichment process led to specialization of the microbiome, but the high diversity in PHA-storing microorganisms could have contributed to the process stability and efficiency, allowing for achieving a maximum PHA content of 35.2 ± 5.5 wt.% (VSS basis) and a yield of 0.61 ± 0.09 CmmolPHA/CmmolVFA in the accumulation assays. Overall, the production of PHA from fermented BSG is a feasible process confirming the valorization potential of the feedstock through the production of added-value products.

COVID-19 collaborative screening: An action-research project for large scale contact tracing in Northern Portugal.

In late November 2020, when Europe reached the highest 14-day incidence of COVID-19 cases, the resource-intensive and time-consuming traditional contact tracing performed by Public Health was challenged. In this context, innovative approaches were necessary to guarantee a timely interruption of disease transmission. "COVID-19 Collaborative Screening" Project was developed as a faster solution, not only because the contact tracing process is simpler for the operator, but mainly because it is possible to quickly scale up the number of operators involved. It was designed to interrupt family and social transmission chains, in a partnership with the Local Public Health Services - allowing these services to dedicate to scenarios of more complex risk assessment, using the traditional contact tracing. To perform contact tracing, this method involves Public Servants, Armed Forces and Medical Dentists. The Project also promotes participatory citizenship, by delegating to the citizen the responsibility of registering his/hers contacts with high-risk exposure in an online form, in contrast to the traditional contact tracing method which is more health professional-dependent. Until the end of January 2021, the Project has trained eight teams, enrolling a total of 213 professionals, and was implemented in eight Health Regions (with an estimated population of 1,346,150 inhabitants). The Project was successful at facing the delays in case interview and contact tracing. The strategy implemented by ColabCOVID is assembled as a sustainable, reproducible and scalable platform and is ready to be re-implemented to face the emergence of more contagious variants, as well as an eventual forthcoming health threat.

Chronic toxicity of polystyrene nanoparticles in the marine mussel Mytilus galloprovincialis.

Nanoplastics (NP) (1-100 nm) are a growing global concern, and their adverse effects in marine organisms are still scarce. This study evaluated the effects of polystyrene nanoplastics (10 µg/L; 50 nm nPS) in the marine mussel Mytilus galloprovincialis after a 21 - day exposure. The hydrodynamic diameter and zeta potential of nPS were analysed, over time, in seawater and ultrapure water. A multibiomarker approach (genotoxicity (the comet assay) was assessed in mussel haemocytes, and the antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)), biotransformation enzyme (glutathione - S - transferase (GST)), and oxidative damage (LPO)) was assessed in gills and digestive glands to evaluate the toxicity of nPS towards mussels. In seawater, aggregation of nPS is favoured and consequently the hydrodynamic diameter increases. Genotoxicity was highly noticeable in mussels exposed to nPS, presenting a higher % tail DNA when compared to controls. Antioxidant enzymes are overwhelmed after nPS exposure, leading to oxidative damage in both tissues. Results showed that mussel tissues are incapable of dealing with the effects that this emerging stressor pursues towards the organism. The Integrated Biomarker Response index, used to summarise the biomarkers analysed into one index, shows that nPS toxicity towards mussels are both tissue and time dependent, being that gills are the tissue most compromised.

Survival predictors and outcomes of patients with recurrent and/or metastatic head and neck cancer treated with chemotherapy plus cetuximab as first-line therapy: A real-world retrospective study.

BACKGROUND: In patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) the estimated prognosis is usually poor. Patient-specific factors that affect prognosis should be considered when choosing therapy. We conducted a retrospective, single-center analysis in patients treated with first line platinum and antiEGFR antibody-containing regimen. The objective was to generate real-world data considering treatment outcomes and to identify predictors of survival. PATIENTS/METHODS: Clinical charts of patients treated with cetuximab and platinum-based chemotherapy (CT) for R/M HNSCC in first-line setting, between January-2009 and December-2018 were assessed. In these 103 patients, the prognostic value of site of the primary tumor, age at diagnosis, gender, Cetuximab induced skin toxicity and prior treatments were studied multivariately. To evaluate progression free survival (PFS) and overall survival (OS), Kaplan-Meier curves and the log-rank test were used. The Coxregression model was used to investigate the effect of these variables on OS. RESULTS: Longer OS was associated with oral cavity tumor location (p = 0,003), European Cooperative Oncology Group-Performance Status 0 (ECOG-PS) (p = 0,01), complete/partial response (p<0,0001), cetuximab monotherapy until disease progression or unacceptable toxicity (p = 0,037) and Grade 2-4 cetuximab induced skin toxicity (p = 0,037). The median follow-up period was 11,7 months. The mortality rate was 90,3% during this retrospective cohort assessment. The PFS was 7,1 months (95% confidence interval (CI), 5,6-8.6). The OS was 11,7 months (95%CI, 10,5-12,8). CONCLUSIONS: The present study demonstrates that the combination of cetuximab with platinum-based CT was effective in R/M HNSCC. Among patients with R/M HSCC treated with platinum plus cetuximab as first-line therapy, primary site, ECOG-PS, grade 2-4 cetuximab induced toxicity, and weekly cetuximab monotherapy have a marked impact on OS.

Case Report of a Rare Adrenocortical Oncocytoma Suspected to be an Adrenal Carcinoma.

An adrenal oncocytic neoplasm is an extremely rare tumour arising from the adrenal gland and it should be considered in the differential diagnosis of an adrenal incidentaloma, since it is frequently non-functioning. The suspicion for malignancy is high when an adrenal incidentaloma is >4 cm in size; however, adrenal oncocytomas are large, measuring an average of 8 cm, are round and encapsulated, and normally have a benign behaviour. We present a case of a 55-year-old male patient with dyslipidaemia, medicated with simvastatin. Upon complaints of abdominal pain, the general physician asked for an abdominal ultrasound that revealed an adrenal lesion, further characterized with a computed tomography scan, which showed an adrenal lesion measuring 49 × 64 × 56 mm and a calcification focus. The patient was referred to the general surgery and endocrinology department. The analytical study was negative for pheochromocytoma or Cushing's syndrome, which allowed surgery to be conducted, as is recommended. The aim of this case report is to contribute to the knowledge on adrenal oncocytomas, since there is scarce information based on singular experiences.

Vertical flow constructed wetland as a green solution for low biodegradable and high nitrogen wastewater: A case study of explosives industry.

The removal of nitrogen compounds from a pretreated explosives wastewater in vertical flow constructed wetland planted with Vetiveria zizanioides (0.24 m2 × 0.70 m), filled with light expanded clay aggregates (Leca®NR 10/20), was studied. Experiments under constant hydraulic load, 50 ± 4 L m-2 d-1 and 83 ± 5 L m-2 d-1 without and with flooding level (25%), respectively, were made at different ammonium (3-48 mg NH4+-N L-1), nitrate (56-160 mg NO3--N L-1) and nitrite (0.3-1.1 mg NO2--N L-1) concentrations. Results indicate that without flooding level (unsaturated) the removal efficiencies obtained were 30 ± 9, 7 ± 1 and 96 ± 2%, respectively to NH4+-N, NO3--N and NO2--N. When using flooding level and an external carbon source (C/N ratio from 1.3 ± 0.19 to 2.5 ± 0.20), the organic matter (COD) removal efficiencies were above 90%, 75% for NH4+-N and 55% to NO3--N. Increasing the C/N ratio from 2.9 ± 0.21 to 4 ± 0.22 did not contributed to upgrade the efficiencies of COD, NH4+-N and NO3--N removal. The denitrification process was occurred in aerobic conditions and nitrite production have ben occurred, probably due to the presence of aerobic conditions that inhibited partially denitrification.

Esophageal Gastrointestinal Stromal Tumor with Rare Intracranial Metastasis.

Introduction. Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors and constitute the largest group of nonepithelial digestive neoplasms. However, they do not represent more than 1% of primary digestive tumors. They commonly metastasize to the liver and peritoneum, but brain metastases are extremely rare. Clinical Case. A 76-year-old woman with a diagnosis of esophageal GIST with liver and lung metastases for 13 years, medicated with imatinib, is presented. She was brought to the emergency department after falling and due to changes in behavior and vertigo with 24 hours of evolution. On physical examination, she presented changes in behavior, dysarthria, dysmetria on the right, gait imbalance, and no motor or sensory deficits. On brain computed tomography and posteriorly on magnetic resonance, 2 lesions were observed, left frontal and right cerebellar, compatible with metastatic lesions. After contribution of neurosurgery, histology was obtained that confirmed the lesions were GIST metastases. Imatinib was maintained, and whole brain radiotherapy was performed. After 6 months, she died. Discussion. The rarity of GIST brain metastases is noteworthy, and because of that, there is not enough experience to be certain of the best treatment. Our patient lived for 13 years with excellent disease control with imatinib, but the fact that it does not cross the blood-brain barrier makes it not useful in preventing or treating brain lesions. New tyrosine kinase inhibitors that may cross the blood-brain barrier could be the answer to these cases.

Valorization of raw brewers' spent grain through the production of volatile fatty acids.

This work is focused on production of volatile fatty acids (VFA) through anaerobic digestion (AD) using raw (without pre-treatment) brewers' spent grain (BSG) as feedstock. VFAs are by-products from AD of organic wastes with wide potential industrial application in bioplastic production. A long term fed batch stirred-tank reactor was operated and the impact of three hydraulic retention times (HRT) and two organic loading rates (OLR) on VFA production was assessed. Results showed clearly that AD of raw BSG is possible without a pre-treatment step. The maximum volumetric VFA productivity of 91.3 ± 9.1 mgCODL-1 h-1 and VFA concentration of 24.9 ± 2.6 g L-1 were obtained for 16 days of HRT and 16 gTSinL-1d-1 of OLR. This is the highest value of VFA concentration so far reported for BSG. Propionic, acetic and butyric acids were the main VFAs produced. Community identification by FISH and its correlation with process parameters was performed by principal component analysis.

Metal-based engineered nanoparticles in the drinking water treatment systems: A critical review.

The emergence of nanotechnologically-enabled materials, compounds or products inevitably leads to engineered nanoparticles (ENPs) released into surface waters. ENPs have already been detected in wastewater streams, drinking water sources and even in tap water at concentrations in the ng/L and µg/L range, making the latter a potential route for humans. The presence of ENPs in raw waters raises concerns over the possibility that ENPs might pose a hazard to the quality and security of drinking water and whether drinking water treatment plants (DWTPs) are prepared to handle this problem. Therefore, it is essential to critically evaluate if ENPs can be effectively removed through water treatment processes to control environmental and human health risks associated with their release. This review includes a summary of the available information on production, presence, potential hazards to human health and environment, and release and behaviour of metal-based ENPs in surface waters and drinking water. In addition, the most extensively studied water treatment processes to remove metal-based ENPs, specifically conventional and advanced processes, are discussed and highlighted in detail. Furthermore, this work identifies the research gaps regarding ENPs removal in DWTPs and discusses future aspects of ENPs in water treatment.

Case Report: Sarcoidosis mimicking head and neck cancer progression.

Several case reports have been published describing the coexistence of sarcoidosis and cancer. In the literature, simultaneous occurrence of head and neck cancer and sarcoidosis is rarely reported. In this paper we present a case of a 42-year-old man with squamous cell carcinoma of the oral cavity, locally advanced, which after surgery and adjuvant radiotherapy developed local persistence and progression in the mediastinal lymph nodes. The patient was submitted to chemotherapy and after a complete response, new suspicious mediastinal and hilar lymph nodes appeared in the thoracic computed tomography (CT) scan and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan. To enroll the patient in a clinical trial, the patient underwent mediastinoscopy with mediastinal lymph node dissection. The histopathological findings were consistent with sarcoidosis and no metastatic disease was found. Since the patient had no symptoms and the levels of serum angiotensin converting enzyme were normal, no further pharmacological intervention was done. After 4 years of follow up the patient remains without evidence of cancer. This case shows that although imagological techniques (CT and FDG-PET scan) are extensively used to assess the tumor response, false-positive cases can occur. Whenever it is possible a biopsy of the suspected metastatic site should always be performed.

Effects of Copper Oxide Nanoparticles on Tissue Accumulation and Antioxidant Enzymes of Galleria mellonella L.

Effects of copper oxide nanoparticles (CuO NPs) were investigated in the midgut and fat body of Galleria mellonella. Fourth instar larvae were exposed to 10 µg Cu/L of CuO until becoming last instar larvae, and catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-s-transferase (GST) and acetylcholinesterase (AChE) and metal accumulation were evaluated. Copper accumulation was observed in midgut and fat body tissues of G. mellonella larvae exposed to CuO NPs. CuO NPs increased CAT activities in midgut and fat body, while SOD activities were decreased. CuO NPs exhibited significant increases in GST activity in fat body, while no significant differences were observed in the midgut of G. mellonella larvae. AChE activity significantly decreased in the midgut of G. mellonella whereas there is no significant effect on fat body in CuO NPs exposed larvae. In overall, these findings demonstrate that tissue accumulation and oxidative stress that is countered by antioxidant enzymes occur when G. mellonella larvae exposed to environmental concentration of CuO nanoparticles.

Effect of chronic methylphenidate treatment on hippocampal neurovascular unit and memory performance in late adolescent rats.

Methylphenidate (MPH) is the classic treatment for attention deficit hyperactivity disorder (ADHD) among children and adults. Despite its beneficial effects, non-medical use of MPH is nowadays a problem with high impact on society. Thus, our goal was to uncover the neurovascular and cognitive effects of MPH chronic use during a critical period of development in control conditions. For that, male Wistar Kyoto rats were treated with MPH (1.5 or 5 mg/kg/day at weekdays, per os) from P28 to P55. We concluded that the higher dose of MPH caused hippocampal blood-brain barrier (BBB) hyperpermeability by vesicular transport (transcytosis) concomitantly with the presence of peripheral immune cells in the brain parenchyma. These observations were confirmed by in vitro studies, in which the knockdown of caveolin-1 in human brain endothelial cells prevented the increased permeability and leukocytes transmigration triggered by MPH (100 µM, 24 h). Furthermore, MPH led to astrocytic atrophy and to a decrease in the levels of several synaptic proteins and impairment of AKT/CREB signaling, together with working memory deficit assessed in the Y-maze test. On the contrary, we verified that the lower dose of MPH (1.5 mg/kg/day) increased astrocytic processes and upregulated several neuronal proteins as well as signaling pathways involved in synaptic plasticity culminating in working memory improvement. In conclusion, the present study reveals that a lower dose of MPH in normal rats improves memory performance being associated with the modulation of astrocytic morphology and synaptic machinery. However, a higher dose of MPH leads to BBB dysfunction and memory impairment.

Antisense STAT3 inhibitor decreases viability of myelodysplastic and leukemic stem cells.

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are associated with disease-initiating stem cells that are not eliminated by conventional therapies. Transcriptomic analysis of stem and progenitor populations in MDS and AML demonstrated overexpression of STAT3 that was validated in an independent cohort. STAT3 overexpression was predictive of a shorter survival and worse clinical features in a large MDS cohort. High STAT3 expression signature in MDS CD34+ cells was similar to known preleukemic gene signatures. Functionally, STAT3 inhibition by a clinical, antisense oligonucleotide, AZD9150, led to reduced viability and increased apoptosis in leukemic cell lines. AZD9150 was rapidly incorporated by primary MDS/AML stem and progenitor cells and led to increased hematopoietic differentiation. STAT3 knockdown also impaired leukemic growth in vivo and led to decreased expression of MCL1 and other oncogenic genes in malignant cells. These studies demonstrate that STAT3 is an adverse prognostic factor in MDS/AML and provide a preclinical rationale for studies using AZD9150 in these diseases.