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.

The American Clinical Neurophysiology Society Guideline on Indications for Continuous Electroencephalography Monitoring in Neonates.

Purpose: Continuous EEG (cEEG) monitoring is increasingly used in the management of neonates with seizures. There remains debate on what clinically relevant information can be gained from cEEG in neonates with suspected seizures, at high risk for seizures, or with definite seizures, as well as the use of cEEG for prognosis in a variety of conditions. In this guideline, we address these questions using American Clinical Neurophysiology Society structured methodology for clinical guideline development.

A propofol binding site in the voltage sensor domain mediates inhibition of HCN1 channel activity.

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) ion channels are members of the cyclic nucleotide-binding family and are crucial for regulating cellular automaticity in many excitable cells. HCN channel activation contributes to pain perception, and propofol, a widely used anesthetic, acts as an analgesic by inhibiting the voltage-dependent activity of HCN channels. However, the molecular determinants of propofol action on HCN channels remain unknown.

Creating a culture, not just a space-A qualitative investigation into reflective practice groups in inpatient mental health settings from the perspectives of facilitators and attendees.

Background: Working in inpatient mental health settings is often characterised by highly emotive work and staff shortages. Despite the suggested benefits of reflective practice groups on staff well-being and clinical practice across healthcare settings, to date, there have been limited empirical studies on reflective practice groups in inpatient mental health settings, especially on group engagement and improvement.

Methods: We interviewed fifteen participants, including both facilitators and attendees of reflective practice groups.

Tocilizumab and rituximab for systemic sclerosis interstitial lung disease: a real-world cohort analysis.

Objectives: Systemic sclerosis (SSc)-interstitial lung disease (ILD) is one of the leading causes of mortality in SSc. Data from randomised controlled trials (RCTs) supports rituximab and tocilizumab monotherapy but there is limited data regarding their use for those who fail standard immunomodulatory therapies.

Methods: SSc patients treated with rituximab or tocilizumab were retrospectively identified in a single centre cohort.

User Experiences of and Preferences for Self-Guided Digital Interventions for the Treatment of Mild to Moderate Eating Disorders: Systematic Review and Metasynthesis.

Background: Digital interventions typically involve using smartphones or PCs to access online or downloadable self-help and may offer a more accessible and convenient option than face-to-face interventions for some people with mild to moderate eating disorders. They have been shown to substantially reduce eating disorder symptoms, but treatment dropout rates are higher than for face-to-face interventions. We need to understand user experiences and preferences for digital interventions to support the design and development of user-centered digital interventions that are engaging and meet users' needs.

Mental Disorders Among Offspring Prenatally Exposed to Systemic Glucocorticoids.

Importance: Current evidence of the association between prenatal exposure to glucocorticoids and long-term mental disorders is scarce and has limitations.

Objective: To investigate the association between prenatal exposure to systemic glucocorticoids and mental disorders in offspring at the age of 15 years, comparing exposed vs unexposed offspring born to mothers with the same underlying disease (risk of preterm delivery and autoimmune or inflammatory disorders).

Design, Setting, And Participants: This nationwide population-based cohort study used data from registries in Denmark with follow-up until December 31, 2018.

Health state utilities associated with invasive pneumococcal disease, pneumonia, and recurrent acute otitis media in young children.

Purpose: Cost-utility analyses examining the value of new vaccines for pneumococcal disease will require health state utilities as inputs. Existing utilities for pneumococcal infections in young children are limited. The purpose of this study was to estimate health state utilities associated with pneumococcal infections in young children.

Basic Science and Pathogenesis.

Background: Psychosis occurs in 30-40% of individuals with AD. New insights into disease mechanisms may lead to novel pharmacological targets and treatments. Previous studies have focused on bulk tissue analysis with limited results.

Basic Science and Pathogenesis.

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder involving pathological deposition of tau that includes glial inclusions and specific regional vulnerability patterns. Therapeutic developments are hampered by incomplete understanding of disease mechanisms. Few studies have examined its cell type-specific effects.

Basic Science and Pathogenesis.

Background: Huntington's disease (HD) is an autosomal dominant condition causing severe neurodegeneration in the striatum and the entorhinal cortex (EC). An epigenome wide association study of DNA methylation in HD by our group, identified potential hypomethylation at the PTGDS gene in the striatum. We aimed to validate this result through pyrosequencing, examining the locus in fine detail, and to assess the signal specificity by profiling multiple neurodegenerative diseases.

A Dynamical Analysis of the Alignment Mechanism Between Two Interacting Cells.

In this work we analytically investigate the alignment mechanism of self-propelled ellipse-shaped cells in two spatial dimensions interacting via overlap avoidance. By considering a two-cell system and imposing certain symmetries, we obtain an analytically tractable dynamical system, which we mathematically analyse in detail. We find that for elongated cells there is a half-stable steady state corresponding to perfect alignment between the cells.

Basic Science and Pathogenesis.

Background: Possession of the APOE4 allele is the strongest genetic risk factor for developing the sporadic form of Alzheimer's disease (AD). Studies investigating APOE4's associated AD risk have largely centered on APOE4's propensity to regulate the deposition of extracellular amyloid beta plaques. More recent attempts to characterize APOE4's role in AD have brought into question the role APOE4 may possess in modulating the pathogenesis of intracellular tau tangles.

Basic Science and Pathogenesis.

Background: We aim to investigate efficacies of Ras homolog (Rho)-associated kinases (ROCK) inhibitors on Alzheimer's disease (AD) pathological proteins in human induced pluripotent stem cell (iPSC)-differentiated human neurons and the P301S tau transgenic mouse model (PS19).

Method: Quantitative liquid chromatography-mass spectrometry (LC-MS/MS) and targeted ELISA were implemented to investigate the effect of treatment with fasudil or its derivatives on the human neurons and brains from PS19 mice. We explored the efficacy of these ROCK inhibitors in reducing tau phosphorylation, and the brain proteomic profiles after their administration in mice.

Basic Science and Pathogenesis.

Background: Astrocytes are a numerous and diverse glial subtype specialised to carry out distinct roles involving maintaining homeostasis and effective functioning of the nervous system. To do so effectively, they respond to and secrete various proteins. In addition, astrocytes have been linked to Alzheimer's disease (AD), where they are believed to become reactive and contribute to neuroinflammation.

Basic Science and Pathogenesis.

Background: Lewy body pathology (LBP) is common in autosomal dominant (ADAD) or sporadic Alzheimer disease (sAD). LBP seems to be the most frequent co-pathology in sAD and even in the relatively young ADAD population, where other co-pathologies are rare. Knowledge of neuropathological distribution patterns of LBP and associated survival and genetic characteristics in both AD variants is incomplete.

Basic Science and Pathogenesis.

Background: While social and medical debate about the efficacy and safety of anti-Aβ immunotherapy is ongoing, one thing that emerged is that we have little understanding of the working mechanisms of these antibodies and this lack of knowledge complicates the interpretation of the clinical results. Here, we aimed to establish if microglia are required for the efficacy of Lecanemab, one of the most promising FDA-approved disease-modifying therapy for AD (Van Dyck et al. N Engl J Med 2023).

Basic Science and Pathogenesis.

Background: Recent studies highlight distinct patterns of cortical atrophy between amnestic (typical) and non-amnestic (atypical, with subtypes: behavioural, dysexecutive, logopenic and visuospatial) clinical phenotypes of Alzheimer's disease (AD). The current study aimed to assess regional MRI patterns of cortical atrophy across AD phenotypes, and their association with amyloid-beta (Aβ), phosphorylated tau (pTau), axonal degeneration (NfL) and microvascular deterioration (COLIV).

Method: Postmortem In-situ 3DT1 3T-MRI data was collected for 33 AD (17 typical, 16 atypical) and 16 control brain donors.

Basic Science and Pathogenesis.

Background: Cardiovascular disease causes vascular dementia and contributes to most clinical dementia. This is embodied in the concept of vascular contributions to cognitive impairment and dementia (VCID). The potent endogenous peptide endothelin-1 (ET1) causes small artery vasoconstriction and fibrosis.

Basic Science and Pathogenesis.

Background: Knowledge of the chemical composition of amyloid plaques and tau tangles at the earlier stages of Alzheimer's disease (AD) pathology is sparse. This is due to limited access to human brain during life and at the earlier stages of AD pathophysiology and technical limitations in quantifying amyloid and tau species at a subcellular level. Understanding the chemical composition of plaques and tangles, how rapidly they grow and what factors drive growth is important for developing and refining therapeutics.

Basic Science and Pathogenesis.

Background: As neurodegenerative diseases advance, postmitotic neurons are affected by disturbed proteostasis and the accumulation of misfolded proteins. This renders neurons sensitive to cell death, ultimately leading to progressive neuron loss. Multiple studies show the involvement of distinct pathways of regulated cell death (RCD) in neurodegenerative diseases, such as necroptosis.

Basic Science and Pathogenesis.

Background: Autosomal dominant progranulin (GRN) mutations are a common genetic cause of frontotemporal lobar degeneration. Though clinical trials for GRN-related therapies are underway, there is an unmet need for biomarkers that can predict symptom onset and track disease progression. We previously showed that presymptomatic GRN carriers exhibit thalamocortical hyperconnectivity that increases with age when they are presumably closer to symptom onset.

Basic Science and Pathogenesis.

Background: Various explanations have been proposed for how hearing impairment might be associated with increased risk of dementia. Several theories have proposed direct links with Alzheimer's disease (AD) neuropathology, either due to shared aetiology (i.e.