Aim: To synthesize the experiences of 15- to 34-year-olds with cerebral palsy (CP) as they participate in key life situations of young adulthood.
Method: A mixed-methods scoping review was undertaken and six electronic databases searched (January 2001 to August 2023). Participation foci and thematic outcomes were mapped to the International Classification of Functioning, Disability and Health.
Hematopoietic stem cells (HSCs) sustain life-long hematopoiesis and emerge during mid-gestation from hemogenic endothelial progenitors via an endothelial-to-hematopoietic transition (EHT). The full scope of molecular mechanisms governing this process remains unclear. The NR4A subfamily of orphan nuclear receptors act as tumor suppressors in myeloid leukemogenesis and have never been implicated in HSC specification.
View Article and Find Full Text PDFPurpose: Hyperpolarized Xe MRI presents opportunities to assess regional pulmonary microstructure and function. Ongoing advancements in hardware, sequences, and image processing have helped it become increasingly adopted for both research and clinical use. As the number of applications and users increase, standardization becomes crucial.
View Article and Find Full Text PDFFormalin-fixed paraffin-embedded (FFPE) samples are valuable but underutilized in single-cell omics research due to their low RNA quality. In this study, leveraging a recent advance in single-cell genomic technology, we introduce snPATHO-seq, a versatile method to derive high-quality single-nucleus transcriptomic data from FFPE samples. We benchmarked the performance of the snPATHO-seq workflow against existing 10x 3' and Flex assays designed for frozen or fresh samples and highlighted the consistency in snRNA-seq data produced by all workflows.
View Article and Find Full Text PDFThe quality of standard single-cell experiments often depends on the immediate processing of cells or tissues post-harvest to preserve fragile and vulnerable cell populations, unless the samples are adequately fixed and stored. Despite the recent rise in popularity of probe-based and aldehyde-fixed RNA assays, these methods face limitations in species and target availability and are not suitable for immunoprofiling or assessing chromatin accessibility. Recently, a reversible fixation strategy known as FixNCut has been successfully deployed to separate sampling from downstream applications in a reproducible and robust manner, avoiding stress or necrosis-related artifacts.
View Article and Find Full Text PDFBackground: MRI with xenon-129 gas (Xe MRI) can assess airflow obstruction and heterogeneity in lung diseases. Specifically, Xe MRI may represent a sensitive modality for future therapeutic trials of cystic fibrosis (CF) therapies. The reproducibility of Xe MRI has not yet been assessed in the context of a multi-site study.
View Article and Find Full Text PDFDeveloping anticancer drugs from preclinical to clinical takes approximately a decade in a cutting-edge biomedical lab and still 97% of most fail at clinical trials. Cell line usage is critical in expediting the advancement of anticancer therapies. Yet developing appropriate cell lines has been challenging and overcoming these obstacles whilst implementing a systematic approach of utilizing 3D models that recapitulate the tumour microenvironment is prudent.
View Article and Find Full Text PDFPurpose: Hyperpolarized Xe MRI benefits from non-Cartesian acquisitions that sample k-space efficiently and rapidly. However, their reconstructions are complex and burdened by decay processes unique to hyperpolarized gas. Currently used gridded reconstructions are prone to artifacts caused by magnetization decay and are ill-suited for undersampling.
View Article and Find Full Text PDFBackground And Aims: Improving the care of decompensated cirrhosis is a significant clinical challenge. The primary aim of this trial was to assess the efficacy of a chronic disease management (CDM) model to reduce liver-related emergency admissions (LREA). The secondary aims were to assess model effects on quality-of-care and patient-reported outcomes.
View Article and Find Full Text PDFOverlaying omics data onto spatial biological dimensions has been a promising technology to provide high-resolution insights into the interactome and cellular heterogeneity relative to the organization of the molecular microenvironment of tissue samples in normal and disease states. Spatial omics can be categorized into three major modalities: () next-generation sequencing-based assays, () imaging-based spatially resolved transcriptomics approaches including in situ hybridization/in situ sequencing, and () imaging-based spatial proteomics. These modalities allow assessment of transcripts and proteins at a cellular level, generating large and computationally challenging datasets.
View Article and Find Full Text PDFMammalian Uracil DNA glycosylase (UNG) removes uracils and initiates high-fidelity base excision repair to maintain genomic stability. During B cell development, activation-induced cytidine deaminase (AID) creates uracils that UNG processes in an error-prone fashion to accomplish immunoglobulin (Ig) somatic hypermutation (SHM) or class switch recombination (CSR). The mechanism that governs high-fidelity versus mutagenic uracil repair is not understood.
View Article and Find Full Text PDFTo identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10).
View Article and Find Full Text PDFTranscriptome-wide association studies (TWASs) have investigated the role of genetically regulated transcriptional activity in the etiologies of breast and ovarian cancer. However, methods performed to date have focused on the regulatory effects of risk-associated SNPs thought to act in cis on a nearby target gene. With growing evidence for distal (trans) regulatory effects of variants on gene expression, we performed TWASs of breast and ovarian cancer using a Bayesian genome-wide TWAS method (BGW-TWAS) that considers effects of both cis- and trans-expression quantitative trait loci (eQTLs).
View Article and Find Full Text PDFSpared regions of the damaged central nervous system undergo dynamic remodeling and exhibit a remarkable potential for therapeutic exploitation. Here, lesion-remote astrocytes (LRAs), which interact with viable neurons, glia and neural circuitry, undergo reactive transformations whose molecular and functional properties are poorly understood. Using multiple transcriptional profiling methods, we interrogated LRAs from spared regions of mouse spinal cord following traumatic spinal cord injury (SCI).
View Article and Find Full Text PDFContinuous methionine restriction (MR) is one of only a few dietary interventions known to dramatically extend mammalian healthspan. For example, continuously methionine-restricted rodents show less age-related pathology and are up to 45% longer-lived than controls. Intriguingly, MR is feasible for humans, andanumberofstudieshavesuggestedthatmethionine-restrictedindividualsmayreceivesimilarhealthspan benefits as rodents.
View Article and Find Full Text PDFThe use of ultraviolet-C (UV-C) irradiation in marine biofouling control is a relatively new and potentially disruptive technology. This study examined effects of UV-C exposure on the biofilm-forming diatom, . UV-C-induced mutations were identified Illumina HiSeq.
View Article and Find Full Text PDFBackground: Laparoscopic colectomy is widely accepted as a safe operation for colorectal cancer, but we have experienced resistance to the introduction of the FreeHand robotic camera holder to augment laparoscopic colorectal surgery.
Aim: To compare the initial results between conventional and FreeHand robot-assisted laparoscopic colectomy in Trinidad and Tobago.
Methods: This was a prospective study of outcomes from all laparoscopic colectomies performed for colorectal carcinoma from November 29, 2021 to May 30, 2022.
Purpose: Hyperpolarized xenon MRI suffers from heterogeneous coil bias and magnetization decay that obscure pulmonary abnormalities. Non-physiological signal variability can be mitigated by measuring and mapping the nominal flip angle, and by rescaling the images to correct for signal bias and decay. While flip angle maps can be calculated from sequentially acquired images, scan time and breath-hold duration are doubled.
View Article and Find Full Text PDFCardiovascular toxicity causes adverse drug reactions and may lead to drug removal from the pharmaceutical market. Cancer therapies can induce life-threatening cardiovascular side effects such as arrhythmias, muscle cell death, or vascular dysfunction. New technologies have enabled cardiotoxic compounds to be identified earlier in drug development.
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