Hui Zhang

• St. Jude Children's Research Hospital

LAG3 is an inhibitory receptor that is highly expressed on exhausted T cells. Although LAG3-targeting immunotherapeutics are currently in clinical trials, how LAG3 inhibits T cell function remains unclear. Here, we show that LAG3 moved to the immunological synapse and associated with the T cell receptor (TCR)-CD3 complex in CD4+ and CD8+ T cells, i...

Activated CD8⁺ T lymphocytes differentiate into heterogeneous subsets. Using super-resolution imaging, we found that prior to the first division, dynein-dependent vesicular transport polarized active TORC1 toward the microtubule-organizing center (MTOC) at the proximal pole. This active TORC1 was physically associated with active eIF4F, required fo...

Lymphocyte activation gene 3 (LAG3) is an inhibitory receptor that is highly expressed on exhausted T cells in the tumor microenvironment. Despite over ten LAG3-targeting immunotherapeutics in clinical trials, we still do not know how LAG3 mediates its inhibitory activity. We show that LAG3 can function in the absence of MHC class II ligation and t...

BACKGROUND Although survivors of adolescent‐onset cancers are at risk of infertility, the majority desire children. Fertility preservation options are available for adolescents, but sperm banking remains underused. To the authors' knowledge, patient factors that influence decisions to bank sperm are poorly understood. METHODS A cross‐sectional stu...

Objective: To investigate the influence of parental sociodemographic, communication, and psychological factors on sperm collection attempts among at-risk adolescent males newly diagnosed with cancer. Design: Prospective, single group, observational study design. Setting: Pediatric oncology centers. Patient(s): Parents (N = 144) of 122 newly...

Purpose To estimate the prevalence of sperm banking among adolescent males newly diagnosed with cancer and to identify factors associated with banking outcomes. Patients and Methods A prospective, single-group, observational study design was used to test the contribution of sociodemographic, medical, psychological/health belief, communication, and...

Purpose: The purpose of this study was to examine provider communication and sociodemographic factors which associate with sperm banking outcomes in at-risk adolescents newly diagnosed with cancer. Methods: A prospective single-group quasi-experimental study design was used to test the contributions of provider factors on sperm banking outcomes....

Background: Retinoblastoma is typically diagnosed in young children and may present unique parenting challenges. Qualitative research suggests that parents experience distress related to the initial diagnosis and treatment that subsequently resolves. The objectives were to systematically assess parenting stress over time in parents of young childr...

Mean-based semi-parametric regression models such as the popular generalized estimating equations are widely used to improve robustness of inference over parametric models. Unfortunately, such models are quite sensitive to outlying observations. The Wilcoxon-score-based rank regression (RR) provides more robust estimates over generalized estimating...

Zero-inflated count outcomes arise quite often in research and practice. Parametric models such as the zero-inflated Poisson and zero-inflated negative binomial are widely used to model such responses. Like most parametric models, they are quite sensitive to departures from assumed distributions. Recently, new approaches have been proposed to provi...

Power analysis for cluster randomized control trials is difficult to perform when a binary response is modeled using the generalized linear mixed-effects model (GLMM). Although methods for clustered binary responses exist such as the generalized estimating equations, they do not apply to the context of GLMM. Also, because popular statistical packag...

Objective: To examine adjustment in parents of children with cancer using a design that minimizes focusing effects and allows for direct comparison with parents of healthy children. Method: Parents of 305 children with cancer and a demographically similar sample of 231 parents of healthy children were evaluated using diagnostic interviews for po...

Taking a genome-wide association study approach, we identified inherited genetic variations in ACYP2 associated with cisplatin-related ototoxicity (rs1872328: P = 3.9 × 10(-8), hazard ratio = 4.5) in 238 children with newly diagnosed brain tumors, with independent replication in 68 similarly treated children. The ACYP2 risk variant strongly predisp...

This study examined whether an intervention designed to reduce secondhand smoke exposure (SHSe) among children being treated for cancer had effects in the specific setting of a motor vehicle. The parents or guardians (n = 71) of children being treated for cancer were randomized to either a behavioral secondhand smoke (SHS) reduction program or a st...

Outliers are commonly observed in psychosocial research, generally resulting in biased estimates when comparing group differences using popular mean-based models such as the analysis of variance model. Rank-based methods such as the popular Mann–Whitney–Wilcoxon (MWW) rank sum test are more effective to address such outliers. However, available met...

Purpose: To examine the influence of age and conditioning with total-body irradiation (TBI) on the trajectory of cognitive functioning after treatment with pediatric hematopoietic stem-cell transplantation (SCT). Patients and methods: Pediatric patients who were scheduled to undergo a SCT were eligible for the study, with 315 patients completing...

Introduction: The current study examined home and full (i.e., home plus car) smoking ban adoption as secondary outcomes to a randomized controlled trial targeting reduced secondhand smoke exposure (SHSe) for children under treatment for cancer. Methods: Families with at least 1 adult smoker who reported SHSe for their children (n = 119) were ran...

Purpose: To determine the developmental trajectory of early cognitive and adaptive skills in young children with retinoblastoma from diagnosis to 5 years of age. Patients and methods: Ninety-four patients with retinoblastoma treated according to an institutional protocol underwent serial assessments of cognitive and adaptive functioning at age 6...

Autoreactive T cells infiltrating the target organ can possess a broad TCR affinity range. However, the extent to which such biophysical parameters contribute to T cell pathogenic potential remains unclear. In this study, we selected eight InsB9-23-specific TCRs cloned from CD4(+) islet-infiltrating T cells that possessed a relatively broad range o...

Intraclass correlation coefficients (ICC) are employed in a wide range of behavioral, biomedical, psychosocial, and health care related research for assessing reliability of continuous outcomes. The linear mixed-effects model (LMM) is the most popular approach for inference about the ICC. However, since LMM is a normal distribution-based model and...

We investigated the 5-year postsurgical developmental trajectory of working memory (WM) in children with medulloblastoma using parent and performance-based measures. This study included 167 patients treated for medulloblastoma. Serial assessments of WM occurred at predetermined time points for 5 years. There was a subtle, statistically significant...

Background The aim of this study was to prospectively examine the effects of hearing loss and posterior fossa syndrome (PFS), in addition to age at diagnosis and disease risk status, on change in intellectual and academic outcomes following diagnosis and treatment in a large sample of medulloblastoma patients.Methods Data from at least 2 cognitive...

To examine posttraumatic stress disorder and posttraumatic stress symptoms (PTSD/PTSS) in children with cancer using methods that minimize focusing effects and allow for direct comparison to peers without a history of cancer. Children with cancer (n = 255) stratified by time since diagnosis, and demographically matched peers (n = 101) were assessed...

Pediatric stem cell transplant (SCT) is a demanding procedure for children and parents. Interventions to promote positive adjustment of parents in this setting are needed. 171 patient/parent dyads from 4 sites received one of 3 interventions to reduce SCT-related distress: a child intervention with massage and humor therapy, an identical child inte...

The half-maximal inhibitory concentration IC[Formula: see text] is an important pharmacodynamic index of drug effectiveness. To estimate this value, the dose response relationship needs to be established, which is generally achieved by fitting monotonic sigmoidal models. However, recent studies on Human Immunodeficiency Virus (HIV) mutants developi...

This randomized controlled trial tested the efficacy of parent-based behavioral counseling for reducing secondhand smoke exposure (SHSe) among children with cancer. It also examined predictors of smoking and SHSe outcomes. Participants were 135 parents or guardians of nonsmoking children with cancer, <18 years, at least 30 days postdiagnosis, and l...

The physiological basis and mechanistic requirements for a large number of functional immunoreceptor tyrosine-based activation motifs (ITAMs; high ITAM multiplicity) in the complex of the T cell antigen receptor (TCR) and the invariant signaling protein CD3 remain obscure. Here we found that whereas a low multiplicity of TCR-CD3 ITAMs was sufficien...

This paper discusses regression analysis of longitudinal data in which the observation process may be related to the longitudinal process of interest. Such data have recently attracted a great deal of attention and some methods have been developed. However, most of those methods treat the observation process as a recurrent event process, which assu...

PURPOSETo examine longitudinal parent-reported social outcomes for children treated for pediatric embryonal brain tumors. PATIENTS AND METHODS Patients (N = 220) were enrolled onto a multisite clinical treatment protocol. Parents completed the Child Behavior Checklist/6-18 at the time of their child's diagnosis and yearly thereafter. A generalized...

Suicide is a major public health problem that both reflects and creates considerable human suffering. Suicide and suicide attempts are leading causes of death and morbidity worldwide at all ages. In the United States, suicide is the 11th leading cause of death, accounting for over 30,000 deaths per year. An even greater number of people attempt sui...

Poisson log-linear regression is a popular model for count responses. We examine two popular extensions of this model – the generalized estimating equations (GEE) and the generalized linear mixed-effects model (GLMM) – to longitudinal data analysis and complement the existing literature on characterizing the relationship between the two dueling par...

Longitudinal studies are quite common in modern clinical trials and cohort studies. Unlike cross-sectional designs, where observations from study subjects are available only at a single time point, individuals in longitudinal or cohort studies are assessed repeatedly over time. By taking advantages of multiple snapshots of a group over time, data f...

Abstract Differential expression analysis of sequence-count expression data involves performing a large number of hypothesis tests that compare the expression count data of each gene or transcript across two or more biological conditions. The assumptions of any specific hypothesis-testing method will probably not be valid for each of a very large n...

Recurrent event data occur in many clinical and observational studies, and in these situations, there may exist a terminal event such as death that is related to the recurrent event of interest. In addition, sometimes more than one type of recurrent events may occur, that is, one may encounter multivariate recurrent event data with some dependent t...

The generalized estimating equations (GEEs) and generalized linear mixed-effects model (GLMM) are the two most popular paradigms to extend models for cross-sectional data to a longitudinal setting. Although the two approaches yield well-interpreted models for continuous outcomes, it is quite a different story when applied to binomial responses. We...

The generalized linear mixed-effects model (GLMM) is a popular paradigm to extend models for cross-sectional data to a longitudinal setting. When applied to modeling binary responses, different software packages and even different procedures within a package may give quite different results. In this report, we describe the statistical approaches th...

Diagnostic tests are used in a wide range of behavioral, medical, psychosocial, and healthcare-related research. Test sensitivity and specificity are the most popular measures of accuracy for diagnostic tests. Available methods for analyzing longitudinal study designs assume fixed gold or reference standards and as such do not apply to studies with...

We develop a duality of sample size calculations given the odds ratio and the risk difference. Given the odds ratio, the sample size attains the minimum if and only if the risks of two groups are symmetric about 1/2, which is equivalent to that the risk difference attains the maximum. On the other hand, given the risk difference, the sample size at...

Models for longitudinal data are employed in a wide range of behavioral, biomedical, psychosocial, and health-care-related research. One popular model for continuous response is the linear mixed-effects model (LMM). Although simulations by recent studies show that LMM provides reliable estimates under departures from the normality assumption for co...