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Resistance to therapies that target homologous recombination deficiency (HRD) in breast cancer limits their overall effectiveness. Multiple, preclinically validated, mechanisms of resistance have been proposed, but their existence and relative frequency in clinical disease are unclear, as is how to target resistance. Longitudinal mutation and methylation profiling of circulating tumour (ct)DNA was carried out in 47 patients with metastatic BRCA1- , BRCA2- or PALB2 -mutant breast cancer treated with HRD-targeted therapy who developed progressive disease—18 patients had primary resistance and 29 exhibited response followed by resistance. ctDNA isolated at multiple time points in the patient treatment course (before, on-treatment and at progression) was sequenced using a novel >750-gene intron/exon targeted sequencing panel. Where available, matched tumour biopsies were whole exome and RNA sequenced and also used to assess nuclear RAD51. BRCA1/2 reversion mutations were present in 60% of patients and were the most prevalent form of resistance. In 10 cases, reversions were detected in ctDNA before clinical progression. Two new reversion-based mechanisms were identified: (i) intragenic BRCA1/2 deletions with intronic breakpoints; and (ii) intragenic BRCA1/2 secondary mutations that formed novel splice acceptor sites, the latter being confirmed by in vitro minigene reporter assays. When seen before commencing subsequent treatment, reversions were associated with significantly shorter time to progression. Tumours with reversions retained HRD mutational signatures but had functional homologous recombination based on RAD51 status. Although less frequent than reversions, nonreversion mechanisms [loss-of-function (LoF) mutations in TP53BP1 , RIF1 or PAXIP1 ] were evident in patients with acquired resistance and occasionally coexisted with reversions, challenging the notion that singular resistance mechanisms emerge in each patient. These observations map the prevalence of candidate drivers of resistance across time in a clinical setting, information with implications for clinical management and trial design in HRD breast cancers. • Longitudinal ctDNA analysis was performed in advanced BRCA -mutant breast cancer during homologous recombination targeted therapy. • BRCA1/2 reversion mutations are observed in ctDNA in 60% of patients who develop resistance. • Large BRCA1/2 deletions were observed leading to novel splicing events that reconstitute in-frame transcripts. • Mutations in other PARPi resistance genes (TP53BP1 , RIF1 and PAXIP1) are rarer and can co-occur with reversion mutations. • Detection of a reversion mutation before therapy was associated with significantly shorter time to progression. [ABSTRACT FROM AUTHOR]

A review of selected studies on fungal endophytes confirms the paucity of Basidiomycota and basal fungi, with almost 90% attributed to Ascomycota. Reasons for the low number of Basidiomycota and basal fungi, including the Chytridiomycota, Mucoromycota, and Mortierellomycota, are advanced, including isolation procedure and media, incubation period and the slow growth of basidiomycetes, the identification of non-sporulating isolates, endophyte competition, and fungus–host interactions. We compare the detection of endophytes through culture-dependent methods and culture-independent methods, the role of fungi on senescence of the host plant, and next-generation studies. [ABSTRACT FROM AUTHOR]

This article is a personal impression of the key scientists who contributed to the study of marine mycology over past 174 years, especially those the author met during his career studying this unique group of fungi. Marine mycology has been a journey of discovery from a few species to nearly 2000 taxa in nine fungal phyla. Techniques for their study have advanced from morphological observations, to the use of scanning and transmission electron microscopy, to the development of high-throughput sequencing technology and the unravelling of the genomes of selected species. Thoughts on the conservation of marine fungi, their adaptation to climate change and potential role in the decomposition of plastics are briefly considered. [ABSTRACT FROM AUTHOR]

Early research on marine fungi was mostly descriptive, with an emphasis on their diversity and taxonomy, especially of those collected at rocky shores on seaweeds and driftwood. Subsequently, further substrata (e.g. salt marsh grasses, marine animals, seagrasses, sea foam, seawater, sediment) and habitats (coral reefs, deep-sea, hydrothermal vents, mangroves, sandy beaches, salt marshes) were explored for marine fungi. In parallel, research areas have broadened from micro-morphology to ultrastructure, ecophysiology, molecular phylogenetics, biogeography, biodeterioration, biodegradation, bioprospecting, genomics, proteomics, transcriptomics and metabolomics. Although marine fungi only constitute a small fraction of the global mycota, new species of marine fungi continue to be described from new hosts/substrata of unexplored locations/habitats, and novel bioactive metabolites have been discovered in the last two decades, warranting a greater collaborative research effort. Marine fungi of Africa, the Americas and Australasia are under-explored, while marine Chytridiomycota and allied taxa, fungi associated with marine animals, the functional roles of fungi in the sea, and the impacts of climate change on marine fungi are some of the topics needing more attention. In this article, currently active marine mycologists from different countries have written on the history and current state of marine fungal research in individual countries highlighting their strength in the subject, and this represents a first step towards a collaborative inter- and transdisciplinary research strategy. [ABSTRACT FROM AUTHOR]

This study introduces two new marine microfungal species, Paraloratospora marina (Phaeosphaeriaceae) and Tremateia phragmitis (Didymosphaeriaceae) based on morphological comparisons and multi-gene phylogenetic analyses. They were collected on decaying woody stems of Phragmites australis at Cardiff Bay Nature Reserve in Wales, United Kingdom. Paraloratospora marina sp. nov. is characterized by immersed, globose to subglobose ascomata with a papillate and periphysate ostiole, cylindrical to subcylindrical, thick-walled, sessile to subsessile asci, fusiform, hyaline to pale brown, 3-septate, guttulate ascospores. Tremateia phragmitis sp. nov. is characterized by semi-immersed to immersed, globose ascomata with a protruding periphysate ostiole, clavate, pedicellate, asci and ascospores that are ellipsoidal to broadly fusiform, 4–6 transversely septate, with 1–2 vertical septa, muriform, golden brown to pale brown ascospores. Dichotomopilus funicola and Pseudofusicoccum ardesiacum are recorded for the first time from marine habitats. Furthermore, based on morphological characteristics and multigene phylogenetic analyses, Phaeosphaeria spartinae was transferred to Septoriella. [ABSTRACT FROM AUTHOR]

The number of marine fungi documented has increased along with the publication of these special issues from 1206 in 2017 (www.marinefungi.org) to 1257 species in 539 genera, 74 orders, 168 families, 20 classes and five phyla ([6]). First and foremost, we dedicate this special issue to three colleagues who have made an invaluable contribution to our knowledge of marine mycology: Frank H. Gleason, Jørgen Koch and Jan Kohlmeyer who passed away in recent years. New marine fungal taxa are continued to be described, and a recent figure of 486 species associated with different salt marsh plant hosts suggests that salt marsh ecosystems are a treasure trove for marine fungi ([3]). Culturing true marine zoosporic fungi will continue to be one of the many challenges in the study of marine fungi. [Extracted from the article]

Background: Finite element model updating (FEMU) is an inverse technique that is used to identify material (constitutive) model parameters based on experimental data. These experimental data, often in the form of full-field strains, may be subject to a filtering bias unique to the measurement technique, which can propagate to material parameter identification error. Objective: Numerically adjusting for this filtering mismatch between the finite element analysis (FEA) and experimental measurements, here from Digital Image Correlation (DIC), is necessary to produce an accurate calibration. We investigate "direct-leveling" the FEA to the DIC data, i.e. computing strains using consistent methods and length scales for both data sets, before performing model calibration. Thus, both data sets have the same spatial resolution and can be quantitatively compared more readily. Methods: We generated two sets of synthetic "experimental" DIC displacement data: one directly from FEA nodal displacements and one from DIC images synthetically deformed according to the FEA displacements. We then explored how the FEMU material model parameter identification is affected by DIC user-defined settings, including virtual strain gauge size, step size, and subset shape function, as well as misalignment between the FEA and DIC datasets. Results: We found that direct-levelling of the FEA data before FEMU calibration returned more accurate results. This accuracy was independent of the DIC settings and spatial resolution. In contrast, performing FEMU with the unlevelled FEA data resulted in significant biases in the identified parameters. Conclusion: In FEMU-based calibrations, it is advantageous to properly level the strain from the FEA to match the filtering and spatial resolution of the DIC results. [ABSTRACT FROM AUTHOR]

X-ray stereo digital image correlation (DIC) measurements were performed at 10 kHz on the internal surface of a jointed structure in a shock tube at a shock Mach number of 1.42 and compared with optical stereo DIC measurements on the outer, visible surface of the structure. The shock tube environment introduces temperature and density gradients in the gas through which the structure was imaged, resulting in spatial and temporal index of refraction variations. These variations cause bias errors in optical DIC measurements due to beam-steering but have minimal influence on x-ray DIC measurements. These results demonstrate the utility of time-resolved x-ray DIC measurements in complicated environments where optical measurements suffer severe errors and/or are precluded by lack of optical access. [ABSTRACT FROM AUTHOR]

Chytrids, often overshadowed by their other fungal counterparts, take center stage as we unravel the mysteries surrounding new species within Rhizophydiales and explore their unique characteristics. In the broader spectrum of chytrids, their significance lies not only in their roles as decomposers but also as key players in nutrient cycling within aquatic ecosystems as parasites and saprobes. Baited soil and aquatic samples collected from various provinces of Thailand, yielded new species of the Rhizophydiales (Chytridiomycota), some of which expanded previously single species genera. Our investigation incorporated a combination of morphological and phylogenetic approaches, enabling us to identify these isolates as distinct taxa. The novel isolates possess distinguishing features, such as variations in size and shape of the sporangium and zoospores, that somewhat differentiate them from described taxa. To confirm the novelty of the species, we employed robust phylogenetic analyses using maximum likelihood and bayesian methods. The results provided strong support for the presence of eight distinct lineages within the Rhizophydiales, representing our newly discovered species. Furthermore, we employed Poisson Tree Processes to infer putative species boundaries and supplement evidence for the establishment of our new Rhizophydiales species. By meticulously exploring their morphological characteristics and genetic makeup, we expand the known catalogue of fungal diversity by describing Alphamyces thailandicus, Angulomyces ubonensis, Gorgonomyces aquaticus, G. chiangraiensis, G. limnicus, Pateramyces pingflumenensis, Terramyces aquatica, and T. flumenensis and also provide valuable insights into the intricacies of this order. This newfound knowledge not only enriches our understanding of Rhizophydiales but also contributes significantly to the broader field of mycology, addressing a critical gap in the documentation of fungal species. The identification and characterization of these eight novel species mark a noteworthy stride towards a more comprehensive comprehension of fungal ecosystems and their vital role. [ABSTRACT FROM AUTHOR]

Fungal endophytes inhabit a similar ecological niche to that occupied by many phytopathogens, with several pathogens isolated from healthy tissues in their latent phase. This study aimed to evaluate the pathogenicity, the colonisation ability, and the enzyme activity of 37 endophytic fungal isolates recovered from apparently healthy apple shoot and leaf tissues. The pathogenicity of the isolates was assessed on 'Royal Gala' and 'Braeburn' fruit and detached 'Royal Gala' shoots. For the non-pathogenic isolates, their ability to endophytically colonise detached 'Royal Gala' shoots was evaluated. Enzyme activity assays were undertaken to determine whether the pathogenicity of the endophytes was related to the production of the extracellular enzymes, amylase, cellulase, pectinase, protease, and xylanase. Of the 37 isolates studied, eight isolates, representing the genera Colletotrichum , Diaporthe , Fusarium, and Penicillium, were shown to be pathogenic on both apple shoots and fruit. Two isolates identified as Trichoderma atroviride , were pathogenic only on shoots, and three isolates, representing the genus Diaporthe , were pathogenic only on fruit. Of the remaining 24 isolates, 22 (Biscogniauxia (n = 8), Chaetomium (n = 4), Trichoderma (n = 3), Epicoccum (n = 2), Neosetophoma (n = 2), Xylaria (n = 1), Daldinia (n = 1), and Paraphaeosphaeria (n = 1)) were recovered from the inoculated apple shoots but two failed to colonise the shoot tissues. Of the isolates tested, 20 produced amylase, 15 cellulase, 25 pectinase, 26 protease, and 13 xylanase. There was no correlation between the range and type of enzymes produced by the isolates and their pathogenicity or ability to endophytically colonise the shoot tissue. The study showed that approximately one-third (13/37) of the isolates recovered from the apparently healthy apple shoot tissues were observed as latent pathogens. The isolates that did not cause disease symptoms may have the ability to reduce colonisation of apple tissues by pathogens including Neonectria ditissima associated with European canker of apple. • Latent plant pathogens isolated from healthy plant tissue identified as endophytes. • Pathogenicity and enzyme production of 37 fungal apple endophyte isolates assessed. • Thirteen isolates produced disease symptoms on apple fruit and/or detached shoots. • Twenty-two isolates endophytically colonised apple shoots, with no symptoms. • Enzyme production did not differentiate between pathogenic and endophytic isolates. [ABSTRACT FROM AUTHOR]

Background: Interpersonal processes influence our physiological states and associated affect. Physiological arousal dysregulation, a core feature of anxiety disorders, has been identified in children of parents with elevated anxiety. However, little is understood about how parent–infant interpersonal regulatory processes differ when the dyad includes a more anxious parent. Methods: We investigated moment-to-moment fluctuations in arousal within parent-infant dyads using miniaturised microphones and autonomic monitors. We continually recorded arousal and vocalisations in infants and parents in naturalistic home settings across day-long data segments. Results: Our results indicated that physiological synchrony across the day was stronger in dyads including more rather than less anxious mothers. Across the whole recording epoch, less anxious mothers showed responsivity that was limited to 'peak' moments in their child's arousal. In contrast, more anxious mothers showed greater reactivity to small-scale fluctuations. Less anxious mothers also showed behaviours akin to 'stress buffering' – downregulating their arousal when the overall arousal level of the dyad was high. These behaviours were absent in more anxious mothers. Conclusion: Our findings have implications for understanding the differential processes of physiological co-regulation in partnerships where a partner is anxious, and for the use of this understanding in informing intervention strategies for dyads needing support for elevated levels of anxiety. [ABSTRACT FROM AUTHOR]

Internalising problems are common within Autism Spectrum Disorder (ASD); early intervention to support those with emerging signs may be warranted. One promising signal lies in how individual differences in temperament are shaped by parenting. Our longitudinal study of infants with and without an older sibling with ASD investigated how parenting associates with infant behavioural inhibition (8–14 months) and later effortful control (24 months) in relation to 3-year internalising symptoms. Mediation analyses suggest nondirective parenting (8 months) was related to fewer internalising problems through an increase in effortful control. Parenting did not moderate the stable predictive relation of behavioural inhibition on later internalising. We discuss the potential for parenting to strengthen protective factors against internalising in infants from an ASD-enriched cohort. [ABSTRACT FROM AUTHOR]

With camera equipment becoming cheaper and computer processing power increasing exponentially, optical test methods are becoming ubiquitous in the mechanics and dynamics communities. However, unlike more traditional methods where the measurement response of interest is obtained directly from the sensor (e.g. an accelerometer directly provides an acceleration), image-based measurement techniques often require a non-trivial amount of post-processing to extract displacements and strains from a series of images. Using experimental images to develop and validate these post-processing algorithms can be a challenge; real images have a finite depth of field, they can have poor contrast, they can be noisy, there can be calibration errors, etc. It is advantageous to create synthetic images with which image processing algorithms can be investigated without the need to deal with all the complexity and cost involved in a real experiment. Synthetic images also provide access to a "true" analytical solution, which is typically not available in an experiment. However, many synthetic image generation tools are either bespoke research codes or built into commercial software, which can limit accessibility. Blender is a free and open-source 3D software package that supports scene modeling and rendering, among other features. It runs an underlying Python scripting engine, so activities such as building and deforming a mesh or rendering a series of images can be automated. For these reasons, Blender has the potential to be used more widely than current synthetic image tools, as well as perform more sophisticated analyses. While Blender was not designed for engineering purposes, this work will demonstrate Blender's suitability for generating synthetic test images for digital image correlation, and show its accuracy is comparable to commercial synthetic image generation software packages. [ABSTRACT FROM AUTHOR]

With the over 2000 marine fungi and fungal-like organisms documented so far, some have adapted fully to life in the sea, while some have the ability to tolerate environmental conditions in the marine milieu. These organisms have evolved various mechanisms for growth in the marine environment, especially against salinity gradients. This review highlights the response of marine fungi, fungal-like organisms and terrestrial fungi (for comparison) towards salinity variations in terms of their growth, spore germination, sporulation, physiology, and genetic adaptability. Marine, freshwater and terrestrial fungi and fungal-like organisms vary greatly in their response to salinity. Generally, terrestrial and freshwater fungi grow, germinate and sporulate better at lower salinities, while marine fungi do so over a wide range of salinities. Zoosporic fungal-like organisms are more sensitive to salinity than true fungi, especially Ascomycota and Basidiomycota. Labyrinthulomycota and marine Oomycota are more salinity tolerant than saprolegniaceous organisms in terms of growth and reproduction. Wide adaptability to saline conditions in marine or marine-related habitats requires mechanisms for maintaining accumulation of ions in the vacuoles, the exclusion of high levels of sodium chloride, the maintenance of turgor in the mycelium, optimal growth at alkaline pH, a broad temperature growth range from polar to tropical waters, and growth at depths and often under anoxic conditions, and these properties may allow marine fungi to positively respond to the challenges that climate change will bring. Other related topics will also be discussed in this article, such as the effect of salinity on secondary metabolite production by marine fungi, their evolution in the sea, and marine endophytes. [ABSTRACT FROM AUTHOR]

Jørgen Koch introduced mycologists to a unique habitat for marine fungi, namely the sand dunes of Grønhøj, Jutland, Denmark. The high diversity of marine fungi obtained from the site provided abundant sporulating structures for a number of research areas in marine mycology including ecological surveys, ultrastructure examination of ascospore appendage development, spore attachment studies and phylogeny. This review highlights the key observations in these areas. Also, a list of 102 species of marine fungi documented for Denmark is provided. [ABSTRACT FROM AUTHOR]

This review brings together the research efforts on salt marsh fungi, including their geographical distribution and host association. A total of 486 taxa associated with different hosts in salt marsh ecosystems are listed in this review. The taxa belong to three phyla wherein Ascomycota dominates the taxa from salt marsh ecosystems accounting for 95.27% (463 taxa). The Basidiomycota and Mucoromycota constitute 19 taxa and four taxa, respectively. Dothideomycetes has the highest number of taxa, which comprises 47.12% (229 taxa), followed by Sordariomycetes with 167 taxa (34.36%). Pleosporales is the largest order with 178 taxa recorded. Twenty-seven genera under 11 families of halophytes were reviewed for its fungal associates. Juncus roemerianus has been extensively studied for its associates with 162 documented taxa followed by Phragmites australis (137 taxa) and Spartina alterniflora (79 taxa). The highest number of salt marsh fungi have been recorded from Atlantic Ocean countries wherein the USA had the highest number of species recorded (232 taxa) followed by the UK (101 taxa), the Netherlands (74 taxa), and Argentina (51 taxa). China had the highest number of salt marsh fungi in the Pacific Ocean with 165 taxa reported, while in the Indian Ocean, India reported the highest taxa (16 taxa). Many salt marsh areas remain unexplored, especially those habitats in the Indian and Pacific Oceans areas that are hotspots of biodiversity and novel fungal taxa based on the exploration of various habitats. [ABSTRACT FROM AUTHOR]

Aims Sclerotinia sclerotiorum is an important pathogen of a wide range of crops, with current control mostly relying on the use of fungicides. This study assessed the effect of biofumigation on in vitro inhibition of mycelial growth and reduction of sclerotial viability of S. sclerotiorum as an attempt to seek an alternative management strategy. Methods and results The effect of different biofumigant crop types to inhibit mycelial growth of ten S. sclerotiorum isolates was investigated, with Brassica juncea 'Caliente 199' being the most effective biofumigant crop. The efficacy of 'Caliente 199' to inhibit mycelial growth and reduce sclerotial viability was influenced by different crop factors. Plant tissue of 'Caliente 199' harvested at 50% or 100% flowering and adjusted to 80% (w/w) moisture resulted in greater mycelial inhibition and a reduction in the sclerotial viability compared with the vegetative tissue with the same plant moisture. Mycelial inhibition and reduction of sclerotial viability were affected by tissue quantity. Whole plant tissue and shoots only resulted in a similar inhibition of mycelial growth, but whole plant tissue resulted in a greater reduction of sclerotial viability. The S. sclerotiorum isolates differed in sensitivity to the volatile bioactive compounds released by the biofumigant plant tissue. Conclusions The volatile bioactive compounds released by 'Caliente 199' resulted in effective mycelial inhibition but did not kill sclerotia completely. [ABSTRACT FROM AUTHOR]

Neocamarosporium aquaticum, collected from a drift dead stem of a halophyte at the Kench Nature Reserve, Hayling Island, UK, is described as a new species in the family Neocamarosporiaceae, Dothideomycetes. Multi-locus analyses based on LSU, SSU, ITS rDNA, and EF1-α placed the new fungus as a distinct species in the genus Neocamarosporium, a sister to Neocamarosporium aesturinum isolated from seawater. The new species is characterized by the asexual morph with pycnidial conidiomata, doliiform, enteroblastic, annellidic conidiogenous cells, and conidia that are initially hyaline, aseptate, with longitudinal and transverse septa when matured, muriform, and turning brown to dark brown on maturity. Neocamarosporium aquaticum and Ne. aesturinum differ in the colour of the conidia, degree of septation, and conidial measurements. [ABSTRACT FROM AUTHOR]

True mangroves and mangrove associates are salt‐tolerant trees and shrubs that serve a critical role in preserving the ecological balance of tropical and subtropical estuarine environments. However, they are not immune to the damage caused by fungal pathogens. In this study, leaves exhibiting leaf spot symptoms were gathered from mangrove estuary and forests in Prachuap Khiri Khan, Thailand. Through morphological and multilocus phylogenetic analyses (LSU, ITS, RPB2 and TUB2) along with genealogical concordance phylogenetic species recognition, we identified Allophoma acanthi sp. nov. from Acanthus ilicifolius. Additionally, A. minor was identified as the causative agent of leaf spots in true mangrove and mangrove associate species, namely, Acanthus ilicifolius, Combretum sp., Hibiscus tiliaceus, Intsia bijuga, Lumnitzera racemosa and Sonneratia alba. We also provide evidence to support the synonymization of A. thunbergiae with A. minor. All eight isolates of Allophoma species in this study demonstrated pathogenicity to their original hosts with varied virulence, confirming Koch's postulates. Our findings contribute to the understanding of fungal pathogens affecting true mangroves and mangrove associates. [ABSTRACT FROM AUTHOR]

Neurons on the left and right sides of the nervous system often show asymmetric properties, but how such differences arise is poorly understood. Genetic screening in zebrafish revealed that loss of function of the transmembrane protein Cachd1 resulted in right-sided habenula neurons adopting left-sided identity. Cachd1 is expressed in neuronal progenitors, functions downstream of asymmetric environmental signals, and influences timing of the normally asymmetric patterns of neurogenesis. Biochemical and structural analyses demonstrated that Cachd1 can bind simultaneously to Lrp6 and Frizzled family Wnt co-receptors. Consistent with this, lrp6 mutant zebrafish lose asymmetry in the habenulae, and epistasis experiments support a role for Cachd1 in modulating Wnt pathway activity in the brain. These studies identify Cachd1 as a conserved Wnt receptor-interacting protein that regulates lateralized neuronal identity in the zebrafish brain. [ABSTRACT FROM AUTHOR]

A novel fungus species, Nemania hydei, isolated from Avicennia marina in Pranburi District, Prachuap Khiri Khan, Thailand is described. The samples were collected from mangrove habitats, and the fungus was isolated and characterised. Nemania species produce carbonaceous, superficial stromata that are multi-peritheciate with papillate ostioles. They are frequently isolated from decomposing angiospermous wood and are primarily considered saprophytic, although some are endophytic, while a few are pathogenic. DNA extraction was performed on pure cultures, and the ITS, LSU, RPB-2, and TUB sequence data were amplified. Molecular phylogenetic investigation revealed that the isolate formed a distinct and well-supported clade with Nemania viridis as a sister taxon. Morphological observations further demonstrated unique characteristics that distinguish N. hydei from its closest taxonomic relative. Primarily, they differ in the shape and size of ascospores, asci, and the characteristic reaction of the apical ring. Despite the existence of over 70 known species within the genus Nemania, only four species have been previously documented from mangrove ecosystems. The discovery of N. hydei contributes to knowledge of species from mangroves, expanding our understanding of the diversity within Nemania in marine habitats. [ABSTRACT FROM AUTHOR]

Background: The management of subacromial shoulder pain represents a significant challenge and is typically managed through either physiotherapy, joint injection or surgical intervention. Recent surgical trials have questioned the efficacy and there is a need to improve the evidence base for the non-surgical management of this condition. The study aims to provide evidence of the feasibility of conducting a randomised controlled trial to compare the efficacy of autologous protein solution (APS) against the current standard of care, corticosteroid injection (CSI) for subacromial shoulder pain. Autologous protein solution (APS) is a blood-derived biological injection which has been shown to have anti-inflammatory effects. Methods: A parallel-group two-arm randomised control trial will be conducted, comparing APS and CSI for shoulder pain. Fifty patients will be recruited. Feasibility will be assessed by examination of the conversion rate of eligible participants to the total number of participants recruited, whether it is possible to collect the appropriate outcome measures and the levels of retention/data compliance at follow-up dates. Discussion: CSI is the mainstay of conservative management of subacromial shoulder pain. Trials and systematic reviews have reported differing conclusions, but the consensus view is that any benefits seen from CSI use are most likely to be short-term and there remains a significant number of patients who go on to have surgical intervention despite CSI. Biological injections, such as APS are being increasingly used, in the anticipation they may offer improved longer lasting outcomes for shoulder pain. However, the evidence to demonstrate the comparative efficacy of CSI versus APS does not currently exist. If feasible, a fully powered study will offer clarity to the treatment pathway of thousands of patients each year with subacromial pain. Trial registration: The study is funded by the National Institute for Health Research–Research for Patient Benefit, NIHR 201473, Trial Registration Number (ISRCTN12536844: SPiRIT. Shoulder pain: randomised trial of injectable treatments–date of Registration 15/9/2021). Protocol Version V1.0_30Jul2021. IRAS Project ID: 294,982. [ABSTRACT FROM AUTHOR]

A collection of isolates of the fungi Leptosphaeria maculans and L. biglobosa, which cause blackleg disease on Brassica napus (canola/oilseed rape) and other Brassicaceae species, was assembled to represent the global diversity of these pathogens and a resource for international research. The collection consists of 226 isolates (205 L. maculans and 21 L. biglobosa) from 11 countries. The genomes of all 205 L. maculans isolates were sequenced, and the distribution and identity of avirulence gene alleles were determined based on genotypic information and phenotypic reactions on B. napus lines that hosted specific resistance genes. Whilst the frequencies of some avirulence alleles were consistent across each of the regions, others differed dramatically, potentially reflecting the canola/oilseed rape cultivars grown in those countries. Analyses of the single‐nucleotide polymorphism (SNP) diversity within these L. maculans isolates revealed geographical separation of the populations. This "open access" resource provides a standardized set of isolates that can be used to define the basis for how these fungal pathogens cause disease, and as a tool for discovery of new resistance traits in Brassica species. [ABSTRACT FROM AUTHOR]

Background: The optimal treatment of colorectal cancer is surgical resection and primary anastomosis. Anastomotic leak can affect up to 20% of patients and creates significant morbidity and mortality. Current diagnosis of a leak is based on clinical suspicion and subsequent radiology. Peritoneal biomarkers have shown diagnostic utility in other conditions and could be useful in providing earlier diagnosis. This pilot study was designed to assess the practical utility of peritoneal biomarkers after abdominal surgery utilising an automated immunoassay system in routine use for quantifying cytokines. Methods: Patients undergoing an anterior resection for a rectal cancer diagnosis were recruited at University Hospital of Wales, Cardiff between June 2019 and June 2021. A peritoneal drain was placed in the proximity of the anastomosis during surgery, and peritoneal fluid was collected at days 1 to 3 post-operatively, and analysed using the Siemens IMMULITE platform for interleukin (IL)-1β, IL-6, IL-10, CXCL8, tumour necrosis factor alpha (TNFα) and C-reactive protein (CRP). Results: A total of 42 patients were recruited (22M:20F, median age 65). Anastomotic leak was detected in four patients and a further five patients had other intra-abdominal complications. The IMMULITE platform was able to provide robust and reliable results from the analysis of the peritoneal fluid. A metric based on the combination of peritoneal IL-6 and CRP levels was able to accurately diagnose three anastomotic leaks, whilst correctly classifying all negative control patients including those with other complications. Conclusions: This pilot study demonstrates that a simple immune signature in surgical drain fluid could accurately diagnose an anastomotic leak at 48 h postoperatively using instrumentation that is already widely available in hospital clinical laboratories. [ABSTRACT FROM AUTHOR]

Bacterial canker of cherry, caused by Pseudomonas syringae pathovars, is a major constraint to cherry growing in New Zealand. The prevalence of strains from cherry orchards in Central Otago, the main growing area for cherries in New Zealand, was studied, to better understand the epidemiology of the disease. Pseudomonas spp. isolates were collected from symptomatic and asymptomatic cherry tissue from 23 commercial cherry orchards in 2015. Isolates were classified into strains belonging to three different taxonomic groups by determining their phylogeny using the gltA gene sequence for all the strains and multilocus sequence analysis (MLSA) of four housekeeping genes for 35 strains. Pathogenicity of all Central Otago strains was tested on immature cherry fruit to support the phylogenetic classification. The two main taxonomic groups were P. syringae pv. syringae (Pss) and P. syringae pv. morsprunorum race 1 (Psm1), in Phylogroup 2 (PG2) and Phylogroup 3 (PG3), respectively. The third group comprised nonpathogenic strains classified as Pseudomonas spp. Strains of Psm1 formed a monophyletic group, representing an almost clonal population. There was more variation detected within strains of Pss, although they were restricted to group PG2d. Nonpathogenic Pseudomonas spp. and pathogenic Pss and Psm1 strains coexisted in the same orchard. It was concluded that Pss is the predominant pathovar in Central Otago. This is the first detailed study of the P. syringae species complex in cherry orchards in New Zealand and provides the basis for future epidemiology studies. [ABSTRACT FROM AUTHOR]

We present a novel adaptive filtering approach to the dynamic characterization of waves of varying frequencies and amplitudes embedded in arbitrary noise backgrounds. This method, known as IWAVE (Iterative Wave Action angle Variable Estimator), possesses critical advantages over conventional techniques, making it a useful new tool in the dynamic characterization of a wide range of data containing embedded oscillating signals. After a review of existing techniques, we present the IWAVE algorithm, derive its key characteristics, and provide tests of its performance using simulated and real world data. [ABSTRACT FROM AUTHOR]

We present results of using a basic binary classification neural network model to identify likely catastrophic outlier photometric redshift estimates of individual galaxies, based only on the galaxies’ measured photometric band magnitude values. We find that a simple implementation of this classification can identify a significant fraction of galaxies with catastrophic outlier photometric redshift estimates while falsely categorizing only a much smaller fraction of non-outliers. These methods have the potential to reduce the errors introduced into science analyses by catastrophic outlier photometric redshift estimates. [ABSTRACT FROM AUTHOR]

Distoseptispora is one of the sporidesmium-like taxa with great variation in asexual morphology and delineation of species. Phylogenetic analyses of four gene regions LSU, ITS, TEF1a, and RPB2 revealed the placement of several sporidesmium-like species in Distoseptispora (Distoseptisporaceae, Distoseptisporales, Sordariomycetes), collected on submerged decaying twigs from streams in China and Thailand. Based on morphological examination and molecular DNA data, six new species, Distoseptispora amniculi, D. atroviridis, D. effusa, D. fusiformis, D. hyalina, and D. verrucosa, are proposed. Among them, D. hyalina is the first sexual morph confirmed in the genus. A new geographical record is reported for D. lignicola in China. Conidial length proved to be of less taxonomic significance for some Distoseptispora species, whereas the type of conidial septa is informative at species level. [ABSTRACT FROM AUTHOR]

Arbuscular mycorrhizal fungi (AMF) deliver potentially significant services in sustainable agricultural ecosystems, yet we still lack evidence showing how AMF abundance and/or community composition can benefit crops. In this study, we manipulated AMF communities in grapevine rootstock and measured plant growth and physiological responses. Glasshouse experiments were set up to determine the interaction between rootstock variety and different AMF communities, using AMF communities originating under their own (i.e., "home") soil and other rootstocks' (i.e., "away") soil. The results revealed that specific AMF communities had differential effects on grapevine rootstock growth and nutrient uptake. It was demonstrated that a rootstock generally performed better in the presence of its own AMF community. This study also showed that AMF spore diversity and the relative abundance of certain species is an important factor as, when present in equal abundance, competition between species was indicated to occur, resulting in a reduction in the positive growth outcomes. Moreover, there was a significant difference between the communities with some AMF communities increasing plant growth and nutrient uptake compared with others. The outcomes also demonstrated that some AMF communities indirectly influenced the chlorophyll content in grapevine leaves through the increase of specific nutrients such as K, Mn, and Zn. The findings also indicated that some AMF species may deliver particular benefits to grapevine plants. This work has provided an improved understanding of community level AMF-grapevine interaction and delivered an increased knowledge of the ecosystem services they provide which will benefit the wine growers and the viticulture industry. [ABSTRACT FROM AUTHOR]

An intragene involves the rearrangement of gene configurations based on switching coding sequences and regulatory regions within a species. The overexpression of specific GSL (Gibberellin Stimulated-Like) genes is known to confer enhanced disease resistance. A potato intragenic expression cassette, with the potato GSL1 gene placed under the regulatory control of the light-inducible Lhca3 gene from potato, was designed and constructed. The resulting intragene was transformed using Agrobacterium-mediated gene transfer into potato cultivar Iwa to investigate whether overexpression of the potato GSL1 intragene can confer disease resistance. The transgenic status of the resulting plants was confirmed by PCR. The majority of the transgenic potato lines were determined to overexpress the GSL1 gene at the mRNA level using quantitative RT–PCR analysis. From these results, seven lines were selected for further characterisation and thoroughly evaluated in bioassays for resistance to Pectobacterium atrosepticum which causes blackleg disease in potato. These pathogenicity bioassays demonstrated that high transcriptional overexpression of GSL1 confers high resistance to blackleg disease. This confirms a functional role of the GSL1 gene in plant defence against pathogens and provides an intragenic approach for disease resistance in potatoes. [ABSTRACT FROM AUTHOR]

Temporal coordination during infant-caregiver social interaction is thought to be crucial for supporting early language acquisition and cognitive development. Despite a growing prevalence of theories suggesting that increased inter-brain synchrony associates with many key aspects of social interactions such as mutual gaze, little is known about how this arises during development. Here, we investigated the role of mutual gaze onsets as a potential driver of inter-brain synchrony. We extracted dual EEG activity around naturally occurring gaze onsets during infant-caregiver social interactions in N = 55 dyads (mean age 12 months). We differentiated between two types of gaze onset, depending on each partners' role. 'Sender' gaze onsets were defined at a time when either the adult or the infant made a gaze shift towards their partner at a time when their partner was either already looking at them (mutual) or not looking at them (non-mutual). 'Receiver' gaze onsets were defined at a time when their partner made a gaze shift towards them at a time when either the adult or the infant was already looking at their partner (mutual) or not (non-mutual). Contrary to our hypothesis we found that, during a naturalistic interaction, both mutual and non-mutual gaze onsets were associated with changes in the sender, but not the receiver's brain activity and were not associated with increases in inter-brain synchrony above baseline. Further, we found that mutual, compared to non-mutual gaze onsets were not associated with increased inter brain synchrony. Overall, our results suggest that the effects of mutual gaze are strongest at the intra-brain level, in the 'sender' but not the 'receiver' of the mutual gaze. [ABSTRACT FROM AUTHOR]

Botryosphaeriales (Dothideomycetes, Ascomycota) occur in a wide range of habitats as endophytes, saprobes, and pathogens. The order Botryosphaeriales has not been subjected to evaluation since 2019 by Phillips and co-authors using phylogenetic and evolutionary analyses. Subsequently, many studies introduced novel taxa into the order and revised several families separately. In addition, no ancestral character studies have been conducted for this order. Therefore, in this study, we re-evaluated the character evolution and taxonomic placements of Botryosphaeriales species based on ancestral character evolution, divergence time estimation, and phylogenetic relationships, including all the novel taxa that have been introduced so far. Maximum likelihood, maximum parsimony, and Bayesian inference analyses were conducted on a combined LSU and ITS sequence alignment. Ancestral state reconstruction was carried out for conidial colour, septation, and nutritional mode. Divergence times estimates revealed that Botryosphaeriales originated around 109 Mya in the early epoch of the Cretaceous period. All six families in Botryosphaeriales evolved in the late epoch of the Cretaceous period (66–100 Mya), during which Angiosperms also appeared, rapidly diversified and became dominant on land. Families of Botryosphaeriales diversified during the Paleogene and Neogene periods in the Cenozoic era. The order comprises the families Aplosporellaceae, Botryosphaeriaceae, Melanopsaceae, Phyllostictaceae, Planistromellaceae and Saccharataceae. Furthermore, current study assessed two hypotheses; the first one being "All Botryosphaeriales species originated as endophytes and then switched into saprobes when their hosts died or into pathogens when their hosts were under stress"; the second hypothesis states that "There is a link between the conidial colour and nutritional mode in botryosphaerialean taxa". Ancestral state reconstruction and nutritional mode analyses revealed a pathogenic/saprobic nutritional mode as the ancestral character. However, we could not provide strong evidence for the first hypothesis mainly due to the significantly low number of studies reporting the endophytic botryosphaerialean taxa. Results also showed that hyaline and aseptate conidia were ancestral characters in Botryosphaeriales and supported the relationship between conidial pigmentation and the pathogenicity of Botryosphaeriales species. [ABSTRACT FROM AUTHOR]

Objective: To understand practices of umbilical venous catheter (UVC) insertion in tertiary level neonatal intensive care units (NICU) and investigate the outcomes of subsequent attempts following a failed initial attempt. Study design: Prospective, multi-center observational study of UVC insertions at tertiary level NICUs between March 2019 and January 2020. Results: Of the 101 UVCs inserted at 4 centers, seventy-two (71%) were central at the first attempt and 50% were central at subsequent attempts. Patients with at least 1 failed attempt at insertion were less likely to have a centrally placed UVC (p = .009). Manipulations were less likely to be required when UVC was centrally placed during the first attempt. Maneuvers such as posterior liver mobilization used during insertion were likely to be associated with successful central placement of UVC (p = .0243). The time to complete the procedure was significantly less when the UVC was central at the first attempt (34.2 ± 20.2 vs 46.9 ± 33.8) (p = .0292). Gestational age, birth weight, and age of the baby at the insertion of the UVC, experience of the provider, and type of catheter were comparable among groups. The Shukla formula was most commonly used by providers to measure the depth of UVC placement. Conclusion: Repetitive attempts and manipulations were less likely to be beneficial in the successful central placement of UVC in neonates. Additionally, repetitive attempts at insertion prolonged the overall duration of the procedure. [ABSTRACT FROM AUTHOR]

Grapevine trunk diseases (GTDs) are a significant problem for New Zealand viticulture. Endophytic actinobacteria are of interest as potential biocontrol agents due to their ability to inhibit plant pathogens and improve plant growth. However, no studies have investigated the diversity of actinobacteria associated with grapevines in New Zealand vineyards and their bioactivity. Actinobacteria diversity in different ‘Sauvignon blanc’ vine tissues from three vineyards (conventional and organic management, and different vine ages) was assessed using different methods and media. Forty-six endophytic actinobacteria were isolated, with more isolates recovered from roots (n = 45) than leaves (n = 1) and shoot internodes (n = 0). More isolates were recovered from the organic (n = 21) than conventional (n = 8) vineyard, mature (25-year old; n = 21) than young (2-year old; n = 2) vines and using a tissue maceration technique (n = 40). Actinomycete Isolation Agar, International Streptomyces Project 2, and Starch Casein media were effective for actinobacteria isolation. Most of the isolates recovered belonged to Streptomyces, with one isolate identified as Mycolicibacterium. Forty isolates were assessed for antifungal activity and plant growth-promoting (PGP) characteristics. Of these, 13 isolates had antifungal activity against test GTD pathogens (Dactylonectria macrodidyma, Eutypa lata, Ilyonectria liriodendri, Neofusicoccum parvum, and N. luteum). Eighteen isolates exhibited more than one PGP trait; 25siderophore production (n = 25), phosphate solubilization (n = 6), and indole acetic acid production (n = 16). Two strains, Streptomyces sp. LUVPK-22 and Streptomyces sp. LUVPK-30, exhibited the best antifungal and PGP properties. This study revealed the diversity of culturable endophytic actinobacteria from grapevines in New Zealand vineyards and their biocontrol potential against GTD pathogens. [ABSTRACT FROM AUTHOR]

Background: Antenatal pelvic floor muscle exercises (PFME) in women without prior urinary incontinence (UI) are effective in reducing postnatal UI; however, UK midwives often do not provide advice and information to women on undertaking PFME, with evidence that among women who do receive advice, many do not perform PFME. Methods: The primary aim of this feasibility and pilot cluster randomised controlled trial is to provide a potential assessment of the feasibility of undertaking a future definitive trial of a midwifery-led antenatal intervention to support women to perform PFME in pregnancy and reduce UI postnatally. Community midwifery teams in participating NHS sites comprise trial clusters (n = 17). Midwives in teams randomised to the intervention will be trained on how to teach PFME to women and how to support them in undertaking PFME in pregnancy. Women whose community midwifery teams are allocated to control will receive standard antenatal care only. All pregnant women who give birth over a pre-selected sample month who receive antenatal care from participating community midwifery teams (clusters) will be sent a questionnaire at 10–12 weeks postpartum (around 1400–1500 women). Process evaluation data will include interviews with midwives to assess if the intervention could be implemented as planned. Interviews with women in both trial arms will explore their experiences of support from midwives to perform PFME during pregnancy. Data will be stored securely at the Universities of Birmingham and Exeter. Results will be disseminated through publications aimed at maternity service users, clinicians, and academics and inform a potential definitive trial of effectiveness. The West Midlands–Edgbaston Research Ethics Committee approved the study protocol. Discussion: Trial outcomes will determine if criteria to progress to a definitive cluster trial are met. These include women's questionnaire return rates, prevalence of UI, and other health outcomes as reported by women at 10–12 weeks postpartum. Progress to a definitive trial however is likely to be prevented in the UK context by new perinatal pelvic health service, although this may be possible elsewhere. Trial registration: https://doi.org/10.1186/ISRCTN10833250. Registered 09/03/2020 [ABSTRACT FROM AUTHOR]

About a third of all marine fish in the world are caught in Small-Scale Fisheries (SSF). SSF are increasingly recognised as essential for food security and livelihoods for vulnerable and economically fragile communities globally. Although individual SSF vessels are usually perceived as having little impact on the ecosystem, the cumulative impact of gear type and number of vessels may be substantial. Bottom trawling is a common fishing method that can greatly influence the marine ecosystem by damaging the seafloor and generating high levels of discards. However, appropriate sampling coverage using on-board observer programmes to collect these data from SSF are rare, as they are expensive and pose logistical constraints. A mobile App was used to assess whether self-reporting by fishers could provide reliable fine-scale information on fishing effort and discards over time in an illegal shrimp trawling fishery in northern Peru. Maps depicting the spatial distribution of trawling effort and the proportion of discards from observers and fishers were compared using the Similarity in Means (SIM) Index, which ranges from 0 when spatial patterns differ completely to 1 when spatial patterns are very similar. High levels of agreement between spatio-temporal patterns of effort (SIM Index = 0.81) and discards (0.96) were found between fisher and observer maps. Moreover, far greater spatial coverage was accomplished by fishers, suggesting that self-reporting via an App represents a useful approach to collect reliable fisheries data as an initial step for effective monitoring and management of these fisheries. [ABSTRACT FROM AUTHOR]

Background: Effective smoking cessation programs exist but are underutilized by smokers, especially by disadvantaged smokers. Cessation interventions in dental settings have been shown to be effective, but are not consistently delivered due to provider burden and lack of training, especially on how to counsel smokers who are not motivated to quit.Methods: This study is a 2-arm, phase III longitudinal randomized controlled efficacy trial to motivate utilization of evidenced based treatments (EBTs) for smoking cessation (e.g., state quitline, clinic-based counseling, the National Cancer Institute's text message program, and pharmacotherapy). Patients attending an urban dental clinic (n = 376) will be randomized to an intervention group (INT; smoking cessation induction video delivered via VR headset during their teeth cleaning, brochure about EBTs, and a 4-week text message program) or control group (CTRL; relaxation video delivered via VR headset during teeth cleaning, the same brochure as INT, and assessment-only text messages). Assessments will occur at baseline, immediately after the clinic appointment, one-month post-appointment and 3-and 6 months later. We hypothesize INT will be more likely to contact EBTs vs CTRL and have greater utilization rates of EBTs. Secondary objectives are to test the efficacy of INT on point-prevalence smoking abstinence, quit smoking attempts, and motivation to quit vs. CTRL.Discussion: Incorporating smoking cessation into a dental clinic visit and targeting all smokers, regardless of motivation to quit, provides proactive reach to cigarette smokers who otherwise may not seek treatment for smoking.Trial Registration: NCT04524533 Registered August 24, 2020. [ABSTRACT FROM AUTHOR]

Aim: Botryosphaeriaceae causing stem blight and dieback of blueberry are important pathogens limiting economic production worldwide. This study investigated the pathogenicity and relative virulence of isolates from the Neofusicoccum species commonly associated with blueberries in New Zealand on different tissues and cultivars of blueberries. Methods and Results: Both wounded and non‐wounded fruit and flower buds and wounded attached soft green and hard green shoots were susceptible to infection by conidia of Neofusicoccum australe, Neofusicoccum parvum and Neofusicoccum ribis. N. ribis was generally most virulent, followed by N. parvum and then N. australe. Inoculation of potting mixture with N. australe or N. ribis conidia showed that potting mixtures were not a source of inoculum for infection of blueberry roots. Wounded and non‐wounded leaf buds, fruit and wounded soft green shoots and hard green shoots of the different cultivars tested were susceptible to infection by N. parvum and N. ribis. Whilst the fruit of all cultivars were similarly infected, infection incidence in inoculated leaf buds was lowest in "Blue Bayou" and "Ocean Blue". Cultivar susceptibility differed when tested on soft green shoots compared with hard green shoots, with shortest lesions developed on "Maru" on soft green shoots, and "Centra Blue" and "Ocean Blue" on hard green shoots. Conclusions: All tested above‐ground blueberry tissues, including non‐wounded tissue, were susceptible to Neofusicoccum spp. All the cultivars assessed were susceptible to infection, although they varied in their relative susceptibility depending on the tissue assessed. Significance and impact of the study: The potential for non‐wounded tissue to become infected indicate that fungicides may need to be applied to protect all tissue, not just wounds. [ABSTRACT FROM AUTHOR]

Summary: Background: Ulceration is a recognized risk factor for surgical site infection (SSI); however, the proportion of patients developing SSI after excision of an ulcerated skin cancer is unknown. Aim: To determine the proportion of participants with SSI after surgical excision of an ulcerated skin cancer. A secondary aim was to assess feasibility outcomes to inform the design of a randomized controlled trial to investigate the benefits and harms of perioperative antibiotics following excision of ulcerated tumours. Methods: This was a multicentre, prospective, observational study of patients undergoing excision of an ulcerated skin cancer between March 2019 and March 2020. Prior to surgical excision, surface swabs of the ulcerated tumours of participants recruited from one centre were undertaken to determine organism growth. At 4 weeks after surgery, all participants were e‐mailed or posted the Wound Healing Questionnaire (WHQ) to determine whether they had developed SSI. Results: In total, 148 participants were recruited 105 (70.9%) males; mean ± SD age 77.1 ± 12.3 years. Primary outcome data were available for 116 (78.4%) participants, of whom 35 (30.2%) were identified as having an SSI using the WHQ with a cutoff score of 8, and 47 (40.5%) were identified with a cutoff score of 6. Using the modified WHQ in participants with wounds left to heal by secondary intention, 33 (28.4%) and 43 (37.1%) were identified to have SSI respectively. Conclusion: This prospective evaluation of SSI identified with the WHQ following excision of ulcerated skin cancers demonstrated a high proportion with SSI. The WHQ was acceptable to patients; however, further evaluation is required to ensure validity in assessing skin wounds. [ABSTRACT FROM AUTHOR]

Background Natural and vaccine-induced immunity will play a key role in controlling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity. Methods In a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, United Kingdom, we investigated the protection from symptomatic and asymptomatic polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role. We estimated protection conferred after 1 versus 2 vaccinations and from infections with the B.1.1.7 variant identified using whole genome sequencing. Results In total, 13 109 HCWs participated; 8285 received the Pfizer-BioNTech vaccine (1407 two doses), and 2738 the Oxford-AstraZeneca vaccine (49 two doses). Compared to unvaccinated seronegative HCWs, natural immunity and 2 vaccination doses provided similar protection against symptomatic infection: no HCW vaccinated twice had symptomatic infection, and incidence was 98% lower in seropositive HCWs (adjusted incidence rate ratio 0.02 [95% confidence interval {CI} < .01–.18]). Two vaccine doses or seropositivity reduced the incidence of any PCR-positive result with or without symptoms by 90% (0.10 [95% CI.02–.38]) and 85% (0.15 [95% CI.08–.26]), respectively. Single-dose vaccination reduced the incidence of symptomatic infection by 67% (0.33 [95% CI.21–.52]) and any PCR-positive result by 64% (0.36 [95% CI.26–.50]). There was no evidence of differences in immunity induced by natural infection and vaccination for infections with S-gene target failure and B.1.1.7. Conclusions Natural infection resulting in detectable anti-spike antibodies and 2 vaccine doses both provide robust protection against SARS-CoV-2 infection, including against the B.1.1.7 variant. [ABSTRACT FROM AUTHOR]

The non-classical class Ib molecule human leukocyte antigen E (HLA-E) has limited polymorphism and can bind HLA class Ia leader peptides (VL9). HLA-E-VL9 complexes interact with the natural killer (NK) cell receptors NKG2A-C/CD94 and regulate NK cell-mediated cytotoxicity. Here we report the isolation of 3H4, a murine HLA-E-VL9-specific IgM antibody that enhances killing of HLA-E-VL9-expressing cells by an NKG2A+ NK cell line. Structural analysis reveal that 3H4 acts by preventing CD94/NKG2A docking on HLA-E-VL9. Upon in vitro maturation, an affinity-optimized IgG form of 3H4 showes enhanced NK killing of HLA-E-VL9-expressing cells. HLA-E-VL9-specific IgM antibodies similar in function to 3H4 are also isolated from naïve B cells of cytomegalovirus (CMV)-negative, healthy humans. Thus, HLA-E-VL9-targeting mouse and human antibodies isolated from the naïve B cell antibody pool have the capacity to enhance NK cell cytotoxicity. The identification and structural analysis of HLA-E-VL9-targeting antibodies that block a natural killer (NK) cell receptor pathway and regulate NK function in vitro. [ABSTRACT FROM AUTHOR]

Black foot disease is one of the main grapevine root diseases observed worldwide and is especially problematic in New Zealand. Arbuscular mycorrhizal fungi (AMF) have been shown to reduce infection and mitigate the effect of black foot disease on grapevine rootstocks. In contrast to prior studies, which have limited their focus to the effect of one, two or a combination of only a small number of AMF species, this study used whole AMF communities identified from 101-14, 5C and Schwarzmann rootstocks sampled from New Zealand vineyards. The effect of AMF on black foot disease was investigated in a 'home' and 'away' experiment using three commercial grapevine rootstocks. The study produced some evidence that AMF treatments lowered disease incidence at 5 cm and disease severity in vines by 40% to 50% compared to the vines inoculated with the pathogen only. This work also showed that the presence of high disease incidence may have limited the potential disease protective effect of AMF community. However, despite the high disease incidence and severity, AMF inoculation increased vine growth parameters by 60% to 80% compared to the vines inoculated with the pathogen only. This study is the first to provide an understanding on how young grapevine rootstocks inoculated with their 'home' and 'away' AMF communities would respond to challenge with a black foot pathogen species mixture. Further research is required to understand the mechanistic effect of AMF colonization on the increase of grapevine growth parameters under high black foot disease pressure. [ABSTRACT FROM AUTHOR]

When a young adult develops a substance use disorder (SUD), a mother often assumes a caregiving role and experiences strain associated with providing off-time caregiving. The purpose of this paper is to obtain a nuanced understanding of how mothers of young adults with SUDs experience the treatment system. We conducted in-depth interviews with 13 mothers of young adults (ages 22-34) and analyzed the results using transcendental phenomenology. Five themes emerged: Participating in a child's treatment evokes strong emotions, Navigating the treatment system, Financial hardships, Mothers' perspective omitted from treatment, and Mothers recommendations for services they believed would have been helpful. Implications include increased parental support, family therapy and access to affordable SUD treatment. [ABSTRACT FROM AUTHOR]