Search

This study presents the development of new software to analyze large sets of genetic markers. In the era of next generation sequencing and high density SNP arrays there is a need for new computer tools to adequately analyze the output. In addition to performing pair-wise relationship computations our software can be used to conduct simulations to obtain expected values for the likelihood ratios (LR). Simulations will give a general idea to when a case can be solved prior to actually sending samples for analyzes. The software, implementing an easy interface, will be most useful for labs obtaining data from clients (or directly using) services provided by companies such as 23andMe or FamilyTreeDNA . In addition, it can use population frequency data from the 1000 Genomes project covering several continents. [ABSTRACT FROM AUTHOR]

Abstract: Adhesion molecules have been implicated in the development and progression of cardiovascular disease, which is highly prevalent in people with diabetes. Adhesion molecules can mediate adhesion of leukocytes to the endothelium. Furthermore, P-selectin expressed on platelets is able to mediate the adhesion of leukocytes to platelets. In this study, we examine the in-vivo and in-vitro effects of rosiglitazone with particular emphasis on three important adhesion molecules (VCAM-1, ICAM-1 and P-selectin). In the aorta of STZ-diabetic apolipoprotein E-deficient (apoE KO) mice, rosiglitazone significantly reduced both total and arch plaque area. The mechanism for this appeared to be reduced macrophage infiltration into the atherosclerotic plaque which was also associated with reduced mRNA levels for VCAM-1, ICAM-1, MCP-1 and P-selectin in the aorta. In-vitro studies revealed reduced cell adhesion of monocytic cells (THP-1) to fibrinogen and endothelial cells (HUVEC) after incubation with rosiglitazone. Furthermore, the reduction in leukocyte adhesion also correlated with significant reductions in mRNA levels for VCAM-1, ICAM-1 and P-selectin indicating that reduced macrophage infiltration in atherosclerotic plaques may occur as a result of a direct effect of rosiglitazone on adhesion molecules in both monocytes and endothelial cells. Thus, we have shown that rosiglitazone appears to have direct anti-atherosclerotic effects in an animal model of diabetes-associated atherosclerosis which are at least partly due to effects on VCAM-1, ICAM-1, MCP-1 and P-selectin expression which leads to decreased leukocyte adhesion and macrophage infiltration. [Copyright &y& Elsevier]

Sudden unexpected death (SUD) is an unexpected event that in many cases are caused by diseases with an underlying genetic background. Forensic molecular autopsy is an approach that has gained wide-spread attention, in part explained by the rapid progress of DNA sequencing techniques. The approach leverages genetic data in combination with medical autopsy findings in post-mortem samples to explore a potential underlying genetic cause of death. Traditional forensic approaches to molecular autopsy focus on a small panel of genes, say <200 genes, with strong association to heart conditions whereas clinical genetics tend to capture entire exomes while subsequently selecting targeted panels bioinformatically. The drop in price and the increased throughput has promoted wider exome sequencing as a viable method to discover genetic variants. We explore a targeted gene panel consisting of 2422 genes, selected based on their broad association to sudden unexplained death. A hybridization capture approach from Twist Bioscience based on double stranded DNA probes was used to target exons of the included genes. We selected and sequenced a total of 98 post-mortem samples from historical forensic autopsy cases where the cause of death could not be unambiguously determined based on medical findings and that had a previous negative molecular autopsy. In the current study, we focus on the performance of the hybridization capture technology on a 2422 gene panel and explore metrics related to sequencing success using a mid-end NextSeq 550 as well as a MiSeq FGx platform. With the latter we demonstrate that our sequence data benefits from 2×300 bp sequencing increasing coverage, in particular, for difficult regions where shadow coverage, i.e. regions outside the probes, are utilized. The results further illustrate a highly uniform capture across the panel of genes (mean fold80=1.5), in turn minimizing excessive sequencing costs to reach sufficient coverage, i.e. 20X. We outline a stepwise procedure to select genes associated with SUD through virtual bioinformatical panels extracting tier of genes with increasing strength of association to SUD. We propose some prioritization strategies to filter variants with highest potential and show that the number of high priority genetic variant requiring manual inspections is few (0-3 for all tiers of genes) when all filters are applied., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 Elsevier B.V. All rights reserved.)

There is an increasing demand for software that can handle an arbitrary number of linked markers in forensic genetics; primarily with application to inference of relationships and direct matching but also in applications such as ancestry inference and mixture interpretation. With the emergence of sequencing technologies, denser sets of SNP markers are generated and analyzed. Additionally, sequence data of low quality and quantity DNA generate uncertainty about the underlying true genotype. We provide an efficient implementation of a general model for pedigree likelihood computations with genetic marker data using a three-layered approach. The top and first layer is the population model where allele frequencies and population substructure are accounted for. The second layer is the inheritance model which efficiently handles linked markers using an IBD model. The third and bottom layer is the observational level where we model the likelihood of the true genotype given underlying reads as well as parameters for errors. We exemplify the utility of our implementation as well as provide validation according to guidelines established by the ISFG using a combination of two published SNP panels. We demonstrate that computations are feasible for panels encompassing 10,000 markers and we argue that, due to the properties of the underlying algorithm, extending the number of markers will result in a linear increase in computation time. In addition we study the impact of parameters used in our model and suggest some guidelines pertaining to their values. The results demonstrate that a probabilistic model for low coverage sequence read data is needed instead of relying on an a threshold based genotype and applying our general model for inference of relationships on a real case can be superior, i.e. higher information content, to other methods relying on either fixed genotypes with low quality sequence data or simple pair wise relationship tests. In summary, the implementation, FamLink2 (freely available at https://famlink.se), can jointly handle genetic linkage, genotype uncertainty and population substructure for an arbitrary pedigree with data for any number of individuals. Whereas the current study will focus on calculations disregarding mutations, FamLink2 has the ability to model mutations for certain built-in pedigrees., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The unique features of the X chromosome can be crucial to complement autosomal profiling or to disentangle complex kinship problems, providing in some cases a similar or even greater power than autosomes in paternity/maternity investigations. While theoretical and informatics approaches for pairwise X-linked kinship analyses are well established for euploid individuals, these are still lacking for individuals with an X chromosome aneuploidy. To trigger the fulfilment of this gap, this research presents a mathematical framework that enables the quantification of DNA evidence in pairwise kinship analyses, involving two non-inbred individuals, one of whom with a non-mosaic X chromosome aneuploidy: Trisomy X (47, XXX), Klinefelter (47, XXY) or Turner (45, X0) syndrome. As previously developed for a regular number of chromosomes, this approach relies on the probability of related individuals sharing identical-by-descent (IBD) alleles at one specific locus and it can be applied to any set of independently transmitted markers, with no gametic association in the population. The kinship hypotheses mostly considered in forensic casework are specifically addressed in this work, but the reasoning and procedure can be applied to virtually any pairwise kinship problem under the referred assumptions. Algebraic formulae for joint genotypic probabilities cover all the possible genotypic configurations and pedigrees. Compared with the analyses assuming individuals with a regular number of chromosomes, complicating factors rely on the different possibilities for both the parental origin of the error (either maternal or paternal), and the type of error occurred (either meiotic or post-zygotic mitotic). These imply that a non-inbred female with Triple X or a male with Klinefelter syndrome may carry two IBD alleles at the same locus. Thus, and contrarily to what occurs for the standard case, IBD partitions depend not only on the kinship hypothesis under analysis but also on the genotypic configuration of the analyzed individuals. For some cases, parameters of interest can be inferred, while for others recommended values based on the available literature are provided. This work is the starting point to analyze X-chromosomal data under the scope of kinship problems, involving individuals with aneuploidies, as it will enhance the quantification of the DNA evidence not only in forensics but also in the medical genetics field. We hope it will trigger the development of approaches including other complicating factors, as a greater number of individuals, possibility of the occurrence of mutations and/or silent alleles, as well as the analysis of linked markers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Anacetrapib, a cholesteryl ester transfer protein (CETP) inhibitor previously under development, exhibited an usually extended terminal half-life and large food effect and accumulated in adipose tissue. Other CETP inhibitors have not shown such effects. Obicetrapib, a potent selective CETP inhibitor, is undergoing Phase III clinical development. Dedicated assessments were conducted in pre-clinical and Phase I and II clinical studies of obicetrapib to examine the pharmacokinetic issues observed with anacetrapib. After 9 months of dosing up to 50 mg/kg/day in cynomolgus monkeys, obicetrapib was completely eliminated from systemic circulation and not detected in adipose tissue after a 13-week recovery period. In healthy humans receiving 1-25 mg of obicetrapib, the mean terminal half-life of obicetrapib was 148, 131, and 121 h at 5, 10, and 25 mg, respectively, and food increased plasma levels by ~1.6-fold with a 10 mg dose. At the end of treatment in Phase II trials, mean plasma levels of obicetrapib ranged from 194.5 ng/mL with 2.5 mg to 506.3 ng/mL with 10 mg. Plasma levels of obicetrapib decreased by 92.2% and 98.5% at four and 15 weeks post-treatment, respectively. Obicetrapib shows no clinically relevant accumulation, is minimally affected by food, and has a mean terminal half-life of 131 h for the 10 mg dose. These data support once daily, chronic dosing of obicetrapib in Phase III trials for dyslipidemia management., (© 2024 The Author(s). Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Titanium (Ti) and Ti alloys are of great interest in bone and dental tissue engineering applications due to their biocompatibility, corrosion resistance, and close mechanical properties to natural bone. However, the formation of fibrous tissue prevents osteointegration and results in implant loosening. Thus, physical and chemical methods are used to improve the surface properties of Ti. This study aimed to understand the role of alkali treatment conditions, including alkali medium concentration, temperature, rotation speed, and post heat treatment. Our results show that alkali treatment using 5 and 10 molar sodium hydroxide (NaOH) solution allows the formation of web-like microstructure. However, a higher concentration of 15 molar resulted in cracks along the surface. Interaction between the human fetal osteoblast cells and Ti samples showed that heat treatment is necessary for increased cellular proliferation, which was not significantly different at later time points compared with the polished Ti. Alkali heat treatment did not induce inflammatory reactions at later time points. It showed an increase in vascular endothelial growth factor, osteoprotegerin/nuclear factor kappa-Β ligand ratio, and osteocalcin expression, which is evidence for accelerated osteoblast cell maturation and bone remodeling in surface-modified samples. Together, these data show that alkali treatment using 5 or 10 molar of NaOH followed by heat treatment may have a therapeutic effect and assist with bone tissue integration with Ti implant.

Objective: New guidelines for the interpretation of cardiotocography (CTG) have been presented by FIGO in 2015 (FIGO-15) and by NICE in 2017 (NICE-17) and 2022 (NICE-22) In Sweden, a previous template from 2009 (SWE-09) was replaced in 2017 (SWE-17).The objective of the study was to compare these five different templates for CTG classification regarding sensitivity, specificity, positive and negative predictive values in identifying neonates with acidemia at birth (cord artery pH <7.10)., Methods: This is a historical cohort study including singleton births in Lund November 2015-February 2016, after spontaneous or induced labor at ≥34 completed gestational weeks with validated umbilical cord acid-base samples.Characteristics of cardiotocographic traces during the last hour before birth were reviewed by two independent assessors blinded to outcome. Each template was then used to classify the CTG as normal, suspicious, or pathological. Traces for which classification differed between the two assessors for any of the templates were assessed by a third assessor. The classification by majority (at least 2 of 3) was used for analyses.Main outcome measures were the sensitivity, specificity, and positive and negative predictive values for each template to identify neonates with cord artery pH <7.10 by the classification pathological. In a secondary analysis, these outcome measures were calculated for the classifications suspicious + pathological together., Results: SWE-09 and NICE-22 had significantly higher sensitivity (both 92%; 95% CI 79-98%) than NICE-17 (68%; 51-82%), FIGO-15 (42%; 26-59%) and SWE-17 (39%; 24-57%) to identify neonates with acidemia by the classification pathological. Specificity was significantly higher for SWE-17 (91%; 88-93%), FIGO-15 (90%; 88-93%) and NICE-17 (78%; 74-81%) than for NICE-22 (63%; 59-67%) and SWE-09 (62%; 58-66%). The positive predictive value of a pathological pattern ranged between 15% (SWE-09 and NICE-22) and 24% (FIGO-15), and negative predictive values between 95% (SWE-17) and 99% (SWE-09 and NICE-22). Combining suspicious and pathological patterns increased the sensitivity and decreased the specificity for all templates., Conclusions: Current CTG interpretation templates either have low sensitivity to identify fetal acidemia or low specificity. Among current guidelines, NICE 2022 had the highest sensitivity to identify neonates with acidemia and is considered the safest current classification system. Efforts to further improve diagnostic precision are warranted.

Background/objectives: Emerging forensic genetic applications, such as forensic investigative genetic genealogy (FIGG), advanced DNA phenotyping, and distant kinship inference, increasingly require dense SNP genotype datasets. However, forensic-grade DNA often contains missing genotypes due to its quality and quantity limitations, potentially hindering these applications. Genotype imputation, a method that predicts missing genotypes, is widely used in population and medical genetics, but its utility in forensic genetics has not been thoroughly explored. This study aims to assess the performance of genotype imputation in forensic contexts and determine the conditions under which it can be effectively applied., Methods: We employed a simulation-based approach to generate realistic forensic SNP genotype datasets with varying numbers, densities, and qualities of observed genotypes. Genotype imputation was performed using Beagle software, and the performance was evaluated based on the call rate and imputation accuracy across different datasets and imputation settings., Results: The results demonstrate that genotype imputation can significantly increase the number of SNP genotypes. However, imputation accuracy was dependent on factors such as the quality of the original genotype data and the characteristics of the reference population. Higher SNP density and fewer genotype errors generally resulted in improved imputation accuracy., Conclusions: This study highlights the potential of genotype imputation to enhance forensic SNP datasets but underscores the importance of optimizing imputation parameters and understanding the limitations of the original data. These findings will inform the future application of imputation in forensic genetics, supporting its integration into forensic workflows., Competing Interests: The authors declare no conflicts of interest.

Aims: Obicetrapib is a highly selective cholesteryl ester transfer protein (CETP) inhibitor shown to reduce low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB), when taken as monotherapy and in combination with ezetimibe on a background of statins, in clinical trials predominantly conducted in Northern European/Caucasian participants. We characterized the efficacy, safety, and tolerability of obicetrapib within an Asian-Pacific region population., Methods: This double-blind, randomized, phase 2 trial examined obicetrapib 2.5, 5, and 10 mg/d, compared with placebo, for 8 weeks as an adjunct to stable statin therapy (atorvastatin 10 or 20 mg/d or rosuvastatin 5 or 10 mg/d) in Japanese men and women who had not achieved 2022 Japan Atherosclerosis Society Guidelines and had LDL-C ＞70 mg/dL or non-high-density lipoprotein cholesterol (non-HDL-C) ＞100 mg/dL and triglycerides (TG) ＜400 mg/dL. Endpoints included LDL-C, non-HDL-C, HDL-C, very low-density lipoprotein cholesterol, apolipoproteins, TG, steady state pharmacokinetics (PK) in obicetrapib arms, safety, and tolerability., Results: In the 102 randomized subjects (mean age 64.8 y, 71.6% male), obicetrapib significantly lowered median LDL-C, apoB, and non-HDL-C, and raised HDL-C at all doses; responses in the obicetrapib 10 mg group were -45.8%, -29.7%, -37.0%, and +159%, respectively (all p＜0.0001 vs. placebo). The PK profile demonstrated near complete elimination of drug by 4 weeks. Obicetrapib was well tolerated and there were no adverse safety signals., Conclusions: All doses of obicetrapib taken as an adjunct to stable statin therapy significantly lowered atherogenic lipoprotein lipid parameters, showed near complete elimination of drug by 4 weeks, and were safe and well tolerated in a Japanese population, similar to previous studies of obicetrapib conducted in predominantly Caucasian participants.

Obicetrapib is a selective inhibitor of cholesteryl ester transfer protein that is currently in phase 3 of development for the treatment of dyslipidemia as adjunct therapy. The purpose of this study was to comprehensively characterize the pharmacokinetic (PK) and pharmacodynamic (PD) disposition of obicetrapib. Data from 7 clinical trials conducted in healthy adults and those with varying degrees of dyslipidemia were included for model development. The structural model that best described obicetrapib PK was a 3-compartment model with 4-compartment transit absorption and first-order elimination. Body weight was the only covariate found to significantly explain observed variability and was therefore included using allometric scaling on all disposition parameters. For a typical patient weighing 75 kg, the estimated apparent total body clearance and apparent volume of distribution of the central compartment was 0.81 L/h and 36.1 L, respectively. The final PK model parameters were estimated with good precision and were ultimately leveraged to sequentially inform 2 turnover models that describe obicetrapib's effect on low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) concentrations. The maximum stimulatory effect of obicetrapib on LDL-C loss was estimated to be 1.046, while the maximum inhibitory effect of obicetrapib on HDL-C loss was 0.691. This corresponds to a predicted typical maximum percent change from baseline LDL-C and HDL-C of 51.1% and 224%, respectively. The final sequential model described obicetrapib PKPD well and was ultimately able to both demonstrate evidence of internal consistency and support decision-making throughout the development lifecycle., (© 2024, The American College of Clinical Pharmacology.)

Obicetrapib is a selective cholesteryl ester transfer protein (CETP) inhibitor. Previous research has demonstrated similar pharmacokinetic (PK) responses to single doses of obicetrapib between Japanese and White males, but the PK responses have not been established in Chinese individuals. The purpose of this randomized, parallel, open-label trial was to characterize the PK and pharmacodynamic (PD; CETP activity and plasma lipids) responses and safety of single doses (5, 10, or 25 mg; N = 36) and multiple doses (10 mg for 14 days; N = 12) of obicetrapib in healthy Chinese individuals. The maximum concentration and area under the drug concentration-time curve of obicetrapib from 0 h to infinity increased with dose after all single doses of obicetrapib. After 7 consecutive days of dosing, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol reached their minimum and maximum changes of 42% reduction and 108% increase, respectively. Primary PK and PD parameters after single- and multiple-dose administration of obicetrapib were similar to those in healthy white participants in previous studies. One participant in the 5 mg dose group experienced a treatment-emergent adverse event of decreased white blood cell and neutrophil counts, which resolved without intervention. In conclusion, these findings support the inclusion of Chinese individuals in the ongoing phase 3 clinical development program of obicetrapib., (© 2024 The Author(s). The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Background: Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] and increases high-density lipoprotein cholesterol (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential to lower atherogenic lipoproteins in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment with available maximally tolerated lipid-modifying therapies, addressing an unmet medical need in a patient population at high risk for cardiovascular events., Methods and Results: BROADWAY (NCT05142722) and BROOKLYN (NCT05425745) are ongoing placebo-controlled, double-blind, randomized Phase III trials designed to examine the efficacy, safety, and tolerability of obicetrapib as an adjunct to dietary intervention and maximally tolerated lipid-modifying therapies in participants with a history of ASCVD and/or underlying HeFH whose LDL-C is not adequately controlled. The primary efficacy endpoint was the percent change in LDL-C from baseline to day 84. Other endpoints included changes in Apo B, non-HDL-C, HDL-C, Apo A1, Lp(a), and triglycerides in addition to parameters evaluating safety, tolerability, and pharmacokinetics. BROADWAY also included an adjudicated assessment of major adverse cardiovascular events, measurements of glucose homeostasis, and an ambulatory blood pressure monitoring substudy. A total of 2,532 participants were randomized in BROADWAY and 354 in BROOKLYN to receive obicetrapib 10 mg or placebo (2:1) for 365 days with follow-up through 35 days after the last dose. Results from both trials are anticipated in 2024., Conclusion: These trials will provide safety and efficacy data to support the potential use of obicetrapib among patients with ASCVD or HeFH with elevated LDL-C for whom existing therapies are not sufficiently effective or well-tolerated., Competing Interests: Conflict of interest Stephen J. Nicholls received grant/research support from AstraZeneca, New Amsterdam Pharma, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and was a consultant for AstraZeneca, Amarin, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, Boehringer Ingelheim, and Vaxxinity. Adam J. Nelson received personal fees from Boehringer Ingelheim, AstraZeneca, Amgen, Novartis, and Sanofi. Marc Ditmarsch is Chief Development Officer for NewAmsterdam Pharma. John J.P. Kastelein is Chief Scientific Officer for NewAmsterdam Pharma and Emeritus Professor of Medicine at the University of Amsterdam, The Netherlands. Christie M. Ballantyne received grant/research support (all paid to the institution, not individual) from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, NewAmsterdam Pharma, Novartis, Novo Nordisk, Regeneron, Roche Diagnostic, NIH, AHA, and ADA and was a consultant for 89Bio, Abbott Diagnostics, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Ionia, Lilly, Matinas BioPharma Inc., Merck, NewAmsterdam Pharma, Novartis, Novo Nordisk, Pfizer, Regeneron, and Roche Diagnostic. Kausik K. Ray reports his institution received unrestricted research grants from Amgen, Daiichi Sankyo, Regeneron, and Sanofi; consulting or advisory board honoraria from Novartis, Esperion, Daiichi Sankyo, Abbott, Bayer, Eli Lilly, Silence Therapeutics, CSL Behring, NewAmsterdam Pharma, Sanofi, Amgen Novo Nordisk, BI, Scribe, Vaxxinity, CRISPR, AZ, Kowa, and Cargene; honoraria for CME and non-CME from Novartis, Novo Nordisk, BI, AZ, Viatris, Daiichi Sankyo, Amgen, and Sanofi; and he has stock options from PEMI-31. Ann Marie Navar reports honoraria and consulting fees from AstraZeneca, Bayer, Bristol Meyer Squibb, Boehringer Ingelheim, Esperion, Janssen, Eli Lilly, Merck, NewAmsterdam Pharma, Novartis, NovoNordisk, Pfizer, and Silence Therapeutics; and funding for research to her institution from Esperion, Janssen, and Amgen. Steven E. Nissen reports that Cleveland Clinic Center for Clinical Research has received funding to perform clinical trials from Abbvie, AstraZeneca, Amgen, Arrowhead, Bristol Myers Squibb, Eli Lilly, Esperion, Medtronic, MyoKardia, NewAmsterdam Pharma, Novartis, Pfizer, and Silence Therapeutics. Dr. Nissen is involved in these clinical trials but receives no personal renumeration for his participation and consults for these pharmaceutical companies but does not accept compensation. Anne C. Goldberg has received research grant(s)/support from Amarin, Amgen, Akcea/IONIS, Arrowhead, Esperion Therapeutics, Inc., Merck, NewAmsterdam Pharma, Novartis, Pfizer, Regeneron, and Sanofi; has served as a consultant for 23andMe, Akcea, Esperion, IONIS, Merck, NewAmsterdam Pharma, Novartis, OptumRX, Regeneron, and Sanofi; and has provided editorial work for Merck. Liam R. Brunham is Reserch Chair, Associate Professor for The University of British Columbia. Danielle Curcio is Executive Director of Clinical Operations for NewAmsterdam Pharma. Erin Wuerdeman is Executive Director of Clinical Operations for NewAmsterdam Pharma. Annie Nield is Executive Vice President and Head of Global Regulatory Affairs for NewAmsterdam Pharma. Douglas Kling is Chief Operating Officer for NewAmsterdam Pharma. Andrew Hsieh is Vice President of Medical Affairs for NewAmsterdam Pharma. Mary R. Dicklin is an employee of Midwest Biomedical Research, which has received consulting fees and/or grant funding from NewAmsterdam Pharma, Acasti Pharma, Beren Therapeutics, Eli Lilly and Company, Indiana University and Foundation, Matinas BioPharma, NorthSea Therapeutics, and 89Bio. Brain A. Ference reports research grants from Merck, Novartis, Amgen, and Esperion Therapeutics, and consulting fees, advisory boards, or lecture honoraria from Novartis, Merck, Amgen, Regeneron, Sanofi, Novartis, Pfizer, Eli Lilly, Novo Nordisk, Daiichi-Sankyo, Viatris, Ionis Pharmaceuticals, NewAmsterdam Pharma, dalCOR, The Medicines Co., Mylan, CiVi Pharma, KrKa Pharmaceuticals, American College of Cardiology, EAS, and European Society of Cardiology. Ulrich Laufs has received honoraria from Amgen, Daiichi Sankyo, MSD, Novartis, and Sanofi. Maciej Banach has received renumeration for lectures from Adamed, Amgen, Daiichi Sankyo, Exceed Orphan, KRKA Polypharma, Mylan/Viatris, Novartis, Novo Nordisk, Pfizer, Sanofi, Teva, and Zentiva; participated in advisory panels for Adamed, Amgen, Daiichi Sankyo, Esperion, NewAmsterdam Pharma, Novartis, Novo Nordisk, and Sanofi; and received grants from Amgen, Daiichi Sankyo, Mylan/Viatris, and Sanofi. Roxana Mehran has institutional research grants from Abbott, Abiomed, Alleviant Medical, Amgen, AM-Pharma, Applied Therapeutics, Arena Pharmaceuticals, AstraZeneca, Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, Cardiawav, CeloNova, Chiesi, Concept Medical, CSL Behring, CytoSorbents, Daiichi Sankyo, Element Science, Faraday Pharmaceuticals, Humacyte, Idorsia Pharmaceuticals, I-Laser, Janssen, Magenta Medical, Mediasphere Medical, Medtelligence, Medtronic, Novartis, OrbusNeich, Penumbra, PhaseBio, Philips, Pi-Cardia, PLx Pharma, Protembis, RenalPro, RM Global, Shockwave, Transverse Medical, Vivasure, and ZOLL Medical; consulting fees from AstraZeneca, Novartis, Cine-Med Research, Ionis Pharmaceuticals, Novo Nordisk, Vectura Inc., and WebMD; honoraria from Novartis Pharmaceuticals, Philips Electronics, Biotronik Inc., and Bayer Healthcare Pharmaceuticals; advisory board participation for Humacyte Inc., PhaseBio, Faraday Pharmaceuticals, Medtronic, Philips, and PLx Pharma; participation on a data safety monitoring board for Pi-Cardia; a leadership role with the American Medical Association (JAMA Cardiology, associate editor), American College of Cardiology (BOT Member, SC Member CTR Program), and Society for Cardiovascular Angiography & Interventions (Women in Innovations Committee Member); stock or stock options from Applied Therapeutics, Elixir Medical, Stel, and ControlRad; and faculty membership with the Cardiovascular Research Foundation. Alberico L. Catapano in the last three years has received honoraria, lecture fees, or research grants from Aegerion, Amarin, Amgen, Amryt Pharma, AstraZeneca, Daiichi Sankyo, Esperion, Ionis Pharmaceutical, Medscape Education, Menarini, MSD, NewAmsterdam Pharma, Novartis, NovoNordisk, PeerVoice, Pfizer, Recordati, Regeneron, Sanofi, The Corpus, Ultragenyx, and Viatris. Michael H. Davidson is Chief Executive Officer for NewAmsterdam Pharma., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)