SenPred: a single-cell RNA sequencing-based machine learning pipeline to classify deeply senescent dermal fibroblast cells for the detection of an in vivo senescent cell burden.

Background: Senescence classification is an acknowledged challenge within the field, as markers are cell-type and context dependent. Currently, multiple morphological and immunofluorescence markers are required. However, emerging scRNA-seq datasets have enabled an increased understanding of senescent cell heterogeneity.

The human milk oligosaccharide 3'sialyllactose reduces low-grade inflammation and atherosclerosis development in mice.

Macrophages contribute to the induction and resolution of inflammation and play a central role in chronic low-grade inflammation in cardiovascular diseases caused by atherosclerosis. Human milk oligosaccharides (HMOs) are complex unconjugated glycans unique to human milk that benefit infant health and act as innate immune modulators. Here, we identify the HMO 3'sialyllactose (3'SL) as a natural inhibitor of TLR4-induced low-grade inflammation in macrophages and endothelium.

Anatomical Description of the Spring Ligament Articular Facet.

Background: The spring ligament fibrocartilaginous complex (SLFC), which is essential for stabilizing the medial longitudinal arch, features a little-explored fibrocartilaginous facet within its superomedial aspect, articulating with the talar head. This research aimed to provide a detailed anatomical description of this facet, designated as the spring ligament articular facet (SLAF).

Methods: Nine normally aligned cadaveric lower limbs were dissected, approaching the SLFC from a superior direction.

Highly Sensitive Terahertz Metasurface Based on Electromagnetically Induced Transparency-Like Resonance in Detection of Skin Cancer Cells.

Terahertz (THz) metasurfaces based on high Q-factor electromagnetically induced transparency-like (EIT-like) resonances are promising for biological sensing. Despite this potential, they have not often been investigated for practical differentiation between cancerous and healthy cells. The present methodology relies mainly on refractive index sensing, while factors of transmission magnitude and Q-factor offer significant information about the tumors.

Correcting PCR amplification errors in unique molecular identifiers to generate accurate numbers of sequencing molecules.

Unique molecular identifiers are random oligonucleotide sequences that remove PCR amplification biases. However, the impact that PCR associated sequencing errors have on the accuracy of generating absolute counts of RNA molecules is underappreciated. We show that PCR errors are a source of inaccuracy in both bulk and single-cell sequencing data, and synthesizing unique molecular identifiers using homotrimeric nucleotide blocks provides an error-correcting solution that allows absolute counting of sequenced molecules.

Controlling the Architecture of Freeze-Dried Collagen Scaffolds with Ultrasound-Induced Nucleation.

Collagen is a naturally occurring polymer that can be freeze-dried to create 3D porous scaffold architectures for potential application in tissue engineering. The process comprises the freezing of water in an aqueous slurry followed by sublimation of the ice via a pre-determined temperature-pressure regime and these parameters determine the arrangement, shape and size of the ice crystals. However, ice nucleation is a stochastic process, and this has significant and inherent limitations on the ability to control scaffold structures both within and between the fabrication batches.

PRMT5 inhibition shows in vitro efficacy against H3K27M-altered diffuse midline glioma, but does not extend survival in vivo.

H3K27-altered Diffuse Midline Glioma (DMG) is a universally fatal paediatric brainstem tumour. The prevalent driver mutation H3K27M creates a unique epigenetic landscape that may also establish therapeutic vulnerabilities to epigenetic inhibitors. However, while HDAC, EZH2 and BET inhibitors have proven somewhat effective in pre-clinical models, none have translated into clinical benefit due to either poor blood-brain barrier penetration, lack of efficacy or toxicity.

Disseminating cells in human oral tumours possess an EMT cancer stem cell marker profile that is predictive of metastasis in image-based machine learning.

Cancer stem cells (CSCs) undergo epithelial-mesenchymal transition (EMT) to drive metastatic dissemination in experimental cancer models. However, tumour cells undergoing EMT have not been observed disseminating into the tissue surrounding human tumour specimens, leaving the relevance to human cancer uncertain. We have previously identified both EpCAM and CD24 as CSC markers that, alongside the mesenchymal marker Vimentin, identify EMT CSCs in human oral cancer cell lines.

Epigenetic-focused CRISPR/Cas9 screen identifies (absent, small, or homeotic)2-like protein (ASH2L) as a regulator of glioblastoma cell survival.

Background: Glioblastoma is the most common and aggressive primary brain tumor with extremely poor prognosis, highlighting an urgent need for developing novel treatment options. Identifying epigenetic vulnerabilities of cancer cells can provide excellent therapeutic intervention points for various types of cancers.

Method: In this study, we investigated epigenetic regulators of glioblastoma cell survival through CRISPR/Cas9 based genetic ablation screens using a customized sgRNA library EpiDoKOL, which targets critical functional domains of chromatin modifiers.

Preliminary assessment of three quantitative approaches for estimating time-since-deposition from autofluorescence and morphological profiles of cell populations from forensic biological samples.

Determining when DNA recovered from a crime scene transferred from its biological source, i.e., a sample's 'time-since-deposition' (TSD), can provide critical context for biological evidence.

Five historical innovations that have shaped modern orthopaedic surgery.

Throughout history, many innovations have contributed to the development of modern orthopaedic surgery, improving patient outcomes and expanding the range of treatment options available to patients. This article explores five key historical innovations that have shaped modern orthopaedic surgery: X-ray imaging, bone cement, the Thomas splint, the Pneumatic tourniquet and robotic-assisted surgery. We will review the development, impact and significance of each innovation, highlighting their contributions to the field of orthopaedic surgery and their ongoing relevance in contemporary and perioperative practice.

The Influence of Cone Age and Urbanisation on the Diversity and Community Composition of Culturable Seed Fungal Endophytes within Native Australian L.f. subsp. .

Seed fungal endophytes play a crucial role in assisting the overall health and success of their host plant; however, little is known about the factors that influence the diversity and composition of these endophytes, particularly with respect to how they change over time and within urban environments. Using culturing techniques, morphological analyses, and Sanger sequencing, we identified the culturable seed fungal endophytes of at two urban and two natural sites in Sydney, New South Wales, Australia. A total of 27 Operational Taxonomic Units were obtained from 1200 seeds.

Differentiation of vaginal cells from epidermal cells using morphological and autofluorescence properties: Implications for sexual assault casework involving digital penetration.

Analysis of DNA mixtures from sexual assault evidence is an ongoing challenge for DNA casework laboratories. To assist the forensic scientist address source and activity level propositions there is a significant need for new techniques that can provide information as to the source of DNA, particularly for sexual assault samples that do not involve semen. The goal of this study was to develop a new biological signature system that provides additional probative value to samples comprised of mixtures of epidermal and vaginal cells, as may be observed in cases involving digital penetration.

Rhinoceros serum labile plasma iron and associated redox potential: interspecific variation, sex bias and iron overload disorder disconnect.

A consequence of the poaching crisis is that managed rhinoceros populations are increasingly important for species conservation. However, black rhinoceroses (BR; ) and Sumatran rhinoceroses (SR; ) in human care often store excessive iron in organ tissues, a condition termed iron overload disorder (IOD). IOD research is impeded by the challenge of accurately monitoring body iron load in living rhinoceroses.

Differentiation of vaginal cells from epidermal cells using morphological and autofluorescence properties: Implications for sexual assault casework involving digital penetration.

Analysis of DNA mixtures from sexual assault evidence is an ongoing challenge for DNA casework laboratories. There is a significant need for new techniques that can provide information as to the source of DNA, particularly for sexual assault samples that do not involve semen. The goal of this study was to develop a new biological signature system that provides additional probative value to samples comprised of mixtures of epidermal and vaginal cells, as may be observed in cases involving digital penetration.

How European Fans in Training (EuroFIT), a lifestyle change program for men delivered in football clubs, achieved its effect: a mixed methods process evaluation embedded in a randomised controlled trial.

Background: A randomised trial of European Fans in Training (EuroFIT), a 12-week healthy lifestyle program delivered in 15 professional football clubs in the Netherlands, Norway, Portugal, and the United Kingdom, successfully increased physical activity and improved diet but did not reduce sedentary time. To guide future implementation, this paper investigates how those effects were achieved. We ask: 1) how was EuroFIT implemented? 2) what were the processes through which outcomes were achieved?

Methods: We analysed qualitative data implementation notes, observations of 29 of 180 weekly EuroFIT deliveries, semi-structured interviews with 16 coaches and 15 club representatives, and 30 focus group discussions with participants (15 post-program and 15 after 12 months).

BRD9-SMAD2/3 orchestrates stemness and tumorigenesis in pancreatic ductal adenocarcinoma.

The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) is linked to the presence of pancreatic cancer stem-like cells (CSCs) that respond poorly to current chemotherapy regimens. By small molecule compound screening targeting 142 epigenetic enzymes, we identified that bromodomain-containing protein BRD9, a component of the BAF histone remodelling complex, is a key chromatin regulator to orchestrate the stemness of pancreatic CSCs via cooperating with the TGFβ/Activin-SMAD2/3 signalling pathway. Inhibition and genetic ablation of BDR9 block the self-renewal, cell cycle entry into G0 phase and invasiveness of CSCs, and improve the sensitivity of CSCs to gemcitabine treatment.

Long-Read Single-Cell Sequencing Using scCOLOR-seq.

Single-cell sequencing allows for the measurement of sequence information from individual cells with next-generation sequencing (NGS). However, its application to third-generation sequencing platforms such as Oxford Nanopore has been challenging because of its lower basecalling accuracy. Here we describe the method to perform highly accurate single-cell COrrected Long-Read sequencing (scCOLOR-seq) by droplet-based encapsulation of cells and sequencing using the Oxford Nanopore Sequencing system.

Professional Student Education and Training During the COVID-19 Pandemic.

Introduction: The ongoing COVID-19 pandemic has presented numerous challenges to education at all levels, but has been particularly challenging for professional schools and other educational sectors that require intensive hands-on training. Those institutions have had to deploy and continuously adapt new learning strategies in response to an ever-changing pandemic landscape over the past two years, while at the same time meeting the rigorous proficiency standards for their students.

Methods: This communication describes how two professional schools at Oregon State University, the College of Pharmacy and the Carlson College of Veterinary Medicine, pivoted in response to the COVID-19 pandemic to ensure continuity in student training.

The psychological and behavioural factors associated with laypeople initiating CPR for out-of-hospital cardiac arrest: a systematic review.

Background: Prompt, effective CPR greatly increases the chances of survival in out-of-hospital c ardiac arrest. However, it is often not provided, even by people who have previously undertaken training. Psychological and behavioural factors are likely to be important in relation to CPR initiation by lay-people but have not yet been systematically identified.

Prolyl-tRNA synthetase as a novel therapeutic target in multiple myeloma.

Multiple myeloma (MM) is a plasma cell malignancy characterised by aberrant production of immunoglobulins requiring survival mechanisms to adapt to proteotoxic stress. We here show that glutamyl-prolyl-tRNA synthetase (GluProRS) inhibition constitutes a novel therapeutic target. Genomic data suggest that GluProRS promotes disease progression and is associated with poor prognosis, while downregulation in MM cells triggers apoptosis.

Attending sporting mega events during COVID-19: mitigation and messaging at UK EURO 2020 matches.

The UEFA EURO 2020 football tournament was one of the largest Sporting Mega Events (SMEs) to take place during the COVID-19 pandemic. Mitigating the risk of virus transmission requires a multi-layered approach for any large event, more so in this case due to staging the tournament across eleven host countries. Yet, little is known about COVID-19 risks and mitigation from attending an event of this scale and nature.

BRD9-containing non-canonical BAF complex maintains somatic cell transcriptome and acts as a barrier to human reprogramming.

Epigenetic reprogramming to pluripotency requires extensive remodeling of chromatin landscapes to silence existing cell-type-specific genes and activate pluripotency genes. ATP-dependent chromatin remodeling complexes are important regulators of chromatin structure and gene expression; however, the role of recently identified Bromodomain-containing protein 9 (BRD9) and the associated non-canonical BRG1-associated factors (ncBAF) complex in reprogramming remains unknown. Here, we show that genetic or chemical inhibition of BRD9, as well as ncBAF complex subunit GLTSCR1, but not the closely related BRD7, increase human somatic cell reprogramming efficiency and can replace KLF4 and c-MYC.