Centiloid recommendations for clinical context-of-use from the AMYPAD consortium.

Amyloid-PET quantification through the tracer-independent Centiloid (CL) scale has emerged as an essential tool for the accurate measurement of amyloid-β (Aβ) pathology in Alzheimer's disease (AD) patients. The AMYPAD consortium set out to integrate existing literature and recent work from the consortium to provide clinical context-of-use recommendations for the CL scale. Compared to histopathology, visual reads, and cerebrospinal fluid, CL quantification accurately reflects the amount of AD pathology.

Quantification Supports Amyloid PET Visual Assessment of Challenging Cases: Results from the AMYPAD Diagnostic and Patient Management Study.

Several studies have demonstrated strong agreement between routine clinical visual assessment and quantification, suggesting that quantification approaches could support assessment by less experienced readers or in challenging cases. However, all studies to date have implemented a retrospective case collection, and challenging cases were generally underrepresented. We included all participants ( = 741) from the AMYPAD diagnostic and patient management study with available baseline amyloid PET quantification.

Fast stomatal kinetics in sorghum enable tight coordination with photosynthetic responses to dynamic light intensity and safeguard high water use efficiency.

In this study, we assessed 43 accessions of sorghum from 16 countries across three continents. Our objective was to identify stomatal and photosynthetic traits that could be exploited in breeding programmes to increase photosynthesis without increasing water use under dynamic light environments. Under field conditions, sorghum crops often have limited water availability and are exposed to rapidly fluctuating light intensities, which influences both photosynthesis and stomatal behaviour.

Manipulation of photosensory and circadian signaling restricts phenotypic plasticity in response to changing environmental conditions in Arabidopsis.

Plants exploit phenotypic plasticity to adapt their growth and development to prevailing environmental conditions. Interpretation of light and temperature signals is aided by the circadian system, which provides a temporal context. Phenotypic plasticity provides a selective and competitive advantage in nature but is obstructive during large-scale, intensive agricultural practices since economically important traits (including vegetative growth and flowering time) can vary widely depending on local environmental conditions.

Association Between Years of Education and Amyloid Burden in Patients With Subjective Cognitive Decline, MCI, and Alzheimer Disease.

Objectives: Higher-educated patients with Alzheimer disease (AD) can harbor greater neuropathologic burden than those with less education despite similar symptom severity. In this study, we assessed whether this observation is also present in potential preclinical AD stages, namely in individuals with subjective cognitive decline and clinical features increasing AD likelihood (SCD+).

Methods: Amyloid-PET information ([F]Flutemetamol or [F]Florbetaben) of individuals with SCD+, mild cognitive impairment (MCI), and AD were retrieved from the AMYPAD-DPMS cohort, a multicenter randomized controlled study.

Inhibition of RNA degradation integrates the metabolic signals induced by osmotic stress into the Arabidopsis circadian system.

The circadian clock system acts as an endogenous timing reference that coordinates many metabolic and physiological processes in plants. Previous studies have shown that the application of osmotic stress delays circadian rhythms via 3'-phospho-adenosine 5'-phosphate (PAP), a retrograde signalling metabolite that is produced in response to redox stress within organelles. PAP accumulation leads to the inhibition of exoribonucleases (XRNs), which are responsible for RNA degradation.

Software compatibility analysis for quantitative measures of [F]flutemetamol amyloid PET burden in mild cognitive impairment.

Rationale: Amyloid-β (Aβ) pathology is one of the earliest detectable brain changes in Alzheimer's disease pathogenesis. In clinical practice, trained readers will visually categorise positron emission tomography (PET) scans as either Aβ positive or negative. However, adjunct quantitative analysis is becoming more widely available, where regulatory approved software can currently generate metrics such as standardised uptake value ratios (SUVr) and individual Z-scores.

Urinary markers differentially associate with kidney inflammatory activity and chronicity measures in patients with lupus nephritis.

Objective: Lupus nephritis (LN) is diagnosed by biopsy, but longitudinal monitoring assessment methods are needed. Here, in this preliminary and hypothesis-generating study, we evaluate the potential for using urine proteomics as a non-invasive method to monitor disease activity and damage. Urinary biomarkers were identified and used to develop two novel algorithms that were used to predict LN activity and chronicity.

The extracellular matrix controls stem cell specification and crypt morphology in the developing and adult mouse gut.

The rapid renewal of the epithelial gut lining is fuelled by stem cells that reside at the base of intestinal crypts. The signal transduction pathways and morphogens that regulate intestinal stem cell self-renewal and differentiation have been extensively characterised. In contrast, although extracellular matrix (ECM) components form an integral part of the intestinal stem cell niche, their direct influence on the cellular composition is less well understood.

Quantification of amyloid PET for future clinical use: a state-of-the-art review.

Amyloid-β (Aβ) pathology is one of the earliest detectable brain changes in Alzheimer's disease (AD) pathogenesis. The overall load and spatial distribution of brain Aβ can be determined in vivo using positron emission tomography (PET), for which three fluorine-18 labelled radiotracers have been approved for clinical use. In clinical practice, trained readers will categorise scans as either Aβ positive or negative, based on visual inspection.

Collagen Type III and VI Remodeling Biomarkers Are Associated with Kidney Fibrosis in Lupus Nephritis.

Background: Lupus nephritis (LN) occurs in <40% of patients with SLE. Reliable biomarkers of kidney damage are needed to identify patients with SLE at risk of developing LN to improve screening, treat the disease earlier, and halt progression to kidney failure. Novel biomarkers of extracellular matrix remodeling were evaluated as markers of kidney fibrosis and disease activity in patients with LN.

Pepsinogen/Proton Pump Co-Expression in Barrett's Esophageal Cells Induces Cancer-Associated Changes.

Educational Objective: At the conclusion of this presentation, participants should better understand the carcinogenic potential of pepsin and proton pump expression in Barrett's esophagus.

Objective: Barrett's esophagus (BE) is a well-known risk factor for esophageal adenocarcinoma (EAC). Gastric H /K ATPase proton pump and pepsin expression has been demonstrated in some cases of BE; however, the contribution of local pepsin and proton pump expression to carcinogenesis is unknown.

Nudging Handwashing among Primary School Students in the Philippines: Evidence from a Cluster Randomized Trial.

Handwashing is key to preventing the transmission of various infectious diseases of which school-aged children are particularly susceptible. Traditional, information-messaging campaigns may increase handwashing awareness but have had limited success in promoting behavior change. Behavioral economics "nudges," which explicitly target the knowledge-behavior gap, is a promising alternative.

GATA4 Controls Epithelial Morphogenesis in the Developing Stomach to Promote Establishment of Glandular Columnar Epithelium.

Background & Aims: The transcription factor GATA4 is broadly expressed in nascent foregut endoderm. As development progresses, GATA4 is lost in the domain giving rise to the stratified squamous epithelium of the esophagus and forestomach (FS), while it is maintained in the domain giving rise to the simple columnar epithelium of the hindstomach (HS). Differential GATA4 expression within these domains coincides with the onset of distinct tissue morphogenetic events, suggesting a role for GATA4 in diversifying foregut endoderm into discrete esophageal/FS and HS epithelial tissues.

GATA4 blocks squamous epithelial cell gene expression in human esophageal squamous cells.

GATA4 promotes columnar epithelial cell fate during gastric development. When ectopically expressed in the developing mouse forestomach, the tissue emerges as columnar-like rather than stratified squamous with gene expression changes that parallel those observed in the pre-malignant squamous to columnar metaplasia known as Barrett's esophagus (BE). GATA4 mRNA up-regulation and gene amplification occur in BE and its associated cancer, esophageal adenocarcinoma (EAC), and GATA4 gene amplification correlates with poor patient outcomes.

Derivation and utility of an Aβ-PET pathology accumulation index to estimate Aβ load.

Objective: To evaluate a novel β-amyloid (Aβ)-PET-based quantitative measure (Aβ accumulation index [Aβ index]), including the assessment of its ability to discriminate between participants based on Aβ status using visual read, CSF Aβ/Aβ, and post-mortem neuritic plaque burden as standards of truth.

Methods: One thousand one hundred twenty-one participants (with and without cognitive impairment) were scanned with Aβ-PET: Swedish BioFINDER, n = 392, [F]flutemetamol; Alzheimer's Disease Neuroimaging Initiative (ADNI), n = 692, [F]florbetapir; and a phase 3 end-of-life study, n = 100, [F]flutemetamol. The relationships between Aβ index and standardized uptake values ratios (SUVR) from Aβ-PET were assessed.

Shades of green: untying the knots of green photoperception.

The development of economical LED technology has enabled the application of different light qualities and quantities to control plant growth. Although we have a comprehensive understanding of plants' perception of red and blue light, the lack of a dedicated green light sensor has frustrated our utilization of intermediate wavelengths, with many contradictory reports in the literature. We discuss the contribution of red and blue photoreceptors to green light perception and highlight how green light can be used to improve crop quality.

H+/K+ATPase Expression in the Larynx of Laryngopharyngeal Reflux and Laryngeal Cancer Patients.

Objectives: The gastric H+/K+ ATPase proton pump has previously been shown to be expressed in the human larynx, however its contribution to laryngopharyngeal reflux (LPR) signs, symptoms and associated diseases such as laryngeal cancer is unknown. Proton pump expression in the larynx of patients with LPR and laryngeal cancer was investigated herein. A human hypopharyngeal cell line expressing the proton pump was generated to investigate its effects.

GATA4 Is Required for Budding Morphogenesis of Posterior Foregut Endoderm in a Model of Human Stomach Development.

Three-dimensional gastrointestinal organoid culture systems provide innovative and tractable models to investigate fundamental developmental biology questions using human cells. The goal of this study was to explore the role of the zinc-finger containing transcription factor GATA4 in gastric development using an organoid-based model of human stomach development. Given GATA4's vital role in the developing mouse gastrointestinal tract, we hypothesized that GATA4 plays an essential role in human stomach development.

The Adult Murine Intestine is Dependent on Constitutive Laminin-γ1 Synthesis.

Laminin-γ1 is required for early embryonic development; however, the need for laminin-γ1 synthesis in adulthood is unknown. A global and inducible mouse model of laminin-γ1 deficiency was generated to address this question. Genetic ablation of the Lamc1 gene in adult mice was rapidly lethal.

Cryptochromes integrate green light signals into the circadian system.

Plants are acutely sensitive of their light environment, adapting their growth habit and prioritizing developmental decisions to maximize fecundity. In addition to providing an energy source and directional information, light quality also contributes to entrainment of the circadian system, an endogenous timing mechanism that integrates endogenous and environmental signalling cues to promote growth. Whereas plants' perception of red and blue portions of the spectrum are well defined, green light sensitivity remains enigmatic.

Centiloid scaling for quantification of brain amyloid with [F]flutemetamol using multiple processing methods.

Introduction: A standardised method for quantifying β-amyloid PET tracers would allow comparison across different tracers and different sites. The development of the Centiloid scale has aimed to achieve this, applying a common scale to better aid the diagnosis and prognosis of Alzheimer's disease (AD) and to monitor anti-amyloid therapeutic interventions. Here, we apply the Centiloid method to [F]flutemetamol and [C]PiB (PiB, Pittsburgh compound B) PET images and derive the scaling factor to express their binding in Centiloids.

Endocannabinoid receptor CB2R is significantly expressed in aspirin-exacerbated respiratory disease: a pilot study.

Background: The endocannabinoid system represents a highly conserved, innate signaling network with direct and indirect control of eicosanoid-mediated inflammation. Activation of the type 2 cannabinoid receptor (CB2R) leads to decreased type 2 inflammation and reduced production of arachidonic acid (AA). Given that altered AA metabolism is associated with aspirin-exacerbated respiratory disease (AERD), we hypothesized that expression of the CB2R gene CNR2 is increased in AERD.