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Given high animal protein costs, protein deficiency is a prevalent form of malnutrition in sub‐Saharan Africa (SSA). Soybean [Glycine max (L.) Merr.] can provide a cheaper high‐quality protein source and fortify lysine‐limited cereal‐based diets. Breeding soybean for seed composition in SSA requires understanding genotype by environment interactions (G × E). African breeding programs submit cultivars for evaluation in the Pan‐African Soybean Variety Trials (PATs), providing the opportunity to examine G × E across diverse environments. With PAT data, we conducted additive main effects and multiplicative interaction (AMMI) and genotype plus genotype‐by‐environment (GGE) biplot analyses on seed protein and oil content of 17 cultivars grown with two replications in nine environments across Zimbabwe. Across environments, protein ranged from 322.8 to 445.1 g kg−1 and oil ranged from 164.8 to 242.7 g kg−1. For protein AMMI analysis, MAKWACHA performed best for both stability and a combination of stability plus content. For oil AMMI analysis, SC SPIKE performed best for stability and KALEYA performed best for a combination of stability plus content. GGE biplot analyses identified three different mega‐environments for protein and oil, with SC EXPT2, KALEYA, and SC EXPT1 having highest protein content and TGX 2002‐9FM, LUKANGA, and SC EXPT3 having highest oil content. We also evaluated genetic diversity of 19 PAT cultivars through phylogenetic analyses with 1059 USDA Germplasm Resources Information Network (GRIN) diversity panel accessions. We recommend stable and adaptable PAT cultivars to breeders and producers while highlighting genetically distinct accessions with valuable traits as a resource for breeding programs. Core Ideas: This is a comprehensive report on seed composition stability within Pan‐African Soybean Variety Trials (PATs).Genotype by environment interaction explained a significant amount of variation in seed protein and oil content.Additive main effects and multiplicative interaction (AMMI) and genotype plus genotype‐by‐environment (GGE) biplot analyses identified PAT cultivars with the highest stability and adaptability in Zimbabwe.We highlight the genetic relatedness of PAT cultivars relative to USDA Germplasm Resources Information Network (GRIN) diversity panel accessions. Plain Language Summary: Soybean is currently promoted in sub‐Saharan Africa as a high‐quality protein source. Breeding soybean for improved seed composition requires understanding how cultivars interact with these new environments. This study evaluated genotype by environment interactions and the genetic diversity of cultivars grown in the Pan‐African Soybean Variety Trials. We used stability analyses to evaluate how the environment, cultivar, and their interaction impacted protein and oil across Zimbabwe. We identified cultivars with increased protein or oil in specific environments or stable performance across environments. We also compared the genetic diversity of the African cultivars to over 1000 genetically diverse accessions from around the world. Our analyses showed that the African cultivars have relatively low genetic diversity and are most closely related to American accessions. Our results provide valuable resources for improving soybean seed composition in sub‐Saharan Africa. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The increasing use of Alzheimer's disease (AD) biomarkers has led to the recognition of a subgroup of non‐AD amnestic mild cognitive impairment (aMCI) patients who have medial temporal hypometabolism on fluorodeoxyglucose‐positron emission tomography (FDG‐PET). METHODS: In this academic memory‐clinic‐based consecutive series, 16 non‐AD aMCI patients and 28 AD controls matched for sex, age, and baseline Mini‐Mental State Examination (MMSE) were followed for a median duration of 4.5 years. Our primary outcome was the MMSE decline rate over the subsequent years. We also determined the final diagnosis over time. RESULTS: FDG‐PET showed more pronounced medial temporal hypometabolism in non‐AD cases and more inferior parietal lobule hypometabolism in AD controls. MMSE decline was slower in non‐AD (β = −0.51) than in AD (β = −2.00) patients. Five non‐AD cases developed frontotemporal dementia years after symptom onset, and one developed dementia with Lewy bodies. DISCUSSION: Non‐AD aMCI patients with medial temporal hypometabolism show slower cognitive decline. Highlights: Non‐AD aMCI with medial temporal hypometabolism shows slower cognitive decline than AD.FDG‐PET revealed distinct metabolic patterns between non‐AD aMCI and AD patients.Approximately one‐third of non‐AD aMCI cases developed frontotemporal dementia.Comprehensive diagnostic biomarkers are crucial for non‐AD aMCI characterization. [ABSTRACT FROM AUTHOR]

Issues: Self‐change from alcohol and drug use problems is increasingly acknowledged in research. Despite the growing number of published studies, the most recent broad review of this dispersed field dates back to 2010. The present review narratively synthesises key findings from empirical studies and critically identifies research gaps and directions for further research. Approach: Following the PRISMA guidelines for scoping reviews, a systematic search was conducted in multiple scientific databases, resulting in the identification of 56 relevant articles with explicit empirical results on self‐change. Key Findings: The scoping review presents findings related to: (i) methods and definitions used; (ii) the prevalence of self‐change; (iii) indicators of self‐change; (iv) the process of self‐change; and (v) population views on self‐change. Conclusion: The review highlights the significant growth in research on self‐change considering key themes as well as the need for a relational and time‐bound approach to self‐change in research and practice. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic negatively affected child and adolescent mental health and at the end of the pandemic (April 2022) child mental health had not returned to pre‐pandemic levels. We investigated whether this observed increase in mental health problems has continued, halted, or reversed after the end of the pandemic in children from the general population and in children in psychiatric care. Methods: We collected parent‐reported and child‐reported data at two additional post‐pandemic time points (November/December 2022 and March/April 2023) in children (8–18 years) from two general population samples (N = 818–1056 per measurement) and one clinical sample receiving psychiatric care (N = 320–370) and compared these with data from before the pandemic. We collected parent‐reported data on internalizing and externalizing problems with the Brief Problem Monitor and self‐reported data on Anxiety, Depressive symptoms, Sleep‐related impairments, Anger, Global health, and Peer relations with the Patient‐Reported Outcomes Measurement Information System (PROMIS®). Results: In the general population, parents reported no changes in externalizing problems but did report higher internalizing problems post‐pandemic than pre‐pandemic (p < 0.001). Children also reported increased mental health problems post‐pandemic, especially in anxiety and depression, to a lesser extent in sleep‐related impairment and global health, and least in anger (all ps < 0.01). In the clinical sample, parents reported higher internalizing (p < 0.001), but not externalizing problems post‐pandemic compared to the start of the pandemic. Children reported greatest increases in problems in anxiety, depression, and global health, to a lesser extent on sleep‐related impairment, and least on anger (all ps < 0.05). Conclusions: Child mental health problems in the general population are substantially higher post‐pandemic compared to pre‐pandemic measurements. In children in psychiatric care mental health problems have increased during the pandemic and are substantially higher post‐pandemic than at the start of the pandemic. Longitudinal and comparative studies are needed to assess what the most important drivers of these changes are. [ABSTRACT FROM AUTHOR]

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To deal with the upcoming challenges and complexity of the nursing profession, it is deemed important to reflect on our current organization of care. However, before starting to rethink the organization of nursing care, an overview of important elements concerning nursing care organization, more specifically nursing models, is necessary. The aim of this study was to conduct a mapping review, accompanied by an evidence map to map the existing literature, to map the field of knowledge on a meta‐level and to identify current research gaps concerning nursing models in a hospital setting. Next to nursing models, two other organizational correlates seem to be of importance when looking at the organization of nursing care: nurse staffing and skill mix. Although it seems that in recent research, the theoretical focus on the organization of nursing care has been left behind, the increasingly complex healthcare environment might gain from the use of nursing theory, or in this case, care delivery models. As almost no fundamental studies have been done toward the combination of care delivery models, nurse staffing, and skill mix, those elements should be taken into account to fully capture the organization of nursing care in future research. [ABSTRACT FROM AUTHOR]

Microplasmas can be used for a wide range of technological applications and to improve the understanding of fundamental physics. Scanning electron microscopy, on the other hand, provides insights into the sample morphology and chemistry of materials from the mm‐ down to the nm‐scale. Combining both would provide direct insight into plasma‐sample interactions in real‐time and at high spatial resolution. Up till now, very few attempts in this direction have been made, and significant challenges remain. This work presents a stable direct current glow discharge microplasma setup built inside a scanning electron microscope. The experimental setup is capable of real‐time in situ imaging of the sample evolution during plasma operation and it demonstrates localized sputtering and sample oxidation. Further, the experimental parameters such as varying gas mixtures, electrode polarity, and field strength are explored and experimental V–I curves under various conditions are provided. These results demonstrate the capabilities of this setup in potential investigations of plasma physics, plasma‐surface interactions, and materials science and its practical applications. The presented setup shows the potential to have several technological applications, for example, to locally modify the sample surface (e.g., local oxidation and ion implantation for nanotechnology applications) on the µm‐scale. [ABSTRACT FROM AUTHOR]

Pathogen genomic epidemiology has the potential to provide a deep understanding of population dynamics, facilitating strategic planning of interventions, monitoring their impact, and enabling timely responses, and thereby supporting control and elimination efforts of parasitic tropical diseases. Plasmodium vivax, responsible for most malaria cases outside Africa, shows high genetic diversity at the population level, driven by factors like sub‐patent infections, a hidden reservoir of hypnozoites, and early transmission to mosquitoes. While Latin America has made significant progress in controlling Plasmodium falciparum, it faces challenges with residual P. vivax. To characterize genetic diversity and population structure and dynamics, we have analyzed the largest collection of P. vivax genomes to date, including 1474 high‐quality genomes from 31 countries across Asia, Africa, Oceania, and America. While P. vivax shows high genetic diversity globally, Latin American isolates form a distinctive population, which is further divided into sub‐populations and occasional clonal pockets. Genetic diversity within the continent was associated with the intensity of transmission. Population differentiation exists between Central America and the North Coast of South America, vs. the Amazon Basin, with significant gene flow within the Amazon Basin, but limited connectivity between the Northwest Coast and the Amazon Basin. Shared genomic regions in these parasite populations indicate adaptive evolution, particularly in genes related to DNA replication, RNA processing, invasion, and motility – crucial for the parasite's survival in diverse environments. Understanding these population‐level adaptations is crucial for effective control efforts, offering insights into potential mechanisms behind drug resistance, immune evasion, and transmission dynamics. [ABSTRACT FROM AUTHOR]

Long‐COVID patients present with a decline in physical fitness. The aim of this study is to reveal the impact of pulmonary rehabilitation (PR) on physical fitness, quality of life (QoL), and parameters of quantified thorax CT. Long‐COVID patients enrolled in a 3‐month PR program were retrospectively studied. PR included endurance and resistance training three times a week. Assessments pre‐ and post‐rehabilitation included quantified chest CT, pulmonary function tests (PFT), six‐minute walk test (6MWT), cardiopulmonary exercise test, and questionnaires: Hospital Anxiety and Depression Scale, post‐COVID‐19 Functional Status scale, Borg score, and EuroQol. Seventeen subjects (5M/12F), mean age 42 ± 13 years, were included. PR improved all questionnaires' results significantly. Only significant difference in PFT parameters was correlation between baseline total lung capacity (TLC) and difference in TLC pre‐ and post‐rehabilitation (p = 0.002). 6MWT increased from 329 to 365 m (p < 0.001), VO2max changed from 21 to 24 mL/kg/min (p = 0.007), peak load increased from 116 to 141 Watt (p < 0.001). Blood volume in small pulmonary vessels of 1.25 to 5 mm2 in cross‐sectional area (BV5%) was higher than observed in patients with acute COVID‐19 infection. After rehabilitation, BV5% decreased from 65% to 62% (p = 0.020). These changes correlated directly with changes in TLC (p = 0.039). Quantified CT airway volume increased after rehabilitation (p = 0.013). After rehabilitation, TLC tended to normalize due to (re)opening of small airways, with decline in air trapping and recruitment of alveoli. Furthermore, this study revealed that pulmonary rehabilitation can improve QoL and physical fitness in long‐COVID patients. [ABSTRACT FROM AUTHOR]

The phenylalanine ammonia‐lyase (PAL) enzyme catalyses the conversion of l‐phenylalanine to trans‐cinnamic acid. This conversion is the first step in phenylpropanoid biosynthesis in plants. The phenylpropanoid pathway produces diverse plant metabolites that play essential roles in various processes, including structural support and defence. Previous studies have shown that mutation of the PAL genes enhances disease susceptibility. Here, we investigated the functions of the rice PAL genes using 2‐aminoindan‐2‐phosphonic acid (AIP), a strong competitive inhibitor of PAL enzymes. We show that the application of AIP can significantly reduce the PAL activity of rice crude protein extracts in vitro. However, when AIP was applied to intact rice plants, it reduced infection of the root‐knot nematode Meloidogyne graminicola. RNA‐seq showed that AIP treatment resulted in a rapid but transient upregulation of defence‐related genes in roots. Moreover, targeted metabolomics demonstrated higher levels of jasmonates and antimicrobial flavonoids and diterpenoids accumulating after AIP treatment. Furthermore, chemical inhibition of the jasmonate pathway abolished the effect of AIP on nematode infection. Our results show that disturbance of the phenylpropanoid pathway by the PAL inhibitor AIP induces defence in rice against M. graminicola by activating jasmonate‐mediated defence. [ABSTRACT FROM AUTHOR]

Background: Prognostic and monitoring capabilities of blood‐based biomarkers for early cognitive decline, amyloid‐β (Aβ) accumulation and grey matter (GM) loss in the asymptomatic phase of Alzheimer disease require further investigation over extended time periods. This longitudinal study investigated serum glial fibrillary acidic protein (GFAP), neurofilament light (NfL) and Aβ1‐42/Aβ1‐40 as potential prognostic and monitoring biomarkers in cognitively unimpaired (CU) elderly. Method: We included 184 CU older adults (Table 1) who underwent baseline serum sampling and 2‐yearly neuropsychological assessment for up to 10 years (median: 6 years, Figure 1). A subset (N = 109) underwent serial blood sampling, Aβ‐PET and structural MRI at 2 (N = 73), 3 (N = 34), or 4 (N = 2) time points (time interval: 2‐10 years, median: 6 years). Cognition was evaluated in memory, language and executive functioning domains through conversion of neuropsychological tests scores to standardised z‐scores and subsequent averaging per domain. Aβ‐accumulation and GM loss were analysed in a voxelwise manner using Voxelstats with cluster‐level pRFT<.05 and voxel‐level puncorrected<.001 significance thresholds.[1] Aβ1‐42/Aβ1‐40 was inverted to facilitate biomarker comparison. Linear‐mixed effects models were used to (i) identify the predictive value of serum biomarkers for longitudinal cognitive decline, Aβ‐accumulation and GM loss, (ii) calculate annual serum biomarker rates of change and (iii) investigate associations between longitudinal biomarker changes and longitudinal changes in cognition, Aβ‐PET and GM volume. Result: High baseline GFAP and NfL predicted a longitudinal decline in memory (βGFAP*time = ‐0.020, pFDR = 0.03; βNfL*time = ‐0.031, pFDR = 0.002) and language (βGFAP*time = ‐0.025, pFDR<0.001, βNfL*time = ‐0.017, pFDR = 0.04), and longitudinal GM loss within the hippocampus. Low Aβ1‐42/Aβ1‐40 predicted memory decline (βAβ1‐42/Aβ1‐40*time = ‐0.022, pFDR = 0.03) as well as Aβ accumulation within Aβ‐vulnerable regions (Figure 1). Serum GFAP (βtime = 0.022, pFDR<.001) and NfL (βtime = 0.040, pFDR<.001) increased over time. Longitudinal serum NfL increases were associated with a concomitant decline in memory (β∆NfL*time = ‐0.031, pFDR=.004), language (β∆NfL*time = ‐0.022, pFDR=.01) and GM volume (Figure 2). Serum GFAP increases were associated with precuneal Aβ accumulation. Aβ1‐42/Aβ1‐40 decreases were stronger in Aβ‐ subjects (pFDR<.001) and did not associate with Aβ accumulation, nor any other longitudinal marker. Conclusion: Serum GFAP, NfL and Aβ1‐42/Aβ1‐40 are prognostic and/or monitoring biomarkers providing complementary information by reflecting different Aβ‐dependent or ‐independent pathophysiological processes. REFERENCE [1] Mathotaarachchi et al. Front Neuroinform 2016. [ABSTRACT FROM AUTHOR]

Background: Prominent theoretical accounts of attention‐deficit/hyperactivity‐disorder (ADHD) hypothesize that reinforcement learning deficits underlie symptoms of ADHD. The Dynamic Developmental Theory and the Dopamine Transfer Deficit hypothesis assume impairments in both the acquisition and extinction of behavior, especially when learning occurs under partial (non‐continuous) reinforcement, and subsequently the Partial Reinforcement Extinction Effect (PREE). Few studies have evaluated instrumental learning in ADHD and the results are inconsistent. The current study investigates instrumental learning under partial and continuous reinforcement schedules and subsequent behavioral persistence when reinforcement is withheld (extinction) in children with and without ADHD. Methods: Large well‐defined samples of children with ADHD (n = 93) and typically developing (TD) children (n = 73) completed a simple instrumental learning task. The children completed acquisition under continuous (100%) or partial (20%) reinforcement, followed by a 4‐min extinction phase. Two‐way (diagnosis by condition) ANOVAs evaluated responses needed to reach the learning criterion during acquisition, and target and total responses during extinction. Results: Children with ADHD required more trials to reach criterion compared to TD children under both continuous and partial reinforcement. After partial reinforcement, children with ADHD executed fewer target responses during extinction than TD children. Children with ADHD executed more responses than TD children during extinction, irrespective of learning condition. Conclusions: The findings demonstrate general difficulties in instrumental learning in ADHD, that is, slower learning irrespective of reinforcement schedule. They also show faster extinction following learning under partial reinforcement in those with ADHD, that is, a diminished PREE. Children with ADHD executed more responses during extinction. Results are theoretically important, with clinical implications for understanding and managing learning difficulties in those with ADHD, as they suggest poorer reinforcement learning and lower behavioral persistence. [ABSTRACT FROM AUTHOR]

Linear ubiquitination is an important post‐translational modification regulating the activation of numerous proinflammatory signalling mediators. Deregulated linear ubiquitination has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. In this issue, Miao et al. have identified a novel role for linear ubiquitination in the stabilisation of the NFAT1 transcription factor, leading to enhanced NFAT1‐mediated gene expression, which might have functional implications in patients with Kawasaki disease. [ABSTRACT FROM AUTHOR]

Patients with post‐acute sequelae of COVID‐19 (PASC) present with a decrease in physical fitness. The aim of this paper is to reveal the relations between the remaining symptoms, blood volume distribution, exercise tolerance, static and dynamic lung volumes, and overall functioning. Patients with PASC were retrospectively studied. Pulmonary function tests (PFT), 6‐minute walk test (6MWT), and cardiopulmonary exercise test were performed. Chest CT was taken and quantified. Patients were divided into two groups: minor functional limitations (MFL) and severe functional limitations (SFL) based on the completed Post‐COVID‐19 Functional Status scale (PCFS). Twenty one patients (3 M; 18 FM), mean age 44 (IQR 21) were studied. Eighteen completed the PCFS (8 MFL; 10 SFL). VO2max was suboptimal in both groups (not significant). 6MWT was significantly higher in MFL‐group (p = 0.043). Subjects with SFL, had significant lower TLC (p = 0.029). The MFL‐group had more air trapping (p = 0.036). Throughout the sample, air trapping correlated significantly with residual volume (RV) in L (p < 0.001). An increase in air trapping was related to an increase in BV5 (p < 0.001). Mean BV5 was 65% (IQR 5%). BV5% in patients with PASC was higher than in patients with acute COVID‐19 infection. This increase in BV5% in patients with PASC is thought to be driven by the air trapping in the lobes. This study reveals that symptoms are more driven by occlusion of the small airways. Patients with more physical complaints have significantly lower TLC. All subjects encounter physical limitations as indicated by suboptimal VO2max. Treatment should focus on opening or re‐opening of small airways by recruiting alveoli. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has had an acute impact on child mental and social health, but long-term effects are still unclear. We examined how child mental health has developed since the start of the COVID-19 pandemic up to 2 years into the pandemic (April 2022). Methods: We included children (age 8-18) from two general population samples (N = 222-1333 per measurement and N = 2401-13,362 for pre-covid data) and one clinical sample receiving psychiatric care (N = 334-748). Behavioral questionnaire data were assessed five times from April 2020 till April 2022 and pre-pandemic data were available for both general population samples. We collected parent-reported data on internalizing and externalizing problems with the Brief Problem Monitor and self-reported data on Anxiety, Depressive symptoms, Sleep-related impairments, Anger, Global health, and Peer relations with the Patient-Reported Outcomes Measurement Information System (PROMIS®). Results: In all samples, parents reported overall increased internalizing problems, but no increases in externalizing problems, in their children. Children from the general population self-reported increased mental health problems from before to during the pandemic on all six PROMIS domains, with generally worst scores in April 2021, and scores improving toward April 2022 but not to pre-pandemic norms. Children from the clinical sample reported increased mental health problems throughout the pandemic, with generally worst scores in April 2021 or April 2022 and no improvement. We found evidence of minor age effects and no sex effects. Conclusions: Child mental health in the general population has deteriorated during the first phase of the COVID-19 pandemic, has improved since April 2021, but has not yet returned to pre-pandemic levels. Children in psychiatric care show worsening of mental health problems during the pandemic, which has not improved since. Changes in child mental health should be monitored comprehensively to inform health care and policy. [ABSTRACT FROM AUTHOR]

The Night Watch, painted in 1642 and on view in the Rijksmuseum in Amsterdam, is considered Rembrandt's most famous work. X‐ray powder diffraction (XRPD) mapping at multiple length scales revealed the unusual presence of lead(II) formate, Pb(HCOO)2, in several areas of the painting. Until now, this compound was never reported in historical oil paints. In order to get insights into this phenomenon, one possible chemical pathway was explored thanks to the preparation and micro‐analysis of model oil paint media prepared by heating linseed oil and lead(II) oxide (PbO) drier as described in 17th century recipes. Synchrotron radiation based micro‐XRPD (SR‐μ‐XRPD) and infrared microscopy were combined to identify and map at the micro‐scale various neo‐formed lead‐based compounds in these model samples. Both lead(II) formate and lead(II) formate hydroxide Pb(HCOO)(OH) were detected and mapped, providing new clues regarding the reactivity of lead driers in oil matrices in historical paintings. [ABSTRACT FROM AUTHOR]

Background: Active oxygen during hypothermic machine perfusion has the potential to improve mitochondrial preservation and subsequently decrease the harmful effects of ischemia reperfusion injury. Brief bubble, and subsequent surface oxygenation are an alternative oxygenation technique for membrane‐oxygenated kidneys during hypothermic machine perfusion (HMP). Methods: Between March 20, 2022, and June 13, 2022, 5 kidney grafts originating from 3 donors after circulatory death were oxygenated by bubble and surface oxygenation during HMP. Results: No adverse events related to this new oxygenation technique were observed. All five recipients experienced no dialysis‐dependency after transplantation with excellent initial graft function at 3 months after transplantation. Conclusions: For the first time in human, this new oxygenation technique was successfully applied to 5 HMP‐kidneys, originating from donation after circulatory death. If confirmed on larger scale cohorts, this innovative oxygenation technique, as alternative oxygenation technique for membrane‐oxygenated kidneys, has the potential to be widely implemented because its simplicity and efficacy, and reducing economic and ecological costs by eliminating the need for a membrane oxygenator and oxygen source during transport. [ABSTRACT FROM AUTHOR]

An increasing number of invasive fruit fly pests are colonizing new grounds. With this study, we aimed to uncover the invasion pathways of the oriental fruit fly, Bactrocera dorsalis into the islands of the Indian Ocean. By using genome‐wide SNP data and a multipronged approach consisting of PCA, ancestry analysis, phylogenetic inference, and kinship networks, we were able to resolve two independent invasion pathways. A western invasion pathway involved the stepping‐stone migration of B. dorsalis from the east African coast into the Comoros, along Mayotte and into Madagascar with a decreasing genetic diversity. The Mascarene islands (Reunion and Mauritius), on the contrary, were colonized directly from Asia and formed a distinct cluster. The low nucleotide diversity suggests that only a few genotypes invaded the Mascarenes. The presence of many long runs of homozygosity (ROH) in the introduced populations is indicative of population bottlenecks, with evidence of a more severe bottleneck for populations along the western migration pathway than on the Mascarene islands. More strict phytosanitary regulations are recommended in order to prevent the further spread of B. dorsalis. [ABSTRACT FROM AUTHOR]

The sensitivity of coarse‐grained daily extreme precipitation to sea surface temperature is analyzed using satellite precipitation estimates over the 300–302.5 K range. A theoretical scaling is proposed, linking changes in coarse‐grained precipitation to changes in fine‐scale hourly precipitation area fraction and changes in conditional fine‐scale precipitation rates. The analysis reveals that the extreme coarse‐grained precipitation scaling with temperature (∼7%/K) is dominated by the fine‐scale precipitating fraction scaling (∼6.5%/K) when using a 3 mm/h fine‐scale threshold to delineate the precipitating fraction. These results are shown to be robust to the selection of the precipitation product and to the percentile used to characterize the extreme. This new coarse‐grained scaling is further related to the well‐known scaling for fine‐scale precipitation extremes, and suggests a compensation between thermodynamic and dynamic contributions or that both contributions are small with respect to that of fractional coverage. These results suggest that processes responsible for the changes in fractional coverage are to be accounted for to assess the sensitivity of coarse‐grained extreme daily precipitation to surface temperature. Plain Language Summary: This study focuses on the processes in the atmosphere that govern extreme coarse‐grained daily precipitation over the 300–302.5 K range. It relies on theoretical developments and satellite observations, to show the importance of the fractional area coverage of fine‐scale hourly precipitation to the scaling of extreme coarse‐grained daily precipitation in the tropics. Our work completes and extends the existing body of theoretical knowledge on the topic, and clarifies the fundamental differences between small‐scale instantaneous and coarse‐grained extremes of precipitation. Our findings open new venues for understanding climate change simulations from cloud‐resolving and earth system models by pointing toward the underappreciated fractional precipitation coverage as a key element of coarsed‐grained extreme precipitation physics. Key Points: A theoretical scaling for coarse‐grained extreme precipitation is introducedObservations reveal that the fraction of fine‐scale precipitation within 1° × 1° domains explains the Clausius‐Clapeyron scaling of coarse‐grained extreme precipitation with SSTThe results are robust to the choice of satellite products used for precipitation [ABSTRACT FROM AUTHOR]

Summary: Plants produce specialized metabolites to protect themselves from biotic enemies. Members of the Solanaceae family accumulate phenylpropanoid–polyamine conjugates (PPCs) in response to attackers while also maintaining a chemical barrier of steroidal glycoalkaloids (SGAs). Across the plant kingdom, biosynthesis of such defense compounds is promoted by jasmonate signaling in which clade IIIe basic helix–loop–helix (bHLH) transcription factors play a central role.By characterizing hairy root mutants obtained through Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)‐CRISPR associated protein 9 (CRISPR‐Cas9) genome editing, we show that the tomato clade IIIe bHLH transcription factors, MYC1 and MYC2, redundantly control jasmonate‐inducible PPC and SGA production, and are also essential for constitutive SGA biosynthesis.Double myc1 myc2 loss‐of‐function tomato hairy roots displayed suppressed constitutive expression of SGA biosynthesis genes, and severely reduced levels of the main tomato SGAs α‐tomatine and dehydrotomatine. In contrast, basal expression of genes involved in PPC biosynthesis was not affected. CRISPR‐Cas9(VQR) genome editing of a specific cis‐regulatory element, targeted by MYC1/2, in the promoter of a SGA precursor biosynthesis gene led to decreased constitutive expression of this gene, but did not affect its jasmonate inducibility.Our results demonstrate that clade IIIe bHLH transcriptional regulators have evolved under the control of distinct regulatory cues to specifically steer constitutive and stress‐inducible specialized metabolism. [ABSTRACT FROM AUTHOR]

The European starling, Sturnus vulgaris, is an ecologically significant, globally invasive avian species that is also suffering from a major decline in its native range. Here, we present the genome assembly and long‐read transcriptome of an Australian‐sourced European starling (S. vulgaris vAU), and a second, North American, short‐read genome assembly (S. vulgaris vNA), as complementary reference genomes for population genetic and evolutionary characterization. S. vulgaris vAU combined 10× genomics linked‐reads, low‐coverage Nanopore sequencing, and PacBio Iso‐Seq full‐length transcript scaffolding to generate a 1050 Mb assembly on 6222 scaffolds (7.6 Mb scaffold N50, 94.6% busco completeness). Further scaffolding against the high‐quality zebra finch (Taeniopygia guttata) genome assigned 98.6% of the assembly to 32 putative nuclear chromosome scaffolds. Species‐specific transcript mapping and gene annotation revealed good gene‐level assembly and high functional completeness. Using S. vulgaris vAU, we demonstrate how the multifunctional use of PacBio Iso‐Seq transcript data and complementary homology‐based annotation of sequential assembly steps (assessed using a new tool, saaga) can be used to assess, inform, and validate assembly workflow decisions. We also highlight some counterintuitive behaviour in traditional busco metrics, and present buscomp, a complementary tool for assembly comparison designed to be robust to differences in assembly size and base‐calling quality. This work expands our knowledge of avian genomes and the available toolkit for assessing and improving genome quality. The new genomic resources presented will facilitate further global genomic and transcriptomic analysis on this ecologically important species. [ABSTRACT FROM AUTHOR]

In vivo angiotensin II (AngII)‐treatment is a widely used experimental model to induce cardiovascular disease and results in a high likelihood of abdominal aorta aneurysm (AAA) formation. This involves progressive and irreversible focal dilation of the abdominal aorta and induces adverse aortic connective tissue remodeling contributing to aortic wall stiffening through inflammation, elastin degradation, and collagen restructuring. Hence, the present study aimed to investigate how AAA formation in AngII‐treated mice affects aortic function and biomechanics. To this end, C57Bl/6J mice were treated with AngII (1000 ng/[kg.min]) or PBS infusion for 28 days. Peripheral blood pressure, echocardiography, and aortic pulse wave velocity were measured in vivo. Thoracic aorta rings were studied ex vivo in organ chambers, while aortic vascular smooth muscle cell (VSMC) phenotype was investigated histologically. We confirmed peripheral hypertension, cardiac hypertrophy, aortic stiffening, and increased VSMC proliferation and migration after AngII‐treatment. Abdominal aorta aneurysm formation was observed in 8/13 AngII‐treated mice. Ex vivo thoracic aortic rings of both aneurysmal and non‐aneurysmal AngII‐treated mice showed high isobaric aortic stiffness, endothelial dysfunction, heightened α1‐adrenergic contractility, and altered VSMC contractile calcium signaling. However, aortic biomechanics were differently affected, with heightened α1‐adrenoreceptor mediated aortic stiffening in non‐aneurysmal mice, whereas contraction‐dependent stiffening was impaired in aneurysmal mice. In conclusion, although aneurysmal and non‐aneurysmal 4‐week AngII‐treated mice displayed similar changes in aortic physiology, aortic biomechanics were dissimilarly affected. [ABSTRACT FROM AUTHOR]

Ascorbic acid (AsA) is an important antioxidant in plants and regulates various physiological processes. In this study, we show that exogenous treatments with the oxidized form of AsA, that is, dehydroascorbate (DHA), activates induced systemic resistance in rice against the root‐knot nematode Meloidogyne graminicola, and investigate the molecular and biochemical mechanisms underlying this phenotype. Detailed transcriptome analysis on roots of rice plants showed an early and robust transcriptional response on foliar DHA treatment, with induction of several genes related to plant stress responses, immunity, antioxidant activity, and secondary metabolism already at 1 day after treatment. Quantitative and qualitative evaluation of H2O2 levels confirmed the appearance of a reactive oxygen species (ROS) burst on DHA treatment, both at the site of treatment and systemically. Experiments using chemical ROS inhibitors or scavengers confirmed that H2O2 accumulation contributes to DHA‐based induced resistance. Furthermore, hormone measurements in DHA‐treated plants showed a significant systemic accumulation of the defence hormone salicylic acid (SA). The role of the SA pathway in DHA‐based induced resistance was confirmed by nematode infection experiments using an SA‐signalling deficient WRKY45‐RNAi line and reverse transcription‐quantitative PCR on SA marker genes. Our results collectively reveal that DHA activates induced systemic resistance in rice against the root‐knot nematode M. graminicola, mediated through the production of ROS and activation of the SA pathway. [ABSTRACT FROM AUTHOR]

Although vaccines are currently used to control the coronavirus disease 2019 (COVID‐19) pandemic, treatment options are urgently needed for those who cannot be vaccinated and for future outbreaks involving new severe acute respiratory syndrome coronavirus virus 2 (SARS‐CoV‐2) strains or coronaviruses not covered by current vaccines. Thus far, few existing antivirals are known to be effective against SARS‐CoV‐2 and clinically successful against COVID‐19. As part of an immediate response to the COVID‐19 pandemic, a high‐throughput, high content imaging–based SARS‐CoV‐2 infection assay was developed in VeroE6 African green monkey kidney epithelial cells expressing a stable enhanced green fluorescent protein (VeroE6‐eGFP cells) and was used to screen a library of 5676 compounds that passed Phase 1 clinical trials. Eight drugs (nelfinavir, RG‐12915, itraconazole, chloroquine, hydroxychloroquine, sematilide, remdesivir, and doxorubicin) were identified as inhibitors of in vitro anti–SARS‐CoV‐2 activity in VeroE6‐eGFP and/or Caco‐2 cell lines. However, apart from remdesivir, toxicity and pharmacokinetic data did not support further clinical development of these compounds for COVID‐19 treatment. [ABSTRACT FROM AUTHOR]

Objective: Plasma phosphorylated‐tau‐181 (p‐tau181) reliably detects clinical Alzheimer's disease (AD) as well as asymptomatic amyloid‐β (Aβ) pathology, but is consistently quantified with assays using antibody AT270, which cross‐reacts with p‐tau175. This study investigates two novel phospho‐specific assays for plasma p‐tau181 and p‐tau231 in clinical and asymptomatic AD. Methods: Plasma p‐tau species were quantified with Simoa in 44 AD patients, 40 spouse controls and an independent cohort of 151 cognitively unimpaired (CU) elderly who underwent Aβ‐PET. Simoa plasma Aβ42 measurements were available in a CU subset (N = 69). Receiver operating characteristics and Aβ‐PET associations were used to evaluate biomarker validity. Results: The novel plasma p‐tau181 and p‐tau231 assays did not show cross‐reactivity. Plasma p‐tau181 accurately detected clinical AD (area under the curve (AUC) = 0.98, 95% CI 0.95–1.00) as well as asymptomatic Aβ pathology (AUC = 0.84, 95% CI 0.76–0.92), while plasma p‐tau231 did not (AUC = 0.74, 95% CI 0.63–0.85 and 0.61, 95% CI 0.52–0.71, respectively). Plasma p‐tau181, but not p‐tau231, detected asymptomatic Aβ pathology more accurately than age, sex and APOE combined (AUC = 0.64). In asymptomatic elderly, correlations between plasma p‐tau181 and Aβ pathology were observed throughout the cerebral cortex (ρ = 0.40, p < 0.0001), with focal associations within AD‐vulnerable regions, particularly the precuneus. The plasma Aβ42/p‐tau181 ratio did not reflect asymptomatic Aβ pathology better than p‐tau181 alone. Interpretation: The novel plasma p‐tau181 assay is an accurate tool to detect clinical as well as asymptomatic AD and provides a phospho‐specific alternative to currently employed immunoassays. [ABSTRACT FROM AUTHOR]

We examined the phylogeny and intrageneric classification of eristaline hoverfly genera from the Afrotropical Region using mitochondrial genomes. Genome skimming was used to obtain (nearly) full mtDNA and nuclear rDNA (18S, 28S) genomes of 120 museum vouchers from eight genera and 98 species. Phylogenetic reconstructions of mitogenomes and mitogenomes + nuclear rDNA yielded comparable phylogenies while that of rDNA only resulted in poorly resolved phylogenies. Phylogenetic analyses focused on six genera and supported the monophyly of the genera Chasmomma Bezzi, Eristalinus Rondani, Mesembrius Rondani and Syritta Le Peletier & Serville, whereas Simoides Loew was not monophyletic and rendered PhytomiaGuérin‐Méneville paraphyletic. We therefore synonymize Simoides with Phytomia. Within Chasmomma, two species‐groups that differ in the colour and the shape of the hind femora (Chasmomma femoratum and Chasmomma nigrum species‐groups) were supported. Within Eristalinus, the monophyly of the subgenera Merodonoides Curran and Eristalodes Mik was supported, but not of the subgenus Eristalinus Rondani. Within Syritta, the monophyly of three out of the five species‐groups tested was rejected. This approach illustrates the importance of integrative and iterative approaches in taxonomy and shows that genomic data may not only clarify the systematic relationships among hoverfly genera and species, but also offer perspectives into the evolution of morphological and ecological variation within the family. [ABSTRACT FROM AUTHOR]

Introduction: The bridging integrator 1(BIN1) rs744373 risk polymorphism has been linked to increased [18F]AV1451 signal in non-demented older adults (ie., mild cognitive impairment [MCI] plus cognitively normal [CN] individuals). However, the association of BIN1 with in vivo tau, amyloid beta (Aß) burden, and cognitive impairment in the asymptomatic stage of Alzheimer's disease (AD) remains unknown. Methods: The BIN1 effect on [18F]AV1451 binding was evaluated in 59 cognitively normal (CN) participants (39% apolipoprotein E [APOE e4]) from the Flemish Prevent AD Cohort KU Leuven (F-PACK), as well as in 66 Alzheimer's Disease Neuroimaging Initiative (ADNI) CNparticipants, using voxelwise and regional statistics. For comparison, 52 MCI patients from ADNI were also studied. Results: Forty-four percent of F-PACK participants were BIN1 rs744373 risk-allele carriers, 21% showed high amyloid burden, and 8% had elevated [18F]AV1451 binding. In ADNI, 53% and 50% of CNs and MCIs, respectively, carried the BIN1 rs744373 risk-allele. Amyloid positivity was present in 23% of CNs and 51% of MCIs, whereas 2% of CNs and 35% of MCIs showed elevated [18F]AV1451 binding. There was no significant effect of BIN1 on voxelwise or regional [18F]AV1451 in F-PACK or ADNI CNs, or in the pooled CN sample. No significant association between BIN1 and [18F]AV1451 was obtained in ADNI MCI patients. However, in the MCI group, numerically higher [18F]AV1451 binding was observed in the BIN1 risk-allele group compared to the BIN1 normal group in regions corresponding to more progressed tau pathology. Discussion: We could not confirm the association between BIN1 rs744373 riskallele and elevated [18F]AV1451 signal in CN older adults or MCI. Numerically higher [18F]AV1451 binding was observed, however, in theMCI BIN1 risk-allele group, indicating that the previously reported positive effect may be confounded by group. Therefore, when studying how the BIN1 risk polymorphism influences AD pathogenesis, a distinction should bemade between asymptomatic, MCI, and dementia stages of AD. [ABSTRACT FROM AUTHOR]

The present study aimed at identifying the members of the Anopheles maculipennis complex (Diptera: Culicidae) occurring in Belgium. Therefore, the second internal transcribed spacer of nuclear ribosomal DNA (ITS2) and the mitochondrial cytochrome oxidase subunit I (COI) loci were sequenced in 175 and 111 specimens, respectively, collected between 2007 and 2019. In parallel, the suitability of two species‐diagnostic PCR‐RFLP assays was tested. The identified specimens included: An. maculipennis s.s. (N = 105), An. daciae (N = 62), An. atroparvus (N = 6) and An. messeae (N = 2). Each species was characterized by unique ITS2 haplotypes, whereas COI only supported the monophyly of An. atroparvus, a historical malaria vector in Belgium. Species identification results were further supported by unique PCR‐RFLP banding patterns. We report for the first time An. daciae in Belgium, where it was found to co‐occur with An. maculipennis s.s. The latter was the most prevalent in the collection studied (60%) and appears to have the widest distribution in Belgium. As in other studies, An. daciae and An. messeae appeared the most closely related species, up to the point that their species status remains debatable, while their ecological differences, including vector competences, need further study. [ABSTRACT FROM AUTHOR]

Although vaccination campaigns are currently being rolled out to prevent coronavirus disease (COVID‐19), antivirals will remain an important adjunct to vaccination. Antivirals against coronaviruses do not exist, hence global drug repurposing efforts have been carried out to identify agents that may provide clinical benefit to patients with COVID‐19. Itraconazole, an antifungal agent, has been reported to have activity against animal coronaviruses. Using cell‐based phenotypic assays, the in vitro antiviral activity of itraconazole and 17‐OH itraconazole was assessed against clinical isolates from a German and Belgian patient infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Itraconazole demonstrated antiviral activity in human Caco‐2 cells (EC50 = 2.3 µM; 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay). Similarly, its primary metabolite, 17‐OH itraconazole, showed inhibition of SARS‐CoV‐2 activity (EC50 = 3.6 µM). Remdesivir inhibited viral replication with an EC50 = 0.4 µM. Itraconazole and 17‐OH itraconazole resulted in a viral yield reduction in vitro of approximately 2‐log10 and approximately 1‐log10, as measured in both Caco‐2 cells and VeroE6‐eGFP cells, respectively. The viral yield reduction brought about by remdesivir or GS‐441524 (parent nucleoside of the antiviral prodrug remdesivir; positive control) was more pronounced, with an approximately 3‐log10 drop and >4‐log10 drop in Caco‐2 cells and VeroE6‐eGFP cells, respectively. Itraconazole and 17‐OH itraconazole exert in vitro low micromolar activity against SARS‐CoV‐2. Despite the in vitro antiviral activity, itraconazole did not result in a beneficial effect in hospitalized COVID‐19 patients in a clinical study (EudraCT Number: 2020‐001243‐15). Highlights: Itraconazole exerted in vitro low micromolar activity against SARS‐CoV‐2 Remdesivir demonstrated potent antiviral activity, confirming validity of the assay Itraconazole has since shown no efficacy (study in hospitalized COVID‐19 patients) [ABSTRACT FROM AUTHOR]

In AMBER and EMERALD, darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg demonstrated high virological response and low virological failure (VF) through week 96. Week 96 resistance analyses are presented. Post‐baseline samples for genotyping/phenotyping were analyzed from protocol‐defined‐VFs with viral load (VL) ≥ 400 copies/ml at failure/later time points. Post‐hoc analyses were deep sequencing (AMBER) and HIV‐1 proviral DNA sequencing from baseline samples (VL < 50 copies/ml) (EMERALD). Through week 96 across studies, no darunavir, primary protease inhibitor (PI), or tenofovir resistance‐associated‐mutations (RAMs) occurred in patients continuing (N = 1125) or switching to D/C/F/TAF (N = 715). M184I/V (emtricitabine RAM) was detected in one patient in each arm of AMBER. In EMERALD D/C/F/TAF patients with prior VF and baseline genoarchive data (N = 98), 4% had darunavir RAMs, 36% emtricitabine RAMs, mainly at position 184 (32%), 4% tenofovir RAMs, and 19% ≥3 thymidine‐analogue‐associated‐mutations at screening. The predicted phenotype showed 0% had reduced susceptibility to darunavir, 37% to emtricitabine, and 22% to tenofovir. All achieved VL < 50 copies/ml at week 96/prior discontinuation, with no VF. D/C/F/TAF has a high barrier to resistance; no darunavir, primary PI, or tenofovir RAMs occurred through 96 weeks in AMBER and EMERALD. In EMERALD, baseline archived darunavir, emtricitabine, and tenofovir RAMs in patients with prior VF did not preclude virologic response. Highlights: In the Phase 3 AMBER (treatment‐naïve patients) and EMERALD (virologically suppressed treatment‐experienced patients) studies through week 96, almost no resistance mutations related to the study drugs were observed: no darunavir, primary protease inhibitor or tenofovir resistance‐associated‐mutations (RAMs) occurred post‐baseline in 1125 patients continuing on the once‐daily, single‐tablet regimen (STR), darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg or in 715 patients switching to D/C/F/TAF. The emtricitabine RAM, M184I/V, was detected in only one patient in each arm of AMBER.In EMERALD in the patients with prior virologic failure and baseline genoarchive data who received D/C/F/TAF, baseline archived darunavir, emtricitabine, and tenofovir RAMs, including those with predicted antiretroviral resistance, did not preclude virologic response.The D/C/F/TAF once‐daily STR provides a convenient treatment option, combining the efficacy and high barrier to resistance of darunavir with the safety advantages of TAF for treatment‐naïve and ‐experienced adults living with HIV‐1. [ABSTRACT FROM AUTHOR]

BACKGROUND: Attractant‐based trapping is used in the establishment of pest‐free areas and areas of low pest prevalence for fruit flies (Diptera: Tephritidae). Male lures are commonly used attractants in fruit fly trapping. In this study, the effects of male lure dispensers, traps and combinations of dispensers and traps on monitoring of two fruit fly pests, Ceratitis capitata (Wiedemann) and Bactrocera dorsalis (Hendel), were investigated in South Africa. RESULTS: In the male‐lure‐based trapping systems evaluated, trimedlure (TML) for C. capitata and methyl eugenol (ME) for B. dorsalis, the type of dispenser affected catches for both species. Higher catches of B. dorsalis males were recorded in bucket traps baited with a dispenser containing 15 g ME compared with traps baited with dispensers containing either 4 g ME or 2 g ME. Catches of C. capitata males were higher with dispensers containing TML than those with TML plus extender (Capilure®). The type of trap used with TML also influenced catches of C. capitata with higher numbers recorded in yellow Delta trap compared with the Sensus bucket trap. CONCLUSIONS: Dispensers with higher ME loadings are more effective for monitoring of B. dorsalis. The yellow Delta trap baited with TML (without extender) would be an effective monitoring system for C. capitata. Fruit fly prevalence levels as determined by specific trapping systems should be related to their efficiency in terms of catches of the target pests. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Background: There is a need for scalable, robust and precise Alzheimer's Disease (AD) plasma phosphorylated Tau (pTau) biomarker tests to support clinical trials and clinical practice. This study evaluated the performance of novel plasma pTau181 and pTau217 assays developed on the LUMIPULSE G1200 automated immunoassay platform and compared them to Quanterix homebrew assays. Method: Homebrew Quanterix Simoa assays for plasma pTau181 and pTau217 were transferred to the LUMIPULSE G instrument using recombinantly expressed versions of respectively α‐pTau181 mAb ADx252 and α‐pTau217 mAb RD‐084 (capture) both combined with an ALP‐conjugated Fab fragment digested from α‐N‐terminal Tau recombinant ADx204/RD‐073 (detector). Analytical performance evaluated specificity, LLOQ and precision. Performance in patient samples was evaluated using a prospective memory cohort of 42 biomarker confirmed AD patients in the prodromal or dementia stage as well as 35 healthy spouse controls. LUMIPULSE G results were compared with results from the Quanterix homebrew assays designed by ADx using the same antibody configuration. Result: Robust LUMIPULSE G1200 measurements (mean intra‐run CV 3%) distinguished AD patients from spouse controls with an area under the curve (AUC) of 0.81 and 0.88 for pTau181 and pTau217, respectively. The Quanterix homebrew assays demonstrated higher AUC of 0.98 for pTau181 (pDeLong = 0.002) and of 0.95 for pTau217 (Figure 1A). Addition of age, sex and ApoE4 status to the LUMIPULSE G‐based models increased the performance of both pTau181 and pTau217 to predict AD diagnosis – relatively to univariate models ‐ with AUCs of respectively 0.91 and 0.95 (Figure 1B, both pDeLong < 0.05), approximating Simoa‐based pTau performance. PTau values measured on both platforms correlated significantly (p<0.0001) for pTau181 (r = 0.66) and pTau217 (r = 0.77). Conclusion: The LUMIPULSE G platform is a scalable, automated, real‐time‐testing platform that is globally available. These data demonstrate that two assays on this platform, pTau181 and pTau217, are capable of distinguishing AD from controls in plasma. The sensitivity and specificity are slightly less on LUMIPULSE G when compared to an assay using the same antibodies developed on the Simoa instrument. Thus, additional experiments are required on the LUMIPULSE G to optimize analytical performance of these assays using an IVD‐grade automated system. [ABSTRACT FROM AUTHOR]

Background: Blood‐based biomarkers have shown good prognostic performance to predict cognitive decline in well‐controlled asymptomatic cohorts. We now investigated whether preclinical serum levels (sampled on average five years prior to Alzheimer's Disease (AD) diagnosis) or longitudinal changes in GFAP, a glial activation marker, or NfL, a marker of neurodegeneration could predict the rate of cognitive decline rate following initial memory clinic presentation. Method: Preclinical serum samples from 115 clinical AD patients (mean age at diagnosis = 74 years, 58% female, 40% biomarker‐proven) were retrospectively retrieved from the Leuven university hospital long‐term sample storage. All preclinical samples were collected during routine clinical visits on average 5 years (range: 2‐10 years) prior to AD diagnosis. GFAP and NfL were measured using Simoa at VUmc Amsterdam. For a subset of 51 AD patients, longitudinal serum biomarker data were available with follow‐up samples taken either before (N = 16), after (N = 16) or at the time of diagnosis (N = 40). Using linear mixed‐effects models, we assessed (i) the relationship between preclinical baseline biomarker levels and MMSE decline following memory clinic presentation, (ii) the annual rates in longitudinal serum biomarker change and (iii) the relationship between longitudinal serum biomarker changes and MMSE decline. Biomarker levels were natural log‐transformed for statistical analyses and reported p‐values were Bonferroni corrected. Result: High preclinical GFAP serum levels were predictive of faster MMSE decline after initial memory clinic presentation (βs = ‐0.97, p < 0.001). Preclinical NfL levels demonstrated no such predictive value (Figure 1). Across the total time period, serial NfL levels (βs = 0.091, 95% CI: 0.060‐0.13) increased more steeply than GFAP levels (βs = 0.052, 95% CI: 0.035‐0.072). However, within the preclinical time window, only serial GFAP levels (βs = 0.057, p = 0.03), and not NfL, displayed a significant time‐dependent rise (Figure 2). Not longitudinal GFAP nor NfL changes since preclinical sampling were associated with subsequent MMSE decline. Conclusion: Serum GFAP levels measured on average five years prior to clinical diagnosis are informative of the rate of global cognitive decline once patients present at the memory clinic and serum GFAP levels increase towards diagnosis. [ABSTRACT FROM AUTHOR]

Epigenetic processes play a crucial role in the regulation of plant stress responses, but their role in plant–pathogen interactions remains poorly understood. Although histone‐modifying enzymes have been observed to be deregulated in galls induced by root‐knot nematodes (RKN, Meloidogyne graminicola) in rice, their influence on plant defence and their genome‐wide impact has not been comprehensively investigated. First, the role of histone modifications in plant–nematode interactions was confirmed by pharmacological inhibition of histone‐modifying enzymes, which all significantly affected rice susceptibility to RKN. For a more specific view, three histone marks, H3K9ac, H3K9me2, and H3K27me3, were subsequently studied by chromatin‐immunoprecipitation‐sequencing on RKN‐induced galls at 3 days postinoculation. While levels of H3K9ac and H3K27me3 were strongly enriched, H3K9me2 was generally depleted in galls versus control root tips. Differential histone peaks were generally associated with plant defence‐related genes. Transcriptome analysis using RNA‐Seq and RT‐qPCR‐based validation revealed that genes marked with H3K9ac or H3K9me2 showed the expected activation or repression gene expression pattern, but this was not the case for H3K27me3 marks. Our results indicate that histone modifications respond dynamically to RKN infection, and that posttranslational modifications mainly at H3K9 specifically target plant defence‐related genes. [ABSTRACT FROM AUTHOR]

Most of our current knowledge on plant molecular biology is based on experiments in controlled laboratory environments. However, translating this knowledge from the laboratory to the field is often not straightforward, in part because field growth conditions are very different from laboratory conditions. Here, we test a new experimental design to unravel the molecular wiring of plants and study gene–phenotype relationships directly in the field. We molecularly profiled a set of individual maize plants of the same inbred background grown in the same field and used the resulting data to predict the phenotypes of individual plants and the function of maize genes. We show that the field transcriptomes of individual plants contain as much information on maize gene function as traditional laboratory‐generated transcriptomes of pooled plant samples subject to controlled perturbations. Moreover, we show that field‐generated transcriptome and metabolome data can be used to quantitatively predict individual plant phenotypes. Our results show that profiling individual plants in the field is a promising experimental design that could help narrow the lab‐field gap. SYNOPSIS: A new experimental design based on profiling individual plants of the same inbred line under uncontrolled field conditions produces gene function and phenotype predictions that complement predictions gathered from traditional lab‐based experiments. There is substantial variability in the transcriptomes, metabolomes and phenotypes of individual plants of the same genetic background grown in the same field.This variability can be used to predict gene functions and phenotypes of individual plants.Profiling individual field‐grown plants enables mapping of gene networks and phenotypes, and may help close the lab‐field gap. [ABSTRACT FROM AUTHOR]

Hirschmanniella oryzae is one of the most devastating nematodes on rice, leading to substantial yield losses. Effector proteins aid the nematode during the infection process by subduing plant defence responses. In this research we characterized two potential H. oryzae effector proteins, chorismate mutase (HoCM) and isochorismatase (HoICM), and investigated their enzymatic activity and their role in plant immunity. Both HoCM and HoICM proved to be enzymatically active in complementation tests in mutant Escherichia coli strains. Infection success by the migratory nematode H. oryzae was significantly higher in transgenic rice lines constitutively expressing HoCM or HoICM. Expression of HoCM, but not HoICM, increased rice susceptibility against the sedentary nematode Meloidogyne graminicola also. Transcriptome and metabolome analyses indicated reductions in secondary metabolites in the transgenic rice plants expressing the potential nematode effectors. The results presented here demonstrate that both HoCM and HoICM suppress the host immune system and that this may be accomplished by lowering secondary metabolite levels in the plant. [ABSTRACT FROM AUTHOR]

The European eel (Anguilla anguilla) has been extensively studied, especially because of its highly specialized migratory behaviour associated with substantial phenotypic transformations. During this migration, one of those transformations the eel undergoes is from yellow to silver eel, a process known as silvering. Although the cranial morphology during the earlier glass, elver and yellow eel stages are well studied, little is known about actual morphological changes during the transformation process from the yellow to the silver eel stage. Yet, literature suggests drastic changes in musculoskeletal anatomy. Here, we investigated the cranial musculoskeletal morphology of 11 male European eels at different stages during silvering, resulting both from natural and artificial maturation. Using 3D‐reconstructed µCT data of the head, the skull and cranial muscles associated with jaw closing and respiration were studied. Eye size was used as a proxy for the silvering stage. Size‐adjusted jaw muscle volumes increased during silvering, although insignificantly. Accordingly, a near‐significant increase in bite force was observed. Respiratory muscles size did increase significantly during silvering, however. Considering the eel's long migration, which often includes deep and thus potentially oxygen‐poor environments, having a better performing respiratory system may facilitate efficient migration. Both overall skull dimensions and specifically orbit size increased with eye index, suggesting they play a role in accommodating the enlarging eyes during silvering. Finally, artificially matured eels had a wider and taller skull, as well as larger jaw muscles than wild silver eels. This could be caused (a) by different conditions experienced during the yellow eel stage, which are maintained in the silver eel stage, (b) by side effects of hormonal injections or (c) be part of the maturation process as artificially induced silver eels had a higher eye index than the wild silver eels. [ABSTRACT FROM AUTHOR]

Four weeks of once‐daily oral JNJ‐56136379 (JNJ‐6379; 25, 75, 150 or 250 mg), a class‐N capsid assembly modulator (CAM‐N), was well tolerated with potent antiviral activity in treatment‐naïve, chronic hepatitis B e antigen–positive and hepatitis B e antigen–negative patients (NCT02662712). Hepatitis B virus (HBV) genome sequence analysis, using HBV DNA next‐generation sequence technology, was performed, and impact of substitutions on efficacy was assessed. Analyses focused on HBV core protein amino acid positions associated with JNJ‐6379 and/or other CAMs in vitro resistance, and those within the CAM‐binding pocket. 31/57 patients had ≥ 1 polymorphism at any of the core amino acid positions of interest, most frequently at positions 38 (32%), 105 (23%) and 109 (14%). None of these polymorphisms are known to reduce JNJ‐6379 in vitro activity (fold change [FC] in 50% effective concentration <3.0). Two JNJ‐6379‐treated patients carried a Y118F baseline core polymorphism known to reduce JNJ‐6379 activity in vitro (FC = 6.6) and had HBV DNA declines of 2.77 (75 mg) and 2.19 log10 IU/mL (150 mg) at the end of treatment. One 75 mg JNJ‐6379‐treated patient had an emerging T109S substitution (FC = 1.8; HBV DNA decline 3.18 log10 IU/mL). A 25 mg JNJ‐6379‐treated patient had on‐treatment enrichment of Y118F variant (HBV DNA decline 2.13 log10 IU/mL). In conclusion, baseline polymorphisms and enrichment of substitutions reducing JNJ‐6379 in vitro activity were rare, with no consistent impact on virological response during a 4‐week phase 1b study. Emergence of resistance to longer treatments of JNJ‐6379 will be evaluated in phase 2 studies. [ABSTRACT FROM AUTHOR]

The European eel (Anguilla anguilla) is a fascinating species, exhibiting a complex life cycle. The species is, however, listed as critically endangered on the IUCN Red List due to an amalgam of factors, including habitat loss. This study investigated the burrowing behaviour and substrate preference of glass, elver and yellow stages of A. anguilla. Preference was determined by introducing eels in aquaria with different substrates and evaluating the chosen substrate for burrowing. In addition, burrowing was recorded using a camera in all substrate types and analysed for kinematics. The experiments showed that all of these life stages sought refuge in the sediments with particle sizes ranging from sand to coarse gravel. Starting from a resting position, they shook their head horizontally in combination with rapid body undulations until half of their body was within the substrate. High‐speed X‐ray videography revealed that once partly in the sediment, eels used only horizontal head sweeps to penetrate further, without the use of their tail. Of the substrates tested, burrowing performance was highest in fine gravel (diameter 1–2 mm; lower burrowing duration, less body movements and/or lower frequency of movements), and all eels readily selected this substrate for burrowing. However, glass eels and elvers were able to use coarse gravel (diameter >8 mm) because their smaller size allowed manoeuvring through the spaces between the grains. Further, burrowing performance increased with body size: glass eels required more body undulations compared to yellow eels. Interestingly, the urge to hide within the sediment was highest for glass eels and elvers. Documentation of substrate preference and burrowing behaviour of A. anguilla provides new information about their potential habitat use. Considering that habitat alterations and deteriorations are partly responsible for the decline of the eel, this information can contribute to the development of more effective conservation measures. [ABSTRACT FROM AUTHOR]

6‐Phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase isoform 3 (PFKFB3) is a key enzyme of the glycolytic pathway, and it plays an essential role in angiogenesis. 3‐(3‐Pyridinyl)‐1‐(4‐pyridinyl)‐2‐propen‐1‐one (3PO) is frequently used as a glycolysis inhibitor and is thought to inhibit PFKFB3. However, this latter effect of 3PO has never been investigated in detail and was the aim of the present study. To demonstrate binding of 3PO to PFKFB3, we used isothermal titration calorimetry. However, 3PO did not bind to PFKFB3, even up to 750 µm, in contrast to 3 µm of AZ67, which is a potent and specific PFKFB3 inhibitor. Instead, 3PO accumulated lactic acid inside the cells, leading to a decrease in the intracellular pH and an inhibition of enzymatic reactions of the glycolytic pathway. [ABSTRACT FROM AUTHOR]

Summary: A role for DNA hypomethylation has recently been suggested in the interaction between bacteria and plants; it is unclear whether this phenomenon reflects a conserved response.Treatment of plants of monocot rice and dicot tomato with nematode‐associated molecular patterns from different nematode species or bacterial pathogen‐associated molecular pattern flg22 revealed global DNA hypomethylation. A similar hypomethylation response was observed during early gall induction by Meloidogyne graminicola in rice. Evidence for the causal impact of hypomethylation on immunity was revealed by a significantly reduced plant susceptibility upon treatment with DNA methylation inhibitor 5‐azacytidine.Whole‐genome bisulphite sequencing of young galls revealed massive hypomethylation in the CHH context, while not for CG or CHG nucleotide contexts. Further, CHH hypomethylated regions were predominantly associated with gene promoter regions, which was not correlated with activated gene expression at the same time point but, rather, was correlated with a delayed transcriptional gene activation. Finally, the relevance of CHH hypomethylation in plant defence was confirmed in rice mutants of the RNA‐directed DNA methylation pathway and DECREASED DNA METHYLATION 1.We demonstrated that DNA hypomethylation is associated with reduced susceptibility in rice towards root‐parasitic nematodes and is likely to be part of the basal pattern‐triggered immunity response in plants. [ABSTRACT FROM AUTHOR]

Background: Insertable cardiac monitors (ICM) allow prolonged rhythm monitoring, but the diagnostic performance can be hampered by false positive arrhythmia alerts related to inadequate R‐wave sensing. This study assesses the prevalence and predictors of inadequate R‐wave sensing (both over‐ and undersensing) among different ICM types. Methods: Patients implanted with an ICM at Ghent University Hospital between January 2017 and August 2018 were included. ICM tracings recorded at interrogation or transmitted by remote monitoring were reviewed for inadequate R‐wave sensing leading to false arrhythmia alerts. Patient and implant characteristics were retrieved from the medical records and implant reports. Results: The study screened 135 patients (age 59 ± 19 years, 44% female) implanted with different ICM types: Reveal LINQ™ and XT (Medtronic): n = 92 (68%), Confirm and Confirm Rx (Abbott): n = 35 (26%), and BioMonitor 2 (Biotronik): n = 8 (6%). ICM tracings were analyzed in 112 patients (83%). False arrhythmia alerts occurred in 22 (20%) patients, most frequently related to undersensing (77%). False diagnosis of bradycardia or pause was documented in 64%, false high ventricular rates in 14%, and false atrial fibrillation alerts in 22%. Occurrence of R‐wave changes was not related to patient characteristics or implant R‐wave sensing. A trend toward higher number of inadequate R‐wave sensing seems to occur with nonparasternal implant sites (P =.074). Conclusions: False arrhythmia alerts due to inadequate R‐wave sensing occurred in 20% of ICM patients independent of implant features and patient characteristics. [ABSTRACT FROM AUTHOR]

Patterns of convergent evolution in head shape, combined with performance measures, provide ideal opportunities to understand the processes driving its evolution. Anole lizards represent an excellent subject to test this, as recurrent habitat specialists or ecomorphs evolved independently across different islands.We show that phenotypic similarity corresponds to both phylogenetic similarity and similarity in habitat, indicating that there is convergent evolution in head shape among ecomorphs. Moreover, we show that the evolution of tall, wide heads correlate with the evolution of higher bite forces, driving head shape variation among and within ecomorphs.In addition, the processes affecting head shape variation can differ between sexes, leading to sexual head shape dimorphism. These processes might, however, still depend on the habitat. Consequently, there could also be convergent evolution in head shape dimorphism among ecomorphs.We found no evidence for convergent evolution in sexual head shape dimorphism. Moreover, the sexual head shape dimorphism correlates poorly with bite force, suggesting that intersexual head shape differences are related to other functions. Different processes are thus driving the evolution of head shape and head shape dimorphism. A free Plain Language Summary can be found within the Supporting Information of this article. [ABSTRACT FROM AUTHOR]

Background: Advanced machine learning methods combined with large sets of health screening data provide opportunities for diagnostic value in human and veterinary medicine. Hypothesis/Objectives: To derive a model to predict the risk of cats developing chronic kidney disease (CKD) using data from electronic health records (EHRs) collected during routine veterinary practice. Animals: A total of 106 251 cats that attended Banfield Pet Hospitals between January 1, 1995, and December 31, 2017. Methods: Longitudinal EHRs from Banfield Pet Hospitals were extracted and randomly split into 2 parts. The first 67% of the data were used to build a prediction model, which included feature selection and identification of the optimal neural network type and architecture. The remaining unseen EHRs were used to evaluate the model performance. Results: The final model was a recurrent neural network (RNN) with 4 features (creatinine, blood urea nitrogen, urine specific gravity, and age). When predicting CKD near the point of diagnosis, the model displayed a sensitivity of 90.7% and a specificity of 98.9%. Model sensitivity decreased when predicting the risk of CKD with a longer horizon, having 63.0% sensitivity 1 year before diagnosis and 44.2% 2 years before diagnosis, but with specificity remaining around 99%. Conclusions and clinical importance: The use of models based on machine learning can support veterinary decision making by improving early identification of CKD. [ABSTRACT FROM AUTHOR]