A computational framework for mapping isoform landscape and regulatory mechanisms from spatial transcriptomics data.

Unlabelled: Transcript diversity including splicing and alternative 3'end usage is crucial for cellular identity and adaptation, yet its spatial coordination remains poorly understood. Here, we present SPLISOSM (SpatiaL ISOform Statistical Modeling), a computational framework for detecting isoform-resolution patterns from spatial transcriptomics data. SPLISOSM leverages multivariate testing to account for spot- and isoform-level dependencies, demonstrating robust and theoretically grounded performance on sparse data.

Perplexity as a Metric for Isoform Diversity in the Human Transcriptome.

Long-read sequencing (LRS) has revealed a far greater diversity of RNA isoforms than earlier technologies, increasing the critical need to determine which, and how many, isoforms per gene are biologically meaningful. To define the space of relevant isoforms from LRS, many existing analysis pipelines rely on arbitrary expression cutoffs, but a single threshold cannot accommodate the broad variability in isoform complexity across genes, cell-types, and disease states captured by LRS. To address this, we propose using -an interpretable measure derived from entropy-that quantifies the effective number of isoforms per gene based on the full, unfiltered isoform ratio distribution.

Pathogenic TP73 variants may lead to premature ovarian insufficiency by hyperactivating primordial follicles via the PI3K/AKT/FOXO3A pathway.

Background: Premature ovarian insufficiency (POI) is characterized by primary or secondary amenorrhoea before the age of 40, alongside high levels of follicle-stimulating hormone (FSH) and reduced levels of estrogen, severely impairing female fertility. This study aimed to identify novel genetic factors contributing to POI.

Methods: We performed whole-exome sequencing and whole-genome sequencing on 93 patients with POI and 465 healthy female controls to identify variants in the TP73 gene.

Meta-analysis of Tuina combined with other treatments for obesity.

Background: To evaluate the efficacy of Tuina (a form of Chinese therapeutic massage) combined with complementary therapies (such as auricular plaster therapy, acupuncture, or herbal medicine) on improving weight, body mass index (BMI), and body composition in obese patients.

Methods: A comprehensive search of CNKI, Wanfang, PubMed, Cochrane Library, and Web of Science (from January 2004 to March 2024) was conducted for randomized controlled trials (RCTs). Heterogeneity among studies was quantified using the I² statistic, and fixed-effects or random-effects models were applied as appropriate.

Investigating the factors influencing users' adoption of artificial intelligence health assistants based on an extended UTAUT model.

As an emerging healthcare technology, artificial intelligence (AI) health assistants have garnered significant attention. However, the acceptance and intention of ordinary users to adopt AI health assistants require further exploration. This study aims to identify factors influencing users' intentions to use AI health assistants and enhance understanding of the acceptance mechanisms for this technology.

An investigation into the acceptance of intelligent care systems: an extended technology acceptance model (TAM).

With the aging population trend becoming increasingly pronounced, the health issues of elderly individuals living alone have become a focal point of societal concern. This study aims to investigate guardians of the elderly's acceptance of intelligent care systems for the elderly. This system integrates millimeter-wave radar and image recognition technologies to monitor the health status of seniors in real time and automatically alert their children in emergency situations.

Huangkui capsules regulate tryptophan metabolism to improve diabetic nephropathy through the Keap1/Nrf2/HO-1 pathway.

Background: Diabetic nephropathy (DN) is a serious complication of diabetes and one of the leading causes of end-stage renal disease. Huangkui capsule (HKC), a traditional Chinese patent medicine, is widely used in clinical practice for the treatment of chronic glomerulonephritis. However, the therapeutic effects and underlying mechanisms of HKC in DN remain poorly understood.

A niche driven mechanism determines response and a mutation-independent therapeutic approach for myeloid malignancies.

Myeloid cancers such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) remain resistant to standard of care (SOC) and targeted therapies. In this study, we demonstrate that responsiveness to therapy is associated with activation of β-catenin-JAG1 in osteoblastic cells of patients treated with all-trans-retinoic acid (ATRA). ATRA suppresses β-catenin activity in patients and leukemic mice.

Validating the accuracy of Omron J760 electronic blood pressure monitor in the general population according to AAMI/ESH/ISO (ISO 81060-2:2018) + AMD1:2020.

Purpose: The accuracy of the Omron J760 electronic blood pressure (BP) monitor for upper arm BP measurement in the adult general population was validated following the AAMI/ESH/ISO (ISO 81060-2:2018) + Amd1:2020 protocol. We expect that this device can be used for home blood pressure monitoring, with its measurements serving as a clinical reference.

Methods: Subjects meeting the age, gender, BP, and cuff distribution criteria as specified by the AAMI/ESH/ISO (ISO 81060-2:2018) + Amd1:2020 were recruited.

Effectiveness and safety of acupuncture for melasma: A meta-analysis of randomized controlled trials.

Background: Treating melasma remains challenging. We conducted a meta-analysis to assess the effectiveness and safety of acupuncture as a treatment option.

Methods: We searched three English and four Chinese databases up to January 2, 2024.

A foundation model of transcription across human cell types.

Transcriptional regulation, which involves a complex interplay between regulatory sequences and proteins, directs all biological processes. Computational models of transcription lack generalizability to accurately extrapolate to unseen cell types and conditions. Here we introduce GET (general expression transformer), an interpretable foundation model designed to uncover regulatory grammars across 213 human fetal and adult cell types.

Disentangling Interpretable Factors with Supervised Independent Subspace Principal Component Analysis.

The success of machine learning models relies heavily on effectively representing high-dimensional data. However, ensuring data representations capture human-understandable concepts remains difficult, often requiring the incorporation of prior knowledge and decomposition of data into multiple subspaces. Traditional linear methods fall short in modeling more than one space, while more expressive deep learning approaches lack interpretability.

The impact of 3 different dietary interventions on overweight or obese adults: A network meta-analysis.

Objective: This network meta-analysis aims to investigate and compare the effectiveness of 3 dietary interventions - Mediterranean, ketogenic, and low-fat diet - on overweight and obese adults, with a comparison to traditional low-calorie diet.

Methods: A systematic review was conducted in both Chinese and English databases, including the China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), SinoMed, PubMed, Web of Science, Cochrane Library and Embase to identify relevant randomized controlled trials (RCTs) up to January 31, 2024. Two researchers independently screened and extracted data from the identified literature.

GET: a foundation model of transcription across human cell types.

Transcriptional regulation, involving the complex interplay between regulatory sequences and proteins, directs all biological processes. Computational models of transcription lack generalizability to accurately extrapolate in unseen cell types and conditions. Here, we introduce GET, an interpretable foundation model designed to uncover regulatory grammars across 213 human fetal and adult cell types.

The Influence of Thermal Parameters on the Self-Nucleation Behavior of Polyphenylene Sulfide (PPS) during Secondary Thermoforming.

During the secondary thermoforming of carbon fiber-reinforced polyphenylene sulfide (CF/PPS) composites, a vital material for the aerospace field, varied thermal parameters profoundly influence the crystallization behavior of the PPS matrix. Notably, PPS exhibits a distinctive self-nucleation (SN) behavior during repeated thermal cycles. This behavior not only affects its crystallization but also impacts the processing and mechanical properties of PPS and CF/PPS composites.

Smoother: a unified and modular framework for incorporating structural dependency in spatial omics data.

Spatial omics technologies can help identify spatially organized biological processes, but existing computational approaches often overlook structural dependencies in the data. Here, we introduce Smoother, a unified framework that integrates positional information into non-spatial models via modular priors and losses. In simulated and real datasets, Smoother enables accurate data imputation, cell-type deconvolution, and dimensionality reduction with remarkable efficiency.

A transcriptome-based single-cell biological age model and resource for tissue-specific aging measures.

Accurately measuring biological age is crucial for improving healthcare for the elderly population. However, the complexity of aging biology poses challenges in how to robustly estimate aging and interpret the biological significance of the traits used for estimation. Here we present SCALE, a statistical pipeline that quantifies biological aging in different tissues using explainable features learned from literature and single-cell transcriptomic data.

Immunotherapy for breast cancer using EpCAM aptamer tumor-targeted gene knockdown.

New strategies for cancer immunotherapy are needed since most solid tumors do not respond to current approaches. Here we used epithelial cell adhesion molecule EpCAM (a tumor-associated antigen highly expressed on common epithelial cancers and their tumor-initiating cells) aptamer-linked small-interfering RNA chimeras (AsiCs) to knock down genes selectively in EpCAM tumors with the goal of making cancers more visible to the immune system. Knockdown of genes that function in multiple steps of cancer immunity was evaluated in aggressive triple-negative and HER2 orthotopic, metastatic, and genetically engineered mouse breast cancer models.

Single-cell transcriptome profiling reveals neutrophil heterogeneity in homeostasis and infection.

The full neutrophil heterogeneity and differentiation landscape remains incompletely characterized. Here, we profiled >25,000 differentiating and mature mouse neutrophils using single-cell RNA sequencing to provide a comprehensive transcriptional landscape of neutrophil maturation, function and fate decision in their steady state and during bacterial infection. Eight neutrophil populations were defined by distinct molecular signatures.

The influence of pore shapes on the band structures in phononic crystals with periodic distributed void pores.

The influence of the pore shapes on the band structures in phononic crystals with periodic distributed void pores are investigated in this paper. By using finite difference time domain (FDTD) scheme, the dispersion properties of the in-plane x-y mode waves in the materials with triangular, circular or square pores are discussed respectively. The influence of the pore shapes and the porosity on the band gap structures is analyzed.