Liquid biopsy in organ damage: introduction of an innovative tool for assessing the complexity of blunt splenic injury.

Liquid biomarkers are essential in trauma cases and critical care and offer valuable insights into the extent of injury, prognostic predictions, and treatment guidance. They can help assess the severity of organ damage (OD), assist in treatment decisions and forecast patient outcomes. Notably, small extracellular vesicles, particularly those involved in splenic trauma, have been overlooked.

Preclinical evaluation of DC-CIK cells as potentially effective immunotherapy model for the treatment of glioblastoma.

Despite the favorable effects of immunotherapies in multiple types of cancers, its complete success in CNS malignancies remains challenging. Recently, a successful clinical trial of cytokine-induced killer (CIK) cell immunotherapy in patients with glioblastoma (GBM) has opened a new avenue for adoptive cellular immunotherapies in CNS malignancies. Prompt from these findings, herein, we investigated whether dendritic cells (DC) in combination with cytokine-induced killer cells (DC-CIK) could also provide an alternative and more effective way to improve the efficacy of GBM treatment.

Addressing inter individual variability in CSF levels of brain derived proteins across neurodegenerative diseases.

Accurate diagnosis and monitoring of neurodegenerative diseases require reliable biomarkers. Cerebrospinal fluid (CSF) proteins are promising candidates for reflecting brain pathology; however, their diagnostic utility may be compromised by natural variability between individuals, weakening their association with disease. Here, we measured the levels of 69 pre-selected proteins in cerebrospinal fluid using antibody-based suspension bead array technology in a multi-disease cohort of 499 individuals with neurodegenerative disorders including Alzheimer's disease (AD), behavioral variant frontotemporal dementia, primary progressive aphasias, amyotrophic lateral sclerosis (ALS), corticobasal syndrome, primary supranuclear palsy, along with healthy controls.

Behind the scenes of EQA - characteristics, capabilities, benefits and assets of external quality assessment (EQA).

This is the first in a series of five papers that detail the role and substantial impact that external quality assessment (EQA) and their providers' services play in ensuring diagnostic (IVD) performance quality. The aim is to give readers and users of EQA services an insight into the processes in EQA, explain to them what happens before EQA samples are delivered and after examination results are submitted to the provider, how they are assessed, what benefits participants can expect, but also who are stakeholders other than participants and what significance do EQA data and assessment results have for them. This first paper presents the history of EQA, insights into legal, financing and ethical matters, information technology used in EQA, structure and lifecycle of EQA programs, frequency and intensity of challenges, and unique requirements of extra-examination and educational EQA programs.

Behind the scenes of EQA - characteristics, capabilities, benefits and assets of external quality assessment (EQA).

External quality assessment (EQA) cycles are the smallest complete units within EQA programs that laboratories can use to obtain external assessments of their performance. In each cycle, several samples are distributed to the laboratories registered for participation, and ideally, EQA programs not only cover the examination procedures but also the pre- and post-examination procedures. The properties and concentration range of measurands in individual samples are selected with regard to the intended challenge for the participants so that each sample fulfils its purpose.

Behind the scenes of EQA - characteristics, capabilities, benefits and assets of external quality assessment (EQA).

External quality assessment (EQA) enhances patient safety through the evaluation of the quality of laboratory-based and point of care testing. Regulatory agencies and accreditation organizations utilize the results and the laboratory's response to them as part of assessing the laboratory's fitness to practice. In addition, where EQA samples are commutable and the assigned value has been determined using reference measurement procedures (RMPs), EQA data contributes to the verification of metrological traceability of assays as part of the post-market surveillance of diagnostic (IVD) medical devices (IVD-MDs).

Behind the scenes of EQA - characteristics, capabilities, benefits and assets of external quality assessment (EQA).

Providers of external quality assessment (EQA) programs evaluate data or information obtained and reported by participant laboratories using their routine procedures to examine properties or measurands in samples provided for this purpose. EQA samples must offer participants an equal chance to obtain accurate results, while being designed to provide results in clinically relevant ranges. It is the responsibility of the EQA provider to meet the necessary requirements for homogeneity, stability and some other properties of the EQA items in order to offer participants a fair, reliable and technically interesting EQA experience.

EEFSEC deficiency: A selenopathy with early-onset neurodegeneration.

Inborn errors of selenoprotein expression arise from deleterious variants in genes encoding selenoproteins or selenoprotein biosynthetic factors, some of which are associated with neurodegenerative disorders. This study shows that bi-allelic selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC) variants cause selenoprotein deficiency, leading to progressive neurodegeneration. EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures.

Disentangling Sources of Momentum Fluctuations in Xe+Xe and Pb+Pb Collisions with the ATLAS Detector.

High-energy nuclear collisions create a quark-gluon plasma, whose initial condition and subsequent expansion vary from event to event, impacting the distribution of the eventwise average transverse momentum [P([p_{T}])]. Disentangling the contributions from fluctuations in the nuclear overlap size (geometrical component) and other sources at a fixed size (intrinsic component) remains a challenge. This problem is addressed by measuring the mean, variance, and skewness of P([p_{T}]) in ^{208}Pb+^{208}Pb and ^{129}Xe+^{129}Xe collisions at sqrt[s_{NN}]=5.

Measurement of CP Violation Observables in D^{+}→K^{-}K^{+}π^{+} Decays.

A search for violation of the charge-parity (CP) symmetry in the D^{+}→K^{-}K^{+}π^{+} decay is presented, with proton-proton collision data corresponding to an integrated luminosity of 5.4  fb^{-1}, collected at a center-of-mass energy of 13 TeV with the LHCb detector. A novel model-independent technique is used to compare the D^{+} and D^{-} phase-space distributions, with instrumental asymmetries subtracted using the D_{s}^{+}→K^{-}K^{+}π^{+} decay as a control channel.

Floquet-Driven Crossover from Density-Assisted Tunneling to Enhanced Pair Tunneling.

We investigate the experimental control of pair tunneling in a double-well potential using Floquet engineering. We demonstrate a crossover from a regime with density-assisted tunneling to dominant pair tunneling by tuning the effective interactions. Furthermore, we show that the pair tunneling rate can be enhanced not only compared to the Floquet-reduced single-particle tunneling but even beyond the static superexchange rate, while keeping the effective interaction in a relevant range.

Basic Science and Pathogenesis.

Background: MicroRNAs have been linked to dementia. However, understanding their relation to cognition in the general population is required to determine their potential use for the detection and prevention of age-associated cognitive decline and preclinical dementia. Therefore, we examined the association of circulating microRNAs with cognitive performance in a population-based cohort and the possible underlying mechanisms.

Basic Science and Pathogenesis.

Background: Western-diet (WD) can induce sterile inflammation and epigenetic reprogramming of myeloid cells, affecting their immune response (Christ et al., 2018). However, the molecular signaling mediating these changes was unknown.

Basic Science and Pathogenesis.

Background: Worldwide, the actual number of 55 million people diagnosed with dementia is estimated to increase to 139 million people affected by dementia in 2050. 61% of these individuals resided in low and middle-income countries (LMIC). Genetic risk factors account for up to 80% of the attributable risk of Alzheimer's disease (AD), the leading cause of dementia.

Clinical Manifestations.

Background: In cognitively unimpaired (CU) older adults, the presence of a subjective cognitive decline (SCD) combined with evidence of abnormal b-amyloid (Ab) is proposed as stage 2 of Alzheimer's disease (AD) by the NIA-AA framework (Jack et al., 2018). However, the associations found between SCD and preclinical AD are inconsistent across studies, highlighting the importance of better understanding which specific SCD features are associated with either Ab or tau burden.

Clinical Manifestations.

Background: The medial temporal lobe (MTL) is the first cortical region affected by tauopathy in Alzheimer's disease (AD) and is implicated in spatial orientation. In early AD stages, navigation deficits, including path integration deficits, could be present, even before memory deficits. We investigated whether these deficits were related to AD pathology (amyloidosis and/or tauopathy) using a path integration task, the "Apple Game".

Clinical Manifestations.

Background: Speech and language impairments are associated with cognitive decline in neurodegenerative dementias, particularly Alzheimer's Disease (AD), where subtle speech changes may precede clinical dementia onset. As clinical trials prioritize early identification for disease-modifying treatments, digital biomarkers for timely screening become imperative. Digital speech-based biomarkers can be employed for screening populations at the earliest AD stages.

Clinical Manifestations.

Background: Previous findings evaluating longitudinal cognition in relation to the MeDi diet are inconsistent, and few studies have examined it in relation to the presence/absence of subjective cognitive decline (SCD). Our current aims are to test whether adherence to the MeDi diet is associated with the risk of clinical progression, future cognitive decline, and atrophy over time in Alzheimer's disease (AD)-sensitive regions in cognitively unimpaired (CU) older adults with or without SCD.

Methods: This longitudinal study includes 171 controls and 228 SCD patients recruited from memory clinics in the DELCODE study.

Clinical Manifestations.

Background: Mental disorders have been linked to an increased risk of developing dementia including Alzheimer's disease. However, previous studies have typically focused on individuals who meet diagnostic criteria for a given psychiatric disorder. The goal of our study was to examine whether diverse neuropsychiatric symptoms are related to early markers of neurodegeneration in the general population.

Clinical Manifestations.

Background: The identification of cognitively unimpaired individuals at risk of short-term cognitive decline is a critical task for Alzheimer´s disease (AD) research. Cognitively normal individuals with amyloid and/or tau pathology have a high risk for short-term cognitive decline. However, not all of these individuals show clinical progression.

Clinical Manifestations.

Background: Anti-amyloid beta (Aβ) immunotherapies have recently evolved as promising treatment options in patients with early symptomatic Alzheimer's disease (AD). Meanwhile, accurate patient selection for these treatments might be challenging mirrored by strict selection criteria of the hitherto published clinical trials. Based on a real-world tertiary care sample of post-mortem validated cases, we aimed to identify the patients matching these selection criteria and their proportion showing post-mortem AD pathology.

Human Footprint and Forest Disturbance Reduce Space Use of Brown Bears (Ursus arctos) Across Europe.

Three-quarters of the planet's land surface has been altered by humans, with consequences for animal ecology, movements and related ecosystem functioning. Species often occupy wide geographical ranges with contrasting human disturbance and environmental conditions, yet, limited data availability across species' ranges has constrained our understanding of how human pressure and resource availability jointly shape intraspecific variation of animal space use. Leveraging a unique dataset of 758 annual GPS movement trajectories from 375 brown bears (Ursus arctos) across the species' range in Europe, we investigated the effects of human pressure (i.

On the Role of Hydrogen Migrations in the Taxadiene System.

Taxa-4,11-diene is made by the taxa-4,11-diene synthase (TxS) from Taxus brevifolia. The unique reactivity of the taxane system is characterised by long distance hydrogen migrations in the biosynthesis. This study demonstrates that selective long range hydrogen migrations also play a role in the high energy process of the EI-MS fragmentation of taxa-4,11-diene.

MVA-based SARS-CoV-2 vaccine candidates encoding different spike protein conformations induce distinct early transcriptional responses which may impact subsequent adaptive immunity.

Introduction: Vaccine platforms such as viral vectors and mRNA can accelerate vaccine development in response to newly emerging pathogens, as demonstrated during the COVID-19 pandemic. However, the differential effects of platform and antigen insert on vaccine immunogenicity remain incompletely understood. Innate immune responses induced by viral vector vaccines are suggested to have an adjuvant effect for subsequent adaptive immunity.

Optimising (re-)irradiation for locally recurrent head and neck cancer: impact of dose-escalation, salvage surgery, PEG tube and biomarkers on oncological outcomes-a single centre analysis.

Introduction: Locoregional recurrence (LR) is common in locally advanced head and neck cancer (HNSCC), posing challenges for treatment. We analysed outcome parameters and toxicities for patients being treated with radiotherapy (RT) for LR-HNSCC and investigated patient and disease related prognostic factors in this prognostically unfavourable group.

Methods: This analysis includes 101 LR-HNSCC patients treated with RT, radio-chemotherapy (RCT) or radio-immunotherapy (RIT) between 2010 and 2018 at a high-volume tertiary centre.