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Cell-free DNA circulates in blood bound to nucleosomes, forming cell-free chromatin (cfChromatin) that retains epigenetic features, including nucleosome positioning and histone modifications. cfChromatin provides a rich source of cancer biomarkers; however, low abundance of tumor-derived cfChromatin and limited availability of clinical samples pose challenges for liquid biopsy research. To address this, we developed a framework to simulate cfChromatin nucleosomal distributions using...

Precision oncology involves the use of predictive biomarkers to personalize treatment. However, for most cancer therapeutics or combination regimens, effective biomarkers have been elusive. This challenge has fuelled efforts to interrogate increasingly diverse and complex clinical and molecular determinants of treatment response. Some molecular predictors have been identified (for example, based on analysis of transcriptomic or imaging data), although the limited reproducibility and robustness...

The 19^(th) Workshop on Recent Issues in Bioanalysis (19^(th) WRIB) took place in New Orleans, LA, USA on April 7-11, 2025. Over 1200 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 19^(th) WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of...

We hypothesized that transcriptomic features among disease-driving hematopoietic stem and progenitor cells (HSPC) could improve the current paradigm for risk stratification in myelofibrosis (MF). Therefore, we performed bulk RNA-seq on blood from 358 MF patients split into training and test cohorts (ClinicalTrials.gov Identifier: NCT02760238). Single-cell (sc) RNA-seq data from Lin-CD34+ MF HSPCs were used to guide the development of a prognostic model trained on the bulk RNA-seq data. A...

Phage genomes integrated within bacterial genomes, known as prophages, frequently encode proteins that provide defense against further phage infection. These proteins often function by altering the cell surface and preventing phages from attaching to their host receptor. Here, we describe prophage-encoded proteins that resemble FimU, a component of the Pseudomonas aeruginosa type IV pilus. These phage FimU proteins are incorporated into the pilus without altering its function, yet they mediate...

Background/Objectives: AXL, a receptor tyrosine kinase of the TAM family, has emerged as a key target in cancer therapy due to its role in tumour growth, metastasis, immune evasion, and therapy resistance. SLC-391, a novel, orally bioavailable and selective AXL inhibitor, has demonstrated potent anti-tumour effects in preclinical studies. This first-in-human, open-label, multi-centre Phase I clinical trial (NCT03990454) was conducted to evaluate the safety, tolerability, pharmacokinetics (PK),...

PURPOSE/BACKGROUND: In patients with major depressive disorder (MDD), anxiety symptoms are common and associated with reduced treatment response. In an 8-week, phase 4, open-label study (ENGAGE), patients with MDD and inadequate antidepressant treatment response showed improvements in patient life engagement, depressive symptoms, and anxiety symptoms following treatment with adjunctive brexpiprazole 0.5 to 2 mg/d. This post hoc analysis of ENGAGE aimed to characterize the utility of adjunctive...

CONCLUSIONS: The inability to enjoy sensory experiences and the lack of interest in food and social activities distinctly predict outcomes with serotonergic versus dopaminergic pharmacotherapy. These findings require replication and extension to other treatments.

INTRODUCTION: Synaptic spine loss in Alzheimer's disease (AD) contributes to cognitive decline. p21-activated kinase 1 (PAK1), a regulator of spine integrity, is aberrantly activated in AD. We investigated whether PAK1 inhibition might preserve dendritic spines in vitro and in vivo.

ObjectivesCurrent pharmacological antidepressant treatments suffer from low remission rates and slow initiation of therapeutic effects. In addition, the development of new antidepressant treatments is confounded by the lack of consensus on efficient and valid neurophysiological targets. Temporal complexity is an alternative measure of dynamic brain activity that estimates brain signal variability at several timescales. It can be easily extracted from non-invasive brain recordings and provides...

CONCLUSION: All data, protocols, reagent sets, and chemical tools are made widely available on the AD Knowledge Portal with no intellectual property claims. Target Risk Scores and biodomains are accessible through Agora. For more information and the full target portfolio see www.treatad.org.

The basal ganglia (BG) are conserved brain regions essential for motor control, learning, emotion, and cognition, and are implicated in neurological and psychiatric disease. Yet a unified cross-species taxonomy of BG cell types is lacking, limiting translation of BG circuit mechanisms, interpretation of human genetic risk, and development of cell type-targeted tools. We present a multiomic consensus atlas of 1.8 million nuclei from human, macaque, and marmoset spanning eight BG structures....

CONCLUSION: YCharOS has established characterization standards that align with funding and journal requirements, and is committed to identify reliable and accessible tools for AD research.

Tuberculosis (TB) is an ongoing global health threat that has been exacerbated by the COVID-19 pandemic. People with TB need comprehensive medical and social supports to ensure they can maintain and complete TB treatment. TB programs globally have turned to eHealth to bridge gaps in access and strengthen the circle of care around people with TB. This study evaluates the implementation of an intervention aimed at improving TB care in Shigatse, using the CFIR framework to identify factors...

CONCLUSION: Automated, AI-ENE node number is a novel risk factor for OPC that may better inform pretreatment risk stratification and decision-making.

CONCLUSION: These findings highlight the myelin-axon interface as a critical site of protein aggregation and disrupted neuro-glial communication in AD. The molecular architecture of the myelin-axon interface uncovered in this study provides a foundation for future mechanistic investigations in health and disease.

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The Reactome Pathway Knowledgebase (www.reactome.org) provides expert-curated information on human biological pathways, molecular interactions, and disease mechanisms. However, its complex data model and keyword-based search interface present accessibility barriers for non-expert users. In contrast, general-purpose conversational AI systems offer intuitive natural language interfaces but lack the domain-specificity, transparent sourcing, and factual reliability required for scientific...

Comparative genomics provides a powerful framework to uncover the molecular and evolutionary mechanisms that shape genetic diversity within and across species, revealing how shared and lineage-specific processes influence their evolutionary trajectories through time. The nematode Caenorhabditis briggsae is distributed world-wide and is a comparative model to Caenorhabditis elegans in the biology of development, cellular mechanisms, neurobiology, genetic mappings of complex traits, and genome...

Primary mismatch-repair-deficient high-grade gliomas (priMMRD-HGG) are lethal tumors characterized by hypermutation, resistance to chemoradiation and variable response to immunotherapy. To investigate the mechanisms governing the emergence of driver mutations and their impact on gliomagenesis and patient outcomes, we analyzed genomic and clinical data from 162 priMMRD-HGG. Here we identified three subgroups defined by secondary driver mutations in replicative DNA polymerases or IDH1. These...