Aims
Immunohistochemical programmed death‐ligand 1 (PD‐L1) staining to predict responsiveness to immunotherapy in patients with advanced non‐small cell lung cancer (NSCLC) has several drawbacks: a ...robust gold standard is lacking, and there is substantial interobserver and intraobserver variance, with up to 20% discordance around cutoff points. The aim of this study was to develop a new deep learning‐based PD‐L1 tumour proportion score (TPS) algorithm, trained and validated on a routine diagnostic dataset of digitised PD‐L1 (22C3, laboratory‐developed test)‐stained samples.
Methods and results
We designed a fully supervised deep learning algorithm for whole‐slide PD‐L1 assessment, consisting of four sequential convolutional neural networks (CNNs), using aiforia create software. We included 199 whole slide images (WSIs) of ‘routine diagnostic’ histology samples from stage IV NSCLC patients, and trained the algorithm by using a training set of 60 representative cases. We validated the algorithm by comparing the algorithm TPS with the reference score in a held‐out validation set. The algorithm had similar concordance with the reference score (79%) as the pathologists had with one another (75%). The intraclass coefficient was 0.96 and Cohen’s κ coefficient was 0.69 for the algorithm. Around the 1% and 50% cutoff points, concordance was also similar between pathologists and the algorithm.
Conclusions
We designed a new, deep learning‐based PD‐L1 TPS algorithm that is similarly able to assess PD‐L1 expression in daily routine diagnostic cases as pathologists. Successful validation on routine diagnostic WSIs and detailed visual feedback show that this algorithm meets the requirements for functioning as a ‘scoring assistant’.
The plant pathogen Erwinia amylovora can be divided into two host-specific groupings; strains infecting a broad range of hosts within the Rosaceae subfamily Spiraeoideae (e.g., Malus, Pyrus, ...Crataegus, Sorbus) and strains infecting Rubus (raspberries and blackberries). Comparative genomic analysis of 12 strains representing distinct populations (e.g., geographic, temporal, host origin) of E. amylovora was used to describe the pan-genome of this major pathogen. The pan-genome contains 5751 coding sequences and is highly conserved relative to other phytopathogenic bacteria comprising on average 89% conserved, core genes. The chromosomes of Spiraeoideae-infecting strains were highly homogeneous, while greater genetic diversity was observed between Spiraeoideae- and Rubus-infecting strains (and among individual Rubus-infecting strains), the majority of which was attributed to variable genomic islands. Based on genomic distance scores and phylogenetic analysis, the Rubus-infecting strain ATCC BAA-2158 was genetically more closely related to the Spiraeoideae-infecting strains of E. amylovora than it was to the other Rubus-infecting strains. Analysis of the accessory genomes of Spiraeoideae- and Rubus-infecting strains has identified putative host-specific determinants including variation in the effector protein HopX1(Ea) and a putative secondary metabolite pathway only present in Rubus-infecting strains.
Objectives
Previous findings suggest a vascular foundation underlying apathy, but transdiagnostic and prospective evidence on vascular apathy is scarce. This study examines the association between ...vascular disease and the presence and development of apathy symptoms in the very old.
Methods
Four cohorts of the Towards Understanding Longitudinal International older People Studies (TULIPS)‐consortium were included in a two‐staged, individual participant data meta‐analysis using generalized linear mixed models. Vascular disease was defined as a history of any clinical atherosclerotic pathology (angina pectoris, myocardial infarction, intermittent claudication, transient ischemic attack, stroke or related surgeries) and was related to apathy symptoms as repeatedly measured by the Geriatric Depression Scale (GDS‐3A ≥2) over a maximum of 5 years.
Results
Of all 1868 participants (median age 85 years old), 53.9% had vascular disease and 44.3% experienced apathy symptoms. Participants with vascular disease had a 76% higher risk of apathy symptoms at baseline (odds ratio (OR) 1.76, 95% confidence interval (CI) 1.32–2.35), irrespective of depressive symptoms and only partially explained by stroke. Conversely, there was no association of vascular disease with the occurrence of apathy symptoms longitudinally, both in those with apathy at baseline (OR 1.00, 95% CI 0.84–1.20) and without (OR 0.96, 95% CI 0.84–1.09).
Conclusions
Vascular disease in the very old is associated with apathy symptoms cross‐sectionally, but not proven longitudinally, independent of depressive symptoms. These findings query a vascular cause underlying apathy symptoms. However, the consistency of our cross‐sectional findings in direction and magnitude across the TULIPS‐consortium do emphasize international relevance of the interplay of vascular factors and apathy in advanced age, which meaning needs further unravelling.
Key points
Apathy symptoms are a common burden in the very old population of which the complex pathophysiology is yet to be unraveled.
Vascular disease might predispose older adults to developing apathy, but prospective evidence on a vascular origin for apathy in old age remains scarce.
Vascular disease is consistently associated with increased risk of concurrent apathy symptoms, but there is no evidence for influence on future apathy symptoms in the very old.
Optimizing cardiovascular disease (CVD) management to attempt to prevent apathy may not be warranted, at least in the very old.
A promising pollution control technology is cold plasma driven chemical processing. The plasma is a pulsed electric gas discharge inside a near atmospheric-pressure-temperature reactor. The system is ...energized by a continuous stream of very short high-voltage pulses. The exhaust gas to be treated flows through the reactor. The methods applied involve the development of robust cold plasma systems, industrial applications and measuring technologies. Tests of the systems were performed at many industrial sites and involved control of airborne VOC (volatile organic compound) and odor. Electrical, chemical and odor measuring data were collected with state-of-the-art methods. To explain the test data an approximate solution of global reaction kinetics of pulsed plasma chemistry was developed. It involves the Lambert function and, for convenience, a simple approximation of it. The latter shows that the amount of removal, in good approximation, is a function of a single variable. This variable is electric plasma power divided by gas flow divided by input concentration. In the results sections we show that in some cases up to 99% of volatile pollution can be removed at an acceptable energy requirement. In the final sections we look into future efficiency enhancements by implementation of (sub)nanosecond pulsed plasma and solid state high-voltage technology and by integration with catalyst technology.
OX2 (CD200) is a broadly expressed membrane glycoprotein, shown here to be important for regulation of the macrophage lineage. In mice lacking CD200, macrophage lineage cells, including brain ...microglia, exhibited an activated phenotype and were more numerous. Upon facial nerve transection, damaged CD200-deficient neurons elicited an accelerated microglial response. Lack of CD200 resulted in a more rapid onset of experimental autoimmune encephalomyelitis (EAE). Outside the brain, disruption of CD200-CD200 receptor interaction precipitated susceptibility to collagen-induced arthritis (CIA) in mice normally resistant to this disease. Thus, in diverse tissues OX2 delivers an inhibitory signal for the macrophage lineage.
pv. tomato is the causal agent of bacterial speck of tomato, an important disease that results in severe crop production losses worldwide. Currently, two races within phylogroup 01a (PG01a) are ...described for this pathogen. Race 0 strains have avirulence genes for the expression of type III system-associated effectors AvrPto1 and AvrPtoB, that are recognized and targeted by the effector-triggered immunity in tomato cultivars having the
race-specific resistance gene. Race 1 strains instead lack the
and
genes and are therefore capable to aggressively attack all tomato cultivars. Here, we have performed the complete genome sequencing and the analysis of
pv. tomato strain DAPP-PG 215, which was described as a race 0 strain in 1996. Our analysis revealed that its genome comprises a 6.2 Mb circular chromosome and two plasmids (107 kb and 81 kb). The results indicate that the strain is phylogenetically closely related to strains Max13, K40, T1 and NYS-T1, all known race 1 strains. The chromosome of DAPP-PG 215 encodes race 1-associated genes like
and
and lacks race 0-associated genes like
, giving it a race 1 genetic background. However, the genome harbors a complete ortholog of
, which allows the strain to display a race 0 phenotype. Comparative genomics with several PG01a genomes revealed that mobile DNA elements are rather involved in the evolution of the two different races.
To explore the associations between different histologically assessed, inflammatory synovial characteristics and subsequent clinical and structural aspects in knee osteoarthritis (OA).
Knee OA ...patients, ranging in stage from early to advanced, were recruited from three different ongoing studies. Synovial tissue biopsies were taken and histologically assessed for six features (four inflammatory related aspects, fibrosis and fibrin deposition). Clinical aspects (WOMAC pain, functioning and stiffness and SF-36 vitality) and structural aspects (Kellgren and Lawrence (KL)-grade, joint space narrowing (JSN; 0–3) and osteophytes (0–3), and reception of total knee replacement (TKR)) were repeatedly assessed during follow-up. Associations between histology and clinical and structural aspects were analysed using linear mixed model analyses and cox proportional hazards analysis.
Biopsies of 83 patients (median complaint duration: 5 2–8 years) were analysed. Follow-up was a median of 1.4 0.8–2.7 years for clinical and 1.8 0.2–5.2 years for structural aspects. Fibrosis and fibrin deposition were inversely correlated with the inflammatory features. A higher fibrosis score was associated with a lower scores for KL-grade, JSN and osteophytes, while higher scores for perivascular oedema, synovial lining thickness and vascularisation were associated with higher scores for structural aspects during follow-up. No associations were found between each of the histological features and any of the clinical aspects or the chance for TKR during follow-up.
Inflammatory related histological aspects are associated with subsequent increased radiological severity in knee OA, while fibrosis seems to protect against this, providing a potential therapeutic target for OA treatment.
Members of the
species complex cause symptoms that are ranging from leaf spots to cankers on a multitude of plant species, including some of the genus
. To date, a total of two species of the
species ...complex and six different pathovars have been associated with diseases on
spp., which were shown to belong to different phylogenetic units (phylogroups, PG) based on sequence similarity of housekeeping genes or whole genomes, suggesting that virulence to
spp. may be the result of convergent pathoadaptation. In this study, a comparative genomics approach was used to determine genes significantly associated with strains isolated from
spp. across a phylogeny of 97 strains belonging to the
species complex. Our study revealed the presence of a set of orthologous proteins which were significantly associated with strains isolated from
spp. than in strains isolated from other hosts or from non-agricultural environments. Among them, the type III effector HopAY predicted to encode for a C58 cysteine protease was found to be highly associated with strains isolated from
spp. and revealed patterns supporting co-evolution and host adaptation.
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