Bayesian Phylogenetic Lineage Reconstruction with Loss of Heterozygosity Mutations Derived from Single-Cell RNA Sequencing.

Mutations are acquired frequently, such t`hat each cell's genome inscribes its history of cell divisions. Loss of heterozygosity (LOH) accumulates throughout the genome, offering large encoding capacity for phylogenetic inference of cell lineage.In this chapter, we demonstrate a method, using single-cell RNA sequencing, for reconstructing cell lineages from inferred LOH events in a Bayesian manner, annotating the lineage with cell phenotypes, and marking developmental time points based on X-chromosome inactivation.

Effects of water and sediment chemistry variables on aquatic macroinvertebrate community structuring in a subtropical Austral river system.

Riverine physical and chemical characteristics are influencing ecosystem integrity while shaping and impacting species richness and diversity. Changes in these factors could potentially influence community structuring through competition, predation and localised species extinctions. In this study, eight sampling sites over multiple seasons were assessed along the streams draining the City of Nelspruit, South Africa, to examine river health based on water and sediment quality, while using macroinvertebrates as bioindicators for pollution.

Water quality assessment of Johor River Basin, Malaysia, using multivariate analysis and spatial interpolation method.

In the Johor River Basin, a comprehensive analysis was conducted on 24 water environmental parameters across 33 sampling sites over 3 years, encompassing both dry and wet seasons. A total of 396 water samples were collected and analyzed to calculate the Water Quality Index (WQI). To further assess water quality and pinpoint potential pollution sources, multivariate techniques such as principal component analysis (PCA) and cluster analysis (CA), alongside spatial analysis using inverse distance weighted (IDW) interpolation, were employed.

Resistance training protects the hippocampus and precuneus against atrophy and benefits white matter integrity in older adults with mild cognitive impairment.

Mild cognitive impairment (MCI) refers to cognitive alterations with preservation of functionality. Individuals with this diagnosis have a higher risk of developing dementia. Non-pharmacological interventions, such as physical exercise, are beneficial for the cognition of this population.

The radiologic spectrum of neuroendocrine tumors in emergent care.

Neuroendocrine tumors (NETs) are a diverse group of neoplasms whose prevalence is increasing globally, primarily due to advancements in diagnostic techniques. NETs arise from cells of the diffuse endocrine system and can occur in various locations, with the gastrointestinal tract being the most common. Their diverse clinical presentations, which range from asymptomatic to severe hormone-induced syndromes, pose significant diagnostic challenges.

Intra- and interobserver agreement in evaluation of image-defined risk factors on computed tomography in pediatric neuroblastoma.

Background: Image-defined risk factors (IDRFs) were introduced to provide a consensus approach for pre-treatment risk stratification on computed tomography (CT) and magnetic resonance imaging (MRI) in patients with neuroblastoma.

Objective: To assess the intra- and inter-reader agreement of radiologists in identifying IDRFs on CT.

Materials And Methods: Approval for this retrospective study was granted by our institutional research ethics board with a waiver of consent.

Artificial intelligence-based cardiovascular/stroke risk stratification in women affected by autoimmune disorders: a narrative survey.

Women are disproportionately affected by chronic autoimmune diseases (AD) like systemic lupus erythematosus (SLE), scleroderma, rheumatoid arthritis (RA), and Sjögren's syndrome. Traditional evaluations often underestimate the associated cardiovascular disease (CVD) and stroke risk in women having AD. Vitamin D deficiency increases susceptibility to these conditions.

Impact of delayed adoption of novel atrial fibrillation treatments.

Objective: To examine the relationship between adoption of direct oral anticoagulants (DOACs) and health and cost outcomes for patients with nonvalvular atrial fibrillation.

Study Design: Real-world cohort study.

Methods: US adults who newly initiated treatment for nonvalvular atrial fibrillation were identified from claims data.

Cost-effectiveness of a multicancer early detection test in the US.

Objectives: Multicancer early detection (MCED) testing could result in earlier cancer diagnosis, thereby improving survival and reducing treatment costs. This study evaluated the cost-effectiveness of MCED testing plus usual care (UC) screening while accounting for the impact of clinical uncertainty and population heterogeneity for an MCED test with broad coverage of solid cancer incidence.

Study Design: Cost-effectiveness analysis of MCED testing plus UC vs UC alone in an adult population in the US.

Adherence to positive airway pressure therapy in patients with Down syndrome: assessing cloud based monitoring data.

Study Objectives: Obstructive sleep apnea (OSA) is common in Down syndrome (DS) with many patients prescribed positive airway pressure (PAP) therapy. This study evaluates PAP adherence and identifies factors influencing adherence.

Methods: Retrospective analysis of electronic health records and cloud-based PAP therapy data from DS patients at Rady Children's Hospital, San Diego, CA.

Prediction of antimicrobial susceptibility of pneumococci based on whole-genome sequencing data: a direct comparison of two genomic tools to conventional antimicrobial susceptibility testing.

Determination of antimicrobial resistance (AMR) in pneumococcal isolates is important for surveillance purposes and in a clinical context. Antimicrobial susceptibility testing (AST) of pneumococci is complicated by the need for exact minimal inhibitory concentrations (MICs) of beta-lactam antibiotics. Two next-generation sequencing (NGS) analysis tools have implemented the prediction of AMR in their analysis workflow, including the prediction of MICs: Pathogenwatch (https://pathogen.

The combination of physiology and machine learning for prediction of CPAP pressure and residual AHI in OSA.

Continuous positive airway pressure (CPAP) is the treatment of choice for obstructive sleep apnea (OSA); however some people have residual respiratory events or require significantly higher CPAP pressure while on therapy. Our objective was to develop predictive models for CPAP outcomes and assess whether the inclusion of physiological traits enhances prediction. We constructed predictive models from baseline information for subsequent residual apnea-hypopnea index (AHI) and optimal CPAP pressure.

Patient- and Provider-Perceived Barriers to Reconstructive Surgery for Patients With Upper Limb Spasticity.

Purpose: The benefits of upper-extremity reconstructive surgery for patients with spastic deformities are well documented, but a small portion of eligible patients undergo surgery. We sought to determine perceptions of upper-extremity reconstructive surgery among brain injury patients and nonsurgical providers to identify potential barriers to surgical evaluation.

Methods: Electronic medical records at a referral center were reviewed for patients diagnosed with upper limb spasticity following brain injury.

Physician Experiences With Implementing a Virtual Observation Unit in Emergency Medicine.

Study Objective: Physician experiences with new care models like the virtual observation unit in emergency departments (EDs) can offer important insights. Virtual observation unit leverages telehealth, remote monitoring, and mobile integrated health to enable home-based ED-level care. We explored physicians' experience with delivering care in the virtual observation unit and perceived effect of this new model.

A phase I clinical trial adding OX40 agonism to in situ therapeutic cancer vaccination in patients with low-grade B cell lymphoma highlights challenges in translation from mouse to human studies.

Purpose: Activating T cell costimulatory receptors is a promising approach for cancer immunotherapy. In preclinical work, adding an OX40 agonist to in situ vaccination (ISV) with SD101, a TLR9 agonist, was curative in a mouse model of lymphoma. We sought to test this combination in a Phase I clinical trial for patients with low-grade B cell lymphoma.

Lung cancer-intrinsic SOX2 expression mediates resistance to checkpoint blockade therapy by inducing Treg cell-dependent CD8+ T-cell exclusion.

Tumor cell-intrinsic signaling pathways can drastically affect the tumor immune microenvironment, promoting tumor progression and resistance to immunotherapy by excluding immune-cell populations from the tumor. Several tumor cell-intrinsic pathways have been reported to modulate myeloid-cell and T-cell infiltration creating "cold" tumors. However, clinical evidence suggests that excluding cytotoxic T cells from the tumor core also mediates immune evasion.

TOP1 Mutations and Cross-Resistance to Antibody-Drug Conjugates in Patients with Metastatic Breast Cancer.

Purpose: Antibody-drug conjugates (ADCs) harboring topoisomerase I (TOP1) inhibitor payloads have improved survival for patients with metastatic breast cancer (MBC). However, knowledge of ADC resistance mechanisms and potential impact on sequential use of ADCs is limited. Here, we report the incidence and characterization of TOP1 mutations arising in the setting of ADC resistance in MBC.

Structurally-oriented classification of FOXA1 alterations identifies prostate cancers with opposing clinical outcomes and distinct molecular and immunologic subtypes.

Purpose: 10-15% of prostate cancers (PCa) harbor recurrent FOXA1 aberrations whereby the alteration type and the effect on the forkhead( FKH) domain impacts protein-function. We developed a FOXA1 classification system to inform clinical management.

Experimental Design: 5,014 PCa were examined using whole exome and transcriptome sequencing from the Caris database.

MICAL2 Promotes Pancreatic Cancer Growth and Metastasis.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid cancers; thus, identifying more effective therapies is a major unmet need. In this study, we characterized the super enhancer (SE) landscape of human PDAC to identify drivers of the disease that might be targetable. This analysis revealed MICAL2 as a super enhancer-associated gene in human PDAC, which encodes the flavin monooxygenase MICAL2 that induces actin depolymerization and indirectly promotes SRF transcription by modulating the availability of serum response factor coactivators myocardin-related transcription factors (MRTF-A and MRTF-B).