TOM complex

For people with profound hearing loss, a cochlear implant (CI) is able to provide access to sounds that support speech perception. With current technology, most CI users obtain very good speech understanding in quiet listening environments. However, many CI users still struggle when listening to music. Efforts have been made to preprocess music for CI users and improve their music enjoyment. This work investigates potential modifications of instrumental music to make it more accessible for CI users. For this purpose, we used two datasets with varying complexity and containing individual tracks of instrumental music...

Pre-surgical clinical assessment of an adnexal mass is a complex process, and ideally requires accurate and rapid identification of disease status. Gold standard biomarker CA125 is extensively used off-label for this purpose; however its performance is typically inadequate, particularly for the detection of early stage disease and discrimination between benign versus malignant status. We recently described a multi-marker panel (MMP) and associated risk index for the differentiation of benign from malignant ovarian disease...

This paper presents a comparative analysis of six prominent registration techniques for solving CAD model alignment problems. Unlike the typical approach of assessing registration algorithms with synthetic datasets, our study utilizes point clouds generated from the Cranfield benchmark. Point clouds are sampled from existing CAD models and 3D scans of physical objects, introducing real-world complexities such as noise and outliers. The acquired point cloud scans, including ground-truth transformations, are made publicly available...

Microtubule (MT) filaments, composed of α/β-tubulin dimers, are fundamental to cellular architecture, function and organismal development. They are nucleated from MT organizing centers by the evolutionarily conserved γ-tubulin ring complex (γTuRC). However, the molecular mechanism of nucleation remains elusive. Here we used cryo-electron tomography to determine the structure of the native γTuRC capping the minus end of a MT in the context of enriched budding yeast spindles. In our structure, γTuRC presents a ring of γ-tubulin subunits to seed nucleation of exclusively 13-protofilament MTs, adopting an active closed conformation to function as a perfect geometric template for MT nucleation...

BACKGROUND: Anaemia following major surgery may be associated with unplanned readmission to hospital. However, the severity-response relationship between the degree of anaemia at discharge and the risk of unplanned readmission is poorly defined. We aimed to describe the severity-response relationship between haemoglobin concentration at the time of discharge and the risk of unplanned readmission in a cohort of patients undergoing different types of major surgery. METHODS: We performed a retrospective cohort study in a single tertiary health service, including all patients who underwent major surgery (orthopaedic, abdominal, cardiac or thoracic) between 1 May 2011 and 1 February 2022...

Primary ciliary dyskinesia (PCD), a disorder of the motile cilia, is now recognised as an underdiagnosed cause of bronchiectasis. Accurate PCD diagnosis comprises clinical assessment, analysis of cilia and the identification of biallelic variants in one of 50 known PCD-related genes, including HYDIN. HYDIN-related PCD is underdiagnosed due to the presence of a pseudogene, HYDIN2, with 98% sequence homology to HYDIN. This presents a significant challenge for Short-Read Next Generation Sequencing (SR-NGS) and analysis, and many diagnostic PCD gene panels do not include HYDIN...

INTRODUCTION: Vascularized Composite Allografts (VCA) are usually performed in a full major histocompatibility complex mismatch setting, with a risk of acute rejection depending on factors such as the type of immunosuppression therapy and the quality of graft preservation. In this systematic review, we present the different immunosuppression protocols used in VCA and point out relationships between acute rejection rates and possible factors that might influence it. METHODS: This systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines...

The use of Carbon Fibre Reinforced Plastic (CFRP) composite materials for critical components has significantly surged within the energy and aerospace industry. With this rapid increase in deployment, reliable post-manufacturing Non-Destructive Evaluation (NDE) is critical for verifying the mechanical integrity of manufactured components. To this end, an automated Ultrasonic Testing (UT) NDE process delivered by an industrial manipulator was developed, greatly increasing the measurement speed, repeatability, and locational precision, while increasing the throughput of data generated by the selected NDE modality...

MOTIVATION: Recent advancements in sequencing technologies have led to the discovery of numerous variants in the human genome. However, understanding their precise roles in diseases remains challenging due to their complex functional mechanisms. Various methodologies have emerged to predict the pathogenic significance of these genetic variants. Typically, these methods employ an integrative approach, leveraging diverse data sources that provide important insights into genomic function...

The presence of autoantibodies is a defining feature of many autoimmune diseases. The number of unique autoantibody clones is conceivably limited by immune tolerance mechanisms, but unknown due to limitations of the currently applied technologies. Here, we introduce an autoantigen-specific liquid chromatography-mass spectrometry-based IgG1 Fab profiling approach using the anti-citrullinated protein antibody (ACPA) repertoire in rheumatoid arthritis (RA) as an example. We show that each patient harbors a unique and diverse ACPA IgG1 repertoire dominated by only a few antibody clones...

PURPOSE: Combination therapies are a promising approach for improving cancer treatment, but it is challenging to predict their resulting adverse events in a real-world setting. EXPERIMENTAL DESIGN: We provide here a proof-of-concept study using 15 million patient records from the FDA Adverse Event Reporting System (FAERS). Complex adverse event frequencies of drugs or their combinations were visualized as heat maps onto a two-dimensional grid. Adverse event frequencies were shown as colors to assess the ratio between individual and combined drug effects...

INTRODUCTION: Spinal cord stimulation is a common treatment option for neuropathic pain conditions. Despite its extensive use and multiple technological evolutions, long term efficacy of spinal cord stimulation is debated. Most studies on spinal cord stimulation include a rather limited number of patients and/or follow-ups over a limited period. Therefore, there is an urgent need for real-world, long-term data. METHODS: In 2018, the Belgian government initiated a nationwide secure platform for the follow-up of all new and existing spinal cord stimulation therapies...

While π-complexes of C=C bonds are ubiquitous in organometallic chemistry, analogous complexes of the isoelectronic but strongly polarized B=N double bond of aminoboranes are extremely scarce. To address this gap, a diphosphine-aminoborane ligand (PhDPBAiPr) is introduced and its coordination with group 10 metals is investigated. The B=N bond does not coordinate to the metal in Pt(0) and Pd(II) complexes. In contrast, side-on coordination of the B=N bond is observed in the Ni(0) complex [PhDPBAiPr]Ni(NCPh), and the X-ray crystal structure reveals B-N bond elongation compared to the free ligand...

Mammalian Notch signaling occurs when the binding of Delta or Jagged to Notch stimulates the proteolytic release of the Notch intracellular domain (NICD), which enters the nucleus to control target gene expression. To determine the temporal dynamics of events associated with Notch signaling under native conditions, we fluorescently tagged Notch and Delta at their endogenous genomic loci and visualized them upon pairing of receiver (Notch) and sender (Delta) cells as a function of time after cell contact. At contact sites, Notch and Delta immediately accumulated at 1:1 stoichiometry in synapses, which resolved by 15-20 min after contact...

Weaning patients from ventilation in intensive care units (ICU) is a complex task. There is a growing desire to build decision-support tools to help clinicians during this process, especially those employing Artificial Intelligence (AI). However, tools built for this purpose should fit within and ideally improve the current work environment, to ensure they can successfully integrate into clinical practice. To do so, it is important to identify areas where decision-support tools may aid clinicians, and associated design requirements for such tools...

INTRODUCTION: Schizophrenia (SCZ) is a complex neurodevelopmental disorder characterised by functional and structural brain dysconnectivity and disturbances in perception, cognition, emotion, and social functioning. In the present study, we investigated whether the microstructural organisation of the uncinate fasciculus (UF) was associated with emotion recognition (ER) performance. Additionally, we investigated the usefulness of an unbiased hit rate (UHR) score to control for response biases (i...

OBJECTIVES: Internationally, there is limited evidence about the role and impact of nurse practitioners (NPs) in complex malignant hematology (CMH). In one Canadian CMH program, NPs have existed for 20 years but not been evaluated. This study aimed to understand stakeholder perceptions of CMH NP role structures, processes, and outcomes and the extent to which the role meets patient and health service needs. METHODS: A qualitative descriptive study was conducted, guided by the PEPPA-Plus framework...

Heat-shocked cells prioritize the translation of heat shock (HS) mRNAs, but the underlying mechanism is unclear. We report that HS in budding yeast induces the disassembly of the eIF4F complex, where eIF4G and eIF4E assemble into translationally arrested mRNA ribonucleoprotein particles (mRNPs) and HS granules (HSGs), whereas eIF4A promotes HS translation. Using in vitro reconstitution biochemistry, we show that a conformational rearrangement of the thermo-sensing eIF4A-binding domain of eIF4G dissociates eIF4A and promotes the assembly with mRNA into HS-mRNPs, which recruit additional translation factors, including Pab1p and eIF4E, to form multi-component condensates...

BACKGROUND: In the present study, we used the data from 14 hospitals to systematically evaluate the in-hospital mortality of patients with colorectal cancer as well as its influencing factors in Germany. METHODS: This multicenter cross-sectional study included hospitalized patients with a main diagnosis of colorectal cancers in the period between January 2019 and July 2023. The outcome of the study was the prevalence of in-hospital mortality. To access the associations between demographic and clinical variables and in-hospital mortality, univariable and multivariable logistic regression analyses were conducted...

The perception and appreciation of food flavor depends on many interacting chemical compounds and external factors, and therefore proves challenging to understand and predict. Here, we combine extensive chemical and sensory analyses of 250 different beers to train machine learning models that allow predicting flavor and consumer appreciation. For each beer, we measure over 200 chemical properties, perform quantitative descriptive sensory analysis with a trained tasting panel and map data from over 180,000 consumer reviews to train 10 different machine learning models...