Targeted protein degradation using chimeric human E2 ubiquitin-conjugating enzymes.

Proteins can be targeted for degradation by engineering biomolecules that direct them to the eukaryotic ubiquitination machinery. For instance, the fusion of an E3 ubiquitin ligase to a suitable target binding domain creates a 'biological Proteolysis-Targeting Chimera' (bioPROTAC). Here we employ an analogous approach where the target protein is recruited directly to a human E2 ubiquitin-conjugating enzyme via an attached target binding domain.

The Relationship Between the Anaerobic Speed Reserve and Acute Responses to High-Intensity Interval Training in Female Soccer Players.

Aspin, GL, Graham, M, Franklin, J, Hicks, KM, and Taylor, JM. The relationship between the anaerobic speed reserve and acute responses to high-intensity interval training in female soccer players. J Strength Cond Res 38(11): 1911-1916, 2024-The anaerobic speed reserve (ASR) is a popular method of profiling soccer players, often used to individualize training prescription.

Photon-efficient optical tweezers via wavefront shaping.

Optical tweezers enable noncontact trapping of microscale objects using light. It is not known how tightly it is possible to three-dimensionally (3D) trap microparticles with a given photon budget. Reaching this elusive limit would enable maximally stiff particle trapping for precision measurements on the nanoscale and photon-efficient tweezing of light-sensitive objects.

Corrigendum to "An Artificial Intelligence Generated Automated Algorithm to Measure Total Kidney Volume in ADPKD" [ Volume 9, Issue 2, February 2024, Pages 249-256].

[This corrects the article DOI: 10.1016/j.ekir.

Inhibition of soluble epoxide hydrolase by natural isothiocyanates.

Goal: The long-term goal of our research is to develop safe and effective soluble epoxide hydrolase (sEH) inhibitors. The objective of this study is to evaluate the potency and selectivity of six natural isothiocyanates (ITCs) as sEH inhibitors.

Methods: Molecular docking was used to model likely interactions between the ligands and receptors.

Lung ultrasound is associated with distinct clinical phenotypes in COVID-19 ARDS: A retrospective observational study.

Background: ARDS is a heterogeneous syndrome with distinct clinical phenotypes. Here we investigate whether the presence or absence of large pulmonary ultrasonographic consolidations can categorize COVID-19 ARDS patients requiring mechanical ventilation into distinct clinical phenotypes.

Methods: This is a retrospective study performed in a tertiary-level intensive care unit in Israel between April and September 2020.

Physical and Cognitive Impairment in Acute Respiratory Failure.

Recent research has brought renewed attention to the multifaceted physical and cognitive dysfunction that accompanies acute respiratory failure (ARF). This state-of-the-art review provides an overview of the evidence landscape encompassing ARF-associated neuromuscular and neurocognitive impairments. Risk factors, mechanisms, assessment tools, rehabilitation strategies, approaches to ventilator liberation, and interventions to minimize post-intensive care syndrome are emphasized.

An Artificial Intelligence Generated Automated Algorithm to Measure Total Kidney Volume in ADPKD.

Introduction: Accurate tools to inform individual prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD) are lacking. Here, we report an artificial intelligence (AI)-generated method for routinely measuring total kidney volume (TKV).

Methods: An ensemble U-net algorithm was created using the nnUNet approach.

Evaluating the performance of artificial intelligence software for lung nodule detection on chest radiographs in a retrospective real-world UK population.

Objectives: Early identification of lung cancer on chest radiographs improves patient outcomes. Artificial intelligence (AI) tools may increase diagnostic accuracy and streamline this pathway. This study evaluated the performance of commercially available AI-based software trained to identify cancerous lung nodules on chest radiographs.

The Effects of Exercise-Based Injury Prevention Programmes on Injury Risk in Adult Recreational Athletes: A Systematic Review and Meta-Analysis.

Background: Injuries are common in adult recreational athletes. Exercise-based injury prevention programmes offer the potential to reduce the risk of injury and have been a popular research topic. Yet, syntheses and meta-analyses on the effects of exercise-based injury prevention programmes for adult recreational athletes are lacking.

Fast algorithm for 3D volume reconstruction from light field microscopy datasets.

Light field microscopy can capture 3D volume datasets in a snapshot, making it a valuable tool for high-speed 3D imaging of dynamic biological events. However, subsequent computational reconstruction of the raw data into a human-interpretable 3D+time image is very time-consuming, limiting the technique's utility as a routine imaging tool. Here we derive improved equations for 3D volume reconstruction from light field microscopy datasets, leading to dramatic speedups.

Brain PET and SPECT imaging and quantification: a survey of the current status in the UK.

Objectives: With disease-modifying therapies in development for neurological disorders, quantitative brain imaging techniques become increasingly relevant for objective early diagnosis and assessment of response to treatment. The aim of this study was to evaluate the use of Brain SPECT and PET scans in the UK and explore drivers and barriers to using quantitative analysis through an online survey.

Methods: A web-based survey with 27 questions was used to capture a snapshot of brain imaging in the UK.

Using Confocal Microscopy and Pigment Analyses to Detect Adverse Insecticide Effects in non-target Freshwater Diatom species - a proof-of-concept Using Nitzschia palea.

The persistence of insecticides in aquatic environments is a cause of concern and to date hardly any studies have focused on the effects that DDT and deltamethrin have on non-target freshwater diatom communities. The application of diatoms in ecotoxicological studies is well acknowledged and therefore this study used laboratory bioassays to determine the effects that DDT and deltamethrin have on a monoculture of a diatom indicator species, Nitzschia palea. The insecticides affected the morphology of chloroplasts at all exposure concentrations.

Point-of-Care Ultrasonography in a Pulmonary Hypertension Clinic: A Randomized Pilot Study.

Pulmonary arterial hypertension (PAH) is a rare condition with the potential to progress to right heart failure. Point-of-Care Ultrasonography (POCUS), used and interpreted in real time at the bedside to further the cardiopulmonary assessment, has the potential to improve the longitudinal care of PAH patients in the ambulatory setting. Patients from PAH clinics at two academic medical centers were randomized to either a POCUS assessment cohort or non-POCUS standard care (ClinicalTrials.

Characterization of the Native Disulfide Isomers of the Novel χ-Conotoxin PnID: Implications for Further Increasing Conotoxin Diversity.

χ-Conotoxins are known for their ability to selectively inhibit norepinephrine transporters, an ability that makes them potential leads for treating various neurological disorders, including neuropathic pain. PnID, a peptide isolated from the venom of , shares high sequence homology with previously characterized χ-conotoxins. Whereas previously reported χ-conotoxins seem to only have a single native disulfide bonding pattern, PnID has three native isomers due to the formation of different disulfide bond patterns during its maturation in the venom duct.

Deep learning estimation of three-dimensional left atrial shape from two-chamber and four-chamber cardiac long axis views.

Aims: Left atrial volume is commonly estimated using the bi-plane area-length method from two-chamber (2CH) and four-chamber (4CH) long axes views. However, this can be inaccurate due to a violation of geometric assumptions. We aimed to develop a deep learning neural network to infer 3D left atrial shape, volume and surface area from 2CH and 4CH views.

Snapshot volumetric imaging with engineered point-spread functions.

The biological world involves intracellular and intercellular interactions that occur at high speed, at multiple scales and in three dimensions. Acquiring 3D images, however, typically requires a compromise in either spatial or temporal resolution compared to 2D imaging. Conventional 2D fluorescence imaging provides high spatial resolution but requires plane-by-plane imaging of volumes.

Fully automatic cardiac four chamber and great vessel segmentation on CT pulmonary angiography using deep learning.

Introduction: Computed tomography pulmonary angiography (CTPA) is an essential test in the work-up of suspected pulmonary vascular disease including pulmonary hypertension and pulmonary embolism. Cardiac and great vessel assessments on CTPA are based on visual assessment and manual measurements which are known to have poor reproducibility. The primary aim of this study was to develop an automated whole heart segmentation (four chamber and great vessels) model for CTPA.

Biologics-based degraders - an expanding toolkit for targeted-protein degradation.

Targeted protein degradation (TPD) is a broadly useful proteome editing tool for biological research and therapeutic development. TPD offers several advantages over functional inhibition alone, including the ability to target previously undruggable proteins and the substantial and sustained knockout of protein activity. A variety of small molecule approaches hijack endogenous protein degradation machinery, but are limited to proteins with a cytosolic domain and suitable binding pocket.

A lentic microcosm approach to determine the toxicity of DDT and deltamethrin on diatom communities.

Worldwide the use of pesticides has increased, especially in the industry and agriculture sector even though they contain highly toxic substances. The use of pesticides has various negative effects on the aquatic ecosystem and organisms within these ecosystems. The paper aimed to assess the effects of increased concentrations of malaria vector control insecticides (Dichlorodiphenyltrichloroethane (DDT) and Deltamethrin (DTM)) on the freshwater diatom community structure using a microcosm approach as well as determine whether a mixture (DDT 1:1 Deltamethrin) exposure will have a greater influence on the diatom community when compared to single exposures of these insecticides.

Uncovering the universality of self-replication in protein aggregation and its link to disease.

Fibrillar protein aggregates are a hallmark of a range of human disorders, from prion diseases to dementias, but are also encountered in several functional contexts. Yet, the fundamental links between protein assembly mechanisms and their functional or pathological roles have remained elusive. Here, we analyze the aggregation kinetics of a large set of proteins that self-assemble by a nucleated-growth mechanism, from those associated with disease, over those whose aggregates fulfill functional roles in biology, to those that aggregate only under artificial conditions.