Intermittent standing does not acutely improve postprandial metabolism in university students.

Height-adjustable workstations offer a practical strategy to reduce sedentary behaviour in student populations, but the effect of standing intervals on young adults' metabolic health remains uncertain. This study investigated the acute impact of breaking up sitting time with intermittent standing on postprandial metabolic responses in university students. Using a randomised, cross-over design, 23 participants (13 females, 10 males; age, 24 ± 5 years; BMI, 23.

Characterising the activity, lifestyle behaviours and health outcomes of UK university students: an observational cohort study with a focus on gender and ethnicity.

Background: Health-related outcomes and behaviours in university students are known to be poor relative to the general population. The substantial contextual shifts related to the COVID-19 pandemic, combined with increased numbers of students from minoritised ethnicity backgrounds and presenting as trans and gender diverse (TGD), means that up-to-date information is unavailable. The primary aim of this study was therefore to characterise the current movement, dietary and lifestyle behaviours, mental health, and Body Mass Index (BMI) of UK university students and assess differences between genders and ethnic groups.

Determining factors of physical activity and sedentary behaviour in university students during the COVID-19 pandemic: A longitudinal study.

Introduction: Historically, university students demonstrate poor movement behaviours that could negatively impact current and future health. Recent literature has focused on identifying determinants of physical activity (PA) and sedentary behaviour (SB) in this population to inform the development of intervention strategies. However, the COVID-19 pandemic substantially restricted movement behaviours in this population, meaning findings of previous research may no longer be applicable within the current societal context.

Multi-Neutrino Entanglement and Correlations in Dense Neutrino Systems.

The time evolution of multi-neutrino entanglement and correlations are studied in two-flavor collective neutrino oscillations, relevant for dense neutrino environments, building upon previous works. Specifically, simulations performed of systems with up to 12 neutrinos using Quantinuum's H1-1 20 qubit trapped-ion quantum computer are used to compute n-tangles, and two- and three-body correlations, probing beyond mean-field descriptions. n-tangle rescalings are found to converge for large system sizes, signaling the presence of genuine multi-neutrino entanglement.

Standard model physics and the digital quantum revolution: thoughts about the interface.

Advances in isolating, controlling and entangling quantum systems are transforming what was once a curious feature of quantum mechanics into a vehicle for disruptive scientific and technological progress. Pursuing the vision articulated by Feynman, a concerted effort across many areas of research and development is introducing prototypical digital quantum devices into the computing ecosystem available to domain scientists. Through interactions with these early quantum devices, the abstract vision of exploring classically-intractable quantum systems is evolving toward becoming a tangible reality.

Entanglement Spheres and a UV-IR Connection in Effective Field Theories.

We show that long-distance quantum correlations probe short-distance physics. Two disjoint regions of the latticized, massless scalar field vacuum are numerically demonstrated to become separable at distances beyond the negativity sphere, which extends to infinity in the continuum limit. The size of this quantum coherent volume is determined by the highest momentum mode supported in the identical regions, each of diameter d.

Nine Months into the COVID-19 Pandemic: A Longitudinal Study Showing Mental Health and Movement Behaviours Are Impaired in UK Students.

Unlabelled: Initial studies indicated that student mental health was impaired during the early stages of the pandemic and that maintaining/improving physical activity gave some protection from mental illness. However, as the pandemic persists, these data may not reflect current circumstances and may have been confounded by exam stress.

Methods: This study used an online survey to assess the changes in, and associations between, mental health and movement behaviours in 255 UK university students from before the COVID-19 pandemic (October 2019) to 9 months following the UK's first confirmed case (October 2020).

Features of YouTube videos produced by individuals who self-identify with borderline personality disorder.

Objectives: Many individuals use YouTubeâ„¢ to seek out information and share first-hand experiences about mental illnesses, as well as to gain a sense of community. YouTubeâ„¢ use may be especially appealing when offline supports are lacking or difficult to access, and when there is a fear of stigmatisation. Borderline personality disorder (BPD), also referred to as emotionally unstable personality disorder (EUPD), is a complex and often stigmatised mental-health disorder.

Long-Term Outcomes in KEYNOTE-052: Phase II Study Investigating First-Line Pembrolizumab in Cisplatin-Ineligible Patients With Locally Advanced or Metastatic Urothelial Cancer.

Purpose: The phase II single-arm KEYNOTE-052 study evaluated the efficacy and safety of first-line pembrolizumab for patients with locally advanced or metastatic cisplatin-ineligible urothelial carcinoma (UC).

Patients And Methods: Three hundred seventy patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 24 months. Positive tumor programmed death ligand 1 (PD-L1) expression was defined as combined positive score (CPS) ≥ 10.

A Machine Learning Approach to Identify a Circulating MicroRNA Signature for Alzheimer Disease.

Background: Accurate diagnosis of Alzheimer disease (AD) involving less invasive molecular procedures and at reasonable cost is an unmet medical need. We identified a serum miRNA signature for AD that is less invasive than a measure in cerebrospinal fluid.

Methods: From the Oxford Project to Investigate Memory and Aging (OPTIMA) study, 96 serum samples were profiled by a multiplex (>500 analytes) microRNA (miRNA) reverse transcription quantitative PCR analysis, including 51 controls, 32 samples from patients with AD, and 13 samples from patients with mild cognitive impairment (MCI).

Discovery of MK-8719, a Potent O-GlcNAcase Inhibitor as a Potential Treatment for Tauopathies.

Inhibition of O-GlcNAcase (OGA) has emerged as a promising therapeutic approach to treat tau pathology in neurodegenerative diseases such as Alzheimer's disease and progressive supranuclear palsy. Beginning with carbohydrate-based lead molecules, we pursued an optimization strategy of reducing polar surface area to align the desired drug-like properties of potency, selectivity, high central nervous system (CNS) exposure, metabolic stability, favorable pharmacokinetics, and robust in vivo pharmacodynamic response. Herein, we describe the medicinal chemistry and pharmacological studies that led to the identification of (3a,5,6,7,7a)-5-(difluoromethyl)-2-(ethylamino)-3a,6,7,7a-tetrahydro-5-pyrano[3,2-]thiazole-6,7-diol (MK-8719), a highly potent and selective OGA inhibitor with excellent CNS penetration that has been advanced to first-in-human phase I clinical trials.

Entanglement Suppression and Emergent Symmetries of Strong Interactions.

Entanglement suppression in the strong-interaction S matrix is shown to be correlated with approximate spin-flavor symmetries that are observed in low-energy baryon interactions, the Wigner SU(4) symmetry for two flavors and an SU(16) symmetry for three flavors. We conjecture that dynamical entanglement suppression is a property of the strong interactions in the infrared, giving rise to these emergent symmetries and providing powerful constraints that predict the nature of nuclear and hypernuclear forces in dense matter.

Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study.

Background: The multicohort, phase II, nonrandomized KEYNOTE-059 study evaluated pembrolizumab ± chemotherapy in advanced gastric/gastroesophageal junction cancer. Results from cohorts 2 and 3, evaluating first-line therapy, are presented.

Methods: Patients ≥ 18 years old had previously untreated recurrent or metastatic gastric/gastroesophageal junction adenocarcinoma.

Clinical Utility of the Combined Positive Score for Programmed Death Ligand-1 Expression and the Approval of Pembrolizumab for Treatment of Gastric Cancer.

Context.—: Regulatory approval of pembrolizumab for treatment of gastric and gastroesophageal junction (G/GEJ) adenocarcinoma required a reproducible scoring method for use of programmed death ligand-1 (PD-L1) protein expression as a companion diagnostic to identify likely responders to therapy.

Objective.

Scalar, Axial, and Tensor Interactions of Light Nuclei from Lattice QCD.

Complete flavor decompositions of the matrix elements of the scalar, axial, and tensor currents in the proton, deuteron, diproton, and ^{3}He at SU(3)-symmetric values of the quark masses corresponding to a pion mass m_{π}∼806  MeV are determined using lattice quantum chromodynamics. At the physical quark masses, the scalar interactions constrain mean-field models of nuclei and the low-energy interactions of nuclei with potential dark matter candidates. The axial and tensor interactions of nuclei constrain their spin content, integrated transversity, and the quark contributions to their electric dipole moments.

Early intervention of tau pathology prevents behavioral changes in the rTg4510 mouse model of tauopathy.

Although tau pathology, behavioral deficits, and neuronal loss are observed in patients with tauopathies, the relationship between these endpoints has not been clearly established. Here we found that rTg4510 mice, which overexpress human mutant tau in the forebrain, develop progressive age-dependent increases in locomotor activity (LMA), which correlates with neurofibrillary tangle (NFT) pathology, hyperphosphorylated tau levels, and brain atrophy. To further clarify the relationship between these endpoints, we treated the rTg4510 mice with either doxycycline to reduce mutant tau expression or an O-GlcNAcase inhibitor Thiamet G, which has been shown to ameliorate tau pathology in animal models.

Extending a Systems Model of the APP Pathway: Separation of - and -Secretase Sequential Cleavage Steps of APP.

The abnormal accumulation of amyloid- (A) in the brain parenchyma has been posited as a central event in the pathophysiology of Alzheimer's disease. Recently, we have proposed a systems pharmacology model of the amyloid precursor protein (APP) pathway, describing the A APP metabolite responses (A40, A42, sAPP, and sAPP) to -secretase 1 (BACE1) inhibition. In this investigation this model was challenged to describe A dynamics following -secretase (GS) inhibition.

First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study.

Background: More than half of all patients with advanced urothelial cancer cannot receive standard, first-line cisplatin-based chemotherapy because of renal dysfunction, poor performance status, or other comorbidities. We assessed the activity and safety of first-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer.

Methods: In this multicentre, single-arm, phase 2 study (KEYNOTE-052), cisplatin-ineligible patients with advanced urothelial cancer who had not been previously treated with systemic chemotherapy were recruited from 91 academic medical centres in 20 countries.

Proton-Proton Fusion and Tritium β Decay from Lattice Quantum Chromodynamics.

The nuclear matrix element determining the pp→de^{+}ν fusion cross section and the Gamow-Teller matrix element contributing to tritium β decay are calculated with lattice quantum chromodynamics for the first time. Using a new implementation of the background field method, these quantities are calculated at the SU(3) flavor-symmetric value of the quark masses, corresponding to a pion mass of m_{π}∼806  MeV. The Gamow-Teller matrix element in tritium is found to be 0.

A multinational study distinguishing Alzheimer's and healthy patients using cerebrospinal fluid tau/Aβ42 cutoff with concordance to amyloid positron emission tomography imaging.

Introduction: Changes in cerebrospinal fluid (CSF) tau and amyloid β (Aβ)42 accompany development of Alzheimer's brain pathology. Robust tau and Aβ42 immunoassays were developed to establish a tau/Aβ42 cutoff distinguishing mild-to-moderate Alzheimer's disease (AD) subjects from healthy elderly control (HC) subjects.

Methods: A CSF tau/Aβ42 cutoff criteria was chosen, which distinguished the groups and maximized concordance with amyloid PET.

The Relevance of Hereditary Cancer Risks to Precision Oncology: What Should Providers Consider When Conducting Tumor Genomic Profiling?

Through tumor genomic profiling (TGP), existing and novel treatments can be selected to better target the specific dysregulated molecular pathways that drive growth and spread of a patient's tumor. Although the primary purpose of TGP is to detect targetable somatic mutations for treatment, TGP may also uncover germline mutations with important implications for patients and family members. Oncology care providers should be aware of the hereditary cancer risks associated with genes commonly tested by TGP.

Unitary Limit of Two-Nucleon Interactions in Strong Magnetic Fields.

Two-nucleon systems are shown to exhibit large scattering lengths in strong magnetic fields at unphysical quark masses, and the trends toward the physical values indicate that such features may exist in nature. Lattice QCD calculations of the energies of one and two nucleons systems are performed at pion masses of m_{π}∼450 and 806 MeV in uniform, time-independent magnetic fields of strength |B|∼10^{19}-10^{20}  G to determine the response of these hadronic systems to large magnetic fields. Fields of this strength may exist inside magnetars and in peripheral relativistic heavy ion collisions, and the unitary behavior at large scattering lengths may have important consequences for these systems.

Systems Pharmacology Analysis of the Amyloid Cascade after β-Secretase Inhibition Enables the Identification of an Aβ42 Oligomer Pool.

The deposition of amyloid-β (Aβ) oligomers in brain parenchyma has been implicated in the pathophysiology of Alzheimer's disease. Here we present a systems pharmacology model describing the changes in the amyloid precursor protein (APP) pathway after administration of three different doses (10, 30, and 125 mg/kg) of the β-secretase 1 (BACE1) inhibitor MBi-5 in cisterna magna ported rhesus monkeys. The time course of the MBi-5 concentration in plasma and cerebrospinal fluid (CSF) was analyzed in conjunction with the effect on the concentrations of the APP metabolites Aβ42, Aβ40, soluble β-amyloid precursor protein (sAPP) α, and sAPPβ in CSF.

Pharmacological Inhibition of O-GlcNAcase Does Not Increase Sensitivity of Glucocorticoid Receptor-Mediated Transrepression.

Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). As O-GlcNAcase (OGA) is an enzyme that removes O-GlcNAc from O-GlcNAcylated proteins, we hypothesized that the potentiation of GC effects following OGT overexpression could be similarly observed via the direct inhibition of OGA, inhibiting O-GlcNAc removal from pol II.