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View article: Fetal hemoglobin enables malaria parasite growth in sickle cells but augments production of transmission stage parasites.
Fetal hemoglobin enables malaria parasite growth in sickle cells but augments production of transmission stage parasites. Open
Sickle cell trait is the quintessential example of the human evolutionary response to malaria, providing protection against severe disease, but leading to sickle cell disease (SCD) in the homozygous state. Fetal Hemoglobin (HbF) reduces th…
View article: A Machine Learning-Based Workflow for Predicting Transplant Outcome in Patients with Sickle Cell Disease
A Machine Learning-Based Workflow for Predicting Transplant Outcome in Patients with Sickle Cell Disease Open
Introduction: Sickle cell disease (SCD) is a prevalent life-threatening condition with limited therapeutic options. A typical feature of the disease is the wide spectrum of clinical severity that will become more apparent as patients age. …
View article: The Amyloidogenic Transthyretin V122I Variant Increase Severity of Cardiac Phenotype and Mortality in Sickle Cell Disease
The Amyloidogenic Transthyretin V122I Variant Increase Severity of Cardiac Phenotype and Mortality in Sickle Cell Disease Open
The amyloidogenic V122I variant (valine to isoleucine substitution at position 122) of the transthyretin (TTR) gene is carried almost exclusively in people of African descent, about 3% African-Americans carry the variant. In the general po…
View article: 8-Oxoguanine DNA Glycosylase 1 Recruits Transcription Factor STAT1 to Promote the Inflammatory Responses in Sickle Cell Disease
8-Oxoguanine DNA Glycosylase 1 Recruits Transcription Factor STAT1 to Promote the Inflammatory Responses in Sickle Cell Disease Open
A key intermediate in the inflammatory pathway is 7,8-dihydro-8-oxoguanine (8-oxoG), the most frequent oxidation DNA product of reactive oxygen species (ROS). In the process of repair and release of 8-oxoG from the genome, 8-Oxoguanine-DNA…
View article: Duffy Status and Hydroxyurea Dosing in Adult Patients with Sickle Cell Disease: A Potential for Iatrogenic Harm?
Duffy Status and Hydroxyurea Dosing in Adult Patients with Sickle Cell Disease: A Potential for Iatrogenic Harm? Open
Introduction: A lower absolute neutrophil count (ANC) is associated with the variant rs2814778 (c.1-67T>C) in the promotor of the ACKR1 gene. Homozygosity for rs2814778 results in the Duffy null phenotype. Duffy null patients have norma…
View article: A machine learning‐based workflow for predicting transplant outcomes in patients with sickle cell disease
A machine learning‐based workflow for predicting transplant outcomes in patients with sickle cell disease Open
Summary Allogeneic haematopoietic cell transplantation (HCT) with HLA‐matched sibling donor remains the most established curative therapeutic option for patients with sickle cell disease (SCD). However, it is not without risks, highlightin…
View article: Activating pyruvate kinase improves red blood cell integrity by reducing band 3 tyrosine phosphorylation
Activating pyruvate kinase improves red blood cell integrity by reducing band 3 tyrosine phosphorylation Open
In a phase 1 study (NCT04000165), we established proof of concept for activating pyruvate kinase (PK) in sickle cell disease (SCD) as a viable antisickling therapy. AG-348 (mitapivat), a PK activator, increased adenosine triphosphate (ATP)…
View article: Fetal hemoglobin enables malaria parasite growth in sickle cells but augments production of transmission stage parasites
Fetal hemoglobin enables malaria parasite growth in sickle cells but augments production of transmission stage parasites Open
Sickle cell trait is the quintessential example of the human response to malaria, providing protection against severe disease, but leading to sickle cell disease (SCD) in the homozygous state. Fetal Hemoglobin (HbF) reduces the pathology o…
View article: Functional and multi-omics signatures of mitapivat efficacy upon activation of pyruvate kinase in red blood cells from patients with sickle cell disease
Functional and multi-omics signatures of mitapivat efficacy upon activation of pyruvate kinase in red blood cells from patients with sickle cell disease Open
Mitapivat, a pyruvate kinase (PK) activator, shows great potential as a sickle cell disease (SCD)- modifying therapy. Safety and efficacy of mitapivat as a long-term maintenance therapy is currently being evaluated in two open-label studie…
View article: In vivo measurement of RBC survival in patients with sickle cell disease before or after hematopoietic stem cell transplantation
In vivo measurement of RBC survival in patients with sickle cell disease before or after hematopoietic stem cell transplantation Open
Stable, mixed-donor–recipient chimerism after allogeneic hematopoietic stem cell transplantation (HSCT) for patients with sickle cell disease (SCD) is sufficient for phenotypic disease reversal, and results from differences in donor/recipi…
View article: Relationships Between Markers of Iron Status and Hematological Parameters in Patients With Sickle Cell Disease
Relationships Between Markers of Iron Status and Hematological Parameters in Patients With Sickle Cell Disease Open
Based on the relationship between the intracellular concentration of sickle hemoglobin S (HbS) and the delay that occurs prior to the onset of sickling following deoxygenation, targeting the intracellular HbS concentration is a recognized …
View article: Recent developments in the use of pyruvate kinase activators as a new approach for treating sickle cell disease
Recent developments in the use of pyruvate kinase activators as a new approach for treating sickle cell disease Open
Pyruvate kinase (PK) is a key enzyme in glycolysis, the sole source of adenosine triphosphate, which is essential for all energy-dependent activities of red blood cells. Activating PK shows great potential for treating a broad range of hem…
View article: Random forest classifiers trained on simulated data enable accurate short read-based genotyping of structural variants in the alpha globin region at Chr16p13.3
Random forest classifiers trained on simulated data enable accurate short read-based genotyping of structural variants in the alpha globin region at Chr16p13.3 Open
In regions where reads don’t align well to a reference, it is generally difficult to characterize structural variation using short read sequencing. Here, we utilize machine learning classifiers and short sequence reads to genotype structur…
View article: Sickle cell allele <scp><i>HBB</i></scp>‐rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa
Sickle cell allele <span><i>HBB</i></span>‐rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa Open
Burkitt lymphoma (BL) is an aggressive B‐cell lymphoma that significantly contributes to childhood cancer burden in sub‐Saharan Africa. Plasmodium falciparum , which causes malaria, is geographically associated with BL, but the evidence re…
View article: Exploring Mitochondrial DNA Heteroplasmy in a Mouse Model of Sickle Cell Disease
Exploring Mitochondrial DNA Heteroplasmy in a Mouse Model of Sickle Cell Disease Open
BACKGROUND: Mitochondria are important in the pathology of sickle cell disease (SCD). They are abnormally retained in sickle red blood cells (RBCs) and the likely source of cell-free mitochondrial DNA (mtDNA), an erythrocytic-DAMP that tri…
View article: Longitudinal Characterization of Hemodynamic Changes with Multimodal Optical Techniques in Patients with Sickle Cell Disease Treated with Mitapivat
Longitudinal Characterization of Hemodynamic Changes with Multimodal Optical Techniques in Patients with Sickle Cell Disease Treated with Mitapivat Open
The physiological impacts of sickle cell disease (SCD) are widespread and severe if left untreated. Sickled RBCs initiate vaso-occlusion (VOC) and have altered biomechanical properties that negatively affect blood rheology and microvascula…
View article: Long-Term Safety and Efficacy of Mitapivat, an Oral Pyruvate Kinase Activator, in Adults with Sickle Cell Disease: Extension of a Phase 1 Dose Escalation Study
Long-Term Safety and Efficacy of Mitapivat, an Oral Pyruvate Kinase Activator, in Adults with Sickle Cell Disease: Extension of a Phase 1 Dose Escalation Study Open
BACKGROUND In a Phase I study (NCT04000165, Xu et al, 2022), we showed that mitapivat, an investigational oral allosteric activator of pyruvate kinase (PK), demonstrated an acceptable safety and tolerability profile at multiple ascending d…
View article: Red Blood Cell Membrane Cholesterol May Be a Key Regulator of Sickle Cell Disease Microvascular Complications
Red Blood Cell Membrane Cholesterol May Be a Key Regulator of Sickle Cell Disease Microvascular Complications Open
Cell membrane lipid composition, especially cholesterol, affects many functions of embedded enzymes, transporters and receptors in red blood cells (RBC). High membrane cholesterol content affects the RBCs’ main vital function, O2 and CO2 t…
View article: Subanesthetic ketamine: the way forward for pain management in sickle cell disease patients?
Subanesthetic ketamine: the way forward for pain management in sickle cell disease patients? Open
After weighing potential risks and benefits, in the absence of better alternatives and in settings where it can be administered safely, ketamine may be a reasonable option for patients with SCD-related acute refractory pain.
View article: Phenotypic screening of the ReFRAME drug repurposing library to discover new drugs for treating sickle cell disease
Phenotypic screening of the ReFRAME drug repurposing library to discover new drugs for treating sickle cell disease Open
Stem cell transplantation and genetic therapies offer potential cures for patients with sickle cell disease (SCD), but these options require advanced medical facilities and are expensive. Consequently, these treatments will not be availabl…
View article: Phenotypic screening of the ReFrame Drug Repurposing Library to discover new drugs for treating sickle cell disease
Phenotypic screening of the ReFrame Drug Repurposing Library to discover new drugs for treating sickle cell disease Open
Stem-cell transplantation and genetic therapies offer potential cures for patients with sickle cell disease (SCD) but these options require advanced medical facilities and are expensive. Consequently, these treatments will not be available…
View article: Revisiting anemia in sickle cell disease and finding the balance with therapeutic approaches
Revisiting anemia in sickle cell disease and finding the balance with therapeutic approaches Open
Chronic hemolytic anemia and intermittent acute pain episodes are the 2 hallmark characteristics of sickle cell disease (SCD). Anemia in SCD not only signals a reduction of red cell mass and oxygen delivery, but also ongoing red cell break…
View article: A phase 1 dose escalation study of the pyruvate kinase activator mitapivat (AG-348) in sickle cell disease
A phase 1 dose escalation study of the pyruvate kinase activator mitapivat (AG-348) in sickle cell disease Open
Polymerization of deoxygenated hemoglobin S underlies the pathophysiology of sickle cell disease (SCD). In activating red blood cell pyruvate kinase and glycolysis, mitapivat (AG-348) increases adenosine triphosphate (ATP) levels and decre…
View article: Safety of liver biopsy in patients with sickle cell related liver disease: A single‐center experience
Safety of liver biopsy in patients with sickle cell related liver disease: A single‐center experience Open
Supplementary Table 1: Definition of Complications Supplemental Table 2: Baseline characteristics of the study cohort Supplementary Table 3: Comparison of baseline characteristics in patients with and without liver biopsy complications Sup…