Assessment of influenza vaccine effectiveness among the elderly in Taiwan using population-based registry data for the 2023-2024 season.

Introduction: Influenza infection can cause serious complications in the elderly, including hospitalizations and death. In Taiwan, government-funded influenza vaccination is offered to the elderly ≥65 years old. We aim to evaluate vaccine effectiveness (VE) among this group during 2023-2024 influenza season using national databases.

Fertility status and risk of pediatric cardiovascular diseases: a population-based nested case-control study.

Study Question: Is parental fertility status and use of IVF associated with the risk of pediatric cardiovascular diseases among offspring aged 0-13 years, and is this association mediated by perinatal factors?

Summary Answer: Children conceived through IVF and those born to parents with subfertility (defined as one partner with an infertility diagnosis and not using ART for the study pregnancy) have an increased risk for congenital heart defects, partly explained by multiple gestations.

What Is Known Already: Evidence indicates that children born following IVF have an increased risk of premature vascular aging. However, the risk of developing cardiovascular diseases during childhood and the extent to which such risks are associated with adverse perinatal outcomes remains uncertain.

Separable Effects of Semicompeting Risks: The Effects of Hepatitis B on Liver Cancer via Liver Cirrhosis.

We are interested in how patients with hepatitis B progress to liver cirrhosis (an intermediate outcome) and liver cancer (a primary outcome). The separable effect has recently been proposed to study causal effects in the setting of competing risks. In this work, we extend the separable effect approach to semicompeting risks involving a primary and intermediate outcome.

Clinical impact of pharmacogenetic risk variants in a large chinese cohort.

Incorporating pharmacogenetics into clinical practice promises to improve therapeutic outcomes by optimizing drug selection and dosage based on genetic factors affecting drug response. A key advantage of PGx-guided therapy is to decrease the likelihood of adverse events. To evaluate the clinical impact of PGx risk variants, we performed a retrospective study using genetic and clinical data from the largest Han Chinese cohort, comprising 486,956 individuals, assembled by the Taiwan Precision Medicine Initiative.

Single-cell signaling network profiling during redox stress reveals dynamic redox regulation in immune cells.

In eukaryotic cells, reactive oxygen species (ROS) serve as crucial signaling components. ROS are potentially toxic, so constant adjustments are needed to maintain cellular health. Here we describe a single-cell, mass cytometry-based method that we call signaling network under redox stress profiling (SN-ROP) to monitor dynamic changes in redox-related pathways during redox stress.

Causal mediation analysis for time-to-event mediator and outcome in the presence of left truncation.

We propose a causal mediation approach to semi-competing risks under left truncation sampling by considering an intermediate event as a mediator and a terminal event as an outcome. We focus on the causal relationship from exposure to the terminal outcome in relation to the intermediate event. In particular, we study the direct effect, the effect of exposure on the terminal event that is not through the intermediate event, and the indirect effect-the effect of exposure on the terminal event that is mediated through the intermediate event.

Paternal age, de novo mutation, and age at onset among co-affected schizophrenia sib-pairs: whole-genome sequencing in multiplex families.

Whether delaying fatherhood leads to more mutations, thereby resulting in adverse psychiatric outcomes in offspring, remains under debate. No study has directly examined the role of de novo mutations (DNMs) between paternal age and offspring psychiatric outcomes. This study aimed to explore the association between paternal age, the number of DNMs, and age at onset of schizophrenia by sequencing the whole genome of multiplex schizophrenia families.

Multiplexed assays of human disease-relevant mutations reveal UTR dinucleotide composition as a major determinant of RNA stability.

Untranslated regions (UTRs) contain crucial regulatory elements for RNA stability, translation and localization, so their integrity is indispensable for gene expression. Approximately 3.7% of genetic variants associated with diseases occur in UTRs, yet a comprehensive understanding of UTR variant functions remains limited due to inefficient experimental and computational assessment methods.

Nonparametric Path-Specific Effects on a Survival Outcome Through Multiple Time-to-Event Mediators.

A causal mediation model with multiple time-to-event mediators is exemplified by the natural course of human disease marked by sequential milestones with a time-to-event nature. For example, from hepatitis B infection to death, patients may experience intermediate events such as liver cirrhosis and liver cancer. The sequential events of hepatitis, cirrhosis, cancer, and death are susceptible to right censoring; moreover, the latter events may preclude the former events.

INCREASED CIRCULATORY KREBS CYCLE METABOLITES IN SEPSIS IS ASSOCIATED WITH INCREASED INTERLEUKIN-6 RELEASE AND WORSE SURVIVAL.

Objective : Recent studies have proposed that Krebs cycle metabolites may serve as potential biomarkers for prognosis in sepsis. However, whether these metabolites are associated with disease severity and can be applied to improve the effectiveness of current prognosis assessment in sepsis remains unclear and is explored in this study. Methods : This prospective multicenter cohort study was conducted in medical intensive care units (ICUs).

Syngeneic natural killer cell therapy activates dendritic and T cells in metastatic lungs and effectively treats low-burden metastases.

Natural killer (NK) cells can control metastasis through cytotoxicity and IFN-γ production independently of T cells in experimental metastasis mouse models. The inverse correlation between NK activity and metastasis incidence supports a critical role for NK cells in human metastatic surveillance. However, autologous NK cell therapy has shown limited benefit in treating patients with metastatic solid tumors.

Familial coaggregation and shared genetic influence between major depressive disorder and gynecological diseases.

The mechanism underlying the co-occurrence of major depressive disorder (MDD) and gynecological diseases remains unclear. This study aimed to investigate the familial co-aggregation and shared genetic loading between MDD and gynecological diseases, namely dysmenorrhea, endometriosis, uterine leiomyomas (UL), and polycystic ovary syndrome (PCOS). Overall, 2,121,632 females born 1970-1999 with parental information were enrolled from the Taiwan National Health Insurance Research Database (NHIRD); 25,142 same-sex twins and 951,779 persons with full-sibling(s) were selected.

Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial.

Background/aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population.

Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal.

A population-based study of familial coaggregation and shared genetic etiology of psychiatric and gastrointestinal disorders.

Background: It has been proposed that having a psychiatric disorder could increase the risk of developing a gastrointestinal disorder, and vice versa. The role of familial coaggregation and shared genetic loading between psychiatric and gastrointestinal disorders remains unclear.

Methods: This study used the Taiwan National Health Insurance Research Database; 4,504,612 individuals born 1970-1999 with parental information, 51,664 same-sex twins, and 3,322,959 persons with full-sibling(s) were enrolled.

Causal Mediation Analyses for the Natural Course of Hepatitis C: A Prospective Cohort Study.

Background: Hepatitis C virus (HCV) infection is a systemic disease. However, the relative contribution of intrahepatic and extrahepatic diseases to mediating HCV-induced mortality is unclear, albeit critical in resource allocation for reducing preventable deaths. To this end, this study comprehensively quantified the extent to which intrahepatic and extrahepatic diseases mediate HCV-induced mortality.

Identifying pleiotropic genes via the composite test amidst the complexity of polygenic traits.

Identifying the causal relationship between genotype and phenotype is essential to expanding our understanding of the gene regulatory network spanning the molecular level to perceptible traits. A pleiotropic gene can act as a central hub in the network, influencing multiple outcomes. Identifying such a gene involves testing under a composite null hypothesis where the gene is associated with, at most, one trait.

SpliceAPP: an interactive web server to predict splicing errors arising from human mutations.

Background: Splicing variants are a major class of pathogenic mutations, with their severity equivalent to nonsense mutations. However, redundant and degenerate splicing signals hinder functional assessments of sequence variations within introns, particularly at branch sites. We have established a massively parallel splicing assay to assess the impact on splicing of 11,191 disease-relevant variants.

Exposure to ambient temperature and heat index in relation to DNA methylation age: A population-based study in Taiwan.

Background: Climate change caused an increase in ambient temperature in the past decades. Exposure to high ambient temperature could result in biological aging, but relevant studies in a warm environment were lacking. We aimed to study the exposure effects of ambient temperature and heat index (HI) in relation to age acceleration in Taiwan, a subtropical island in Asia.

Immunometabolic features of natural killer cells are associated with infection outcomes in critical illness.

Immunosuppression increases the risk of nosocomial infection in patients with chronic critical illness. This exploratory study aimed to determine the immunometabolic signature associated with nosocomial infection during chronic critical illness. We prospectively recruited patients who were admitted to the respiratory care center and who had received mechanical ventilator support for more than 10 days in the intensive care unit.

Genome-wide multimediator analyses using the generalized Berk-Jones statistics with the composite test.

Motivation: Mediation analysis is performed to evaluate the effects of a hypothetical causal mechanism that marks the progression from an exposure, through mediators, to an outcome. In the age of high-throughput technologies, it has become routine to assess numerous potential mechanisms at the genome or proteome scales. Alongside this, the necessity to address issues related to multiple testing has also arisen.

Unified semicompeting risks analysis of hepatitis natural history through mediation modeling.

Natural history of hepatitis B or C is comprised of multiple milestones such as liver cirrhosis and liver cancer. To fully characterize its natural course, semicompeting risks represent a common problem where liver cirrhosis and liver cancer are both of interest, but only the former may be censored by the latter. Copula, frailty and multistate models serve as well-established analytics for semicompeting risks.

Model-based hypothesis tests for the causal mediation of semi-competing risks.

Analyzing the causal mediation of semi-competing risks has become important in medical research. Semi-competing risks refers to a scenario wherein an intermediate event may be censored by a primary event but not vice versa. Causal mediation analyses decompose the effect of an exposure on the primary outcome into an indirect (mediation) effect: an effect mediated through a mediator, and a direct effect: an effect not through the mediator.