Distinguishing Doors and Floors on All Fours: Landmarks as Tools for Vertical Navigation Learning in Domestic Dogs ().

Spatial navigation allows animals to understand their environment position and is crucial to survival. An animal's primary mode of spatial navigation (horizontal or vertical) is dependent on how they naturally move in space. Observations of the domestic dog () have shown that they, like other terrestrial animals, navigate poorly in vertical space.

Shake It Off: Investigating the Function of a Domestic Dog Behavior in Social Contexts.

Shaking in domestic dogs-a rapid side-to-side movement of the body or head-is a commonly observed behavior, yet its function remains minimally researched. The present study aimed to investigate the use of shaking behavior in naturalistic social contexts, with the hypothesis that shaking functions as a marker of transition between behaviors or activities. In addition, as the prior literature has suggested that shaking more frequently occurred in postures or conditions of stress, either to signal stress or to mitigate it, we looked at postures related to affect before and after shaking.

The HLA-B -21 M/T dimorphism associates with disease severity in COVID-19.

Host genetics shape immune responses and influence severity of infectious diseases. The HLA-B -21 M/T dimorphism tunes the functionality of natural killer (NK) cells expressing the inhibitory receptor NKG2A. NKG2A NK cells have been reported to recognize SARS-CoV-2-infected cells, but it remains unclear whether the HLA-B -21 M/T dimorphism associates with COVID-19 severity.

End-To-End Automated Intact Protein Mass Spectrometry for High-Throughput Screening and Characterization of Bispecific and Multispecific Antibodies.

Bispecific antibodies (bsAbs) and multispecific antibodies (msAbs) represent a promising frontier in therapeutic antibody development, offering unique capabilities not achievable with traditional monoclonal antibodies. Despite their potential, significant challenges remain due to their increased molecular complexity. One prominent challenge is the correct assembly of light and heavy chains, as improper pairing leads to mispaired or incompletely assembled species that lack therapeutic efficacy and possess undesired properties, impairing the developability, manufacturability, and safety.

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guerin (BCG) is the primary treatment for non-muscle-invasive bladder cancer (NMIBC), known to stimulate inflammatory cytokines, notably interferon (IFN)-γ. We observed that prolonged IFN-γ exposure fosters adaptive resistance in recurrent tumors, aiding immune evasion and tumor proliferation. We identify HLA-E and NKG2A, part of a novel NK and T cell checkpoint pathway, as key mediators of resistance in BCG-unresponsive NMIBC.

NK Cell-Targeted Immunotherapies in Bladder Cancer: Beyond Checkpoint Inhibitors.

Background: For decades, immunotherapies have been integral for the treatment and management of bladder cancer, with immune checkpoint inhibitors (ICIs) transforming patient care in recent years. However, response rates are poor to T cell-targeted ICIs such as programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) blocking antibodies, framing a critical need for complementary immunotherapies. Promising strategies involve harnessing the activation potential of natural killer (NK) cells.

Single-Cell View of Tumor Microenvironment Gradients in Pleural Mesothelioma.

Immunotherapies have shown great promise in pleural mesothelioma (PM), yet most patients still do not achieve significant clinical response, highlighting the importance of improving the understanding of the tumor microenvironment (TME). Here, we utilized high-throughput, single-cell RNA sequencing (scRNA-seq) to de novo identify 54 expression programs and construct a comprehensive cellular catalog of the PM TME. We found four cancer-intrinsic programs associated with poor disease outcome and a novel fetal-like, endothelial cell population that likely responds to VEGF signaling and promotes angiogenesis.

Pan-cancer profiling of tumor-infiltrating natural killer cells through transcriptional reference mapping.

The functional diversity of natural killer (NK) cell repertoires stems from differentiation, homeostatic, receptor-ligand interactions and adaptive-like responses to viral infections. In the present study, we generated a single-cell transcriptional reference map of healthy human blood- and tissue-derived NK cells, with temporal resolution and fate-specific expression of gene-regulatory networks defining NK cell differentiation. Transfer learning facilitated incorporation of tumor-infiltrating NK cell transcriptomes (39 datasets, 7 solid tumors, 427 patients) into the reference map to analyze tumor microenvironment (TME)-induced perturbations.

High-dimensional single-cell analysis of human natural killer cell heterogeneity.

Natural killer (NK) cells are innate lymphoid cells (ILCs) contributing to immune responses to microbes and tumors. Historically, their classification hinged on a limited array of surface protein markers. Here, we used single-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to dissect the heterogeneity of NK cells.

A monoclonal antibody that recognizes a unique 13-residue epitope in the cytoplasmic tail of HLA-E.

The Class I MHC molecule (MHC-I) HLA-E presents peptides that are derived from the signal sequences, either those of other MHC-I products, or of viral type I membrane glycoproteins. Monoclonal antibodies with proven specificity for HLA-E, and with no cross-reactions with other MHC-I products, have yet to be described. To obtain anti-HLA-E-specific antibodies suitable for a range of applications, we generated monoclonal antibodies against a unique feature of HLA-E: its cytoplasmic tail.

Performance Evaluation of a Novel Artificial Intelligence-Assisted Digital Microscopy System for the Routine Analysis of Bone Marrow Aspirates.

Bone marrow aspiration (BMA) smear analysis is essential for diagnosis, treatment, and monitoring of a variety of benign and neoplastic hematological conditions. Currently, this analysis is performed by manual microscopy. We conducted a multicenter study to validate a computational microscopy approach with an artificial intelligence-driven decision support system.

Single-cell transcriptomic-informed deconvolution of bulk data identifies immune checkpoint blockade resistance in urothelial cancer.

Interactions within the tumor microenvironment (TME) significantly influence tumor progression and treatment responses. While single-cell RNA sequencing (scRNA-seq) and spatial genomics facilitate TME exploration, many clinical cohorts are assessed at the bulk tissue level. Integrating scRNA-seq and bulk tissue RNA-seq data through computational deconvolution is essential for obtaining clinically relevant insights.

Impact of a pharmacist-led oral chemotherapy monitoring clinic at the South Texas Veterans Health Care System.

As cancer treatments shift from traditional intravenous chemotherapy to inclusion of oral oncolytics, there is a critical need for structured oral chemotherapy monitoring and follow-up programs. To provide continuous care and minimize clinical gaps to Veterans receiving oral chemotherapy, the hematology/oncology clinical pharmacy practitioners designed and initiated a pilot, pharmacist-driven, Oral Chemotherapy Monitoring Clinic at the South Texas Veterans Health Care System supported by an oral chemotherapy certified pharmacy technician. A retrospective evaluation of patients receiving oral chemotherapy at the South Texas Veterans Health Care System was performed before (Phase I) and after (Phase II) pilot implementation to assess the impact of an Oral Chemotherapy Monitoring Clinic on compliance with drug-specific lab and symptom monitoring.

Natural Killer Cell Dysfunction In Human Bladder Cancer Is Caused By Tissue-Specific Suppression of SLAMF6 Signaling.

NK cells are innate lymphocytes critical for surveillance of viruses and tumors, however the mechanisms underlying NK cell dysfunction in cancer are incompletely understood. We assessed the effector function of NK cells from bladder cancer patients and found severe dysfunction in NK cells derived from tumors versus peripheral blood. While both peripheral and tumor-infiltrating NK cells exhibited conserved patterns of inhibitory receptor over-expression, this did not explain the observed defects in NK surveillance in bladder tumors.

Folding molecular origami from ribosomal RNA.

Approximately 80 percent of the total RNA in cells is ribosomal RNA (rRNA), making it an abundant and inexpensive natural source of long, single-stranded nucleic acid, which could be used as raw material for the fabrication of molecular origami. In this study, we demonstrate efficient and robust construction of 2D and 3D origami nanostructures utilizing cellular rRNA as a scaffold and DNA oligonucleotide staples. We present calibrated protocols for the robust folding of contiguous shapes from one or two rRNA subunits that are efficient to allow folding using crude extracts of total RNA.

Premix versus On-Demand Workflow Models in a Veterans Affairs Hematology/Oncology Pharmacy: Impact on Estimated Waste Costs and Patient Wait Time.

The balance between reducing patient wait time and mitigating waste of parenteral products has not been well described in literature. Evaluate the patient wait times and cost-effectiveness of employing a premix versus an on-demand workflow model for compounding parenteral admixtures in a hematology/oncology infusion setting. This single center, retrospective cost analysis compiled manually documented monthly waste reports and estimated drug pricing for the institution to calculate the cost of waste during both premix and on-demand compounding workflows.

Characterization of renal masses with MRI-based radiomics: assessment of inter-package and inter-observer reproducibility in a prospective pilot study.

Objectives: To evaluate radiomics features' reproducibility using inter-package/inter-observer measurement analysis in renal masses (RMs) based on MRI and to employ machine learning (ML) models for RM characterization.

Methods: 32 Patients (23M/9F; age 61.8 ± 10.