Deciphering genetic factors contributing to enhanced resistance against Cercospora leaf blight in soybean (Glycine max L.) using GWAS analysis.

Cercospora leaf blight (CLB), caused by Cercospora cf. flagellaris, C. kikuchii, and C. cf. sigesbeckiae, is a significant soybean [Glycine max (L.) Merr.] disease in regions with hot and humid conditions causing yield loss in the United States and Canada. There is limited information regarding resistant soybean cultivars, and there have been marginal efforts to identify the genomic regions underlying resistance to CLB. A Genome-Wide Association Study was conducted using a diverse panel of 460 soybean accessions from maturity groups III to VII to identify the genomic regions associated to the CLB disease. These accessions were evaluated for CLB in different regions of the southeastern United States over 3 years. In total, the study identified 99 Single Nucleotide Polymorphism (SNPs) associated with the disease severity and 85 SNPs associated with disease incidence. Across multiple environments, 47 disease severity SNPs and 23 incidence SNPs were common. Candidate genes within 10 kb of these SNPs were involved in biotic and abiotic stress pathways. This information will contribute to the development of resistant soybean germplasm. Further research is warranted to study the effect of pyramiding desirable genomic regions and investigate the role of identified genes in soybean CLB resistance.

On the trail of a critically endangered fungus: A world-first application of wildlife detection dogs to fungal conservation.

Plant and animal conservation have benefited from the assistance of wildlife detection dogs (WDDs) since 1890, but their application to fungal conservation has not been trialed. In a world-first, we tested the effectiveness of WDDs and human surveyors when searching for experimentally outplanted fungi in natural habitat. We focused on a critically endangered fungus from Australia, Hypocreopsis amplectens, and showed that a WDD outperformed a human surveyor: our WDD detected a greater proportion of targets, had a faster time to first discovery, and had fewer false negatives. Our study highlights the tremendous potential for WDDs to enhance fungal conservation by demonstrating their utility in one of the most challenging fungal systems: a rare species with low population densities and low volatility. Our findings suggest that the application of WDDs to fungal conservation should enhance continuing efforts to document and conserve an understudied kingdom that is threatened by habitat loss and climate change.

Identifying Post-Acute Sequelae of SARS-CoV-2 Among Children in New York State Medicaid Managed Care.

Persons who contract COVID-19 are at risk of developing post-acute sequelae of SARS-CoV-2 (PASC). The objective of this study was to describe the incidence of PASC in a pediatric Medicaid population. Using a retrospective cohort of children enrolled in New York State Medicaid Managed Care we compared incident diagnoses between children with a positive laboratory test for SARS-CoV-2 in 2021 to children without a positive test in 2021 and children with a viral respiratory diagnosis in 2019. Logistic regression models estimated adjusted odds ratios using the Cohen's d statistic to assess the strength of associations. Most unadjusted incidence of clinical outcomes were less than 1% for all cohorts. Relative to the 2021 comparison cohort, significant increases among SARS-CoV-2 cases were observed in sequela of infectious disease conditions, general signs and symptoms, and pericarditis and pericardial disease and for the 2019 comparison, sequela of infectious disease conditions and suicidal ideation. However, associations were mostly determined to be weak or marginal. In this low socioeconomic status pediatric population, incidence of new clinical sequelae was low with mostly weak or marginal increases associated with SARS-CoV-2 infection. Though the incidence was low, some outcomes may be severe. Observed associations may have been impacted by pandemic behavior modification including social distancing policies.

Untangling the relationship between smoking and systemic sclerosis: an analysis of the EUSTAR cohort.

OBJECTIVES: To untangle the association between smoking and systemic sclerosis (SSc). METHODS: In the European Scleroderma Trials and Research cohort, the autoantibody status was compared between ever-smokers and never-smokers. Time until disease progression was assessed using Kaplan-Meier curves. Cox models were built to investigate the influence of smoking over 15 years of follow-up. All analyses were performed for the total cohort and stratified for sex and for positivity of anti-centromere (ACA) and anti-topoisomerase antibodies (ATA). RESULTS: Overall, 12 314 patients were included in the study. Of these, 10 393 were women (84%), 4637 were ACA-positive (38%), 3919 were ATA-positive (32%) and 4271 (35%) were ever-smokers. In men, but not in women, smoking was associated with mortality (HR 1.63, 95% CI 1.23 to 2.16, p=0.001). Ever-smoking women were at higher risk for skin progression (HR 1.10, 95% CI 1.00 to 1.22, p=0.046) and for 'any organ progression' (HR 1.07, 95% CI 1.00 to 1.13, p=0.036). In women, 34% of never-smokers were ATA-positive compared with 21% of ever-smokers (p<0.001). In the group of ever-smokers, higher exposure rates, reflected by the number of pack-years (OR 0.98, 95% CI 0.97 to 0.99, p<0.001) and by smoking duration (OR 0.96, 95% CI 0.95 to 0.97, p<0.001), were associated with lower frequency of ATA. In ACA-positive patients, the risk of mortality (HR 1.29, 95% CI 1.02 to 1.63, p=0.033), cardiac involvement (HR 1.25, 95% CI 1.03 to 1.43, p=0.001), skin progression (HR 1.21, 95% CI 1.03 to 1.42, p=0.018) and 'any organ progression' (HR 1.14, 95% CI 1.05 to 1.24, p=0.002) was increased among smokers. In ATA-positive smoking patients, mortality (HR 1.40, 95% CI 1.10 to 1.78, p=0.006), skin progression (HR 1.19, 95% CI 1.03 to 1.37, p=0.020) digital ulcers (HR 1.17, 95% CI 1.02 to 1.34, p=0.029) and 'any organ progression' (HR 1.11, 95% CI 1.00 to 1.22, p=0.048) occurred more frequently. CONCLUSIONS: Our stratified analysis demonstrates that smoking is associated with an increased risk for mortality in male SSc patients but not in women. Strikingly, smoking is associated with lower prevalence of ATA positivity, in particular in women. In both ATA-positive and ACA-positive patients, smoking is a risk factor for mortality, skin progression and 'any organ progression'.

Free-breathing high-resolution respiratory-gated radial stack-of-stars magnetic resonance imaging of the upper abdomen at 7 T.

Ultrahigh field magnetic resonance imaging (MRI) (≥ 7 T) has the potential to provide superior spatial resolution and unique image contrast. Apart from radiofrequency transmit inhomogeneities in the body at this field strength, imaging of the upper abdomen faces additional challenges associated with motion-induced ghosting artifacts. To address these challenges, the goal of this work was to develop a technique for high-resolution free-breathing upper abdominal MRI at 7 T with a large field of view. Free-breathing 3D gradient-recalled echo (GRE) water-excited radial stack-of-stars data were acquired in seven healthy volunteers (five males/two females, body mass index: 19.6-24.8 kg/m2) at 7 T using an eight-channel transceive array coil. Two volunteers were also examined at 3 T. In each volunteer, the liver and kidney regions were scanned in two separate acquisitions. To homogenize signal excitation, the time-interleaved acquisition of modes (TIAMO) method was used with personalized pairs of B1 shims, based on a 23-s Cartesian fast low angle shot (FLASH) acquisition. Utilizing free-induction decay navigator signals, respiratory-gated images were reconstructed at a spatial resolution of 0.8 × 0.8 × 1.0 mm3. Two experienced radiologists rated the image quality and the impact of B1 inhomogeneity and motion-related artifacts on multipoint scales. The images of all volunteers showcased effective water excitation and were accurately corrected for respiratory motion. The impact of B1 inhomogeneity on image quality was minimal, underscoring the efficacy of the multitransmit TIAMO shim. The high spatial resolution allowed excellent depiction of small structures such as the adrenal glands, the proximal ureter, the diaphragm, and small blood vessels, although some streaking artifacts persisted in liver image data. In direct comparisons with 3 T performed for two volunteers, 7-T acquisitions demonstrated increases in signal-to-noise ratio of 77% and 58%. Overall, this work demonstrates the feasibility of free-breathing MRI in the upper abdomen at submillimeter spatial resolution at a magnetic field strength of 7 T.

plantMASST - Community-driven chemotaxonomic digitization of plants.

Understanding the distribution of hundreds of thousands of plant metabolites across the plant kingdom presents a challenge. To address this, we curated publicly available LC-MS/MS data from 19,075 plant extracts and developed the plantMASST reference database encompassing 246 botanical families, 1,469 genera, and 2,793 species. This taxonomically focused database facilitates the exploration of plant-derived molecules using tandem mass spectrometry (MS/MS) spectra. This tool will aid in drug discovery, biosynthesis, (chemo)taxonomy, and the evolutionary ecology of herbivore interactions.

Proteomic features of soft tissue tumours in adolescents and young adults.

BACKGROUND: Adolescents and young adult (AYA) patients with soft tissue tumours including sarcomas are an underserved group with disparities in treatment outcomes. METHODS: To define the molecular features between AYA and older adult (OA) patients, we analysed the proteomic profiles of a large cohort of soft tissue tumours across 10 histological subtypes (AYA n = 66, OA n = 243), and also analysed publicly available functional genomic data from soft tissue tumour cell lines (AYA n = 5, OA n = 8). RESULTS: Biological hallmarks analysis demonstrates that OA tumours are significantly enriched in MYC targets compared to AYA tumours. By comparing the patient-level proteomic data with functional genomic profiles from sarcoma cell lines, we show that the mRNA splicing pathway is an intrinsic vulnerability in cell lines from OA patients and that components of the spliceosome complex are independent prognostic factors for metastasis free survival in AYA patients. CONCLUSIONS: Our study highlights the importance of performing age-specific molecular profiling studies to identify risk stratification tools and targeted agents tailored for the clinical management of AYA patients.

Soft tissue tumours are cancers that develop in the connective and supporting tissues of the body, such as muscle or fat. These tumours arise in patients across the entire age range. However, improvements in survival outcomes in adolescent and young adult (AYA) patients have lagged behind outcomes in older adults (OA) and children. To better understand the biology of AYA patients with soft tissue tumours, we analysed protein profiles across 10 different types. We identified biological differences between AYA and OA patients and report an age-specific signature that can potentially be used to help predict which AYA patients are more likely to have aggressive cancers that will spread to other parts of the body. Our study highlights the importance of performing age-specific studies to identify new tools to predict patient outcomes and potentially find more suitable treatments.

How to evaluate perfusion imaging in post-treatment glioma: a comparison of three different analysis methods.

INTRODUCTION: Dynamic susceptibility contrast (DSC) perfusion weighted (PW)-MRI can aid in differentiating treatment related abnormalities (TRA) from tumor progression (TP) in post-treatment glioma patients. Common methods, like the 'hot spot', or visual approach suffer from oversimplification and subjectivity. Using perfusion of the complete lesion potentially offers an objective and accurate alternative. This study aims to compare the diagnostic value and assess the subjectivity of these techniques. METHODS: 50 Glioma patients with enhancing lesions post-surgery and chemo-radiotherapy were retrospectively included. Outcome was determined by clinical/radiological follow-up or biopsy. Imaging analysis used the 'hot spot', volume of interest (VOI) and visual approach. Diagnostic accuracy was compared using receiving operator characteristics (ROC) curves for the VOI and 'hot spot' approach, visual assessment was analysed with contingency tables. Inter-operator agreement was determined with Cohens kappa and intra-class coefficient (ICC). RESULTS: 29 Patients suffered from TP, 21 had TRA. The visual assessment showed poor to substantial inter-operator agreement (κ = -0.72 - 0.68). Reliability of the 'hot spot' placement was excellent (ICC = 0.89), while reference placement was variable (ICC = 0.54). The area under the ROC (AUROC) of the mean- and maximum relative cerebral blood volume (rCBV) (VOI-analysis) were 0.82 and 0.72, while the rCBV-ratio ('hot spot' analysis) was 0.69. The VOI-analysis had a more balanced sensitivity and specificity compared to visual assessment. CONCLUSIONS: VOI analysis of DSC PW-MRI data holds greater diagnostic accuracy in single-moment differentiation of TP and TRA than 'hot spot' or visual analysis. This study underlines the subjectivity of visual placement and assessment.

Long-term clinical outcomes in early rheumatoid arthritis that was treated-to-target in the BeSt and IMPROVED studies.

OBJECTIVES: To assess disease outcomes after 20 and 12 years of patients with rheumatoid (RA) or undifferentiated arthritis (UA), treated-to-target in the BeSt and IMPROVED trials. METHODS: In BeSt (inclusion 2000-2002, duration 10 years), 508 patients with early RA were randomized to: 1. sequential monotherapy, 2. step-up combination therapy, 3. initial csDMARD combination therapy, 4. initial bDMARD/csDMARD combination therapy. The treatment target was low disease activity (DAS ≤ 2.4).In IMPROVED (inclusion 2007-2010, duration 5 years), 610 patients with early RA/UA started MTX with prednisone bridging. The treatment target was remission (DAS < 1.6). Patients not in early remission were randomized to 1. csDMARD combination therapy or 2. bDMARD/csDMARD combination therapy.Between 2019-2022, these patients were invited for long-term follow-up. RESULTS: One-hundred-fifty-three ex-Best and 282 ex-IMPROVED patients participated in the follow-up study after median 12 and 20 years since study start.In ex-BeSt and ex-IMPROVED patients the rate of low disease activity was 91%, and 68% were in DAS remission. Median SHS was 14.0 in ex-BeSt (IQR 6.0-32.5; progression since end BeSt 6.0, IQR 2.0-12.5) and 8 in ex-IMPROVED participants (IQR 3-16; progression since end IMPROVED 4, IQR 2-9). Mean HAQ was 0.8 ± 0.6 in ex-BeSt (change since end BeSt: 0.3 ± 0.5) and 0.6 ± 0.6 in ex-IMPROVED participants (change since end IMPROVED: 0.06 ± 0.5). CONCLUSION: At 12/20 years after treatment start, the majority of RA and UA patients who had been treated to target low DAS or DAS remission were in DAS remission and had limited functional disability. Radiographic damage progression was mild although not completely suppressed.

ReClassification of Patients with Ambiguous CA125 for Optimised Pre-Surgical Triage.

Pre-surgical clinical assessment of an adnexal mass is a complex process, and ideally requires accurate and rapid identification of disease status. Gold standard biomarker CA125 is extensively used off-label for this purpose; however its performance is typically inadequate, particularly for the detection of early stage disease and discrimination between benign versus malignant status. We recently described a multi-marker panel (MMP) and associated risk index for the differentiation of benign from malignant ovarian disease. In this study we applied a net reclassification approach to assess the use of MMP index to rescue those cases where low CA125 incorrectly excludes cancer diagnoses, or where benign disease is incorrectly assessed as "high risk" due to elevated CA125. Reclassification of such patients is of significant value to assist in the timely and accurate referral for patients where CA125 titer is uninformative.

Antigen-specific Fab profiling achieves molecular-resolution analysis of human autoantibody repertoires in rheumatoid arthritis.

The presence of autoantibodies is a defining feature of many autoimmune diseases. The number of unique autoantibody clones is conceivably limited by immune tolerance mechanisms, but unknown due to limitations of the currently applied technologies. Here, we introduce an autoantigen-specific liquid chromatography-mass spectrometry-based IgG1 Fab profiling approach using the anti-citrullinated protein antibody (ACPA) repertoire in rheumatoid arthritis (RA) as an example. We show that each patient harbors a unique and diverse ACPA IgG1 repertoire dominated by only a few antibody clones. In contrast to the total plasma IgG1 antibody repertoire, the ACPA IgG1 sub-repertoire is characterised by an expansion of antibodies that harbor one, two or even more Fab glycans, and different glycovariants of the same clone can be detected. Together, our data indicate that the autoantibody response in a prominent human autoimmune disease is complex, unique to each patient and dominated by a relatively low number of clones.

Prednisone use, disease activity and the occurrence of hyperglycaemia and diabetes in patients with early rheumatoid arthritis: a 10-year subanalysis of the BeSt study.

OBJECTIVES: To assess whether prednisone use and/or disease activity score (DAS) are associated with the development of hyperglycaemia and diabetes in rheumatoid arthritis (RA). METHODS: We included 504 non-diabetic early RA patients from the BeSt study (Dutch acronym for treatment strategies). Patients were randomised to four DAS-steered treatment arms and followed for 10 years. The associations between DAS and prednisone use with glucose levels and the occurrence of hyperglycaemia over time were assessed with linear and logistic mixed effects regression models. Development of diabetes was analysed with Cox regression. Sensitivity analyses were performed in patients who had a first episode of hyperglycaemia. RESULTS: 31 of 504 patients (6.2%) with a mean age of 54 years developed diabetes during follow-up; 11 of these (35%) had received prior treatment with prednisone. Prednisone use was not associated with development of hyperglycaemia or diabetes after correction for multiple testing in main or sensitivity analyses. In the main analyses, DAS was significantly associated with development of diabetes (HR 1.802 per 1 point DAS increase, 95% CI 1.284 to 2.529) but not with glucose levels nor hyperglycaemia. In patients with previous hyperglycaemia, DAS was associated with glucose levels, recurrence of hyperglycaemia and diabetes. CONCLUSIONS: In non-diabetic early RA patients, the use of prednisone was not associated with developing hyperglycaemia or diabetes. However, high DAS increased the risk of diabetes. Potential risks associated with prednisone use may have been mitigated by its effect on DAS.

The prospect of artificial intelligence to personalize assisted reproductive technology.

Infertility affects 1-in-6 couples, with repeated intensive cycles of assisted reproductive technology (ART) required by many to achieve a desired live birth. In ART, typically, clinicians and laboratory staff consider patient characteristics, previous treatment responses, and ongoing monitoring to determine treatment decisions. However, the reproducibility, weighting, and interpretation of these characteristics are contentious, and highly operator-dependent, resulting in considerable reliance on clinical experience. Artificial intelligence (AI) is ideally suited to handle, process, and analyze large, dynamic, temporal datasets with multiple intermediary outcomes that are generated during an ART cycle. Here, we review how AI has demonstrated potential for optimization and personalization of key steps in a reproducible manner, including: drug selection and dosing, cycle monitoring, induction of oocyte maturation, and selection of the most competent gametes and embryos, to improve the overall efficacy and safety of ART.

A marine heatwave changes the stabilizing effects of biodiversity in kelp forests.

Biodiversity can stabilize ecological communities through biological insurance, but climate and other environmental changes may disrupt this process via simultaneous ecosystem destabilization and biodiversity loss. While changes to diversity-stability relationships (DSRs) and the underlying mechanisms have been extensively explored in terrestrial plant communities, this topic remains largely unexplored in benthic marine ecosystems that comprise diverse assemblages of producers and consumers. By analyzing two decades of kelp forest biodiversity survey data, we discovered changes in diversity, stability, and their relationships at multiple scales (biological organizational levels, spatial scales, and functional groups) that were linked with the most severe marine heatwave ever documented in the North Pacific Ocean. Moreover, changes in the strength of DSRs during/after the heatwave were more apparent among functional groups than both biological organizational levels (population vs. ecosystem levels) and spatial scales (local vs. broad scales). Specifically, the strength of DSRs decreased for fishes, increased for mobile invertebrates and understory algae, and were unchanged for sessile invertebrates during/after the heatwave. Our findings suggest that biodiversity plays a key role in stabilizing marine ecosystems, but the resilience of DSRs to adverse climate impacts primarily depends on the functional identities of ecological communities.

Dispersal synchronizes giant kelp forests.

Spatial synchrony is the tendency for population fluctuations to be correlated among different locations. This phenomenon is a ubiquitous feature of population dynamics and is important for ecosystem stability, but several aspects of synchrony remain unresolved. In particular, the extent to which any particular mechanism, such as dispersal, contributes to observed synchrony in natural populations has been difficult to determine. To address this gap, we leveraged recent methodological improvements to determine how dispersal structures synchrony in giant kelp (Macrocystis pyrifera), a global marine foundation species that has served as a useful system for understanding synchrony. We quantified population synchrony and fecundity with satellite imagery across 11 years and 880 km of coastline in southern California, USA, and estimated propagule dispersal probabilities using a high-resolution ocean circulation model. Using matrix regression models that control for the influence of geographic distance, resources (seawater nitrate), and disturbance (destructive waves), we discovered that dispersal was an important driver of synchrony. Our findings were robust to assumptions about propagule mortality during dispersal and consistent between two metrics of dispersal: (1) the individual probability of dispersal and (2) estimates of demographic connectivity that incorporate fecundity (the number of propagules dispersing). We also found that dispersal and environmental conditions resulted in geographic clusters with distinct patterns of synchrony. This study is among the few to statistically associate synchrony with dispersal in a natural population and the first to do so in a marine organism. The synchronizing effects of dispersal and environmental conditions on foundation species, such as giant kelp, likely have cascading effects on the spatial stability of biodiversity and ecosystem function.

Prostate-Specific Membrane Antigen-Targeted Radioguided Pelvic Lymph Node Dissection in Newly Diagnosed Prostate Cancer Patients with a Suspicion of Locoregional Lymph Node Metastases: The DETECT Trial.

Prostate-specific membrane antigen (PSMA)-targeted radioguided surgery (RGS) aims to optimize the peroperative detection and removal of PSMA-avid lymph node (LN) metastases (LNMs) and has been described in patients with recurrent prostate cancer (PCa). In newly diagnosed PCa patients undergoing pelvic LN dissections, PSMA RGS could guide the urologist toward PSMA-expressing LNMs as identified on preoperative 18F-PSMA PET/CT imaging. The objective was to evaluate the safety and feasibility of 111In-PSMA RGS in primary PCa patients with one or more suggestive LNs on preoperative 18F-PSMA PET/CT. Methods: This prospective, phase I/II study included 20 newly diagnosed PCa patients with at least 1 suggestive LN on preoperative 18F-PSMA PET/CT. PSMA RGS was performed 24 h after 111In-PSMA-I&T administration, and postoperative 18F-PSMA PET/CT was performed to verify successful removal of the suggestive lesions. The primary endpoint was determination of the safety and feasibility of 111In-PSMA RGS. Safety was assessed by monitoring adverse events. Feasibility was described as the possibility to peroperatively detect suggestive LNs as identified on preoperative imaging. Secondary outcomes included the accuracy of 111In-PSMA RGS compared with histopathology, tumor- and lesion-to-background ratios, and biochemical recurrence. Results: No tracer-related adverse events were reported. In 20 patients, 43 of 49 (88%) 18F-PSMA PET-suggestive lesions were successfully removed. 111In-PSMA RGS facilitated peroperative identification and resection of 29 of 49 (59%) RGS-target lesions, of which 28 (97%) contained LNMs. Another 14 of 49 (29%) resected LNs were not detected with 111In-PSMA RGS, of which 2 contained metastases. Conclusion: 111In-PSMA RGS is a safe and feasible procedure that allows peroperative detection of 18F-PSMA PET/CT-suggestive lesions in newly diagnosed PCa patients. The use of a radioactive PSMA tracer and a detection device (γ-probe) during surgery helps in identifying LNs that were suggestive of PCa metastases on the 18F-PSMA PET/CT before surgery and thus may improve the peroperative identification and removal of these LNs.