Uncertainty-aware probabilistic graph neural networks for road-level traffic crash prediction.

Traffic crashes present substantial challenges to human safety and socio-economic development in urban areas. Developing a reliable and responsible traffic crash prediction model is crucial to address growing public safety concerns and improve the safety of urban mobility systems. Traditional methods face limitations at fine spatiotemporal scales due to the sporadic nature of high-risk crashes and the predominance of non-crash characteristics.

The biogenesis and transport of triglyceride-rich lipoproteins.

Triglyceride-rich lipoproteins (TRLs) play essential roles in human health and disease by transporting bulk lipids into the circulation. This review summarizes the fundamental mechanisms and diverse factors governing lipoprotein production, secretion, and regulation. Emphasizing the broader implications for human health, we outline the intricate landscape of lipoprotein research and highlight the potential coordination between the biogenesis and transport of TRLs in physiology, particularly the unexpected coupling of metabolic enzymes and transport machineries.

Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Stapokibart in Healthy Volunteers and Adult Subjects with Atopic Dermatitis.

Introduction: Stapokibart, a novel humanized anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits the signaling of IL-4 and IL-13, which are key drivers of type 2 inflammation in atopic dermatitis (AD). This study aimed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of stapokibart in a randomized, double-blind, placebo-controlled single ascending dose (SAD) study and a multiple ascending dose (MAD) study.

Methods: The SAD study enrolled 33 healthy male adults aged 18-65 years at a single center.

A pharmacokinetic study comparing the biosimilar HEC14028 and Dulaglutide (Trulicity®) in healthy Chinese subjects.

This study aimed to evaluate the pharmacokinetics (PKs), safety, and immunogenicity of the biosimilar HEC14028 compared to reference Trulicity® (dulaglutide) in healthy male Chinese subjects. This study was a single-center, randomized, open, single-dose, parallel-controlled comparative Phase I clinical trial, including a screening period of up to 14 days, a 17-day observation period after administration, and a 7-day safety follow-up period. A total of 68 healthy male subjects were randomly assigned (1:1) to the test group (HEC14028) and the reference group (dulaglutide) (single 0.

Collagen 1-mediated CXCL1 secretion in tumor cells activates fibroblasts to promote radioresistance of esophageal cancer.

Esophageal squamous-cell carcinoma (ESCC) is commonly treated with radiotherapy; however, radioresistance hinders its clinical effectiveness, and the underlying mechanism remains elusive. Here, we develop patient-derived xenografts (PDXs) from 19 patients with ESCC to investigate the mechanisms driving radioresistance. Using RNA sequencing, cytokine arrays, and single-cell RNA sequencing, we reveal an enrichment of cancer-associated fibroblast (CAF)-derived collagen type 1 (Col1) and tumor-cell-derived CXCL1 in non-responsive PDXs.

Circular RNA encoded MET variant promotes glioblastoma tumorigenesis.

Activated by its single ligand, hepatocyte growth factor (HGF), the receptor tyrosine kinase MET is pivotal in promoting glioblastoma (GBM) stem cell self-renewal, invasiveness and tumorigenicity. Nevertheless, HGF/MET-targeted therapy has shown limited clinical benefits in GBM patients, suggesting hidden mechanisms of MET signalling in GBM. Here, we show that circular MET RNA (circMET) encodes a 404-amino-acid MET variant (MET404) facilitated by the N-methyladenosine (mA) reader YTHDF2.

A Bioequivalence Study of Ezetimibe/Rosuvastatin Fixed Dose Combination (10 mg/10 mg) Versus the Individual Formulations Taken Concomitantly.

Introduction: This study evaluated the bioequivalence of ezetimibe/rosuvastatin fixed dose combination compared to the concomitant administration of individual formulations (ezetimibe and rosuvastatin) in Chinese healthy subjects under fasting conditions.

Methods: This was a phase I, randomized, open-label, two-treatment, two-period, two-sequence, crossover study conducted in healthy Chinese participants under fasting conditions. C, AUC, and AUC from test and individual reference formulations were evaluated to assess bioequivalence.

Pharmacokinetics, pharmacodynamics, safety and immunogenicity of recombinant, fully human anti-RANKL monoclonal antibody (MW031) versus denosumab in Chinese healthy subjects: a single-center, randomized, double-blind, single-dose, parallel-controlled trial.

Background: MW031 is a biosimilar candidate of denosumab (Prolia®). This study aimed to compare the pharmacokinetics, pharmacodynamics, safety and immunogenicity of MW031 to denosumab in healthy Chinese participants.

Research Design And Methods: In this single-center, randomized, double-blind, parallel-controlled, single-dose trial, participants were given 60 mg MW031 (N = 58) or denosumab (N = 61) by subcutaneous injection and observed for 140 days.

Pharmacokinetic Interactions and Tolerability of Rosuvastatin and Ezetimibe: A Randomized, Phase 1, Crossover Study in Healthy Chinese Participants.

Background And Objective: The combination of rosuvastatin and ezetimibe has promising clinical benefits with a significant safety and tolerability profile. However, there is a lack of clinical data supporting the drug-drug interaction (DDI) in Chinese population. Thus, the aim of this study is to assess the potential pharmacokinetic DDI between rosuvastatin and ezetimibe in a Chinese population.

Computational Identification of Preneoplastic Cells Displaying High Stemness and Risk of Cancer Progression.

Unlabelled: Evidence points toward the differentiation state of cells as a marker of cancer risk and progression. Measuring the differentiation state of single cells in a preneoplastic population could thus enable novel strategies for early detection and risk prediction. Recent maps of somatic mutagenesis in normal tissues from young healthy individuals have revealed cancer driver mutations, indicating that these do not correlate well with differentiation state and that other molecular events also contribute to cancer development.

The similarity of pharmacokinetics, pharmacodynamics, safety, and immunogenicity between recombinant fully human anti-RANKL monoclonal antibody injection (MW032) and denosumab (Xgeva®) in healthy Chinese subjects: A single-center, randomized, double-blind, single-dose, parallel-controlled clinical study.

Objective: To compare the pharmacokinetics (PK), pharmacodynamics (PD), safety and immunogenicity between MW032 (denosumab biosimilar) and Xgeva® (denosumab) in healthy Chinese subjects.

Study Design: In this single-center, randomized, double-blind, single-dose, parallel-controlled design study, 120 healthy male subjects were randomized 1:1 to receive a single dose subcutaneous injection of 120 mg MW032 or Xgeva®, with an observation period of 161 days. The primary endpoint was the bioequivalence of PK parameters (C, AUC), and secondary endpoints including PD parameters, safety, and immunogenicity.

Trends in Diabetes Mortality in Urban and Rural China, 1987-2019: A Joinpoint Regression Analysis.

Purpose: Diabetes mellitus is emerging as an epidemic worldwide, and the incidence and prevalence of diabetes have drastically changed in China over the past 30 years, but data on its mortality rate are scarce. This study aimed to analyze the time trends of mortality rates among patients with diabetes in the rural and urban population in China between 1987 and 2019.

Methods: The research data come from China's annual report on national health statistics and the Chinese Health Statistics Yearbook.

A body map of somatic mutagenesis in morphologically normal human tissues.

Somatic mutations that accumulate in normal tissues are associated with ageing and disease. Here we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies of 9 organs from 5 donors. We found that somatic mutation accumulations and clonal expansions were widespread, although to variable extents, in morphologically normal human tissues.

Novel Risk Loci Associated With Genetic Risk for Bipolar Disorder Among Han Chinese Individuals: A Genome-Wide Association Study and Meta-analysis.

Importance: The genetic basis of bipolar disorder (BD) in Han Chinese individuals is not fully understood.

Objective: To explore the genetic basis of BD in the Han Chinese population.

Design, Setting, And Participants: A genome-wide association study (GWAS), followed by independent replication, was conducted to identify BD risk loci in Han Chinese individuals.

Using community health workers to deliver a scalable integrated parenting program in rural China: A cluster-randomized controlled trial.

Inadequate care during early childhood can lead to long-term deficits in skill development. Parenting programs are promising tools for improving parenting practices and opportunities for healthy development. We implemented a non-masked cluster-randomized controlled trial in rural China in order to assess the effectiveness of an integrated home-visitation program that includes both psychosocial stimulation and health promotion at fostering development and health outcomes of infants and toddlers in rural China.

A Culture-Behavior-Brain Loop Model of Human Development.

Increasing evidence suggests that cultural influences on brain activity are associated with multiple cognitive and affective processes. These findings prompt an integrative framework to account for dynamic interactions between culture, behavior, and the brain. We put forward a culture-behavior-brain (CBB) loop model of human development that proposes that culture shapes the brain by contextualizing behavior, and the brain fits and modifies culture via behavioral influences.

Decoding Visual Location From Neural Patterns in the Auditory Cortex of the Congenitally Deaf.

Sensory cortices of individuals who are congenitally deprived of a sense can exhibit considerable plasticity and be recruited to process information from the senses that remain intact. Here, we explored whether the auditory cortex of congenitally deaf individuals represents visual field location of a stimulus-a dimension that is represented in early visual areas. We used functional MRI to measure neural activity in auditory and visual cortices of congenitally deaf and hearing humans while they observed stimuli typically used for mapping visual field preferences in visual cortex.

A new high-resolution N2O emission inventory for China in 2008.

The amount and geographic distribution of N2O emissions over China remain largely uncertain. In this study, county-level and 0.1° × 0.

Calcite microneedle arrays produced by inorganic ion-assisted anisotropic dissolution of bulk calcite crystal.

Besides studies on the mineralization process, research on the demineralization of minerals provides another way to understand the crystallization mechanism of biominerals and fabricate crystals with complicated morphologies. The formation of ordered arrays of c-axis-oriented calcite microneedles with a tri-symmetric structure and lengths of more than 20 μm was realized on a large scale for the first time through anisotropic dissolution of calcite substrates in undersaturated aqueous solution in the presence of ammonium salts. The lengths and the aspect ratios of the calcite microneedles can be tuned by simply changing the concentrations of the ammonium salts and the dissolution time.