Biology subjects

Collins, N.

Publications and source records attributed to Collins, N..

5 recordsLinked to original sources

bioRxiv2026

LeadWeaver: Topology-Aware Masked-Lead Modeling for Robust 12-Lead ECG Diagnosis

Clinical electrocardiography is organized as a structured set of correlated leads, yet most neural ECG classifiers assume that all twelve leads are present, correctly ordered, and acquired under the same device conditions at training and deployment. We propose LeadWeaver, a topology-aware ECG representation model designed for diagnosis under missing, corrupted, or device-shifted leads. LeadWeaver represents each lead as a temporal token stream, couples leads through a fixed-plus-learned physiological lead graph, and performs masked-lead latent completion rather than waveform synthesis. A reliability router estimates which observed leads should dominate each diagnostic decision, while a consistency objective aligns complete-lead and incomplete-lead predictions. We evaluate the model on PTB-XL and CPSC-style settings using complete-input diagnosis, arbitrary missing-lead subsets, lead corruption, cross-dataset transfer, calibration, and selective prediction. The central hypothesis is that robust ECG diagnosis requires explicitly modeling both inter-lead topology and uncertainty about unavailable evidence, rather than treating missing channels as zero-valued inputs.

bioinformatics↗

bioRxiv2026

Metastatic Osteosarcoma is Characterized by Loss of Osteoblastic Lineage Fidelity

Osteosarcoma (OS) is a rare and aggressive bone cancer with limited therapeutic progress in several decades. To characterize the transcriptional diversity of malignant cell states in OS, we analyzed single-nucleus RNA sequencing data from 24 tumors, including both primary and metastatic lesions. We identified a canonical osteoblastic cell state that predominated in primary tumor cells, but was dampened in metastases. Integrating tumor data with data from embryonic skeletal development and an experimental osteoblast differentiation model revealed that metastatic OS cells resemble poorly specified mesenchyme enriched for non-osseous programs. Clonal populations in metastatic samples acquired mesenchymal cell states distinct from paired primary tumors. Similar cell state shifts were evident in post-treatment primary tumors relative to paired pre-treatment samples. Our results suggest that localized post-treatment and metastatic OS malignant cells lose osteoblastic lineage fidelity, which may represent a unifying axis of disease evolution and reveal new therapeutic vulnerabilities.

Cancer Biology↗

bioRxiv2024

Metabolic Adaptations in Adult Spiny Mouse (Acomys) Cardiomyocytes Facilitate Enhanced Cardiac Recovery Following Myocardial Infarction

The adult mammalian heart has limited regenerative capacity following injury, leading to progressive heart failure and mortality. Recent studies have identified the spiny mouse (Acomys) as a unique model for mammalian cardiac regeneration, exhibiting enhanced recovery after myocardial infarction compared to commonly used laboratory mouse strains. However, the cellular and molecular mechanisms underlying this regenerative response remain poorly understood. In this study, we performed a comprehensive characterization of the metabolic adaptations to ischemic injury in cardiomyocytes of Acomys in comparison to the non-regenerative Mus Musculus. To investigate the transcriptomic and metabolomic profiles of cardiomyocytes in response to myocardial infarction, we utilized single-nucleus RNA sequencing (snRNA-seq) in sham-operated animals and 1, 3, and 7 days post-myocardial infarction. Complementary targeted metabolomics, stable isotope-resolved metabolomics, and functional mitochondrial assays were performed on heart tissues from both species to validate the transcriptomic findings and elucidate the metabolic adaptations in cardiomyocytes following ischemic injury. Transcriptomic analysis revealed that Acomys cardiomyocytes upregulate genes associated with glycolysis, the pentose phosphate pathway, and glutathione metabolism while downregulating genes involved in oxidative phosphorylation following injury. These metabolic changes were linked to decreased production of reactive oxygen species and increased antioxidant capacity, evidenced by the upregulation of genes such as Prdx1, Sod1, Sod2, and G6pd. Our targeted metabolomic studies supported these findings, showing a shift from fatty acid oxidation to glycolysis and ancillary biosynthetic pathways in Acomys cardiomyocytes post-injury. Functional mitochondrial studies indicated a higher reliance on glycolysis in Acomys compared to Mus, underscoring the unique metabolic adaptations of Acomys cardiomyocytes. Stable isotope tracing experiments confirmed a shift in glucose utilization from oxidative phosphorylation in Acomys. In conclusion, our study identifies unique metabolic adaptations in Acomys cardiomyocytes that contribute to their enhanced regenerative capacity following myocardial infarction. These findings provide novel insights into the role of metabolism in regulating cardiomyocyte proliferation and cardiac repair in adult mammals. By targeting the specific metabolic pathways and regulators identified in Acomys, such as glycolytic enzymes and PCK2, we may be able to develop innovative therapies to promote cardiac regeneration in patients with ischemic heart disease. Our work highlights the importance of metabolic flexibility in determining cardiomyocyte regenerative responses and establishes Acomys as a valuable model for studying cardiac regeneration in adult mammals. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=119 SRC="FIGDIR/small/595229v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@dba53aorg.highwire.dtl.DTLVardef@3c8a74org.highwire.dtl.DTLVardef@a60251org.highwire.dtl.DTLVardef@e2142c_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2021

Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery Against Intranasal and Intratracheal SARS-CoV-2 Challenge in Rhesus Macaques

Live oral vaccines have been explored for their protective efficacy against respiratory viruses, particularly for adenovirus serotypes 4 and 7. The potential of a live oral vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, remains unclear. In this study, we assessed the immunogenicity of live SARS-CoV-2 delivered to the gastrointestinal tract in rhesus macaques and its protective efficacy against intranasal and intratracheal SARS-CoV-2 challenge. Post-pyloric administration of SARS-CoV-2 by esophagogastroduodenoscopy resulted in limited virus replication in the gastrointestinal tract and minimal to no induction of mucosal antibody titers in rectal swabs, nasal swabs, and bronchoalveolar lavage. Low levels of serum neutralizing antibodies were induced and correlated with modestly diminished viral loads in nasal swabs and bronchoalveolar lavage following intranasal and intratracheal SARS-CoV-2 challenge. Overall, our data show that post-pyloric inoculation of live SARS-CoV-2 is weakly immunogenic and confers partial protection against respiratory SARS-CoV-2 challenge in rhesus macaques. ImportanceSARS-CoV-2 remains a global threat, despite the rapid deployment but limited coverage of multiple vaccines. Alternative vaccine strategies that have favorable manufacturing timelines, greater ease of distribution and improved coverage may offer significant public health benefits, especially in resource-limited settings. Live oral vaccines have the potential to address some of these limitations; however no studies have yet been conducted to assess the immunogenicity and protective efficacy of a live oral vaccine against SARS-CoV-2. Here we report that oral administration of live SARS-CoV-2 in non-human primates may offer prophylactic benefits, but that formulation and route of administration will require further optimization.

microbiology↗

bioRxiv2021

The anthropometric and physical qualities of womens rugby league Super League and international players; identifying differences in playing position and standard

Participation in womens rugby league has been growing since the foundation of the English womens rugby league Super League in 2017. However, the evidence base to inform womens rugby league remains sparse. This study provides the largest quantification of anthropometric and physical qualities of womens rugby league players to date, identifying differences between positions (forwards & backs) and playing standard (Womens Super League [WSL] vs. International). The height, weight, body composition, lower body strength, jump height, speed and aerobic capacity of 207 players were quantified during the pre-season period. Linear mixed models and effects sizes were used to determine differences between positions and standards. Forwards were significantly (p < 0.05) heavier (forwards: 82.5 {+/-} 14.8kg; backs: 67.7 {+/-} 9.2kg) and have a greater body fat % (forwards: 37.7 {+/-} 6.9%; backs: 30.4 {+/-} 6.3%) than backs. Backs had significantly greater lower body power measured via jump height (forwards: 23.5 {+/-} 4.4cm; backs: 27.6 {+/-} 4.9cm), speed over 10m (forwards: 2.12 {+/-} 0.14s; backs: 1.98 {+/-} 0.11s), 20m (forwards: 3.71 {+/-} 0.27s; backs: 3.46 {+/-} 0.20s), 30m (forwards: 5.29 {+/-} 0.41s; backs: 4.90 {+/-} 0.33s), 40m (forwards: 6.91 {+/-} 0.61s; backs: 6.33 {+/-} 0.46s) and aerobic capacity (forwards: 453.4 {+/-} 258.8m; backs: 665.0 {+/-} 298.2m) than forwards. Additionally, international players were found to have greater anthropometric and physical qualities in comparison to their WSL counterparts. This study adds to the limited evidence base surrounding the anthropometric and physical qualities of elite womens rugby league players. Comparative values for anthropometric and physical qualities are provided which practitioners may use to evaluate the strengths and weaknesses of players, informing training programs to prepare players for the demands of womens rugby league.

physiology↗