Accelerating Genome- and Phenome-Wide Association Studies using GPUs - A case study using data from the Million Veteran Program.

The expansion of biobanks has significantly propelled genomic discoveries yet the sheer scale of data within these repositories poses formidable computational hurdles, particularly in handling extensive matrix operations required by prevailing statistical frameworks. In this work, we introduce computational optimizations to the SAIGE (Scalable and Accurate Implementation of Generalized Mixed Model) algorithm, notably employing a GPU-based distributed computing approach to tackle these challenges. We applied these optimizations to conduct a large-scale genome-wide association study (GWAS) across 2,068 phenotypes derived from electronic health records of 635,969 diverse participants from the Veterans Affairs (VA) Million Veteran Program (MVP).

Diversity and Scale: Genetic Architecture of 2,068 Traits in the VA Million Veteran Program.

Genome-wide association studies (GWAS) have underrepresented individuals from non-European populations, impeding progress in characterizing the genetic architecture and consequences of health and disease traits. To address this, we present a population-stratified phenome-wide GWAS followed by a multi-population meta-analysis for 2,068 traits derived from electronic health records of 635,969 participants in the Million Veteran Program (MVP), a longitudinal cohort study of diverse U.S.

Effect of Ultrasonic Shot Peening and Laser Shock Peening on the Microstructure and Microhardness of IN738LC Alloys.

IN738LC is a conventional-cast Ni-based superalloy intended for power generation and aerospace applications. Typically, ultrasonic shot peening (USP) and laser shock peening (LSP) are utilized to enhance cracking, creep, and fatigue resistance. In this study, the optimal process parameters for USP and LSP were established by observing the microstructure and measuring the microhardness of the near-surface region of IN738LC alloys.

The Busan Regional CardioCerebroVascular Center Project's Experience Over a Decade in the Treatment of ST-segment Elevation Myocardial Infarction.

Objectives: The Regional CardioCerebroVascular Center (RCCVC) project was initiated to improve clinical outcomes for patients with acute myocardial infarction or stroke in non-capital areas of Korea. The purpose of this study was to evaluate the outcomes and issues identified by the Busan RCCVC project in the treatment of ST-segment elevation myocardial infarction (STEMI).

Methods: Among the patients who were registered in the Korean Registry of Acute Myocardial Infarction for the RCCVC project between 2007 and 2019, those who underwent percutaneous coronary intervention (PCI) for STEMI at the Busan RCCVC were selected, and their medical data were compared with a historical cohort.

ω-3 fatty acid-enriched parenteral nutrition shortens hospital stay in acute variceal bleeding cirrhotic patients.

Acute variceal bleeding, a crucial complication of liver cirrhosis requires high energy expenditures but gastrointestinal bleeding limits enteral feeding in the acute stage. We investigated the safety and efficacy of ω-3 fatty acid-enriched parenteral nutrition in acute variceal bleeding patients.In this retrospective study, a total of 208 cirrhotic patients with acute variceal bleeding who underwent parenteral nutrition in the absence of enteral nutrition were enrolled.

NSrp70 is a lymphocyte-essential splicing factor that controls thymocyte development.

Alternative pre-mRNA splicing is a critical step to generate multiple transcripts, thereby dramatically enlarging the proteomic diversity. Thus, a common feature of most alternative splicing factor knockout models is lethality. However, little is known about lineage-specific alternative splicing regulators in a physiological setting.

Modeling Sialidosis with Neural Precursor Cells Derived from Patient-Derived Induced Pluripotent Stem Cells.

Sialidosis, caused by a genetic deficiency of the lysosomal sialidase gene (), is a systemic disease involving various tissues and organs, including the nervous system. Understanding the neurological dysfunction and pathology associated with sialidosis remains a challenge, partially due to the lack of a human model system. In this study, we have generated two types of induced pluripotent stem cells (iPSCs) with sialidosis-specific and mutations (sialidosis-iPSCs), and further differentiated them into neural precursor cells (iNPCs).

Local Stabilization of Hypoxia-Inducible Factor-1α Controls Intestinal Inflammation Enhanced Gut Barrier Function and Immune Regulation.

Intestinal epithelial cells are adapted in mucosal hypoxia and hypoxia-inducible factors in these cells can fortify barrier integrity to support mucosal tissue healing. Here we investigated whether hypoxia-related pathways could be proposed as potential therapeutic targets for inflammatory bowel disease. We developed a novel hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, CG-598 which stabilized HIF-1α in the gut tissue.

Prognostic effect of increased left ventricular wall thickness in severe aortic stenosis.

Background: It is unclear whether increased left ventricular (LV) thickness is associated with worse clinical outcomes in severe aortic stenosis (AS). The aim of this study was to determine the effect of increased LV wall thickness (LVWT) on major clinical outcomes in patients with severe AS.

Methods And Results: This study included 290 severe AS patients (mean age 69.

HDAC Inhibitor, CG-745, Enhances the Anti-Cancer Effect of Anti-PD-1 Immune Checkpoint Inhibitor by Modulation of the Immune Microenvironment.

Histone deacetylase inhibitors (HDACis) are well-known epigenetic regulators with therapeutic potential in various diseases. Recent studies have shown that HDACis are involved in immune-mediated anti-cancer effects and may modulate the activity of immunotherapy agents. CG-745, a histone deacetylase inhibitor, has shown anti-cancer effects in pancreatic cancer, colorectal cancer, and non-small cell lung cancer.

Comparison between ticagrelor and clopidogrel on myocardial blood flow in patients with acute coronary syndrome, using 13 N-ammonia positron emission tomography.

Background: The PLEIO (comParison of ticagreLor and clopidogrEl on mIcrocirculation in patients with acute cOronary syndrome) study showed that 6 months of ticagrelor therapy significantly improved microvascular dysfunction in acute coronary syndrome (ACS) patients with stent implantation compared to clopidogrel. Improved microvascular function may affect myocardial blood flow (MBF). We compared the effects of ticagrelor and clopidogrel on MBF over a 6-month follow-up period among patients diagnosed with ACS treated with percutaneous coronary intervention (PCI).

Comparison of the Effects of Ticagrelor and Clopidogrel on Microvascular Dysfunction in Patients With Acute Coronary Syndrome Using Invasive Physiologic Indices.

Background: Ticagrelor reduced the rate of myocardial infarction and death compared with clopidogrel in patients with acute coronary syndrome. However, little is understood about chronic treatment of ticagrelor on microvascular dysfunction. The objective of this study was to assess the impact of ticagrelor maintenance treatment on microvascular system and coronary flow in comparison with clopidogrel.

Asymmetric aortic valve is related to development of eccentric aortic regurgitation in patients with tricuspid aortic valve.

Background: It is unclear whether asymmetry itself plays a role in developing eccentric aortic regurgitation (AR) in patients with tricuspid aortic valve (TAV). The aim of this study was to determine whether an asymmetric aortic valve structure may have association with the development of eccentric AR in patients with TAV.

Methods: Of the 164 410 patients who underwent echocardiography between January 2006 and January 2018 at Dong-A University Hospital, 306 (mean age 69.

Left ventricular geometric patterns in patients with type A aortic dissection.

Background: Aortic dilatation is a major risk factor for aortic dissection. The aim of the present study was to assess the relationship between left ventricular (LV) geometry and maximal ascending aorta (MAA).

Methods: We reviewed data from patients who were diagnosed with acute type A aortic dissection and who underwent surgical management from December 2002 to March 2016 at Dong-A University Hospital.

A formulated red ginseng extract inhibits autophagic flux and sensitizes to doxorubicin-induced cell death.

Background: Ginseng is believed to have antitumor activity. Autophagy is largely a prosurvival cellular process that is activated in response to cellular stressors, including cytotoxic chemotherapy; therefore, agents that inhibit autophagy can be used as chemosensitizers in cancer treatment. We examined the ability of Korean Red Ginseng extract (RGE) to prevent autophagic flux and to make hepatocellular carcinoma (HCC) cells become more sensitive to doxorubicin.

Changes in mitral annular velocities after cardioversion of atrial fibrillation.

Aims: The early diastolic mitral annular velocity (e') and mitral E/e' criteria for clinically evaluating diastolic dysfunction in patients with atrial fibrillation (AF) are almost the same as in patients with sinus rhythm. In this study, we aimed to investigate whether e' is useful to assess diastolic function in AF patients.

Methods: Thirty patients who underwent successful electric cardioversion (EC) due to persistent AF and who maintained sinus rhythm for 1 month after EC were enrolled in this study.

Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids.

Human pluripotent stem cell (hPSC)-derived intestinal organoids (hIOs) form 3D structures organized into crypt and villus domains, making them an excellent in vitro model system for studying human intestinal development and disease. However, hPSC-derived hIOs still require in vivo maturation to fully recapitulate adult intestine, with the mechanism of maturation remaining elusive. Here, we show that the co-culture with human T lymphocytes induce the in vitro maturation of hIOs, and identify STAT3-activating interleukin-2 (IL-2) as the major factor inducing maturation.

ESRP1-Induced CD44 v3 Is Important for Controlling Pluripotency in Human Pluripotent Stem Cells.

The importance of alternative splicing (AS) events in pluripotency regulation has been highlighted by the determination of different roles and contributions of different splice isoforms of pluripotency-related genes and by the identification of distinct pluripotency-related splicing factors. In particular, epithelial splicing regulatory protein 1 (ESRP1) has been characterized as an essential splicing factor required for the regulation of human pluripotency and differentiation. Nevertheless, a detailed molecular characterization of ESRP1 (mRNA splice variants 1-6) in human pluripotency is lacking.

Design and Rationale for comParison Between ticagreLor and clopidogrEl on mIcrocirculation in Patients with Acute cOronary Syndrome Undergoing Percutaneous Coronary Intervention (PLEIO) Trial.

It has been previously demonstrated that ticagrelor can reduce mortality compared to clopidogrel in acute coronary syndrome (ACS) patients. However, the mechanism for this mortality reduction remains uncertain. The objective of the present study is to assess the impact of chronic ticagrelor treatment on microvascular circulation.

The impact of a dose of the angiotensin receptor blocker valsartan on post-myocardial infarction ventricular remodelling.

Aims: Although clinical guidelines advocate the use of the highest tolerated dose of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers after acute myocardial infarction (MI), the optimal dosing or the risk-benefit profile of different doses have not been fully identified.

Methods And Results: In this multicentre trial, 495 Korean patients with acute ST segment elevation MI and subnormal left ventricular (LV) ejection fraction (<50%) were randomly allocated (2:1) to receive maximal tolerated dose of valsartan (titrated up to 320 mg/day, n = 333) or low-dose valsartan (80 mg/day, n = 162) treatment. The primary objective was to assess the changes in echocardiographic parameters of LV remodelling from baseline to 12 months after discharge.

Clinical factors associated with the development of atrial fibrillation in the year following STEMI treated by primary PCI.

Background: Advanced age, poor left ventricular function, and congestive heart failure are known predictors of atrial fibrillation (AF) in acute myocardial infarction (AMI) patients. Recent advances in AMI treatment may have changed the occurrence of new-onset AF. Thus, we investigated the factors associated with the development of new-onset AF in ST elevation myocardial infarction (STEMI) patients.