The Egyptian wheat cultivar Gemmeiza-12 is a source of resistance against the fungus Zymoseptoria tritici.

BACKGROUND: Wheat is one of the world's most important cereal crops. However, the fungal pathogen Zymoseptoria tritici can cause disease epidemics, leading to reduced yields. With climate change and development of new agricultural areas with suitable environments, Z. tritici may advance into geographical areas previously unaffected by this pathogen. It is currently unknown how Egyptian wheat will perform in the face of this incoming threat. This project aimed to assess the resistance of Egyptian wheat germplasm to Z. tritici, to identify cultivars with high levels of resistance and characterise the mechanism(s) of resistance present in these cultivars. RESULTS: Eighteen Egyptian wheat cultivars were screened against two Z. tritici model isolates and exhibited a wide spectrum of responses. This ranged from resistance to complete susceptibility to one or both isolates tested. The most highly resistant cultivars from the initial screen were then tested under two environmental conditions against modern UK field isolates. Disease levels under UK-like conditions were higher, however, symptom development on the cultivar Gemmeiza-12 was noticeably slower than on other Egyptian wheats. The robustness of the resistance shown by Gemmeiza-12 was confirmed in experiments mimicking Egyptian environmental conditions, where degree of Z. tritici infection was lower. The Kompetitive allele-specific PCR (KASP) diagnostic assay suggested the presence of an Stb6 resistant allele in several Egyptian wheats including Gemmeiza-12. Infection assays using the IPO323 WT and IPO323ΔAvrStb6 mutant confirmed the presence of Stb6 in several Egyptian cultivars including Gemmeiza-12. Confocal fluorescence microscopy demonstrated that growth of the IPO323 strain is blocked at the point of stomatal penetration on Gemmeiza-12, consistent with previous reports of Stb gene mediated resistance. In addition to this R-gene mediated resistance, IPO323 spores showed lower adherence to leaves of Gemmeiza-12 compared to UK wheat varieties, suggesting other aspects of leaf physiology may also contribute to the resistance phenotype of this cultivar. CONCLUSION: These results indicate that Gemmeiza-12 will be useful in future breeding programs where improved resistance to Z. tritici is a priority.

Creating a Low-Stimulus Clinic to improve immunization success rates for children with alternate environment needs: A quality improvement initiative.

Patients with specific sensory needs may face barriers to receiving their immunizations. Therefore, a Low-Stimulus Clinic was created in Alberta. Modifications to regular clinic space included lower visual and auditory input, access to longer appointment times and private clinic spaces, development of pre-appointment comfort plans, and offering of in-vehicle immunization. Between April 2021 and May 2022, 90% (641/712) of booked patients were successfully immunized. The top reasons for accessing the clinic included autism spectrum disorder (229/712, 32%), and needle fear/phobia (195/712, 27%). The Low-Stimulus Clinic had a high rate of successful vaccination for populations that may otherwise have been less likely to receive immunizations. Its workflows support the principles of choice, collaboration, and control in creating a positive immunization experience for patients and their families. Having such clinics widely available is a key step in reducing barriers to accessing vaccines for individuals with specific sensory needs.

Evolution of the Toxb Gene in Pyrenophora tritici-repentis and Related Species.

Pyrenophora tritici-repentis (tan spot) is a destructive foliar pathogen of wheat with global impact. This ascomycete fungus possesses a highly plastic open pangenome shaped by the gain and loss of effector genes. This study investigated the allelic variations in the chlorosis-encoding gene ToxB across 422 isolates representing all identified pathotypes and worldwide origins. To gain better insights into ToxB evolution, we examined its presence and variability in other Pyrenophora spp. A ToxB haplotype network was constructed, revealing the evolutionary relationships of this gene (20 haplotypes) across four Pyrenophora species. Notably, toxb, the homolog of ToxB, was detected for the first time in the barley pathogen Pyrenophora teres. The ToxB/toxb genes display evidence of selection that is characterized by loss of function, duplication, and diverse mutations. Within the ToxB/toxb open reading frame, 72 mutations were identified, including 14 synonymous, 55 nonsynonymous, and 3 indel mutations. Remarkably, a, ∼5.6-kb Copia-like retrotransposon, named Copia-1_Ptr, was found inserted in the toxb gene of a race 3 isolate. This insert disrupted the ToxB gene's function, a first case of effector gene disruption by a transposable element in P. tritici-repentis. Additionally, a microsatellite with 25 nucleotide repeats (0 to 10) in the upstream region of ToxB suggested a potential mechanism influencing ToxB expression and regulation. Exploring ToxB-like protein distribution in other ascomycetes revealed the presence of ToxB-like proteins in 19 additional species, including the Leotiomycetes class for the first time. The presence/absence pattern of ToxB-like proteins defied species relatedness compared with a phylogenetic tree, suggesting a past horizontal gene transfer event during the evolution of the ToxB gene. [Formula: see text] Copyright © 2024 His Majesty the King in Right of Canada, as represented by the Minister of Agriculture and Agri-Food. This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

That's no moon, it's a Starship: Giant transposons driving fungal horizontal gene transfer.

To date, most reports of horizontal gene transfer (HGT) in fungi rely on genome sequence data and are therefore an indirect measure of HGT after the event has occurred. However, a novel group of class II-like transposons known as Starships may soon alter this status quo. Starships are giant transposable elements that carry dozens of genes, some of which are host-beneficial, and are linked to many recent HGT events in the fungal kingdom. These transposons remain active and mobile in many fungal genomes and their transposition has recently been shown to be driven by a conserved tyrosine-recombinase called 'Captain'. This perspective explores some of the remaining unanswered questions about how these Starship transposons move, both within a genome and between different species. We seek to outline several experimental approaches that can be used to identify the genes essential for Starship-mediated HGT and draw links to other recently discovered giant transposons outside of the fungal kingdom.

Microbial Communities in Gynecological Cancers and Their Association with Tumor Somatic Variation.

There are strong correlations between the microbiome and human disease, including cancer. However, very little is known about potential mechanisms associated with malignant transformation in microbiome-associated gynecological cancer, except for HPV-induced cervical cancer. Our hypothesis is that differences in bacterial communities in upper genital tract epithelium may lead to selection of specific genomic variation at the cellular level of these tissues that may predispose to their malignant transformation. We first assessed differences in the taxonomic composition of microbial communities and genomic variation between gynecologic cancers and normal samples. Then, we performed a correlation analysis to assess whether differences in microbial communities selected for specific single nucleotide variation (SNV) between normal and gynecological cancers. We validated these results in independent datasets. This is a retrospective nested case-control study that used clinical and genomic information to perform all analyses. Our present study confirms a changing landscape in microbial communities as we progress into the upper genital tract, with more diversity in lower levels of the tract. Some of the different genomic variations between cancer and controls strongly correlated with the changing microbial communities. Pathway analyses including these correlated genes may help understand the basis for how changing bacterial landscapes may lead to these cancers. However, one of the most important implications of our findings is the possibility of cancer prevention in women at risk by detecting altered bacterial communities in the upper genital tract epithelium.

A thousand-genome panel retraces the global spread and adaptation of a major fungal crop pathogen.

Human activity impacts the evolutionary trajectories of many species worldwide. Global trade of agricultural goods contributes to the dispersal of pathogens reshaping their genetic makeup and providing opportunities for virulence gains. Understanding how pathogens surmount control strategies and cope with new climates is crucial to predicting the future impact of crop pathogens. Here, we address this by assembling a global thousand-genome panel of Zymoseptoria tritici, a major fungal pathogen of wheat reported in all production areas worldwide. We identify the global invasion routes and ongoing genetic exchange of the pathogen among wheat-growing regions. We find that the global expansion was accompanied by increased activity of transposable elements and weakened genomic defenses. Finally, we find significant standing variation for adaptation to new climates encountered during the global spread. Our work shows how large population genomic panels enable deep insights into the evolutionary trajectory of a major crop pathogen.

A Revised Nomenclature for ToxA Haplotypes Across Multiple Fungal Species.

ToxA is one of the most studied proteinaceous necrotrophic effectors produced by plant pathogens. It has been identified in four pathogens (Pyrenophora tritici-repentis, Parastagonospora nodorum, Parastagonospora pseudonodorum [formerly Parastagonospora avenaria f. sp. tritici], and Bipolaris sorokiniana) causing leaf spot diseases on cereals worldwide. To date, 24 different ToxA haplotypes have been identified. Some P. tritici-repentis and related species also express ToxB, another small protein necrotrophic effector. We present here a revised and standardized nomenclature for these effectors, which could be extended to other poly-haplotypic genes found across multiple species.

Metformin for Prevention of Anthropometric and Metabolic Complications of Androgen Deprivation Therapy in Prostate Cancer Patients Receiving Radical Radiotherapy: A Phase II Randomized Controlled Trial.

BACKGROUND: Patients with prostate cancer undergoing treatment with radical radiation therapy (RT) plus androgen deprivation therapy (ADT) experience a constellation of deleterious metabolic and anthropometric changes related to hypogonadism that are associated with increased morbidity and mortality. We assessed the effect of metformin versus placebo to blunt the adverse effects of ADT on body weight, waist circumference, and other metabolic parameters. METHODS AND MATERIALS: This phase 2, multicenter, randomized controlled trial (RCT) randomized normoglycemic men with locally advanced prostate cancer receiving radical RT and ADT (18-36 months) in a 1:1 ratio to receive metformin 500 mg by mouth 3 times a day (for 30-36 months) versus identical placebo. RESULTS: From December 2015 to October 2019, 83 men were randomized with median follow-up of 23 months. Baseline mean body mass Index (BMI) of the cohort was 30.2 (range 22.2-52.5). Change in mean weight relative to baseline was lower among men who received metformin compared with placebo at 5 months (-1.80 kg, P = .038), but was not significant with longer follow-up (1 year: +0.16 kg, P = .874). Although participants on ADT had increases in waist circumference in both study arms, metformin did not significantly reduce these changes (1 year: +2.79 cm (placebo) versus +1.46 cm (metformin), P = .336). Low-density lipoprotein (LDL) cholesterol was lower in the metformin arm (-0.32 mmol/L) compared with the placebo arm (-0.03 mmol/L) at 5 months (P = .022), but these differences were not significant with longer follow-up (1 year: -0.17 mmol/L vs -0.19 mmol/L, P = .896). There were no differences in HbA1C, triglyceride, high-density lipoprotein (HDL) cholesterol, and total cholesterol by study arm. CONCLUSIONS: Men receiving radical RT and ADT gained weight and had increases in waist circumference over time that metformin did not significantly mitigate. Although this study did not observe any preventive effect of metformin on the anthropometric and metabolic complications of ADT, metformin continues to be studied in phase 3 RCTs in this patient population to assess its potential antineoplastic effects.

Integration of Genomic and Clinical Retrospective Data to Predict Endometrioid Endometrial Cancer Recurrence.

Endometrial cancer (EC) incidence and mortality continues to rise. Molecular profiling of EC promises improvement of risk assessment and treatment selection. However, we still lack robust and accurate models to predict those at risk of failing treatment. The objective of this pilot study is to create models with clinical and genomic data that will discriminate patients with EC at risk of disease recurrence. We performed a pilot, retrospective, case−control study evaluating patients with EC, endometrioid type: 7 with recurrence of disease (cases), and 55 without (controls). RNA was extracted from frozen specimens and sequenced (RNAseq). Genomic features from RNAseq included transcriptome expression, genomic, and structural variation. Feature selection for variable reduction was performed with univariate ANOVA with cross-validation. Selected variables, informative for EC recurrence, were introduced in multivariate lasso regression models. Validation of models was performed in machine-learning platforms (ML) and independent datasets (TCGA). The best performing prediction models (out of >170) contained the same lncRNA features (AUC of 0.9, and 95% CI: 0.75, 1.0). Models were validated with excellent performance in ML platforms and good performance in an independent dataset. Prediction models of EC recurrence containing lncRNA features have better performance than models with clinical data alone.

Multi-stage resistance to Zymoseptoria tritici revealed by GWAS in an Australian bread wheat diversity panel.

Septoria tritici blotch (STB) has been ranked the third most important wheat disease in the world, threatening a large area of wheat production. Although major genes play an important role in the protection against Zymoseptoria tritici infection, the lifespan of their resistance unfortunately is very short in modern wheat production systems. Combinations of quantitative resistance with minor effects, therefore, are believed to have prolonged and more durable resistance to Z. tritici. In this study, new quantitative trait loci (QTLs) were identified that are responsible for seedling-stage resistance and adult-plant stage resistance (APR). More importantly was the characterisation of a previously unidentified QTL that can provide resistance during different stages of plant growth or multi-stage resistance (MSR). At the seedling stage, we discovered a new isolate-specific QTL, QSt.wai.1A.1. At the adult-plant stage, the new QTL QStb.wai.6A.2 provided stable and consistent APR in multiple sites and years, while the QTL QStb.wai.7A.2 was highlighted to have MSR. The stacking of multiple favourable MSR alleles was found to improve resistance to Z. tritici by up to 40%.

The pangenome of the wheat pathogen Pyrenophora tritici-repentis reveals novel transposons associated with necrotrophic effectors ToxA and ToxB.

BACKGROUND: In fungal plant pathogens, genome rearrangements followed by selection pressure for adaptive traits have facilitated the co-evolutionary arms race between hosts and their pathogens. Pyrenophora tritici-repentis (Ptr) has emerged recently as a foliar pathogen of wheat worldwide and its populations consist of isolates that vary in their ability to produce combinations of different necrotrophic effectors. These effectors play vital roles in disease development. Here, we sequenced the genomes of a global collection (40 isolates) of Ptr to gain insights into its gene content and genome rearrangements. RESULTS: A comparative genome analysis revealed an open pangenome, with an abundance of accessory genes (~ 57%) reflecting Ptr's adaptability. A clear distinction between pathogenic and non-pathogenic genomes was observed in size, gene content, and phylogenetic relatedness. Chromosomal rearrangements and structural organization, specifically around effector coding genes, were detailed using long-read assemblies (PacBio RS II) generated in this work in addition to previously assembled genomes. We also discovered the involvement of large mobile elements associated with Ptr's effectors: ToxA, the gene encoding for the necrosis effector, was found as a single copy within a 143-kb 'Starship' transposon (dubbed 'Horizon') with a clearly defined target site and target site duplications. 'Horizon' was located on different chromosomes in different isolates, indicating mobility, and the previously described ToxhAT transposon (responsible for horizontal transfer of ToxA) was nested within this newly identified Starship. Additionally, ToxB, the gene encoding the chlorosis effector, was clustered as three copies on a 294-kb element, which is likely a different putative 'Starship' (dubbed 'Icarus') in a ToxB-producing isolate. ToxB and its putative transposon were missing from the ToxB non-coding reference isolate, but the homolog toxb and 'Icarus' were both present in a different non-coding isolate. This suggests that ToxB may have been mobile at some point during the evolution of the Ptr genome which is contradictory to the current assumption of ToxB vertical inheritance. Finally, the genome architecture of Ptr was defined as 'one-compartment' based on calculated gene distances and evolutionary rates. CONCLUSIONS: These findings together reflect on the highly plastic nature of the Ptr genome which has likely helped to drive its worldwide adaptation and has illuminated the involvement of giant transposons in facilitating the evolution of virulence in Ptr.

Association of Distance to Gynecologic Oncologist and Survival in a Rural Midwestern State.

Objectives: Rural ovarian cancer patients experience worse survival compared to urban patients. We assessed whether distance to gynecologic oncology specialists was associated with survival for patients in a rural state. Methods: Demographic, tumor, and treatment characteristics were extracted from the Iowa Cancer Registry for patients diagnosed between 1990 and 2018. Data were linked to the county-level 2018-2019 Area Health Resource File (number of surgeons and hospital beds per 100,000 population). Rurality was defined using 2013 Rural-Urban Continuum Codes; distance to the nearest gynecologic oncologist was calculated from the centroid of the county of residence to the centroid of the nearest county with a high volume health care center with a gynecologic oncologist. Associations with survival were assessed using multivariable Cox proportional hazards models. Results: Analyses included 1,562 ovarian cancer patients. Mean distance to gynecologic oncology was 60.8 miles, and median survival was 23 months. Unadjusted models showed increased distance from gynecologic oncology had progressively greater risk of death 30-49 miles (hazard ratio [HR] = 1.09, confidence interval [CI]: 1.04-1.15), 50-69 miles (HR = 1.19, CI: 1.07-1.32), 70+ miles (HR = 1.30, CI: 1.11-1.51). In adjusted models, association of distance to gynecologic oncology with risk of death was not significant; however, more advanced cancer stage and age, unmarried status, and higher county-level poverty were independently associated with increased risk of death. Conclusions: Above and beyond demographics and stage, distance to gynecologic oncology care was not an independent predictor of ovarian cancer survival. Further studies are needed to determine how to mitigate the factors contributing to worsened ovarian cancer survival among rural patients.

TP53 Sequencing and p53 Immunohistochemistry Predict Outcomes When Bevacizumab Is Added to Frontline Chemotherapy in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study.

PURPOSE: The status of p53 in a tumor can be inferred by next-generation sequencing (NGS) or by immunohistochemistry (IHC). We examined the association between p53 IHC and sequence and whether p53 IHC alone, or integrated with TP53 NGS, predicts the outcome. METHODS: From GOG-86P, a randomized phase II study of chemotherapy combined with either bevacizumab or temsirolimus in advanced endometrial cancer, 213 cases had p53 protein expression data measured by IHC and TP53 NGS data. An analysis was designed to integrate p53 expression by IHC with the presence or absence of a TP53 mutation. These variables were further correlated with progression-free survival (PFS) and overall survival (OS) in the chemotherapy plus bevacizumab arms versus the chemotherapy plus temsirolimus arm. RESULTS: In the analysis of p53 IHC, the most striking treatment effect favoring bevacizumab was in cases where p53 was overexpressed (PFS hazard ratio [HR]: 0.46, 95% CI, 0.26 to 0.88; OS HR: 0.31, 95% CI, 0.16 to 0.62). On integrated analysis, patients with TP53 missense mutations and p53 protein overexpression had a similar treatment effect on PFS (HR: 0.41, 95% CI, 0.22 to 0.83) and OS (HR: 0.28, 95% CI, 0.14 to 0.59) favoring bevacizumab plus chemotherapy relative to temsirolimus plus chemotherapy. Concordance between TP53 NGS and p53 IHC was 88%. Concordance was 92% when cases with TP53 mutations and POLE mutations or mismatch repair deficiency were removed. CONCLUSION: IHC for p53 alone or when integrated with sequencing for TP53 identifies a specific, high-risk tumor genotype/phenotype for which bevacizumab is particularly beneficial in improving outcomes when combined with chemotherapy.

Scaling-up to understand tree-pathogen interactions: A steep, tough climb or a walk in the park?

Plants have proficient tools that allow them to survive interactions with pathogens. Upon attack, they respond with specific countermeasures, which are controlled by the immune system. However, defences can fail and this failure exposes plants to fast-spreading devastation. Trees face similar challenges to other plants and their immune system allows them to mount defences against pathogens. However, their slow growth, longevity, woodiness, and size can make trees a challenging system to study. Here, we review scientific successes in plant systems, highlight the key challenges and describe the enormous opportunities for pathology research in trees. We discuss the benefits that scaling-up our understanding on tree-pathogen interactions can provide in the fight against plant pathogenic threats.

Disparity of ovarian cancer survival between urban and rural settings.

OBJECTIVE: To determine if there is a difference in overall survival of patients with epithelial ovarian cancer in rural, urban, and metropolitan settings in the United States. METHODS: We performed a retrospective cohort study using 2004-2016 National Cancer Database (NCDB) data including high and low grade, stage I-IV disease. Bivariate analyses used Student's t-test for continuous variables and χ2 test for dichotomous variables. Kaplan-Meier curves estimated survival of patients based on location of residence, and univariate analyses using Cox proportional HR assessed survival based on baseline characteristics. Multivariate analysis was performed to account for significant covariates. Propensity score matching was used to validate the multivariate survival model. For all tests, p<0.05 was considered statistically significant. RESULTS: A total of 111 627 patients were included with a mean age of 62.5 years for metroolitan (range 18-90), 64.0 years for rural (range 19-90) and 63.2 years for urban areas (range 18-90). Of all patients included, 94 290 were in a metropolitan area (counties >1 million population or 50 000-999 999), 15 386 were in an urban area (population of 10 000-49 999), and 1951 were in a rural area (non-metropolitan/non-core population). Univariate Cox proportional hazards models showed clinically significant differences in survival in patients from metropolitan, urban, and rural areas. Multivariate Cox proportional hazards models showed a clinically significant increase in HRs for patients in rural settings (HR 1.17; 95% CI 1.06 to 1.29). Increasing age and stage, non-insured status, non-white race, and comorbidity were also significant for poorer survival. CONCLUSION: Patients with ovarian cancer who live in rural settings with small populations and greater distance to tertiary care centers have poorer survival. These differences hold after controlling for stage, age, and other significant risk factors related to poorer outcomes. To improve clinical outcomes, we need further studies to identify which of these factors are actionable.

Gynecologic oncologist impact on adjuvant chemotherapy care for stage II-IV ovarian cancer patients.

OBJECTIVE: We aim to evaluate the impact gynecologic oncologists have on ovarian cancer adjuvant chemotherapy care from their role as surgeons recommending adjuvant chemotherapy care and their role as adjuvant chemotherapy providers while considering rural-urban differences. METHODS: Multivariable adjusted logistic regressions and Cox proportional hazards models were developed using a population-based, retrospective cohort of stage II-IV and unknown stage ovarian cancer patients diagnosed in Iowa, Kansas, and Missouri in 2010-2012 whose medical records were abstracted in 2017-2018. RESULTS: Gynecologic oncologist surgeons (versus other type of surgeon) were associated with increased odds of adjuvant chemotherapy initiation (adjusted odds ratio (OR) 2.18; 95% confidence interval (CI) 1.10-4.33) and having a gynecologic oncologist adjuvant chemotherapy provider (OR 10.0; 95% CI 4.58-21.8). Independent of type of surgeon, rural patients were less likely to have a gynecologic oncologist chemotherapy provider (OR 0.52; 95% CI 0.30-0.91). Gynecologic oncologist adjuvant chemotherapy providers (versus other providers) were associated with decreased surgery-to-chemotherapy time (rural: 6 days; urban: 8 days) and increased distance to chemotherapy (rural: 22 miles; urban: 11 miles). Rural women (versus urban) traveled 38 miles farther when their chemotherapy provider was a gynecologic oncologist and 27 miles farther when it was not. CONCLUSION: Gynecologic oncologist surgeons may impact adjuvant chemotherapy initiation. Gynecologic oncologists serving as adjuvant chemotherapy providers were associated with some care benefits, such as reduced time from surgery-to-chemotherapy, and some care barriers, such as travel distance. The barriers and benefits of having a gynecologic oncologist involved in adjuvant chemotherapy care, including rural-urban differences, warrant further research in other populations.

Gastrointestinal and genitourinary toxicity profiles of metformin versus placebo in men with prostate cancer receiving prostate radiotherapy: interim toxicity results of a double-blinded, multicenter, phase II randomized controlled trial.

Androgen deprivation therapy (ADT) used for prostate cancer (PCa) management is associated with metabolic and anthropometric toxicity. Metformin given concurrent to ADT is hypothesized to counteract these changes. This planned interim analysis reports the gastrointestinal and genitourinary toxicity profiles of PCa patients receiving ADT and prostate/pelvic radiotherapy plus metformin versus placebo as part of a phase 2 randomized controlled trial. Men with intermediate or high-risk PCa were randomized 1:1 to metformin versus placebo. Both groups were given ADT for 18-36 months with minimum 2-month neoadjuvant phase prior to radiotherapy. Acute gastrointestinal and genitourinary toxicities were quantified using CTCAE v4.0. Differences in ≥ grade 2 toxicities by treatment were assessed by chi-squared test. 83 patients were enrolled with 44 patients randomized to placebo and 39 randomized to metformin. There were no significant differences at any time point in ≥ grade 2 gastrointestinal toxicities or overall gastrointestinal toxicity. Overall ≥ grade 2 gastrointestinal toxicity was low prior to radiotherapy (7.9% (placebo) vs. 3.1% (metformin), p = 0.39) and at the end of radiotherapy (2.8% (placebo) vs 3.1% (metformin), p = 0.64). There were no differences in overall ≥ grade 2 genitourinary toxicity between treatment arms (19.0% (placebo) vs. 9.4% (metformin), p = 0.30). Metformin added to radiotherapy and ADT did not increase rates of ≥ grade 2 gastrointestinal or genitourinary toxicity and is generally safe and well-tolerated.

Impact of Surgeon Type and Rurality on Treatment and Survival of Ovarian Cancer Patients.

BACKGROUND: National Comprehensive Cancer Network guidelines recommend ovarian cancer patients receive cancer-directed surgery from a gynecologic oncologist surgeon. We aimed to determine if rurality impacts type of surgeon and estimate if the interaction between rurality and type of surgeon impacts cytoreductive surgery, chemotherapy initiation, and survival. METHODS: Our population-based cohort of Iowan (N=675) ovarian cancer patients included women diagnosed with histologically confirmed stages IB-IV cancer in 2010 to 2016 at the ages of 18 to 89 years old and who received cancer-directed surgery in Iowa. Multivariable logistic regression analysis and Cox proportional hazards models were used. RESULTS: Rural (vs. urban) patients were less likely to receive surgery from a gynecologic oncologist (adjusted odds ratio [OR]: 0.48; 95% confidence interval [CI]: 0.30-0.78). Rural patients with a gynecologic oncologist (vs. nongynecologic oncologist) surgeon were more likely to receive cytoreduction (OR: 2.84; 95% CI: 1.31-6.14) and chemotherapy (OR: 4.22; 95% CI: 1.82-9.78). Gynecologic oncologist-provided surgery conferred a 3-year cause-specific survival advantage among rural patients (adjusted hazard ratio: 0.57; 95% CI: 0.33-0.97) and disadvantage among urban patients (hazard ratio: 1.77; 95% CI: 1.02-3.06) in the model without treatment covariates. Significance dissipated in models with treatment variables. DISCUSSION: The variation in the gynecologic oncologist survival advantage may be because of treatment, referral, volume, or nongynecologic oncologist surgeons' specialty difference by rurality. This is the first study to investigate the ovarian cancer survival advantage of having a gynecologic oncologist surgeon by rurality.

Remarkable recent changes in the genetic diversity of the avirulence gene AvrStb6 in global populations of the wheat pathogen Zymoseptoria tritici.

Septoria tritici blotch (STB), caused by the fungus Zymoseptoria tritici, is one of the most economically important diseases of wheat. Recently, both factors of a gene-for-gene interaction between Z. tritici and wheat, the wheat receptor-like kinase Stb6 and the Z. tritici secreted effector protein AvrStb6, have been identified. Previous analyses revealed a high diversity of AvrStb6 haplotypes present in earlier Z. tritici isolate collections, with up to c.18% of analysed isolates possessing the avirulence isoform of AvrStb6 identical to that originally identified in the reference isolate IPO323. With Stb6 present in many commercial wheat cultivars globally, we aimed to assess potential changes in AvrStb6 genetic diversity and the incidence of haplotypes allowing evasion of Stb6-mediated resistance in more recent Z. tritici populations. Here we show, using targeted resequencing of AvrStb6, that this gene is universally present in field isolates sampled from major wheat-growing regions of the world in 2013-2017. However, in contrast to the data from previous AvrStb6 population studies, we report a complete absence of the originally described avirulence isoform of AvrStb6 amongst modern Z. tritici isolates. Moreover, a remarkably small number of haplotypes, each encoding AvrStb6 protein isoforms conditioning virulence on Stb6-containing wheat, were found to predominate among modern Z. tritici isolates. A single virulence isoform of AvrStb6 was found to be particularly abundant throughout the global population. These findings indicate that, despite the ability of Z. tritici to sexually reproduce on resistant hosts, AvrStb6 avirulence haplotypes tend to be eliminated in subsequent populations.

The identification of a transposon affecting the asexual reproduction of the wheat pathogen Zymoseptoria tritici.

Zymoseptoria tritici, the causal agent of Septoria tritici blotch, is a fungal wheat pathogen that causes significant global yield losses. Within Z. tritici populations, quantitative differences in virulence among different isolates are commonly observed; however, the genetic components that underpin these differences remain elusive. In this study, intraspecific comparative transcriptomic analysis was used to identify candidate genes that contribute to differences in virulence on the wheat cultivar WW2449. This led to the identification of a multicopy gene that was not expressed in the high-virulence isolate when compared to the medium- and low-virulence isolates. Further investigation suggested this gene resides in a 7.9-kb transposon. Subsequent long-read sequencing of the isolates used in the transcriptomic analysis confirmed that this gene did reside in an active Class II transposon, which is composed of four genes named REP9-1 to -4. Silencing and overexpression of REP9-1 in two distinct genetic backgrounds demonstrated that its expression alone reduces the number of pycnidia produced by Z. tritici during infection. The REP9-1 gene identified within a Class II transposon is the first discovery of a gene in a transposable element that influences the virulence of Z. tritici. This discovery adds further complexity to genetic loci that contribute to quantitative virulence in this important pathogen.