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BACKGROUND: Entomopathogenic fungi can provide a set of ecological services, such as suppressing arthropod pests and plant pathogens. In this study, novel indigenous Beauveria caledonica (Bc) strains were isolated from naturally infected banana weevils (Cosmopolites sordidus) occurring in commercial banana plantations in Brazil. RESULTS: The prevalence of infection by Bc strains on field‐caught C. sordidus ranged from 1.3% to 12.9%. Similar to the Beauveria bassiana strains tested, none of the Bc strains caused more than 50% weevil mortality at a concentration of 1 × 108 conidia ml−1. Bc strain CMAA1810 caused the highest mortality in C. sordidus and had enhanced insecticidal activity when formulated with an emulsifiable oil. In paired co‐culture assays, this same strain showed a significant growth‐inhibitory effect on the causal agent of Fusarium banana wilt (Fusarium oxysporum f. sp. cubense, Foc) of twofold magnitude compared with the control. Cell‐free crude filtrates derived from the red‐pigmented culture broth of Bc (CMAA1810) strongly reduced Foc conidial viability, and this inhibitory activity was inversely related to the age of the Bc culture. Crude concentrated filtrates from 4‐day‐old cultures exhibited the strongest antifungal activity (13‐fold) compared with untreated Foc conidia. The abundant compound identified in the crude filtrate of Bc was oosporein (1,4‐dibenzoquinone) present at a concentration of 0.829 ± 0.018 mg g−1 dry matter, and the antifungal activity of the filtrate was demonstrated. CONCLUSION: These results indicated that Bc strains might have the potential to manage both C. sordidus and Foc, two of the major phytosanitary problems in banana crops worldwide. Further research under field conditions using suitable formulations of virulent Bc strains in combination with the metabolite oosporein is needed to evaluate their efficacy in the management of C. sordidus and Foc in banana plantations. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

This study is designed to illuminate the specific role and underlying mechanism of collagen type III alpha 1 chain (COL3A1) in triple negative breast cancer (TNBC). Quantitative real‐time polymerase chain reaction was applied to examine mRNA expression of COL3A1. Western blot analysis was employed to determine protein levels of COL3A1, programmed death ligand 1 (PD‐L1), Bcl‐2, and cleaved caspase‐3. Immunohistochemistry staining was utilized for assessing protein expression of Ki67 and COL3A1 in tissues. The proliferous capacity of cells was assessed through CCK‐8 assay and 5‐Ethynyl‐2′‐deoxyuridine assay. Cell apoptosis and the percentage of CD8+ T cells were measured using flow cytometry. Migration and invasion of TNBC cells were examined via transwell assay. Lactate dehydrogenase (LDH) release was measured via a LDH assay kit. For establishing a xenograft tumor model, MDA‐MB‐231 cells were injected into the flank of mice through subcutaneous injection. COL3A1 expression was raised in TNBC tissues and cells, and it was inversely associated with overall survival data of TNBC patients. COL3A1 downregulation repressed proliferation, invasion, migration, and immune escape of TNBC cells along with tumor growth of xenograft mice. In TNBC cells and tumor tissues of mice, protein expression of PD‐L1 was reduced by COL3A1 knockdown. COL3A1 knockdown‐mediated inhibitory effects on cell proliferation, migration, invasion, and immune escape were reversed by PD‐L1 upregulation in vitro. Silencing of COL3A1 exerted an antitumor role in TNBC, implying its potential as a therapeutic target for TNBC. [ABSTRACT FROM AUTHOR]

The error‐related negativity (ERN) is sensitive to individual differences relating to anxiety and is modulated by manipulations that increase the threat‐value of committing errors. In adults, the ERN magnitude is enhanced when errors are followed by punishment, especially among anxious individuals. Punitive parenting is related to an elevated ERN in children; however, the effects of task‐based punishment on the ERN in children have yet to be understood. Furthermore, there is a need to assess developmental periods wherein the ERN might be especially prone to modulation by punishment. We examined the impact of punishment on the ERN in a sample of children and assessed whether the impact of punishment on the ERN was moderated by age and anxiety. Punishment potentiated the ERN in children, especially among higher trait‐anxious individuals; the punishment potentiation of the ERN was also associated with older age. The interaction between child age and anxiety symptoms did not significantly predict the punishment potentiation of the ERN; however, both child age and anxiety symptoms uniquely predicted the punishment potentiation of the ∆ERN. Anxious children may be especially prone to punishment‐related alterations in error monitoring, and the impact of punishment on the ERN may become more pronounced as children age. [ABSTRACT FROM AUTHOR]

Background: The CHA2DS2‐VASc score, widely used to estimate cardioembolic risk in patients with atrial fibrillation (AF), appears to be useful also in predicting vascular adverse events and death in different sets of patients without AF. The R2CHA2DS2‐VASc score, which includes renal impairment, allows a better prediction of death and thromboembolism in patients without AF. The aims of our study were to assess, in a large sample of patients at high cardiovascular (CV) risk, (i) the correlation between CHA2DS2‐VASc and R2CHA2DS2‐VASc with all‐cause mortality, and (ii) to compare the performances of CHA2DS2‐VASc and R2CHA2DS2‐VASc in predicting all‐cause mortality. Methods: In this single‐centre prospective observational study, conducted at the Research Hospital 'Casa Sollievo della Sofferenza' between June 2016 and December 2018, 1017 CV patients at high risk of undergoing coronary angiography were enrolled. Results: CHA₂DS₂‐VASc and R2CHA2DS2‐VASc scores significantly associated with all‐cause mortality. For each one‐point increase in CHA2DS2‐VASc or R2CHA2DS2‐VASc scores, mortality increased by almost 1.5‐fold. The R2CHA2DS2‐VASc score (C‐statistic = 0.71; 95% CI = 0.65–76) outperformed the CHA2DS2‐VASc score (C‐statistic = 0.66; 95% CI = 0.61–0.71) in predicting 4‐year mortality (delta C‐statistic = 0.05; 95% CI = 0.02–0.07). The better predictive ability of the R‐CHA2DS2‐VASc score was also demonstrated by an IDI = 0.027 (95% CI = 0.021–0.034, p <.00001) and a relative IDI = 62.8% (95% CI = 47.9%–81.3%, p <.00001). The R2CHA2DS2‐VASc score correctly reclassified the patients with a NRI = 0.715 (95% = 0.544–0.940, p <.00001). Conclusions: The CHA₂DS₂‐VASc and R2CHA2DS2‐VASc scores are useful predictors of all‐cause mortality in subjects at high CV risk, with the R2CHA2DS2‐VASc score being the best performer. [ABSTRACT FROM AUTHOR]

Non‐proportional hazards have been observed in many studies especially in immuno‐oncology clinical trials. Traditional analysis using the combined approach with log‐rank test as the significance test and Cox model for treatment effect estimation becomes questionable as this approach relies heavily on the proportional hazards assumption. Inspired by the MCP‐Mod (multiple comparisons and modeling approach) that has been widely used in dose‐finding studies, we propose a similar approach to handle non‐proportional hazards. Using this approach, efficacy signal is first established by a max‐combo test, after which hazard ratios across time will be estimated using a logically nested splines model. Simulations studies and real‐data examples are used to illustrate the use of this approach. [ABSTRACT FROM AUTHOR]

In clinical studies or trials comparing survival times between two treatment groups, the restricted mean lifetime (RML), defined as the expectation of the survival from time 0 to a prespecified time‐point, is often the quantity of interest that is readily interpretable to clinicians without any modeling restrictions. It is well known that if the treatments are not randomized (as in observational studies), covariate adjustment is necessary to account for treatment imbalances due to confounding factors. In this article, we propose a simple doubly‐robust pseudo‐value approach to effectively estimate the difference in the RML between two groups (akin to a metric for estimating average causal effects), while accounting for confounders. The proposed method combines two general approaches: (a) group‐specific regression models for the time‐to‐event and covariate information, and (b) inverse probability of treatment assignment weights, where the RMLs are replaced by the corresponding pseudo‐observations for survival outcomes, thereby mitigating the estimation complexities in presence of censoring. The proposed estimator is double‐robust, in the sense that it is consistent if at least one of the two working models remains correct. In addition, we explore the potential of available machine learning algorithms in causal inference to reduce possible bias of the causal estimates in presence of a complex association between the survival outcome and covariates. We conduct extensive simulation studies to assess the finite‐sample performance of the pseudo‐value causal effect estimators. Furthermore, we illustrate our methodology via application to a dataset from a breast cancer cohort study. The proposed method is implementable using the R package drRML, available in GitHub. [ABSTRACT FROM AUTHOR]

In a stroke of good luck for aquatic scientists and insect enthusiasts, the May 2022 Joint Aquatic Sciences Meeting (JASM) in Grand Rapids, Michigan coincided with a spectacular hatch of hydropsychid caddisflies. To estimate density, we enumerated caddisflies on 12 polarized window panels on the western face of the DeVos Place, which faced the Grand River. We found an average of 57.8 caddisflies per 2.0 × 2.3 m window panel (density of 12.6 caddisflies m−2). We observed American robins, swallows, sparrows, and jumping spiders preying and scavenging during the hatch. We also describe here our observations of a novel precopulatory behavior in the species Hydropsyche morosa, which we describe as a "head‐to‐tail" position. We discuss our natural history observations and share thoughts on how conferences can be a springboard for networking and collaborative science, natural history‐focused or otherwise. [ABSTRACT FROM AUTHOR]

The first examples of meso‐triaryl 22‐oxabenzonorroles were synthesized in 18–21% yields by oxidation of appropriate meso‐triaryl oxabenzobilane. The key precursors, the meso‐triaryl oxabenzobilanes were synthesized readily by treating 16‐oxatripyrrane with (1H‐indol‐3‐yl)(p‐tolyl)methanol under acid catalyzed conditions. The meso‐triaryl 22‐oxabenzonorroles were obtained in free base form by following our simple straight‐forward synthetic strategy. The X‐ray structure obtained for meso‐tritolyl 22‐oxabenzonorroles revealed that the indole ring was deviated by an angle of 41.27° from the mean plane. The NMR studies supported the presence of diatropic ring current effect as inner NH and CH protons were observed in the upfield region. The absorption spectra of 22‐oxabenzonorroles exhibited one strong Soret band and four weak Q‐bands. The electrochemical studies revealed that the macrocycles are electron rich and undergo easier oxidations. The DFT and TD‐DFT studies were in agreement with the experimental observations and NICS and HOMA values supports the aromatic nature of meso‐triaryl oxabenzonorroles. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to develop a new risk stratification tool to predict freedom from progression (FFP) for newly diagnosed advanced classical Hodgkin lymphoma (cHL). Methods: We collected data from 386 patients with advanced cHL diagnosed between December 8, 2000 and October 29, 2018, and treated with curative intent with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or an ABVD‐equivalent regimen. Cases were randomly divided into training and validation cohorts at a ratio of 7:3. The new model was constructed based on the results of Cox proportional hazards model in the training cohort. Comparisons of discrimination between the new model and other models in the training and validation cohorts for FFP prediction were measured by time‐dependent area under curve (tAUC) and Harrell's C‐index. Calibration plots were constructed to compare the consistency between the predicted and observed estimates of survival probability for the new model in the training and validation cohorts. Results: The new model (IPSPLR) composed of International Prognostic Score (IPS)‐3 and platelet/lymphocyte ratio (PLR) provided four distinct risk groups. The IPSPLR showed better discriminative ability when compared with IPS‐3 and IPS‐7. The AUC of IPSPLR was consistently higher than that of IPS‐3 and IPS‐7 between 12 and 120 months. The C‐index of the IPSPLR was higher than that of IPS‐7 and IPS‐3. The calibration plots showed an excellent agreement between the IPSPLR‐predicted and observed estimates of 5‐year FFP. Conclusion: The IPSPLR is an easily used tool for FFP prediction for newly diagnosed advanced cHL. Validation of this tool in other large datasets is needed. [ABSTRACT FROM AUTHOR]

Nested case control (NCC) is a sampling method widely used for developing and evaluating risk models with expensive biomarkers on large prospective cohort studies. In a typical NCC design, biomarker values are obtained on a subcohort, where cases consist of all the events (subjects who experience the event during the follow‐up). However, when the number of events is not small, due to the cost and limited availability of biospecimen, one may select only a subset of events as cases. We refer to such a variation as the untypical NCC. Unfortunately, existing inverse probability weighted (IPW) estimators for the untypical NCC are biased, and they only focus on relative risk parameters under the proportional hazards (PH) model. In this manuscript, we propose new weighting methods that produce consistent IPW estimators for not only relative risk parameters but also several metrics that evaluate a risk model's predictive performance. We also provide the inference procedure via perturbation resampling, which captures all the variance and between‐subject covariance induced by the sampling processes for both case and control selections. In addition, our methods are not limited to the PH model, and they can be applied to the time‐specific generalized linear model. Under the typical NCC design, our new weights are equivalent to the weight proposed by Samuelsen; under the untypical NCC, the IPW estimators using our weights have smaller bias and variance than the existing methods. We will demonstrate this improved performance via both analytical and numerical investigations. [ABSTRACT FROM AUTHOR]

Understanding the factors affecting thermal tolerance is crucial for predicting the impact climate change will have on ectotherms. However, the role developmental plasticity plays in allowing populations to cope with thermal extremes is poorly understood. Here, we meta‐analyse how thermal tolerance is initially and persistently impacted by early (embryonic and juvenile) thermal environments by using data from 150 experimental studies on 138 ectothermic species. Thermal tolerance only increased by 0.13°C per 1°C change in developmental temperature and substantial variation in plasticity (~36%) was the result of shared evolutionary history and species ecology. Aquatic ectotherms were more than three times as plastic as terrestrial ectotherms. Notably, embryos expressed weaker but more heterogenous plasticity than older life stages, with numerous responses appearing as non‐adaptive. While developmental temperatures did not have persistent effects on thermal tolerance overall, persistent effects were vastly under‐studied, and their direction and magnitude varied with ontogeny. Embryonic stages may represent a critical window of vulnerability to changing environments and we urge researchers to consider early life stages when assessing the climate vulnerability of ectotherms. Overall, our synthesis suggests that developmental changes in thermal tolerance rarely reach levels of perfect compensation and may provide limited benefit in changing environments. [ABSTRACT FROM AUTHOR]

Summary: Older patients with cancer often receive treatment regimens based on their age without considering other objective factors that may influence outcomes. Assessment of frailty can identify older patients who are robust and therefore more likely to benefit from intensive treatment, or conversely, frail and might instead be offered alternative approaches. However, such assessment requires specialised training and dedicated clinical resources. Alternative quantitative biomarkers associated with frailty are lacking. Here, we asked if expression signatures of 74 immune cell, ageing, and senescence‐related messenger RNAs in purified peripheral blood T cells could identify associations with clinical frailty in patients with haematological malignancies. We studied 69 patients between the ages of 36 and 92 years (median 76 years) with leukaemia, lymphoma, or multiple myeloma, across two institutions. Expression of four genes (aryl hydrocarbon receptor [AHR], CD27, CD28, and interleukin‐2 receptor subunit alpha [IL2RA; CD25]) in T cells was associated with frailty, independent of age. An expression‐based regression model had 76% sensitivity and 90% specificity to assign a patient as robust. These data identify measurable peripheral blood correlates of clinical frailty and suggest biomarkers for future prospective assessment. [ABSTRACT FROM AUTHOR]

Aims: We aim to investigate the additive effect of B‐lines on lung ultrasound (LUS) for predicting outcome in patients with heart failure (HF) when combined with conventional assessment of clinical congestion. Methods and results: This study prospectively enrolled 117 hospitalized HF patients (61 ± 16 years, 70.1% males) who underwent congestion assessment by the 'wet/dry' status, clinical congestion score (CCS), and B‐lines on LUS. The primary endpoint was all‐cause mortality or hospitalization for HF during the 180‐day follow‐up after discharge. The 'Wet', CCS ≥ 3, and B‐lines >5, indicators of congestion positive (+), were observed in 83.8%, 76.1%, and 70.1% of the patients on admission, respectively; and the numbers significantly decreased to 41.9%, 41.9%, and 35.9% at discharge, respectively. The agreement between the 'wet/dry' status and B‐lines (58.1%) or between CCS and B‐lines (56.4%) was moderate at discharge, in terms of both positive and both negative. By incorporating the B‐lines with assessment of clinical congestion, the patients at discharge were divided into three phenotypes as clinical congestion (+), clinical congestion (−) with B‐lines (+), and clinical congestion (−) with B‐lines (−). The Kaplan–Meier analysis showed a better survival in the both (−) group ('wet/dry' with B‐lines: Chi‐square 10.591, P = 0.005; CCS with B‐lines: χ2 6.239, P = 0.031). When the 'wet' patients (n = 49) being taken as the reference, the 'dry' patients with B‐lines (+) (n = 21) had an identical risk of the composite endpoint (hazard ratio [HR] adjusted for clinical covariates 1.021, 95% confidence interval [CI] 0.480–2.134, P = 0.974), while the 'dry' patients with B‐lines (−) (n = 47) had a lower risk (HR 0.264, 95% CI 0.113–0.617, P = 0.002). When the CCS (+) patients (n = 49) being regarded as the reference, similar results were obtained in the patients with CCS (−) but B‐lines (+) (n = 22) (HR 1.348, 95% CI 0.627–2.896, P = 0.444) as well as in those with both CCS (−) and B‐lines (−) (n = 46) (HR 0.447, 95% CI 0.202–0.992, P = 0.048). Conclusions: The combination of B‐lines on LUS and conventional assessment helped to identify new phenotypes of congestion that aid in the risk stratification of discharged HF patients. Further investigation is warranted to determine whether this strategy could be adopted as a guide for decongestion therapy. [ABSTRACT FROM AUTHOR]

Background: Patients with acute myocardial infarction (MI) are at high risk of upcoming events, in particular heart failure (HF), but reliable stratification methods are lacking. Our goal was to evaluate the potential role of circulating miRNAs as prognostic biomarkers in patients presenting with MI. Methods and results: We conducted a prospective study among 311 consecutive patients hospitalized with MI (65% ST‐segment elevation MI & median age of 55 years) with long‐term follow‐up. An initial screening was conducted to select candidate miRNAs, with subsequent study of 14 candidate miRNAs. The primary outcome was the composite of hospital admission for HF or cardiovascular death. During a mean follow‐up of 2.1 years miR‐21‐5p, miR‐23a‐3p, miR27b‐3p, miR‐122‐5p, miR210‐3p, and miR‐221‐3p reliably predicted the primary outcome. Multivariate Cox regression analyses highlighted that miR‐210‐3p [hazard ratio (HR) 2.65 per 1 SD increase, P < 0.001], miR‐23a‐3p (HR 2.11 per 1 SD increase, P < 0.001), and miR‐221‐3p (HR 2.03 per 1 SD increase, P < 0.001) were able to accurately predict the primary outcome, as well as cardiovascular death, HF hospitalizations, and long‐term New York Heart Association (NYHA) functional class. These three miRNAs clearly improved the performance of multivariate clinical models: ΔC‐statistic = 0.10 [95% confidence interval (CI), 0.03–0.17], continuous net reclassification index = 34.8% (95%CI, 5.8–57.4%), and integrated discrimination improvement (P < 0.001). Conclusions: This is the largest study evaluating the prognostic value of circulating miRNAs for HF‐related events among patients with MI. We show that several miRNAs predict HF hospitalizations, cardiovascular mortality, and poor long‐term NYHA status and improve current risk prediction methods. [ABSTRACT FROM AUTHOR]

Aims: Data on long‐term treatment effects are scarce, despite the intent to use new therapies for many years and the need of patients, physicians and payers to have a better understanding of the lifetime benefits of treatments. The restricted mean or median survival time (RMST) calculated using age instead of time, hypothetically enables estimation of long‐term gain in event‐free or overall survival from the short‐term (within‐trial) effects of an intervention, compared with its control. Tha aim of the study is to use trials with long‐term follow‐up available through extension studies to compare the long‐term projections estimated using RMST from within‐trial follow‐up data with the actual long‐term outcomes in the extension studies. Methods and results: We estimated the median long‐term survival time using age instead of follow‐up time and compared these model‐based projections with the actual long‐term estimates in the (i) SCD‐HeFT trial vs. SCD‐HeFT long‐term outcomes; (ii) SOLVD trial vs. SOLVD 12 year follow‐up; (iii) STICH trial vs. STICHES; and (iv) ACCORD study vs. ACCORDION. In the long‐term follow‐up of SCD‐HeFT, gain in survival with ICD vs. placebo over a median of 11.0 years was +1.4 years of life. The RMST model‐derived survival projection from the within‐trial data (median follow‐up of 3.4 years) gave an estimated survival gain of +1.2 years. In STICHES, over a median follow‐up of 9.8 years, coronary artery bypass grafting (CABG) vs. medical care led to a survival extension of +1.4 years in favour of CABG. RMST projections using within‐trial data from STICH (median follow‐up of 4.9 years), gave an extended survival of +2.4 years in favour of CABG in younger patients. In the long‐term follow‐up of SOLVD, enalapril vs. placebo led to a survival gain of +0.8 years over a median follow‐up of 12.1 years. The RMST projections from the within‐trial data (median follow‐up of 2.8 years) gave a survival extension of +0.3 years in favour of enalapril. In the long‐term follow‐up ACCORDION study, with a median follow‐up of 8.8 years, intensive vs. a standard anti‐hyperglycaemic treatment did not influence long‐term survival, which was concordant with the RMST projections from the short‐term ACCORD study with median follow‐up of 4.9 years. Conclusions: Age‐based survival projections using within‐trial data generally provided concordant results with the actual survival measured in long‐term follow‐up extension studies. Our findings suggest that age‐based lifetime projections may be used as means to assess the long‐term treatment effects. [ABSTRACT FROM AUTHOR]

Background: Many clinical and financial decisions for older adults depend on the future risk of disability and mortality. Prognostic tools for long‐term disability risk in a general population are lacking. We aimed to create a comprehensive prognostic tool that predicts the risk of mortality, of activities of daily living (ADL) disability, and walking disability simultaneously using the same set of variables. Methods: We conducted a longitudinal analysis of the nationally‐representative Health and Retirement Study (HRS). We included community‐dwelling adults aged ≥70 years who completed a core interview in the 2000 wave of HRS, with follow‐up through 2018. We evaluated 40 predictors encompassing demographics, diseases, physical functioning, and instrumental ADLs. We applied novel methods to optimize three models simultaneously while prioritizing variables that take less time to ascertain during backward stepwise elimination. The death prediction model used Cox regression and both the models for walking disability and for ADL disability used Fine and Gray competing‐risk regression. We examined calibration plots and generated optimism‐corrected statistics of discrimination using bootstrapping. To simulate unavailable patient data, we also evaluated models excluding one or two variables from the final model. Results: In 6646 HRS participants, 2662 developed walking disability, 3570 developed ADL disability, and 5689 died during a median follow‐up of 9.5 years. The final prognostic tool had 16 variables. The optimism‐corrected integrated area under the curve (iAUC) was 0.799 for mortality, 0.685 for walking disability, and 0.703 for ADL disability. At each percentile of predicted mortality risk, there was a substantial spread in the predicted risks of walking disability and ADL disability. Discrimination and calibration remained good even when missing one or two predictors from the model. This model is now available on ePrognosis (https://eprognosis.ucsf.edu/alexlee.php) Conclusions: Given the variability in disability risk for people with similar mortality risks, using individualized risks of disabilities may inform clinical and financial decisions for older adults. [ABSTRACT FROM AUTHOR]