The ability to obtain genome-wide sequences of very large numbers of individuals from natural populations raises questions about optimal sampling designs and the limits to extracting information on key population-genetic parameters from temporal-survey data. Methods are introduced for evaluating whether observed temporal fluctuations in allele frequencies are consistent with the hypothesis of random genetic drift, and expressions for the expected sampling variances for the relevant statistics are given in terms of sample sizes and numbers. Estimation methods and aspects of statistical reliability are also presented for the mean and temporal variance of selection coefficients. For nucleotide sites that pass the test of neutrality, the current effective population size can be estimated by a method of moments, and expressions for its sampling variance provide insight into the degree to which such methodology can yield meaningful results under alternative sampling schemes. Finally, some caveats are raised regarding the use of the temporal covariance of allele-frequency change to infer selection. Taken together, these results provide a statistical view of the limits to population-genetic inference in even the simplest case of a closed population.
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http://dx.doi.org/10.1093/gbe/evaa056 | DOI Listing |
HLA
January 2025
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
COVID-19 remains a significant global health problem with uncertain long-term consequences for convalescents. We investigated the relationships between anti-N protein antibody levels, severe acute respiratory syndrome (SARS)-CoV-2-associated TCR repertoire parameters, HLA type and epidemiological information from three cohorts of 524 SARS-CoV-2-infected subjects subgrouped in acute phase, seronegative and seropositive convalescents from the Emilia Romagna region. Epidemiological information and anti-N antibody index were associated with TCR repertoire data.
View Article and Find Full Text PDFInt J Surg
December 2024
Department of Urology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People's Republic of China.
Background: Benign prostatic hyperplasia (BPH) is a common disease in middle-aged and elderly men, and its etiology is not completely clear. Late-onset hypogonadism (LOH) is a relatively common disease in the aging process of men. BPH is often accompanied by varying degrees of LOH, and the pathogenesis and progression of the two diseases are related.
View Article and Find Full Text PDFBMC Cancer
January 2025
Department of Pathology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi Province, 030013, People's Republic of China.
Purpose: To evaluate the prognostic significance of progesterone receptor (PR) expression and the PIK3CA mutation status in HR+/HER2 - breast cancer patients, with the goal of screening patients who may derive the greatest benefit from PI3K-targeted therapy.
Methods: A retrospective analysis was conducted on 152 HR+/HER2 - breast cancer patients stratified by PR expression levels and PIK3CA mutation status. The study population was divided into groups on the basis of a median PR threshold of 50% and further subdivided by PIK3CA mutation status.
AAPS J
January 2025
Clinical Pharmacology Modeling and Simulation, Amgen, One Amgen Center Drive, Thousand Oaks, CA, 91320-0777, USA.
Sotorasib is a novel KRAS inhibitor that has shown robust efficacy, safety, and tolerability in patients with KRAS mutation. The objectives of the population pharmacokinetic (PK) analysis were to characterize sotorasib population PK in healthy subjects and patients with advanced solid tumors with KRAS mutation from 6 clinical studies, evaluate the effects of intrinsic and extrinsic factors on PK parameters, and perform simulations to further assess the impact of identified covariates on sotorasib exposures. A two-compartment disposition model with three transit compartments for absorption and time-dependent clearance and bioavailability well described sotorasib PK.
View Article and Find Full Text PDFClin Biochem
January 2025
Clinical Medicine Research Center, Jiangxi Cancer Hospital & Institute (The Second Affiliated Hospital of Nanchang Medical College), Nanchang, China; Jiangxi Clinical Research Center for Cancer, China; Jiangxi Key Laboratory of Translational Research for Cancer, Nanchang, China. Electronic address:
Background: Acarbose is an α-glucosidase inhibitor widely used clinically for its significant hypoglycemic effect, albeit with inter-individual variations in response. The sucrase-isomaltase (SI) enzyme is the primary target of acarbose. This study aims to investigate the impact of genetic polymorphisms in the SI gene on the pharmacodynamics of acarbose.
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