The EUTOS long-term survival (ELTS) score is superior to the Sokal score for predicting survival in chronic myeloid leukemia

Prognostic scores support clinicians in selecting risk-adjusted treatments and in comparatively assessing different results. For patients with chronic-phase chronic myeloid leukemia (CML), four baseline prognostic scores are commonly used. Our aim was to compare the prognostic performance of the scores and to arrive at an evidence-based score recommendation. In 2949 patients not involved in any score development, higher hazard ratios and concordance indices in any comparison demonstrated the best discrimination of long-term survival with the ELTS score. In a second step, of 5154 patients analyzed to investigate risk group classification differences, 23% (n = 1197) were allocated to high-risk by the Sokal score. Of the 1197 Sokal high-risk patients, 56% were non-high-risk according to the ELTS score and had a significantly more favorable long-term survival prognosis than the 526 high-risk patients according to both scores. The Sokal score identified too many patients as high-risk and relatively few (40%) as low-risk (versus 60% with the ELTS score). Inappropriate risk classification jeopardizes optimal treatment selection. The ELTS score outperformed the Sokal score, the Euro, and the EUTOS score regarding risk group discrimination. The recent recommendation of the European LeukemiaNet for preferred use of the ELTS score was supported with significant statistical evidence.Peer reviewe

Landscape of HER2-low metastatic breast cancer (MBC): results from the Austrian AGMT_MBC-Registry

BACKGROUND: About 50% of all primary breast cancers show a low-level expression of HER2 (HER2-low), defined as immunohistochemically 1+ or 2+ and lack of HER2 gene amplification measured by in situ hybridization. This low HER2 expression is a promising new target for antibody-drug conjugates (ADCs) currently under investigation. Until now, little is known about the frequency and the prognostic value of low HER2-expression in metastatic breast cancer (MBC). PATIENTS AND METHODS: The MBC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT) is a multicenter nationwide ongoing registry for MBC patients in Austria. Unadjusted, univariate survival probabilities of progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method and compared by the log-rank test. Multivariable adjusted hazard ratios were estimated by Cox regression models. In this analysis, only patients with known HER2 status and available survival data were included. RESULTS: As of 11/15/2020, 1,973 patients were included in the AGMT-MBC-Registry. Out of 1,729 evaluable patients, 351 (20.3%) were HER2-positive, 608 (35.2%) were HER2-low and 770 (44.5%) were completely HER2-negative (HER2-0). Low HER2-expression was markedly more frequent in the hormone-receptor(HR)+ subgroup compared to the triple-negative subgroup (40% vs. 23%). In multivariable analysis, low HER2 expression did not significantly influence OS neither in the HR+ (HR 0.89; 95% CI 0.74-1.05; P = 0.171) nor in the triple-negative subgroup (HR 0.92; 95% CI 0.68-1.25; P = 0.585), when compared to completely HER2-negative disease. Similar results were observed when HER2 IHC 2+ patients were compared to IHC 1+ or 0 patients. CONCLUSION: Low-HER2 expression did not have any impact on prognosis of metastatic breast cancer in this real-world population

Radar vision in the mapping of forest biodiversity from space

Recent progress in remote sensing provides much-needed, large-scale spatio-temporal information on habitat structures important for biodiversity conservation. Here we examine the potential of a newly launched satellite-borne radar system (Sentinel-1) to map the biodiversity of twelve taxa across five temperate forest regions in central Europe. We show that the sensitivity of radar to habitat structure is similar to that of airborne laser scanning (ALS), the current gold standard in the measurement of forest structure. Our models of different facets of biodiversity reveal that radar performs as well as ALS; median R² over twelve taxa by ALS and radar are 0.51 and 0.57 respectively for the first non-metric multidimensional scaling axes representing assemblage composition. We further demonstrate the promising predictive ability of radar-derived data with external validation based on the species composition of birds and saproxylic beetles. Establishing new area-wide biodiversity monitoring by remote sensing will require the coupling of radar data to stratified and standardized collected local species data

Cox proportional hazards deep neural network identifies peripheral blood complete remission to be at least equivalent to morphologic complete remission in predicting outcomes of patients treated with azacitidine - a prospective cohort study by the AGMT

The current gold standard of response assessment in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) is morphologic complete remission (CR) and CR with incomplete count recovery (CRi), both of which require an invasive BM evaluation. Outside of clinical trials, BM evaluations are only performed in ~50% of patients during follow-up, pinpointing a clinical need for response endpoints that do not necessitate BM assessments. We define and validate a new response type termed "peripheral blood complete remission" (PB-CR) that can be determined from the differential blood count and clinical parameters without necessitating a BM assessment. We compared the predictive value of PB-CR with morphologic CR/CRi in 1441 non-selected, consecutive patients diagnosed with MDS (n = 522; 36.2%), CMML (n = 132; 9.2%), or AML (n = 787; 54.6%), included within the Austrian Myeloid Registry (aMYELOIDr; NCT04438889). Time-to-event analyses were adjusted for 17 covariates remaining in the final Cox proportional hazards (CPH) model. DeepSurv, a CPH neural network model, and permutation-based feature importance were used to validate results. 1441 patients were included. Adjusted median overall survival for patients achieving PB-CR was 22.8 months (95%CI 18.9-26.2) versus 10.4 months (95%CI 9.7-11.2) for those who did not; HR = 0.366 (95%CI 0.303-0.441; p < .0001). Among patients achieving CR, those additionally achieving PB-CR had a median adjusted OS of 32.6 months (95%CI 26.2-49.2) versus 21.7 months (95%CI 16.9-27.7; HR = 0.400 [95%CI 0.190-0.844; p = .0161]) for those who did not. Our deep neural network analysis-based findings from a large, prospective cohort study indicate that BM evaluations solely for the purpose of identifying CR/CRi can be omitted

Prognosis of patients with chronic myeloid leukemia presenting in advanced phase is defined mainly by blast count, but also by age, chromosomal aberrations and hemoglobin

Chronic myeloid leukemia (CML) is usually diagnosed in chronic phase, yet there is a small percentage of patients that is diagnosed in accelerated phase or blast crisis. Due to this rarity, little is known about the prognosis of these patients. Our aim was to identify prognostic factors for this cohort. We identified 283 patients in the EUTOS population-based and out-study registries that were diagnosed in advanced phase. Nearly all patients were treated with tyrosine kinase inhibitors. Median survival in this heterogeneous cohort was 8.2 years. When comparing patients with more than 30% blasts to those with 20-29% blasts, the hazard ratio (HR) was 1.32 (95%-confidence interval (CI): [0.7-2.6]). Patients with 20-29% blasts had a significantly higher risk than patients with less than 20% blasts (HR: 2.24, 95%-CI: [1.2-4.0], P = .008). We found that the blast count was the most important prognostic factor; however, age, hemoglobin, basophils and other chromosomal aberrations should be considered as well. The ELTS score was able to define two groups (high risk vs non-high risk) with an HR of 3.01 (95%-CI: [1.81-5.00], P <.001). Regarding the contrasting definitions of blast crisis, our data clearly supported the 20% cut-off over the 30% cut-off in this cohort. Based on our results, we conclude that a one-phase rather than a two-phase categorization of de novo advanced phase CML patients is appropriate.Peer reviewe

The contribution of insects to global forest deadwood decomposition

The amount of carbon stored in deadwood is equivalent to about 8 per cent of the global forest carbon stocks. The decomposition of deadwood is largely governed by climate with decomposer groups—such as microorganisms and insects—contributing to variations in the decomposition rates. At the global scale, the contribution of insects to the decomposition of deadwood and carbon release remains poorly understood. Here we present a field experiment of wood decomposition across 55 forest sites and 6 continents. We find that the deadwood decomposition rates increase with temperature, and the strongest temperature effect is found at high precipitation levels. Precipitation affects the decomposition rates negatively at low temperatures and positively at high temperatures. As a net effect—including the direct consumption by insects and indirect effects through interactions with microorganisms—insects accelerate the decomposition in tropical forests (3.9% median mass loss per year). In temperate and boreal forests, we find weak positive and negative effects with a median mass loss of 0.9 per cent and −0.1 per cent per year, respectively. Furthermore, we apply the experimentally derived decomposition function to a global map of deadwood carbon synthesized from empirical and remote-sensing data, obtaining an estimate of 10.9 ± 3.2 petagram of carbon per year released from deadwood globally, with 93 per cent originating from tropical forests. Globally, the net effect of insects may account for 29 per cent of the carbon flux from deadwood, which suggests a functional importance of insects in the decomposition of deadwood and the carbon cycle

Data from: Distribution models and a dated phylogeny for Chilean Oxalis species reveal occupation of new habitats by different lineages, not rapid adaptive radiation

Among the World’s most challenging environments for plant life is the Atacama Desert, an arid zone extending over 1300 km and from sea level to 2000/3000 m along the southwestern Andean foothills. Plants there and in the adjacent Mediterranean zone exhibit striking adaptations, and we here use a species-rich such group to address the question whether adaptations arose in parallel, at different times, or simultaneously. Answering this type of question has been a major concern of evolutionary biology over the past few years, with a growing consensus that lineages tend to be conservative in their vegetative traits and niche requirements. Combined nuclear and chloroplast DNA sequences for 112 species of Oxalidales (4900 aligned nucleotides) yielded a fossil-calibrated phylogeny that includes 43 of the 54 species of Oxalis occurring in Chile. Distribution models (SDMs) for these species that included precipitation, temperature, fog and/or vegetation types and the phylogeny were used to reconstruct ancestral habitat preferences, relying on likelihood and Bayesian techniques. Since uneven collecting can reduce the power of SDMs, we used a background sample from 1224 Chilean Oxalis collections to correct models for collecting effort. Models with just 10 of 19 bioclim parameters did as well as more parameter-rich models. Results reveal that the Oxalis flora of Chile consists of seven distant lineages that originated at different times prior to the last Andean uplift pulse and some of which had features pre-adapting them to seasonally arid or xeric conditions. The Mediterranean core zone, south of the Atacama, offered an ecological refuge for insufficiently arid-adapted species and harbors a mix of ancient and young groups. There is no evidence of rapid adaptive radiation

Data from: Distribution models and a dated phylogeny for Chilean Oxalis species reveal occupation of new habitats by different lineages, not rapid adaptive radiation

Among the World’s most challenging environments for plant life is the Atacama Desert, an arid zone extending over 1300 km and from sea level to 2000/3000 m along the southwestern Andean foothills. Plants there and in the adjacent Mediterranean zone exhibit striking adaptations, and we here use a species-rich such group to address the question whether adaptations arose in parallel, at different times, or simultaneously. Answering this type of question has been a major concern of evolutionary biology over the past few years, with a growing consensus that lineages tend to be conservative in their vegetative traits and niche requirements. Combined nuclear and chloroplast DNA sequences for 112 species of Oxalidales (4900 aligned nucleotides) yielded a fossil-calibrated phylogeny that includes 43 of the 54 species of Oxalis occurring in Chile. Distribution models (SDMs) for these species that included precipitation, temperature, fog and/or vegetation types and the phylogeny were used to reconstruct ancestral habitat preferences, relying on likelihood and Bayesian techniques. Since uneven collecting can reduce the power of SDMs, we used a background sample from 1224 Chilean Oxalis collections to correct models for collecting effort. Models with just 10 of 19 bioclim parameters did as well as more parameter-rich models. Results reveal that the Oxalis flora of Chile consists of seven distant lineages that originated at different times prior to the last Andean uplift pulse and some of which had features pre-adapting them to seasonally arid or xeric conditions. The Mediterranean core zone, south of the Atacama, offered an ecological refuge for insufficiently arid-adapted species and harbors a mix of ancient and young groups. There is no evidence of rapid adaptive radiation