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Two decades have passed since the strawberry (Fragaria x ananassa) disease caused by Macrophomina phaseolina, a necrotrophic soilborne fungal pathogen, began surfacing in California, Florida, and elsewhere. This disease has since become one of the most common causes of plant death and yield losses in strawberry. The Macrophomina problem emerged and expanded in the wake of the global phase-out of soil fumigation with methyl bromide and appears to have been aggravated by an increase in climate change-associated abiotic stresses. Here we show that sources of resistance to this pathogen are rare in gene banks and that the favorable alleles they carry are phenotypically unobvious. The latter were exposed by transgressive segregation and selection in populations phenotyped for resistance to Macrophomina under heat and drought stress. The genetic gains were immediate and dramatic. The frequency of highly resistant individuals increased from 1% in selection cycle 0 to 74% in selection cycle 2. Using GWAS and survival analysis, we found that phenotypic selection had increased the frequencies of favorable alleles among 10 loci associated with resistance and that favorable alleles had to be accumulated among four or more of these loci for an individual to acquire resistance. An unexpectedly straightforward solution to the Macrophomina disease resistance breeding problem emerged from our studies, which showed that highly resistant cultivars can be developed by genomic selection per se or marker-assisted stacking of favorable alleles among a comparatively small number of large-effect loci.
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IMPORTANCE: Informed consent is essential to ethical, rigorous research and is important to recruitment and retention in cancer trials. OBJECTIVE: To examine cancer clinical trial (CCT) participants' perceptions of informed consent processes and variations in perceptions by cancer type. DESIGN AND SETTING AND PARTICIPANTS: Cross-sectional survey from mixed-methods study at National Cancer Institute-designated Northeast comprehensive cancer center. Open-ended and forced-choice items addressed: (1) enrollment and informed consent experiences and (2) decision-making processes, including risk-benefit assessment. Eligibility: CCT participant with gastro-intestinal or genitourinary, hematologic-lymphatic malignancies, lung cancer, and breast or gynecological cancer (N = 334). MAIN OUTCOME MEASURES: Percentages satisfied with consent process and information provided; and assessing participation's perceptions of risks/benefits. Multivariable logistic or ordinal regression examined differences by cancer type. RESULTS: Most patient-participants felt well informed by the consent process (more than 90% overall and by cancer type) and. most (87.4%) reported that the consent form provided all the information they wanted, although nearly half (44.8%) reported that they read the form somewhat carefully or less. More than half (57.9%) said that talking to research staff (i.e., the consent process) had a greater impact on participation decisions than reading the consent form (2.1%). A third (31.1%) were very sure of joining in research studies before the informed consent process (almost half of lung cancer patients did-47.1%). Most patients personally assessed the risks and benefits before consenting. However, trust in physicians played an important role in the decision to enroll in CCT. CONCLUSIONS AND RELEVANCE: Cancer patients rely less on written features of the informed consent process than on information obtained from the research staff and their own physicians. Research should focus on information and communication strategies that support informed consent from referring physicians, researchers, and others to improve patient risk-benefit assessment and decision-making.
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Importance: Attrition in cancer clinical trials (CCTs) can lead to systematic bias, underpowered analyses, and a loss of scientific knowledge to improve treatments. Little attention has focused on retention, especially the role of perceived benefits and burdens, after participants have experienced the trial. Objectives: To examine the association between patients' perceived benefits and burdens of research participation and CCT retention. Design, Setting, and Participants: This survey study was conducted at a National Cancer Institute-designated comprehensive cancer center in the Northeast region of the US. The sample included adult patients with a cancer diagnosis participating in cancer therapeutic trials. Data were collected from September 2015 to June 2019. Analysis of study data was ongoing since November 2019 through October 2022. Exposures: Self-reported validated survey instrument with a list of 22 benefits and 23 burdens of research participation that can be rated by patients with a 5-point Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree). Main Outcomes and Measures: A primary outcome was actual withdrawal from the CCT, and a composite outcome was composite withdrawal that included both actual withdrawal and thoughts of withdrawing. Bivariate and multivariable logistic regressions were used. Results: Among the 334 participants in the sample, the mean (SD) age was 61.9 (11.5) years and 174 women (52.1%) were included. Top-cited benefits included both aspirational and action-oriented goals, including helping others (94.2%), contributing to society (90.3%), being treated respectfully (86.2%), and hoping for a cure (86.0%). Worry over receiving a placebo (61.3%), rearranging one's life (41.9%), and experiencing bothersome adverse effects (41.6%) were notable burdens. An increased burden score was associated with a higher probability of actual withdrawal (adjusted odds ratio [OR], 1.86; 95% CI, 1.1-3.17; P = .02) or composite withdrawal (adjusted OR, 3.44; 95% CI, 2.09-5.67; P < .001). An increased benefit score was associated with lower composite withdrawal (adjusted OR, 0.40; 95% CI, 0.24-0.66; P < .001). For participants who reported the benefits as being equal to or greater than the burdens, 13.4% withdrew. For those who perceived the benefits as being less than the burdens, 33.3% withdrew (adjusted OR, 3.38; 95% CI, 1.13-10.14; P = .03). The risk of withdrawal was even higher for the composite outcome (adjusted OR, 7.70; 95% CI, 2.76-21.48; P < .001). Conclusions and Relevance: This survey study found that patients perceived important benefits from CCT participation, and this perception was associated with trial retention, even among those who also perceived substantial burdens. A broader dialogue among stakeholders can inform an ethical and patient-centric focus on benefits throughout the course of a CCT to increase retention.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Neoplasias , Estados Unidos , Adulto , Humanos , Femenino , Persona de Mediana Edad , National Cancer Institute (U.S.) , Neoplasias/terapia , Trastorno de Personalidad Antisocial , EsperanzaRESUMEN
Lens-epithelial derived growth factor (LEDGF/DFS70) autoantibodies result in the commonly observed dense fine speckled (DFS) pattern by anti-nuclear antibody (ANA) assay. However, there is no consensus approach for confirmation of this autoantibody specificity. To evaluate current approaches, we examined inter-assay agreement between six anti-LEDGF/DFS70 assays. A total of 395 consecutive sera samples from routine ANA diagnostics were obtained, tested by routine ANA, anti-ENA line immunoblot assay (LIA) and anti-dsDNA assay and with six anti-DFS/LEDGF assays: the EuroLine-LIA (Euro-LIA), Medical and Biological Laboratories ELISA (MBL-ELISA), Phadia-EliA (EliA), QUANTA Flash CLIA, EuroImmun ELISA (Euro-ELISA) and Immco-Diagnostics HEp-2 ELITE/DFS-Knockout (HEp-2KO). Of 395 sera, 108 tested positive by at least one assay. Despite general good concordance between all assays across the cohort (Gwet's AC1=0.89), within the target DFS-ANA pattern group inter-assay agreement was poor (AC1=0.59). Euro-LIA, CLIA and MBL-ELISA assays were most concordant, but CLIA and Euro-LIA were also most likely to identify discordant positive results. EliA and Euro-ELISA had poorer agreement, which could be attributable to ill-matched cut-offs between assays. HEp-2KO was frequently discordant with all other assays tested. Euro-LIA, CLIA and MBL-ELISA were most concordant at manufacturer's specifications and are suited for use in clinical laboratories. Modified assay thresholds are required to ensure comparative results for Euro-ELISA and EliA. HEp-2KO assay is frequently discordant with all other assays, making it less suited for routine diagnostics. The study highlights the importance of considering inter-assay variability when developing a diagnostic strategy for anti-LEDGF/DFS70 autoantibodies in clinical laboratories.
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Enfermedades Autoinmunes , Humanos , Enfermedades Autoinmunes/diagnóstico , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Factores de Transcripción/metabolismo , Anticuerpos Antinucleares , Autoanticuerpos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Técnica del Anticuerpo Fluorescente Indirecta/métodosRESUMEN
Anecdotal evidence supports than engaging with violent extremist content online facilitates the radicalization process. However, there is a consistent lack of empirically grounded research to provide insight into the psychological process through which this influence occurs (if at all). As such, most theories often fail to accommodate both the multifinality (the concept that many people are exposed to violent extremist material, yet never engage in violent extremism), and equifinality (the concept that people can view a range violent extremist content, yet all end up engaging in violent extremism) that naturally is observed in those who engage with violent extremist content online and those who engage in violent extremist behavior. This paper presents Reinforcement Sensitivity Theory (RST) as a theoretical framework to inform understanding of the process that governs the interaction between violent extremist material online and engaging with violent extremism. RST is a motivational theory which has been applied to a range of benevolent and deviant behaviors. Specifically, we argue that RST is suitable to explain the effect of violent extremist content online because (1) it outlines multiple differentiated motivational pathways that can account for multifinality and equifinality observed in those who engage in violent extremist behavior and (2) the extant neurological and psychophysiological research using RST provides a empirically supported framework for developing both research methods and verifiable hypotheses to advance our understanding of how, if at all, violent extremist content online contributes to the process of radicalization.
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KEY MESSAGE: Several Fusarium wilt resistance genes were discovered, genetically and physically mapped, and rapidly deployed via marker-assisted selection to develop cultivars resistant to Fusarium oxysporum f. sp. fragariae, a devastating soil-borne pathogen of strawberry. Fusarium wilt, a soilborne disease caused by Fusarium oxysporum f. sp. fragariae, poses a significant threat to strawberry (Fragaria [Formula: see text] ananassa) production in many parts of the world. This pathogen causes wilting, collapse, and death in susceptible genotypes. We previously identified a dominant gene (FW1) on chromosome 2B that confers resistance to race 1 of the pathogen, and hypothesized that gene-for-gene resistance to Fusarium wilt was widespread in strawberry. To explore this, a genetically diverse collection of heirloom and modern cultivars and octoploid ecotypes were screened for resistance to Fusarium wilt races 1 and 2. Here, we show that resistance to both races is widespread in natural and domesticated populations and that resistance to race 1 is conferred by partially to completely dominant alleles among loci (FW1, FW2, FW3, FW4, and FW5) found on three non-homoeologous chromosomes (1A, 2B, and 6B). The underlying genes have not yet been cloned and functionally characterized; however, plausible candidates were identified that encode pattern recognition receptors or other proteins known to confer gene-for-gene resistance in plants. High-throughput genotyping assays for SNPs in linkage disequilibrium with FW1-FW5 were developed to facilitate marker-assisted selection and accelerate the development of race 1 resistant cultivars. This study laid the foundation for identifying the genes encoded by FW1-FW5, in addition to exploring the genetics of resistance to race 2 and other races of the pathogen, as a precaution to averting a Fusarium wilt pandemic.
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Fragaria , Fusarium , Cromosomas , Fragaria/genética , Enfermedades de las Plantas/genéticaRESUMEN
OBJECTIVE: To comparatively analyse the aberrant affinity maturation of the antinuclear and rheumatoid factor (RF) B cell repertoires in blood and tissues of patients with Sjögren's syndrome (SjS) using an integrated omics workflow. METHODS: Peptide sequencing of anti-Ro60, anti-Ro52, anti-La and RF was combined with B cell repertoire analysis at the DNA, RNA and single cell level in blood B cell subsets, affected salivary gland and extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) of patients with SjS. RESULTS: Affected tissues contained anti-Ro60, anti-Ro52, anti-La and RF clones as a small part of a polyclonal infiltrate. Anti-Ro60, anti-La and anti-Ro52 clones outnumbered RF clones. MALT lymphoma tissues contained monoclonal RF expansions. Autoreactive clones were not selected from a restricted repertoire in a circulating B cell subset. The antinuclear antibody (ANA) repertoires displayed similar antigen-dependent and immunoglobulin (Ig) G1-directed affinity maturation. RF clones displayed antigen-dependent, IgM-directed and more B cell receptor integrity-dependent affinity maturation. This coincided with extensive intra-clonal diversification in RF-derived lymphomas. Regeneration of clinical disease manifestations after rituximab coincided with large RF clones, which not necessarily belonged to the lymphoma clone, that displayed continuous affinity maturation and intra-clonal diversification. CONCLUSION: The ANA and RF repertoires in patients with SjS display tissue-restricted, antigen-dependent and divergent affinity maturation. Affinity maturation of RF clones deviates further during RF clone derived lymphomagenesis and during regeneration of the autoreactive repertoire after temporary disruption by rituximab. These data give insight into the molecular mechanisms of autoreactive inflammation in SjS, assist MALT lymphoma diagnosis and allow tracking its response to rituximab.
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Linfoma de Células B de la Zona Marginal , Proteogenómica , Síndrome de Sjögren , Linfocitos B/inmunología , Linfocitos B/metabolismo , Humanos , Inmunoglobulina G/inmunología , Factor Reumatoide/metabolismo , Rituximab/uso terapéutico , Síndrome de Sjögren/inmunologíaRESUMEN
Previous research determined that Fusarium acuminatum and F. avenaceum are important causal agents of a canker disease in bareroot-propagated fruit and nut trees in California that emerges during cold storage or after transplanting. The disease largely disappeared after 2001, but it reemerged in 2011 in almond trees in at least one nursery. This motivated further study of the etiology and epidemiology of the disease by undertaking studies to determine distribution of the pathogens throughout almond nursery propagation systems and trace possible sources of inoculum. Research initiated in 2013 detected pathogenic Fusarium spp. throughout the almond propagation system, including in healthy trees, in soils, on wheat rotation crops, on equipment, and in the cold-storage facility air. In addition to the two Fusarium spp. implicated previously, F. brachygibbosum and a new Fusarium species, F. californicum, were found to be pathogenic on almond trees. Multilocus sequence typing and somatic compatibility testing confirmed that isolates within a species collected from different materials in the nursery were all highly genetically similar and likely of one clonal lineage. These findings affirm that equipment surfaces, wheat rotation crops, soil, cold-storage facility air, and asymptomatic almond tree materials (i.e., rootstock cuttings, budwood, and scions) can potentially contribute inoculum to increase disease prevalence and severity.
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Fusarium , Casas Cuna , Prunus dulcis , Fusarium/genética , Variación Genética , Humanos , Lactante , Árboles , TriticumRESUMEN
Filamentous fungi grow by the elaboration of hyphae, which may fuse to form a network as a colony develops. Fusion of hyphae can occur between genetically different individuals, provided they share a common allele at loci affecting somatic compatibility. Diversity in somatic compatibility phenotypes reduces the frequency of hyphal fusion in a population, thereby slowing the spread of deleterious genetic elements such as viruses and plasmids, which require direct cytoplasmic contact for transmission. Diverse somatic compatibility phenotypes can be generated by recombining alleles through sexual reproduction, but this mechanism may not fully account for the diversity found in nature. For example, multiple compatibility phenotypes of Fusarium circinatum were shown to be associated with the same clonal lineage, which implies they were derived by a mutation rather than recombination through sexual reproduction. Experimental tests of this hypothesis confirmed that spontaneous changes in somatic compatibility can occur at a frequency between 5 and 8 per million spores. Genomic analysis of F. circinatum strains with altered somatic compatibility revealed no consistent evidence of recombination and supported the hypothesis that a spontaneous mutation generated the observed phenotypic change. Genes known to be involved in somatic compatibility had no mutations, suggesting that mutation occurred in a gene with an as yet unexplored function in somatic compatibility.
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Fusarium , Hifa , Fusarium/fisiología , Genes Fúngicos/genética , Humanos , Hifa/genética , Mutación , Esporas Fúngicas/genéticaRESUMEN
Efferent cholinergic neurons inhibit sensory hair cells of the vertebrate inner ear through the combined action of calcium-permeable α9α10-containing nicotinic acetylcholine receptors (nAChRs) and associated calcium-dependent potassium channels. The venom of cone snails is a rich repository of bioactive peptides, many with channel blocking activities. The conopeptide analog, RgIA-5474, is a specific and potent antagonist of α9α10-containing nAChRs. We added an alkyl functional group to the N-terminus of the RgIA-5474, to enable click chemistry addition of the fluorescent cyanine dye, Cy3. The resulting peptide, Cy3-RgIA-5727, potently blocked mouse α9α10 nAChRs expressed in Xenopus oocytes (IC50 23 pM), with 290-fold less activity on α7 nAChRs and 40,000-fold less activity on all other tested nAChR subtypes. The tight binding of Cy3-RgIA-5727 provided robust visualization of hair cell nAChRs juxtaposed to cholinergic efferent terminals in excised, unfixed cochlear tissue from mice. Presumptive postsynaptic sites on outer hair cells (OHCs) were labeled, but absent from inner hair cells (IHCs) and from OHCs in cochlear tissue from α9-null mice and in cochlear tissue pre-incubated with non-Cy3-conjugated RgIA-5474. In cochlear tissue from younger (postnatal day 10) mice, Cy3-RgIA-5727 also labeled IHCs, corresponding to transient efferent innervation at that age. Cy3 puncta in Kölliker's organ remained in the α9-null tissue. Pre-exposure with non-Cy3-conjugated RgIA-5474 or bovine serum albumin reduced this non-specific labeling to variable extents in different preparations. Cy3-RgIA-5727 and RgIA-5474 blocked the native hair cell nAChRs, within the constraints of application to the excised cochlear tissue. Cy3-RgIA-5727 or RgIA-5474 block of efferent synaptic currents in young IHCs was not relieved after 50 min washing, so effectively irreversible.
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Importance: Cancer clinical trials (CCTs) provide patients an opportunity to receive experimental drugs, tests, and/or procedures that can lead to remission. For some, a CCT may seem like their only option. Little is known about experiences of patient-participants who withdraw or are withdrawn from CCTs. Objective: To examine patient-participants' experiences during withdrawal from CCTs. Design, Setting, and Participants: This qualitative, descriptive study used a semistructured interview designed specifically for it, with open-ended and probing questions. The study took place at a National Cancer Institute-designated comprehensive cancer center affiliated with the University of Pennsylvania. The need for a sample of 20 interviewees was determined by code and meaning saturation (ie, no new themes revealed and identified themes fully elaborated). Interviews were transcribed verbatim and analyzed with a qualitative software program. Data coded with the software were refined into categories reflecting broad themes. A criterion-based sampling approach was used to select a subset of adult patients with cancer who were former CCT participants and who agreed on exit from those CCTs to a later interview about withdrawal experiences. They were contacted one by one by telephone from September 2015 through June 2019 until 20 agreed. Data analysis was completed in October 2020. Main Outcomes and Measures: Themes characterizing patient-participants' perceptions of their withdrawal experiences. Results: Respondents' mean (SD) age was 64.42 (8.49) years; 12 (63.2%) were men. Most respondents were White (18 respondents [94.7%]) and college educated (11 respondents [55.0%]). Cancer stage data were available for 17 participants, 11 of whom (64.7%) had stage IV cancer at CCT enrollment. Thirteen respondents reported withdrawal as a result of disease progression, and 5 withdrew because of adverse effects. Other reasons for withdrawal included acute illness and participant uncertainty about the reason. Analysis of interview data yielded 5 themes: posttrial prognostic awareness, goals of care discussions, emotional coping, burden of adverse effects, and professional trust and support. Subthemes included regrets or hindsight, urgency to start next treatment, and weighing benefits and burdens of treatment. Limited discussions about patient-participants' immediate posttrial care needs left many feeling that there was no clear path forward. Conclusions and Relevance: Patient-participants transitioning from a CCT described feeling intense symptoms and emotions and awareness that their life span was short and options seemed to be limited. Communication that includes attention to posttrial needs is needed throughout the CCT to help patient-participants navigate posttrial steps. Research should focus on components of responsible and ethical CCT transitions, including types and timing of discussions and who should begin these discussions with patient-participants and their families.
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Adaptación Psicológica , Ensayos Clínicos como Asunto/psicología , Neoplasias/psicología , Participación del Paciente/psicología , Participación del Paciente/estadística & datos numéricos , Satisfacción del Paciente/estadística & datos numéricos , Estrés Psicológico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación CualitativaRESUMEN
Fusarium circinatum, the causal agent of pitch canker in pines and a cryptic endophyte of grasses, was examined for heritable variation in tolerance of the grass defense compound 2-benzoxazolinone (BOA). A diverse population of F. circinatum progeny was assayed for growth rate on potato dextrose agar amended with BOA. Matings were conducted to allow for selection of progeny with lower and higher tolerance of BOA. The results confirmed heritable variation in BOA tolerance in F. circinatum. A subset of differentially tolerant progeny was used for inoculations of growth chamber-grown Zea mays and greenhouse-grown Pinus radiata. No differences were detected in the rate of infection or extent of colonization of Z. mays inoculated with F. circinatum progeny differing in tolerance of BOA. Pitch canker symptoms in inoculated P. radiata trees showed that high BOA-tolerating isolates induced significantly longer lesion lengths than those induced by low BOA-tolerating isolates. Results from this study were consistent with the proposition that F. circinatum evolved from grass-colonizing ancestors and that pathogenicity to pine is a relatively recent evolutionary innovation.
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Pinus , Poaceae , Benzoxazoles , Fusarium , Enfermedades de las PlantasRESUMEN
The genes required for host-specific pathogenicity in Fusarium oxysporum can be acquired through horizontal chromosome transfer (HCT). However, it is unknown if HCT commonly contributes to the diversification of pathotypes. Using comparative genomics and pathogenicity phenotyping, we explored the role of HCT in the evolution of F. oxysporum f. sp. fragariae, the cause of Fusarium wilt of strawberry, with isolates from four continents. We observed two distinct syndromes: one included chlorosis ('yellows-fragariae') and the other did not ('wilt-fragariae'). All yellows-fragariae isolates carried a predicted pathogenicity chromosome, 'chrY-frag ', that was horizontally transferred at least four times. chrY-frag was associated with virulence on specific cultivars and encoded predicted effectors that were highly upregulated during infection. chrY-frag was not present in wilt-fragariae; isolates causing this syndrome evolved pathogenicity independently. All origins of F. oxysporum f. sp. fragariae occurred outside of the host's native range. Our data support the conclusion that HCT is widespread in F. oxysporum, but pathogenicity can also evolve independently. The absence of chrY-frag in wilt-fragariae suggests that multiple, distinct pathogenicity chromosomes can confer the same host specificity. The wild progenitors of cultivated strawberry (Fragaria × ananassa) did not co-evolve with this pathogen, yet we discovered several sources of genetic resistance.
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Fragaria , Fusarium , Cromosomas , Fragaria/genética , Fusarium/genética , Enfermedades de las PlantasRESUMEN
Fusarium oxysporum f. sp. mori, the causal agent of Fusarium wilt of blackberry, was first reported in California and Mexico in 2016. A limited survey of the population revealed this pathogen to be one of the most diverse formae speciales of F. oxysporum. We explored the possibility that strains of F. oxysporum pathogenic to commercial blackberry could also be recovered from wild blackberry (Rubus spp.) in California. For this purpose, wild Rubus species in blackberry nurseries, fruit production fields, and nearby areas were collected between 2017 and 2019. Thirty-four isolates of F. oxysporum were recovered from asymptomatic Rubus armeniacus and Rubus ursinus plants. Based on sequence of the translation elongation factor 1-α, somatic compatibility, and pathogenicity to blackberry, 16 isolates were confirmed as F. oxysporum f. sp. mori. These isolates were associated with three somatic compatibility groups, one of which was first identified in this study. Recovery of the pathogen confirmed that wild blackberry plants can act as a reservoir of inoculum of F. oxysporum f. sp. mori and that it can move from wild blackberry plants to commercial cultivars or vice versa.
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Fusarium , Rubus , California , México , Enfermedades de las PlantasRESUMEN
Women with early-stage unilateral breast cancer and no familial or genetic risk factors are increasingly electing contralateral prophylactic mastectomy (CPM), despite the lack of evidence demonstrating improved outcomes. To better understand and extend the literature focused on treatment decision-making, a survey was conducted among women with early-stage breast cancer and no associated risk factors, who were in the process of making a surgical decision. This prospective study sought to expand our understanding of the factors that influence patients' decision to have CPM, with the goal of providing healthcare providers with useful guidance in supporting breast cancer patients who are making treatment decisions. Data were collected for this prospective study through an internet survey. Results were analyzed using perceptual mapping, a technique that provides visual insight into the importance of specific variables to groups of women making different surgical decisions, not available through conventional analyses. Results suggest that women more likely to elect CPM demonstrate greater worry about breast cancer through experiences with others and feel the need to take control of their health through selection of the most aggressive treatment option. The information obtained offers guidance for the development of targeted intervention and counsel that will support patients' ability to make high quality, informed decisions.
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Neoplasias de la Mama , Mastectomía Profiláctica , Neoplasias de la Mama/cirugía , Toma de Decisiones , Femenino , Humanos , Mastectomía , Estudios ProspectivosRESUMEN
Fusarium oxysporum f. sp. lactucae, the cause of Fusarium wilt of lettuce, can survive on crop residue in soil. Persistence of the pathogen over time will be influenced by the rate at which residue decomposes. We evaluated the effect of drying and fragmenting crop residue on the rate of decomposition and survival of F. oxysporum f. sp. lactucae. In a controlled experiment that represented optimal drying conditions, fragmenting and oven drying infested lettuce taproots at 30°C significantly reduced the frequency of recovery of the pathogen, compared with untreated tissue. However, in a field experiment, drying infested crop residue on the soil surface prior to incorporation did not significantly reduce survival of F. oxysporum f. sp. lactucae after 1 year. Regardless of treatment, there was not a significant decrease in soil inoculum density between 1 and 12 months after residue was incorporated. In a greenhouse experiment, fragmenting crop residue prior to incorporation in pathogen-free soil resulted in significantly higher inoculum densities of F. oxysporum f. sp. lactucae after 1 year. The increase in inoculum levels was associated with a faster rate of residue decomposition, which may be beneficial in the long run but not where lettuce will be replanted within the next year.
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Fusarium , Lactuca , Suelo , Microbiología del SueloRESUMEN
INTRODUCTION: The coronavirus disease 2019 (COVID-19) has created unprecedented challenges on the healthcare system. The aim of this multi-centre study was to measure the impact of COVID-19 on IR services in the UK. MATERIAL AND METHODS: Retrospective cross-sectional study of IR practice in six UK centres during the COVID-19 pandemic was carried out. All therapeutic IR procedures were identified using the respective hospital radiology information systems and COVID-19 status found on the hospital patient record systems. The total number of therapeutic IR procedures was recorded over two time periods, 25/03/2019-21/04/2019 (control group) and 30/03/2020-26/04/2020 (COVID-19 group). The data points collected were: procedure type, aerosol-generating nature, acute or elective case, modality used, in- or out-of-hours case and whether the procedure was done at the bedside (portable). RESULTS: A 31% decrease in overall number of IR procedures was observed during COVID-19 compared to the control group (1363 cases vs 942 cases); however, the acute work decreased by only 0.5%. An increase in out-of-hours work by 10% was observed. COVID-19 was suspected or laboratory proved in 9.9% of cases (n = 93), and 15% of total cases (n = 141) were classed as aerosol-generating procedures. A 66% rise in cholecystostomy was noted during COVID-19. Image-guided ablation, IVC filters, aortic stent grafting and visceral vascular stenting had the greatest % decreases in practice during COVID-19, with 91.7%, 83.3%, 80.8% and 80.2% decreases, respectively. CONCLUSION: During the global pandemic, IR has continued to provide emergency and elective treatment highlighting the adaptability of IR in supporting other specialties.
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COVID-19/prevención & control , Radiología Intervencionista/métodos , Radiología Intervencionista/estadística & datos numéricos , Estudios Transversales , Femenino , Humanos , Masculino , Pandemias , Estudios Retrospectivos , SARS-CoV-2 , Reino UnidoRESUMEN
Glioblastomas (GBMs), the most frequent and aggressive human primary brain tumours, have altered cell metabolism, and one of the strongest indicators of malignancy is an increase in choline compounds. Choline is also a selective agonist of some neuronal nicotinic acetylcholine receptor (nAChR) subtypes. As little is known concerning the expression of nAChR in glioblastoma cells, we analysed in U87MG human grade-IV astrocytoma cell line and GBM5 temozolomide-resistant glioblastoma cells selected from a cancer stem cell-enriched culture, molecularly, pharmacologically and functionally which nAChR subtypes are expressed and,whether choline and nicotine can affect GBM cell proliferation. We found that U87MG and GBM5 cells express similar nAChR subtypes, and choline and nicotine increase their proliferation rate and activate the anti-apoptotic AKT and pro-proliferative ERK pathways. These effects are blocked by the presence of non-cell-permeable peptide antagonists selective for α7- and α9-containing nicotinic receptors. siRNA-mediated silencing of α7 or α9 subunit expression also selectively prevents the effects of nicotine and choline on GBM cell proliferation. Our findings indicate that nicotine and choline activate the signalling pathways involved in the proliferation of GBM cells, and that these effects are mediated by α7 and α9-containing nAChRs. This suggests that these nicotinic receptors may contribute to the aggressive behaviour of this tumor and may indicate new therapeutic strategies against high-grade human brain tumours.
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Neoplasias Encefálicas/metabolismo , Colina/farmacología , Glioblastoma/metabolismo , Nicotina/farmacología , Receptores Nicotínicos/metabolismo , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Interferente Pequeño/genética , Receptores Nicotínicos/genética , Receptor Nicotínico de Acetilcolina alfa 7/genéticaRESUMEN
Scientific communication is facilitated by a data-driven, scientifically sound taxonomy that considers the end-user's needs and established successful practice. In 2013, the Fusarium community voiced near unanimous support for a concept of Fusarium that represented a clade comprising all agriculturally and clinically important Fusarium species, including the F. solani species complex (FSSC). Subsequently, this concept was challenged in 2015 by one research group who proposed dividing the genus Fusarium into seven genera, including the FSSC described as members of the genus Neocosmospora, with subsequent justification in 2018 based on claims that the 2013 concept of Fusarium is polyphyletic. Here, we test this claim and provide a phylogeny based on exonic nucleotide sequences of 19 orthologous protein-coding genes that strongly support the monophyly of Fusarium including the FSSC. We reassert the practical and scientific argument in support of a genus Fusarium that includes the FSSC and several other basal lineages, consistent with the longstanding use of this name among plant pathologists, medical mycologists, quarantine officials, regulatory agencies, students, and researchers with a stake in its taxonomy. In recognition of this monophyly, 40 species described as genus Neocosmospora were recombined in genus Fusarium, and nine others were renamed Fusarium. Here the global Fusarium community voices strong support for the inclusion of the FSSC in Fusarium, as it remains the best scientific, nomenclatural, and practical taxonomic option available.