Affinity purification mass spectrometry characterisation of the interactome of receptor tyrosine kinase proline-rich motifs in cancer.

Receptor tyrosine kinase (RTK) overexpression is linked to the development and progression of multiple cancers. RTKs are classically considered to initiate cytoplasmic signalling pathways via ligand-induced tyrosine phosphorylation, however recent evidence points to a second tier of signalling contingent on interactions mediated by the proline-rich motif (PRM) regions of non-activated RTKs. The presence of PRMs on the C-termini of >40 % of all RTKs and the abundance of PRM-binding proteins encoded by the human genome suggests that there is likely to be a large number of previously unexplored interactions which add to the RTK intracellular interactome.

Accuracy of wrist fracture detection on radiographs by artificial intelligence compared to human clinicians. A systematic review and meta-analysis.

Purpose: The aim of the study is to perform a systematic review and meta-analysis comparing the diagnostic performance of artificial intelligence (AI) and human readers in the detection of wrist fractures.

Method: This study conducted a systematic review following PRISMA guidelines. Medline and Embase databases were searched for relevant articles published up to August 14, 2023.

New Approaches for Robot-Assisted Neck Surgery: Clavicular and Submental Approaches Using the da Vinci SP System.

Background: Minimally invasive robot-assisted thyroid surgery or neck dissection can improve cosmetic results and reduce surgical trauma. Several approaches have been described but each has both advantages and limitations. We aimed to determine the feasibility of performing robot-assisted neck surgery using the da Vinci SP system.

Differential labelling of human sub-cellular compartments with fluorescent dye esters and expansion microscopy.

Amine-reactive esters of aromatic fluorescent dyes are emerging as imaging probes for nondescript staining of cellular and tissue architectures. We characterised the staining patterns of 14 fluorescent dye ester species with varying physical and spectral properties in the broadly studied human HeLa cell line. When combined with the super-resolution technique expansion microscopy (ExM) involving swellable acrylamide hydrogels, fluorescent esters reveal nanoscale features including cytoplasmic membrane-bound compartments and nucleolar densities.

Correction: Expansion microscopy reveals subdomains in germ granules.

Correction to Materials and Methods.

The emerging role of receptor tyrosine kinase phase separation in cancer.

Receptor tyrosine kinase (RTK)-mediated signal transduction is fundamental to cell function and drives important cellular outcomes which, when dysregulated, can lead to malignant tumour growth and metastasis. The initiation of signals from plasma membrane-bound RTKs is subjected to multiple regulatory mechanisms that control downstream effector protein recruitment and function. The high propensity of RTKs to condense via liquid-liquid phase separation (LLPS) into membraneless organelles with downstream effector proteins provides a further fundamental mechanism for signal regulation.

Factors Affecting the Choice to Specialize in Medical Toxicology.

Introduction: Medical toxicology is a small but growing specialty. To ensure that the specialty continues to grow and attract strong candidates, it is important to understand what influences physicians to pursue medical toxicology training. This would allow for targeted interventions to recruit strong candidates to the field.

Identification of putative reader proteins of 5-methylcytosine and its derivatives in RNA.

Methylation of carbon-5 of cytosines (m C) is a conserved post-transcriptional nucleotide modification of RNA with widespread distribution across organisms. It can be further modified to yield 5-hydroxymethylcytidine (hm C), 5-formylcytidine (f C), 2´-O-methyl-5-hydroxymethylcytidine (hm Cm) and 2´-O-methyl-5-formylcytidine (f Cm). How m C, and specially its derivates, contribute to biology mechanistically is poorly understood.

The combined action of the intracellular regions regulates FGFR2 kinase activity.

Receptor tyrosine kinases (RTKs) are typically activated through a precise sequence of intracellular phosphorylation events starting with a tyrosine residue on the activation loop (A-loop) of the kinase domain (KD). From this point the mono-phosphorylated enzyme is active, but subject to stringent regulatory mechanisms which can vary dramatically across the different RTKs. In the absence of extracellular stimulation, fibroblast growth factor receptor 2 (FGFR2) exists in the mono-phosphorylated state in which catalytic activity is regulated to allow rapid response upon ligand binding, whilst restricting ligand-independent activation.

Urinary tract infection is associated with 2.4-fold increased risk of surgical site infection in hip fracture surgery: systematic review and meta-analysis.

Background: There is no consensus regarding whether urinary tract infection (UTI) should be screened for or treated in hip fracture patients.

Aim: To assess the relationship between perioperative UTI and surgical site infection (SSI) in hip fracture patients, and the relationship between urinary catheterization and SSI in these patients.

Methods: PubMed, Embase, CINAHL and Cochrane Library were searched to identify studies that evaluated the relationship between perioperative UTI and SSI and/or between urinary catheterization and SSI.

A Preclinical Feasibility Study of Single-Port Robotic Subcostal Anatomical Lung Resection and Subxiphoid Thymectomy Using the da Vinci SP System.

Despite the recent introduction of technologically advanced single-port (SP) robotic systems, their use in the field of thoracic surgery has been rarely explored. Here, we report our preclinical experience concerning SP robotic thoracic surgery using the da Vinci SP system. The da Vinci SP system was used to perform subcostal anatomical lung resection and subxiphoid thymectomy in three cadavers.

Phase separation enhances probability of receptor signalling and drug targeting.

The probability of a given receptor tyrosine kinase (RTK) triggering a defined cellular outcome is low because of the promiscuous nature of signalling, the randomness of molecular diffusion through the cell, and the ongoing nonfunctional submembrane signalling activity or noise. Signal transduction is therefore a 'numbers game', where enough cell surface receptors and effector proteins must initially be engaged to guarantee formation of a functional signalling complex against a background of redundant events. The presence of intracellular liquid-liquid phase separation (LLPS) at the plasma membrane provides a mechanism through which the probabilistic nature of signalling can be weighted in favour of the required, discrete cellular outcome and mutual exclusivity in signal initiation.

Expansion microscopy reveals subdomains in germ granules.

Light and electron microscopy techniques have been indispensable in the identification and characterization of liquid-liquid phase separation membraneless organelles. However, for complex membraneless organelles such as the perinuclear germ granule in , our understanding of how the intact organelle is regulated is hampered by (1) technical limitations in confocal fluorescence imaging for the simultaneous examination of multiple granule protein markers and (2) inaccessibility of electron microscopy. We take advantage of the newly developed super resolution method of expansion microscopy (ExM) and in situ staining of the whole proteome to examine the germ granule, the P granule.

Characterization of Nonfatal Opioid, Cocaine, Methamphetamine, and Polydrug Exposure and Clinical Presentations Reported to the Toxicology Investigators Consortium Core Registry, January 2010-December 2021.

Introduction: To characterize and compare opioid-only, cocaine-only, methamphetamine-only, opioid-and-cocaine exposure, and opioid-and-methamphetamine exposure and to examine clinical presentations, leading to a better understanding of overdose effects involving these drug exposures.

Methods: We examined drug exposures in the Toxicology Investigators Consortium (ToxIC) Core Registry from January 2010 to December 2021, a case registry of patients presenting to participating healthcare sites that receive a medical toxicology consultation. Demographic and clinical presentations of opioid-only, cocaine-only, methamphetamine-only, and opioid-and-cocaine exposure, and opioid-and-methamphetamine exposure consultations were described; differences between single and polydrug exposure subgroups were calculated to determine statistical significance.

Using Simulated Annealing to Investigate Sensitivity of SEM to External Model Misspecification.

Sensitivity analyses encompass a broad set of post-analytic techniques that are characterized as measuring the potential impact of any factor that has an effect on some output variables of a model. This research focuses on the utility of the simulated annealing algorithm to automatically identify path configurations and parameter values of omitted confounders in structural equation modeling (SEM). An empirical example based on a past published study is used to illustrate how strongly related an omitted variable must be to model variables for the conclusions of an analysis to change.

Total plasma homocysteine measurement: Evaluation of the Abbott immunoassay, comparison with the JEOL ion exchange chromatography and investigation of its clinical utility.

Objectives: Homocysteine is an intermediary amino acid formed in methionine metabolism, with elevated total homocysteine (tHCY) being a biomarker of cardiovascular and cerebrovascular diseases. We evaluated the Abbott ARCHITECT tHCY immunoassay, compared it with the current established JEOL ion exchange chromatography (IEC) method and evaluated its clinical utility.

Design And Methods: Following immunoassay method verification, plasma samples of 91 patients were analysed for tHCY using immunoassay and IEC.

Receptor tyrosine kinases regulate signal transduction through a liquid-liquid phase separated state.

The recruitment of signaling proteins into activated receptor tyrosine kinases (RTKs) to produce rapid, high-fidelity downstream response is exposed to the ambiguity of random diffusion to the target site. Liquid-liquid phase separation (LLPS) overcomes this by providing elevated, localized concentrations of the required proteins while impeding competitor ligands. Here, we show a subset of phosphorylation-dependent RTK-mediated LLPS states.

Multidimensional Computerized Adaptive Testing: A Potential Path Toward the Efficient and Precise Assessment of Applied Cognition, Daily Activity, and Mobility for Hospitalized Patients.

Objective: To develop and evaluate an efficient and precise variable-length functional assessment of applied cognition, daily activity, and mobility to inform mobility preservation and rehabilitation service delivery among hospitalized patients.

Design: A multidimensional item bank tapping into these dimensions was developed, with all items calibrated using a multidimensional graded response model. The items were adaptively selected from the item banks to maximize the test information, and the test ended when a joint stopping rule was satisfied.

Can Proxy Ratings Supplement Patient Report to Assess Functional Domains Among Hospitalized Patients?

Objective: To (1) characterize the agreement between patient and proxy responses on a multidimensional computerized adaptive testing measure of function, and to (2) determine whether patient, proxy, or multidimensional computerized adaptive testing score characteristics identify when a proxy report can be used as a substitute for patient report in clinical decision making.

Design: A psychometric study of the Functional Assessment in Acute Care Multidimensional Computerized Adaptive Testing (FAMCAT) and its 3 scales (Applied Cognition, Daily Activity, and Basic Mobility).

Setting: An upper midwestern quaternary academic medical center PARTICIPANTS: A total of 300 pairs of patients (average age 60.

Does the Mode of PROM Administration Affect the Responses of Hospitalized Patients?

Objective: To determine whether a multidimensional computerized adaptive test, the Functional Assessment in Acute Care Multidimensional Computerized Adaptive Test (FAMCAT), could be administered to hospitalized patients via a tablet computer rather than being orally administered by an interviewer.

Design: A randomized comparison of the responses of hospitalized patients to interviewer vs tablet delivery of the FAMCAT and its assessment of applied cognition, daily activity, and basic mobility.

Setting: Two quaternary teaching hospitals in the Upper Midwest.

Grb2 binding induces phosphorylation-independent activation of Shp2.

The regulation of phosphatase activity is fundamental to the control of intracellular signalling and in particular the tyrosine kinase-mediated mitogen-activated protein kinase (MAPK) pathway. Shp2 is a ubiquitously expressed protein tyrosine phosphatase and its kinase-induced hyperactivity is associated with many cancer types. In non-stimulated cells we find that binding of the adaptor protein Grb2, in its monomeric state, initiates Shp2 activity independent of phosphatase phosphorylation.

Surgical Repair of Triangular Fibrocartilage Complex Tears: A Systematic Review.

 This study systematically reviews the outcomes of surgical repair of triangular fibrocartilage complex (TFCC) tears. Existing surgical techniques include capsular sutures, suture anchors, and transosseous sutures. However, there is still no consensus as to which is the most reliable method for ulnar-sided peripheral and foveal TFCC tears.

DEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans.

Membraneless organelles are sites for RNA biology including small non-coding RNA (ncRNA) mediated gene silencing. How small ncRNAs utilise phase separated environments for their function is unclear. We investigated how the PIWI-interacting RNA (piRNA) pathway engages with the membraneless organelle P granule in Caenorhabditis elegans.

Review 2: Primary graft dysfunction after lung transplant-pathophysiology, clinical considerations and therapeutic targets.

Primary graft dysfunction (PGD) is one of the most common complications in the early postoperative period and is the most common cause of death in the first postoperative month. The underlying pathophysiology is thought to be the ischaemia-reperfusion injury that occurs during the storage and reperfusion of the lung engraftment; this triggers a cascade of pathological changes, which result in pulmonary vascular dysfunction and loss of the normal alveolar architecture. There are a number of surgical and anaesthetic factors which may be related to the development of PGD.