Prevalence and Clinical Correlates of Radiologically Detected Coronary Artery Disease in COPD: A Cross-Sectional Observational Study.

Rationale: Unrecognised coronary artery disease (CAD) may contribute to adverse outcomes in chronic obstructive pulmonary disease (COPD). Improved identification of at-risk groups could inform better preventative care. We aimed to evaluate the burden and relationships of radiologically detectable CAD in COPD, establish frequency of occult disease, and examine potential cardiovascular screening methods.

Long-Term Outcomes After Severe Acute Brain Injury Requiring Mechanical Ventilation: Recovery Trajectories Among Patients and Mental Health Symptoms of Their Surrogate Decision Makers.

Background: Long-term outcomes of patients with severe acute brain injury (SABI) and their surrogate decision makers (SDMs) are insufficiently explored.

Methods: We conducted a prospective, single-center, observational study of patients with SABI who required mechanical ventilation between September and November 2021. Two telephonic interviews were conducted at 6-12 months and 18-24 months post SABI.

Adult risk groups for vaccine preventable respiratory infections: an overview of the UK environment.

Introduction: Vaccine-preventable respiratory infections (VPRI) including those caused by Streptococcus pneumoniae, influenza, respiratory syncytial virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose substantial challenges to health and social care systems. In the UK, routine adult respiratory vaccination programs are in place. The objective of this article is to review the current evidence on the impact of four seasonal VPRIs in adults risk group definitions and to explore the strengths and limitations of current recommendations, and to identify evidence gaps for further research.

Healthy Drinks, Healthy Teeth - Ciunerkaq Tanqigtuq (The Future is Bright): A study protocol for a community-based, non-randomized sociobehavioral trial to reduce added sugar intake in Alaska Native Yup'ik children in the Yukon-Kuskokwim Delta.

Background: This study protocol describes a community-based intervention that will seek to reduce added sugar intake in Yup'ik Alaska Native children by targeting reductions in sugar-sweetened fruit drinks.

Methods: A two-group non-randomized design will be used to evaluate the intervention in three Yup'ik communities in Alaska focusing on children age 1 to less than age 12 years with a minimum enrollment target of 192 children. Families in the intervention arm will participate in a program consisting of five sessions plus four brief check-ins, all delivered by a Yup'ik Community Health Worker.

The E592K variant of SF3B1 creates unique RNA missplicing and associates with high-risk MDS without ring sideroblasts.

Among the most common genetic alterations in myelodysplastic syndromes (MDS) are mutations in the spliceosome gene SF3B1. Such mutations induce specific RNA missplicing events, directly promote ring sideroblast (RS) formation, and generally associate with a more favorable prognosis. However, not all SF3B1 mutations are the same, and little is known about how distinct hotspots influence disease.

Interferon-sensitized hematopoietic progenitors dynamically alter organismal immunity.

Inflammation has enduring impacts on organismal immunity. However, the precise mechanisms by which tissue-restricted inflammation conditions systemic responses are poorly understood. Here, we leveraged a highly compartmentalized model of skin inflammation and identified a surprising type I interferon (IFN)- mediated activation of hematopoietic stem/progenitor cells (HSPCs) that results in profound changes to systemic host responses.

Respiratory Syncytial Virus-related Community Chronic Obstructive Pulmonary Disease Exacerbations and Novel Diagnostics: A Binational Prospective Cohort Study.

Respiratory syncytial virus (RSV) is a common global respiratory virus that is increasingly recognized as a major pathogen in frail older adults and as a cause of chronic obstructive pulmonary disease (COPD) exacerbations. There is no single test for RSV in adults that has acceptable diagnostic accuracy. Trials of RSV vaccines have recently shown excellent safety and efficacy against RSV in older adults; defining the frequency of RSV-related community infections and COPD exacerbations is important for vaccine deployment decisions.

Using an electronic diary and wristband accelerometer to detect exacerbations and activity levels in COPD: a feasibility study.

Background: Early and accurate identification of acute exacerbations of COPD may lead to earlier treatment and prevent hospital admission. Electronic diaries have been developed for symptom monitoring and accelerometers to monitor activity. However, it is unclear whether this technology is usable in the COPD population.

Therapeutic targeting of EP300/CBP by bromodomain inhibition in hematologic malignancies.

CCS1477 (inobrodib) is a potent, selective EP300/CBP bromodomain inhibitor which induces cell-cycle arrest and differentiation in hematologic malignancy model systems. In myeloid leukemia cells, it promotes rapid eviction of EP300/CBP from an enhancer subset marked by strong MYB occupancy and high H3K27 acetylation, with downregulation of the subordinate oncogenic network and redistribution to sites close to differentiation genes. In myeloma cells, CCS1477 induces eviction of EP300/CBP from FGFR3, the target of the common (4; 14) translocation, with redistribution away from IRF4-occupied sites to TCF3/E2A-occupied sites.

Differentiation block in acute myeloid leukemia regulated by intronic sequences of .

Iroquois transcription factor gene is highly expressed in 20-30% of acute myeloid leukemia (AML) and contributes to the pathognomonic differentiation block. Intron 8 sequences ∼220kB downstream of exhibit histone acetylation, DNA methylation, and contacts with the promoter, which correlate with expression. Deletion of these intronic elements confirms a role in positively regulating .

Pathogen and human NDPK-proteins promote AML cell survival via monocyte NLRP3-inflammasome activation.

A history of infection has been linked with increased risk of acute myeloid leukaemia (AML) and related myelodysplastic syndromes (MDS). Furthermore, AML and MDS patients suffer frequent infections because of disease-related impaired immunity. However, the role of infections in the development and progression of AML and MDS remains poorly understood.

Loss of TET2 in human hematopoietic stem cells alters the development and function of neutrophils.

Somatic mutations commonly occur in hematopoietic stem cells (HSCs). Some mutant clones outgrow through clonal hematopoiesis (CH) and produce mutated immune progenies shaping host immunity. Individuals with CH are asymptomatic but have an increased risk of developing leukemia, cardiovascular and pulmonary inflammatory diseases, and severe infections.

The diverse roles of macrophages in metabolic inflammation and its resolution.

Macrophages are one of the most functionally diverse immune cells, indispensable to maintain tissue integrity and metabolic health. Macrophages perform a myriad of functions ranging from promoting inflammation, through inflammation resolution to restoring and maintaining tissue homeostasis. Metabolic diseases encompass a growing list of diseases which develop from a mix of genetics and environmental cues leading to metabolic dysregulation and subsequent inflammation.