Publications by authors named "Colin Wu"
Immune aplastic anemia (iAA) frequently results in transfusion dependence for platelets and packed red blood cells (PRBC), increasing the risk for complications. The most common immune mediated cause for platelet transfusion refractoriness is due to alloimmunization with human leukocyte antigen (HLA) antibody (Ab) to non-self class I antigens (Ag). The clinical impact of the HLA alloimmunization has not been well studied in patients with iAA.
View Article and Find Full Text PDF18S nonfunctional rRNA decay (NRD) detects and eliminates translationally nonfunctional 18S rRNA. Although this process is critical for ribosome quality control, the mechanisms underlying nonfunctional 18S rRNA turnover remain elusive, particularly in mammals. Here, we show that mammalian 18S NRD initiates through the integrated stress response (ISR) via GCN2.
View Article and Find Full Text PDFObjectives: Heart failure (HF) and atrial fibrillation (AF) frequently coexist, exacerbate each other and are associated with increased morbidity and mortality rates. However, no previous study has specifically calculated the risk of experiencing either event following the occurrence of the other and also considered competing risks. The aim of this study was to examine the bidirectional relationship of AF and HF in a multiethnic population, taking competing risks into account.
View Article and Find Full Text PDFThe concept that ribosomes are sensors of translational distress has sparked significant interest, although much of the research has been conducted in vitro. A new study by Vind et al. provides in vivo evidence that the ribotoxic stress response (RSR) serves as the first line of defense against ultraviolet (UV) radiation.
View Article and Find Full Text PDFBackground: Statistical shape atlases have been used in large-cohort studies to investigate relationships between heart shape and risk factors. The generalisability of these relationships between cohorts is unknown. The aims of this study were to compare left ventricular (LV) shapes in patients with differing cardiovascular risk factor profiles from two cohorts and to investigate whether LV shape scores generated with respect to a reference cohort can be directly used to study shape differences in another cohort.
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- Psoriasis is linked to higher cardiovascular risk, but how this connection works is not well understood, especially regarding systemic inflammation and skin disease severity.
- The study aims to determine if systemic inflammation acts as a mediator between the severity of psoriasis and cardiovascular disease using data from two patient cohorts in the U.S. and Sweden.
- Key outcomes analyzed include coronary artery health using advanced imaging and rates of hospitalization or death due to cardiovascular issues, with a focus on the roles of psoriasis severity and inflammation markers.
Article Synopsis
- Ribosomal function is enhanced by trans-acting factors and ribosomal elements, with phosphorylation playing a key regulatory role.
- The ribosomal P-stalk, which consists of five phosphorylated C-terminal domains, activates translational GTPases and connects to the Gcn2 kinase within the integrated stress response (ISR) pathway.
- Unlike most ribosomal proteins, P-stalk proteins remain in a constantly phosphorylated state, promoting optimal translation efficiency and allowing flexible interaction with various protein partners.
Article Synopsis
- - Allogeneic hematopoietic cell transplantation (HCT) with HLA-matched siblings is a leading treatment option for sickle cell disease (SCD) but carries associated risks, indicating a need for better risk assessment.
- - A machine learning (ML) method was used to analyze both clinical data and imaging results, identifying red cell distribution width and kidney damage as key risk factors for patients undergoing HCT.
- - This ML algorithm could help in discovering risk factors in future studies, building on previous methods that predicted mortality in SCD patients.
Article Synopsis
- * The study analyzed telemedicine encounters from January 2020 to December 2021, focusing on differences in visit types (video vs. audio-only) based on patient demographics.
- * Results indicated that older age, non-White race, lack of private insurance, and higher social deprivation were linked to increased likelihood of audio-only visits, highlighting the need to address these disparities.
Telomere biology disorders (TBDs), caused by pathogenic germ line variants in telomere-related genes, present with multiorgan disease and a predisposition to cancer. Clonal hematopoiesis (CH) as a marker of cancer development and survival in TBDs is poorly understood. Here, we characterized the clonal landscape of a large cohort of 207 patients with TBD with a broad range of age and phenotype.
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- The study focused on cardiovascular health among Chinese American immigrants in the MESA cohort, analyzing data from 746 participants over a median follow-up of 17.8 years.
- Results indicated that longer residence in the U.S. is linked to a greater risk of cardiovascular disease death, while geographical differences showed varying survival probabilities between immigrants in Los Angeles and Chicago.
- Key risk factors identified included elevated levels of certain biomarkers and cardiac imaging results, with no significant impact from the time of immigration on cardiovascular outcomes.
Article Synopsis
- The study explores the process of 18S nonfunctional rRNA decay (NRD), which is crucial for maintaining ribosome quality by removing nonfunctional rRNA in mammals.
- It reveals that NRD operates through the integrated stress response (ISR) involving GCN2 and RNF10-mediated ubiquitination of ribosomal proteins, linking stress responses to ribosome function.
- The research shows that nonfunctional 18S rRNA can cause translational arrest, and the ISR works to prevent translation initiation failures, highlighting a feedback system that monitors ribosome functionality during protein synthesis.
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- The study investigates how imbalances in left and right ventricular stroke volumes, measured through cardiac MRI, affect clinical outcomes in asymptomatic individuals without cardiovascular disease.
- It analyzed data from over 4,000 participants, finding that those with a greater difference in stroke volumes had a significantly higher risk of mortality, heart failure, and atrial fibrillation compared to those with balanced volumes.
- Interestingly, while a decreased differential stroke volume initially seemed to increase heart failure risk, this association disappeared when factoring in baseline left ventricular function, indicating its significance in the findings.
Article Synopsis
- A study was conducted to evaluate the safety of immunosuppressive therapy (IST) using anti-thymocyte globulin (ATG) and cyclosporine (CSA) in older patients with severe aplastic anemia (SAA), comparing outcomes with younger patients.
- Although older patients experienced similar rates of serious adverse events (SAEs) and hospital stays as younger ones, they showed a higher incidence of cardiac events related to IST, though none were fatal.
- Despite older patients facing worse overall survival rates and more relapse or clonal evolution, those who responded well to IST had survival rates comparable to younger patients, suggesting that disease factors rather than treatment complications primarily drive the outcomes.
Background: Recent evidence has shown that reproductive factors are associated with an increased risk of heart failure with preserved ejection fraction in women. However, the pathogenic pathways underlying this relationship are unclear. Subclinical myocardial fibrosis has been found to be a common pathway in a large proportion of patients with heart failure with preserved ejection fraction.
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- A study investigated how changes in left atrial (LA) function may indicate the risk of developing heart failure (HF) in a diverse group of nearly 2,500 participants over an average of 9 years.
- The researchers found that a decrease in peak LA strain is closely linked to heart failure with preserved ejection fraction (HFpEF), while a decrease in indexed LA volume is linked to heart failure with reduced ejection fraction (HFrEF).
- Both LA function metrics significantly improved the prediction models for these conditions, highlighting their potential as early indicators of heart failure in subjects with early signs of cardiovascular disease.
Machine Learning of Cardiac Anatomy and the Risk of New-Onset Atrial Fibrillation After TAVR.
JACC Clin Electrophysiol
August 2024
Article Synopsis
- New-onset atrial fibrillation (NOAF) occurs in 5% to 15% of patients after transcatheter aortic valve replacement (TAVR), highlighting the need for better predictive tools using cardiac imaging.
- This study compared traditional echocardiographic measurements and machine learning-derived cardiac computed tomography (cCT) data to identify risk factors for NOAF among 1,385 TAVR patients.
- Key findings revealed that larger left atrial volume index and specific body measurements significantly increased the likelihood of developing NOAF, with certain thresholds identified for optimal risk assessment.
Article Synopsis
- Cardiovascular disease is linked to frailty in individuals, but the exact reasons for this connection are not fully understood; the study aims to explore this relationship through the MESA study.
- A total of 3,045 participants underwent heart imaging procedures and completed a walking test and questionnaires to assess their frailty status, with analysis done on various cardiovascular health indicators.
- Results indicated that older age, female gender, and specific cardiac conditions (like left ventricular remodeling and myocardial fibrosis) were significantly associated with an increased likelihood of being frail and performing poorly on the walking test.
Article Synopsis
- The study investigates the links between vascular health and the development of dementia in a diverse group of participants with cardiovascular issues.
- Using a large database of 6806 individuals, researchers analyzed various health metrics and found 326 cases of dementia over 14 years.
- Key factors influencing dementia risk included coronary artery health, inflammation, and lifestyle choices, highlighting that age is not the only significant determinant of cognitive decline.
Article Synopsis
- Biolayer interferometry (BLI) is a technique for real-time observation of how proteins interact with G4 DNA, specifically using TDP43 and a G4 DNA made from (GGGGCC).
- The article highlights key considerations for designing experiments, including precautions against nonspecific binding, to ensure accurate results.
- It serves as a comprehensive guide for researchers, covering required materials, procedures, and data analysis to help them effectively use BLI in their studies of protein-G4 interactions.
Article Synopsis
- Diamond-Blackfan anaemia (DBA) is a rare genetic condition that leads to bone marrow failure, primarily due to problems with ribosomal function, resulting in issues with red blood cell (RBC) production and excess reactive iron.
- A pilot study tested the effectiveness of eltrombopag, a drug that acts as an iron chelator, in improving RBC production among DBA patients, with some positive results but limited overall response rates.
- While eltrombopag showed promise in increasing hemoglobin levels and reducing blood transfusion needs in one patient, complications like thrombocytosis led to dose adjustments or discontinuation in a significant portion of participants, highlighting challenges in treatment and the need for further research.
Article Synopsis
- VEXAS syndrome is an autoinflammatory disorder linked to mutations in the UBA1 gene, with thrombosis being a significant clinical feature affecting 49% of patients.
- The majority of thrombosis cases were venous thromboembolism (VTE), often occurring unprovoked, recurrent, and sometimes even in patients on anticoagulants.
- Despite the high incidence of VTE, overall patient survival was good, with an 88% survival rate over nearly 5 years, indicating that thrombosis does not significantly impact long-term survival in these patients.
Article Synopsis
- * Out of 28 patients who received GT, 50% survived to the last follow-up, and 64% were discharged from the hospital, with those responding well to treatment showing significantly better overall survival rates.
- * While some patients developed alloimmunization during transfusions and overall survival remains low, GT may provide critical support for patients awaiting hematopoietic stem cell transplants (HSCT).
Article Synopsis
- The study examines the link between lipoprotein(a) (Lp[a]) levels and myocardial fibrosis (IMF) as well as cardiac remodeling using advanced imaging techniques in a diverse group of participants from the MESA cohort.
- Results showed that higher Lp(a) levels were significantly associated with increased measures of myocardial fibrosis and a greater risk of clinically significant IMF, as measured by the extracellular volume fraction and native T1 times.
- The findings suggest that elevated Lp(a) levels not only indicate higher prevalence of myocardial scarring but also correlate with left atrial enlargement and dysfunction, highlighting Lp(a) as a potential marker for adverse cardiovascular outcomes.
Article Synopsis
- Traditional risk scores for recurrent atrial fibrillation (AF) after catheter ablation lack accuracy, prompting the exploration of cardiac imaging and deep learning to enhance prediction.
- The study analyzed 653 patients undergoing AF ablation, identifying five key predictors for late recurrence, with left atrial volume index (LAVi) and early recurrence being the most significant factors.
- Findings suggest that higher LAVi levels and the occurrence of early recurrence notably increase the risk of late recurrence, highlighting the utility of machine learning in AF risk assessment.