Inhaled alpha-1 antitrypsin (AAT) restores lower respiratory tract protease-antiprotease homoeostasis and reduces inflammation in AAT-deficient individuals: a randomised phase 2 study.

Background: Alpha-1 antitrypsin (AAT)-deficient individuals have a greater risk for developing COPD than individuals with normal AAT levels.

Methods: This was a double-blind, randomised, parallel group, placebo-controlled trial to examine the safety and tolerability of "Kamada-AAT for Inhalation" (inhaled AAT) in subjects with AAT deficiency, and to explore its effect on AAT and biomarkers in the lung epithelial lining fluid (ELF). 36 patients with severe AAT deficiency were randomised 2:1 to receive 80 mg or 160 mg inhaled AAT or placebo once daily for 12 weeks.

The Evolution of Next-Generation Sequencing Technologies.

The genetic information that dictates the structure and function of all life forms is encoded in the DNA. In 1953, Watson and Crick first presented the double helical structure of a DNA molecule. Their findings unearthed the desire to elucidate the exact composition and sequence of DNA molecules.

Healthcare Access Domains and Treatment as Mediators of Ovarian Cancer Racial Disparities in Survival: A Structural Equation Modeling Analysis in SEER-Medicare.

Racial differences in healthcare access (HCA) may contribute to disparities in ovarian cancer (OC) survival. We used structural equation models (SEM) to examine associations between race and HCA domains (affordability, availability, accessibility) in relation to overall and OC-specific mortality. Non-Hispanic (NH)-Black and non-Black (Hispanic, NH-White) women diagnosed with OC in 2008-2015 were identified from SEER-Medicare.

Enhancing clinical genomic accuracy with panelGC: a novel metric and tool for quantifying and monitoring GC biases in hybridization capture panel sequencing.

Accurate assessment of fragment abundance within a genome is crucial in clinical genomics applications such as the analysis of copy number variation (CNV). However, this task is often hindered by biased coverage in regions with varying guanine-cytosine (GC) content. These biases are particularly exacerbated in hybridization capture sequencing due to GC effects on probe hybridization and polymerase chain reaction (PCR) amplification efficiency.

COVID-19 and Rates of Cancer Diagnosis in the US.

Importance: US cancer diagnoses were substantially lower than expected during the COVID-19 pandemic in 2020. A national study on the extent to which rates recovered in 2021 has not yet been conducted.

Objective: To examine observed vs expected cancer rate trends for January 2020 to December 2021.

Frailty in patients with ovarian cancer and the role of healthcare access, race, and ethnicity.

Objective: Ovarian cancer has poor 5-year survival, particularly among non-Hispanic (NH) Black patients. Efforts to identify patients at high-risk of functional limitations and frailty may improve outcomes. In this study, we examined how healthcare access (HCA) and race/ethnicity relate to frailty among patients with ovarian cancer.

Unbalanced MYC break-apart FISH patterns indicate the presence of a MYC rearrangement in HGBCL-DH-BCL2.

Fluorescence in situ hybridization (FISH) using break-apart probes is recommended for identifying high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-DH-BCL2). Unbalanced MYC break-apart patterns, in which the red or green signal is lost, are commonly reported as an equivocal result by clinical laboratories. In a cohort of 297 HGBCL-DH-BCL2, 13% of tumors had unbalanced MYC break-apart patterns with loss of red (LR; 2%) or loss of green (LG; 11%) signal.

NCI SEER-Linked Virtual Tissue Repository Pilot.

Background: The Surveillance, Epidemiology, and End Results (SEER) Program with the National Cancer Institute tested whether population-based cancer registries can serve as honest brokers to acquire tissue and data in the SEER-Linked Virtual Tissue Repository (VTR) Pilot.

Methods: We collected formalin-fixed, paraffin-embedded tissue and clinical data from patients with pancreatic ductal adenocarcinoma (PDAC) and breast cancer (BC) for two studies comparing cancer cases with highly unusual survival (≥5 years for PDAC and ≤30 months for BC) to pair-matched controls with usual survival (≤2 years for PDAC and ≥5 years for BC). Success was defined as the ability for registries to acquire tissue and data on cancer cases with highly unusual outcomes.

Scrotal Cancer Incidence Rates and Trends-United States, 1999-2020.

Objective: To examine population-level scrotal cancer incidence rates and trends among adult men in the United States.

Methods: Data from the United States Cancer Statistics, covering approximately 96% of the United States population, were analyzed to calculate age-standardized incidence rates of scrotal cancer among men aged 18 years and older from 1999 to 2020. Trends in incidence rates were evaluated by age, race and ethnicity, Census region, and histology using joinpoint regression.

N-lysine acetylation of the histone-like protein HBsu influences antibiotic survival and persistence in .

N-lysine acetylation is recognized as a prevalent post-translational modification (PTM) that regulates proteins across all three domains of life. In , the histone-like protein HBsu is acetylated at seven sites, which regulates DNA compaction and the process of sporulation. In Mycobacteria, DNA compaction is a survival strategy in response antibiotic exposure.

Feasibility of Remote Blood Pressure Monitoring for Detection and Management of Maternal Hypertension in a predominantly Black, Rural and Medicaid Population in Mississippi.

Remote patient monitoring (RPM) has potential in hypertension management, but limited studies have focused on maternal hypertension, especially among vulnerable populations. The objective of this study was to integrate RPM into perinatal care for pregnant patients at elevated risk of hypertensive disorders to show feasibility, acceptability, and safety. A prospective pilot cohort study was conducted at the University of Mississippi Medical Center 2021-2023.

A narrative review of non-infected painful total shoulder arthroplasty: evaluation and treatment.

Background And Objective: The prevalence of shoulder arthroplasty has increased significantly over the past two decades outpacing both total hip and total knee arthroplasty. Total shoulder arthroplasty (TSA) has been shown to significantly improve function and pain in most patients, however, complications after shoulder arthroplasty have been reported to be greater than 10% in anatomic shoulder arthroplasty and 10-47% in reverse shoulder arthroplasty leading to a painful shoulder. As the number of performed primary shoulder arthroplasty increases, the incidence of painful total shoulders and the need for revision shoulder arthroplasty will see a similar trend.

Population-level incidence of human papillomavirus-positive oropharyngeal, cervical, and anal cancers, by smoking status.

We estimated the population-level incidence of human papillomavirus (HPV)-positive oropharyngeal, cervical, and anal cancers by smoking status. We combined HPV DNA genotyping data from the Centers for Disease Control and Prevention's Cancer Registry Sentinel Surveillance System with data from the Kentucky Cancer Registry and Behavioral Risk Factor Surveillance System across smoking status. During 2004-2005 and 2014-2015 in Kentucky, most cases of oropharyngeal (63.

MtDNA deletions and aging.

Aging is the major risk factor in most of the leading causes of mortality worldwide, yet its fundamental causes mostly remain unclear. One of the clear hallmarks of aging is mitochondrial dysfunction. Mitochondria are best known for their roles in cellular energy generation, but they are also critical biosynthetic and signaling organelles.

Dietary Changes of Youth during the COVID-19 Pandemic: A Systematic Review.

Background: The coronavirus disease 2019 (COVID-19) pandemic has taken the lives of millions and disrupted countless more worldwide. Simply living through the pandemic has had drastic effects on the health of citizens. Diet, an important aspect of health, has been uniquely affected by the pandemic, although these changes have not been sufficiently studied among youth.

Undiagnosed Cancer Cases in the US During the First 10 Months of the COVID-19 Pandemic.

Importance: The COVID-19 pandemic disrupted the normal course of cancer screening and detection in the US. A nationwide analysis of the extent of this disruption using cancer registry data has not been conducted.

Objective: To assess the observed and expected cancer rate trends for March through December 2020 using data from all 50 US states and the District of Columbia.

Myocardin regulates fibronectin expression and secretion from human pleural mesothelial cells.

During the progression of pleural fibrosis, pleural mesothelial cells (PMCs) undergo a phenotype switching process known as mesothelial-mesenchymal transition (MesoMT). During MesoMT, transformed PMCs become myofibroblasts that produce increased extracellular matrix (ECM) proteins, including collagen and fibronectin (FN1) that is critical to develop fibrosis. Here, we studied the mechanism that regulates FN1 expression in myofibroblasts derived from human pleural mesothelial cells (HPMCs).

Role of ZIP kinase in development of myofibroblast differentiation from HPMCs.

During the development of pleural fibrosis, pleural mesothelial cells (PMCs) undergo phenotypic switching from differentiated mesothelial cells to mesenchymal cells (MesoMT). Here, we investigated how external stimuli such as TGF-β induce HPMC-derived myofibroblast differentiation to facilitate the development of pleural fibrosis. TGF-β significantly increased di-phosphorylation but not mono-phosphorylation of myosin II regulatory light chain (RLC) in HPMCs.

Geographic and temporal trends in pediatric and young adult brain tumors in Kentucky, 1995-2019.

Introduction: Pediatric and young adult brain tumors (PYBT) account for a large share of cancer-related morbidity and mortality among children in the United States, but their etiology is not well understood. Previous research suggests the Appalachian region of Kentucky has high rates of PYBT. This study explored PYBT incidence over 25 years in Kentucky to identify geographic and temporal trends and generate hypotheses for future research.

Upscaling the remediation of acidic landscapes - the coastal floodplain prioritisation method.

Over 24 million hectares of the world's coastal floodplains are underlain by acid sulfate soils (ASS). Drainage of these sediments has led to widespread environmental degradation, raising serious health concerns. To date, onsite rehabilitation has been complicated by differing stakeholder priorities, with resources often allocated to sites with more vocal proponents rather than those exposed to more significant environmental impacts.

DOCK2 Promotes Atherosclerosis by Mediating the Endothelial Cell Inflammatory Response.

The pathology of atherosclerosis, a leading cause of mortality in patients with cardiovascular disease, involves inflammatory phenotypic changes in vascular endothelial cells. This study explored the role of the dedicator of cytokinesis (DOCK)-2 protein in atherosclerosis. Mice with deficiencies in low-density lipoprotein receptor and Dock2 (LdlrDock2) and controls (Ldlr) were fed a high-fat diet (HFD) to induce atherosclerosis.