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1.	George, Jan Peter, et al. (author) Method comparison of indirect assessments of understory leaf area index (LAIu) : A case study across the extended network of ICOS forest ecosystem sites in Europe 2021 In: Ecological Indicators. - : Elsevier BV. - 1470-160X .- 1872-7034. ; 128 Journal article (peer-reviewed)abstract Leaf area index (LAI) is a key ecological indicator for describing the structure of canopies and for modelling energy exchange between atmosphere and biosphere. While LAI of the forest overstory can be accurately assessed over large spatial scales via remote sensing, LAI of the forest understory (LAIu) is still largely ignored in ecological studies and ecosystem modelling due to the fact that it is often too complex to be destructively sampled or approximated by other site parameters. Additionally, so far only few attempts have been made to retrieve understory LAI via remote sensing, because dense canopies with high LAI are often hindering retrieval algorithms to produce meaningful estimates for understory LAI. Consequently, the forest understory still constitutes a poorly investigated research realm impeding ecological studies to properly account for its contribution to the energy absorption capacity of forest stands. This study aims to compare three conceptually different indirect retrieval methodologies for LAIu over a diverse panel of forest understory types distributed across Europe. For this we carried out near-to-surface measurements of understory reflectance spectra as well as digital surface photography over the extended network of Integrated Carbon Observation System (ICOS) forest ecosystem sites. LAIu was assessed by exploiting the empirical relationship between vegetation cover and light absorption (Beer-Lambert- Bouguer law) as well as by utilizing proposed relationships with two prominent vegetation indices: normalized difference vegetation index (NDVI) and simple ratio (SR). Retrievals from the three methods were significantly correlated with each other (r = 0.63–0.99, RMSE = 0.53–0.72), but exhibited also significant bias depending on the LAI scale. The NDVI based retrieval approach most likely overestimates LAI at productive sites when LAIu > 2, while the simple ratio algorithm overestimates LAIu at sites with sparse understory vegetation and presence of litter or bare soil. The purely empirical method based on the Beer-Lambert law of light absorption seems to offer a good compromise, since it provides reasonable LAIu values at both low and higher LAI ranges. Surprisingly, LAIu variation among sites seems to be largely decoupled from differences in climate and light permeability of the overstory, but significantly increased with vegetation diversity (expressed as species richness) and hence proposes new applications of LAIu in ecological modelling.
2.	Groß, Rüdiger, et al. (author) Macromolecular Viral Entry Inhibitors as Broad-Spectrum First-Line Antivirals with Activity against SARS-CoV-2 2022 In: Advanced Science. - : Wiley. - 2198-3844. ; 9:20 Journal article (peer-reviewed)abstract Inhibitors of viral cell entry based on poly(styrene sulfonate) and its core–shell nanoformulations based on gold nanoparticles are investigated against a panel of viruses, including clinical isolates of SARS-CoV-2. Macromolecular inhibitors are shown to exhibit the highly sought-after broad-spectrum antiviral activity, which covers most analyzed enveloped viruses and all of the variants of concern for SARS-CoV-2 tested. The inhibitory activity is quantified in vitro in appropriate cell culture models and for respiratory viral pathogens (respiratory syncytial virus and SARS-CoV-2) in mice. Results of this study comprise a significant step along the translational path of macromolecular inhibitors of virus cell entry, specifically against enveloped respiratory viruses.
3.	Bejanyan, Nelli, et al. (author) Myeloablative Conditioning for Allogeneic Transplantation Results in Superior Disease-Free Survival for Acute Myelogenous Leukemia and Myelodysplastic Syndromes with Low/Intermediate but not High Disease Risk Index : A Center for International Blood and Marrow Transplant Research Study 2021 In: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 27:1, s. 68.e1-68.e9 Journal article (peer-reviewed)abstract Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/ intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR],.74; 95% confidence interval [CI],.62 to.88; P <.001) but significantly greater relapse risk (HR, 1.54; 95% CI, 1.35 to 1.76; P <.001) and thus inferior disease-free survival (DFS) (HR, 1.19; 95% CI, 1.07 to 1.33; P =.001). In the high/ very high-risk DRI cohort, RIC was associated with marginally lower NRM (HR,.83; 95% CI,.68 to 1.00; P =.051) and significantly higher relapse risk (HR, 1.23; 95% CI, 1.08 to 1.41; P =.002), leading to similar DFS using either RIC or MAC. These data support MAC over RIC as the preferred conditioning intensity for patients with AML/MDS with low/intermediate-risk DRI, but with a similar benefit as RIC in high/very high-risk DRI. Novel MAC regimens with less toxicity could benefit all patients, but more potent antineoplastic approaches are needed for the high/ very-high risk DRI group.
4.	DeFilipp, Zachariah, et al. (author) Maintenance Tyrosine Kinase Inhibitors Following Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelogenous Leukemia : A Center for International Blood and Marrow Transplant Research Study 2020 In: Biology of blood and marrow transplantation. - : Elsevier. - 1083-8791 .- 1523-6536. ; 26:3, s. 472-479 Journal article (peer-reviewed)abstract It remains unknown whether the administration of tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 after allogeneic hematopoietic cell transplantation (HCT) is associated with improved outcomes for patients with chronic myelogenous leukemia (CML). In this registry study, we analyzed clinical outcomes of 390 adult patients with CML who underwent transplantation between 2007 and 2014 and received maintenance TKI following HCT (n = 89) compared with no TKI maintenance (n = 301), as reported to the Center for International Blood and Marrow Transplant Research. All patients received TKI therapy before HCT. The majority of patients had a disease status of first chronic phase at HCT (n = 240; 62%). The study was conducted as a landmark analysis, excluding patients who died, relapsed, had chronic graft-versus-host disease, or were censored before day +100 following HCT. Of the 89 patients who received TKI maintenance, 77 (87%) received a single TKI and the other 12 (13%) received multiple sequential TKIs. The most common TKIs used for maintenance were dasatinib (n = 50), imatinib (n = 27), and nilotinib (n = 27). As measured from day +100, the adjusted estimates for 5-year relapse (maintenance, 35% versus no maintenance, 26%; P = .11), leukemia-free survival (maintenance, 42% versus no maintenance, 44%; P = .65), or overall survival (maintenance, 61% versus no maintenance, 57%; P = .61) did not differ significantly between patients receiving TKI maintenance or no maintenance. These results remained unchanged in multivariate analysis and were not modified by disease status before transplantation. In conclusion, our data from this day +100 landmark analysis do not demonstrate a significant impact of maintenance TKI therapy on clinical outcomes. The optimal approach to TKI administration in the post-transplantation setting in patients with CML remains undetermined.
5.	Gowin, Krisstina, et al. (author) Survival following allogeneic transplant in patients with myelofibrosis 2020 In: Blood Advances. - : AMER SOC HEMATOLOGY. - 2473-9529 .- 2473-9537. ; 4:9, s. 1965-1973 Journal article (peer-reviewed)abstract Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). In this large multicenter retrospective study, overall survival (OS) in MF patients treated with allogeneic HCT (551 patients) and without HCT (non-HCT) (1377 patients) was analyzed with Cox proportional hazards model. Survival analysis stratified by the Dynamic International Prognostic Scoring System (DIPSS) revealed that the first year of treatment arm assignment, due to upfront risk of transplant-related mortality (TRM), HCT was associated with inferior OS compared with non-HCT (non-HCT vs HCT: DIPSS intermediate 1 [Int-1]: hazard ratio [HR] = 0.26, P < .0001; DIPSS-Int-2 and higher: HR, 0.39, P < .0001). Similarly, in the DIPSS low-risk MF group, due to upfront TRM risk, OS was superior with non-HCT therapies compared with HCT in the first-year post treatment arm assignment (HR, 0.16, P = .006). However, after 1 year, OS was not significantly different (HR, 1.38, P = .451). Beyond 1 year of treatment arm assignment, an OS advantage with HCT therapy in Int-1 and higher DIPSS score patients was observed (non-HCT vs HCT: DIPSS-Int-1: HR, 2.64, P < .0001; DIPSS-Int-2 and higher: HR, 2.55, P < .0001). In conclusion, long-term OS advantage with HCT was observed for patients with Int-1 or higher risk MF, but at the cost of early TRM. The magnitude of OS benefit with HCT increased as DIPSS risk score increased and became apparent with longer follow-up.
6.	Graf, Alexander, et al. (author) Altered energy partitioning across terrestrial ecosystems in the European drought year 2018 : Energy partitioning in the drought 2018 2020 In: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 375:1810 Journal article (peer-reviewed)abstract Drought and heat events, such as the 2018 European drought, interact with the exchange of energy between the land surface and the atmosphere, potentially affecting albedo, sensible and latent heat fluxes, as well as CO 2 exchange. Each of these quantities may aggravate or mitigate the drought, heat, their side effects on productivity, water scarcity and global warming. We used measurements of 56 eddy covariance sites across Europe to examine the response of fluxes to extreme drought prevailing most of the year 2018 and how the response differed across various ecosystem types (forests, grasslands, croplands and peatlands). Each component of the surface radiation and energy balance observed in 2018 was compared to available data per site during a reference period 2004-2017. Based on anomalies in precipitation and reference evapotranspiration, we classified 46 sites as drought affected. These received on average 9% more solar radiation and released 32% more sensible heat to the atmosphere compared to the mean of the reference period. In general, drought decreased net CO 2 uptake by 17.8%, but did not significantly change net evapotranspiration. The response of these fluxes differed characteristically between ecosystems; in particular, the general increase in the evaporative index was strongest in peatlands and weakest in croplands. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.
7.	Grünwald, Jan, et al. (author) Ecological traits predict population trends of urban birds in Europe 2024 In: Ecological Indicators. - 1470-160X. ; 160 Journal article (peer-reviewed)abstract The population dynamics of urban animals has been so far remarkably understudied. At the same time, urban species’ population trends can provide important information on the consequences of environmental changes in cities. We modelled long-term population trends of 93 bird species breeding in urban areas in 16 European countries as a function of species’ traits, characterising variability in their urbanization and ecology. We found that: (i) earlier colonisers have more negative population trends than recent colonisers; (ii) more urbanized open habitat species had more positive population trends than less urbanized open habitat species; (iii) highly urbanized birds breeding above the ground had more negative trends than highly urbanized ground breeders. These patterns can be explained by several processes occurring in cities as well as outside city borders. Namely, (i) pre-industrial colonisers might struggle to persist in rapidly changing urban areas, limiting their foraging and breeding opportunities of the birds. (ii) Open habitats are under pressure of intensive agricultural exploitation in rural areas, which may negatively affect populations of less urbanized birds. In contrast, urban areas do not experience such pressure keeping the trends of urbanized open habitat species more positive. (iii) Differences in population trends between highly urbanized ground and above-ground breeders suggest that the latter may lose their breeding opportunities in modern buildings that do not provide suitable breeding sites. Our results indicate that even once successful, city dwellers may not keep pace with changes in urban areas, but these areas may also provide suitable habitats for biodiversity.
8.	Haeni, M., et al. (author) Winter respiratory C losses provide explanatory power for net ecosystem productivity 2017 In: Journal of Geophysical Research - Biogeosciences. - 2169-8953. ; 122:1, s. 243-260 Journal article (peer-reviewed)abstract Accurate predictions of net ecosystem productivity (NEPc) of forest ecosystems are essential for climate change decisions and requirements in the context of national forest growth and greenhouse gas inventories. However, drivers and underlying mechanisms determining NEPc (e.g., climate and nutrients) are not entirely understood yet, particularly when considering the influence of past periods. Here we explored the explanatory power of the compensation day (cDOY)-defined as the day of year when winter net carbon losses are compensated by spring assimilation-for NEPc in 26 forests in Europe, North America, and Australia, using different NEPc integration methods. We found cDOY to be a particularly powerful predictor for NEPc of temperate evergreen needleleaf forests (R2=0.58) and deciduous broadleaf forests (R2=0.68). In general, the latest cDOY correlated with the lowest NEPc. The explanatory power of cDOY depended on the integration method for NEPc, forest type, and whether the site had a distinct winter net respiratory carbon loss or not. The integration methods starting in autumn led to better predictions of NEPc from cDOY then the classical calendar method starting 1 January. Limited explanatory power of cDOY for NEPc was found for warmer sites with no distinct winter respiratory loss period. Our findings highlight the importance of the influence of winter processes and the delayed responses of previous seasons' climatic conditions on current year's NEPc. Such carry-over effects may contain information from climatic conditions, carbon storage levels, and hydraulic traits of several years back in time.
9.	Hill, Brian T., et al. (author) Assessment of Impact of HLA Type on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia 2018 In: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 24:3, s. 581-586 Journal article (peer-reviewed)abstract Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplantation (allo-HCT) for medically fit patients. Although the use of allo-HCT has declined since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT, the only known curative treatment for CLL. The potential benefit of transplantation is most likely due to the presence of alloreactive donor T cells that mediate the graft-versus-leukemia (GVL) effect. The recognition of potentially tumor-specific antigens in the context of class I and II major histocompatibility complex on malignant B lymphocytes by donor T cells may be influenced by subtle differences in the highly polymorphic HLA locus. Given previous reports of specific HLA alleles impacting the incidence of CLL and the clinical outcomes of allo-HCT for CLL, we sought to study the overall survival and progression-free survival of a large cohort of patients with CLL who underwent allo-HCT from fully HLA-matched related and unrelated donors at Center for International Blood and Marrow Transplant Research transplantation centers. We found no statistically significant association of allo-HCT outcomes in CLL based on previously reported HLA combinations. Additional study is needed to further define the immunologic features that portend a more favorable GVL effect after allo-HCT for CLL.
10.	Hu, Bei, et al. (author) Timing of allogeneic hematopoietic cell transplantation (alloHCT) for chronic myeloid leukemia (CML) patients 2020 In: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 61:12, s. 2811-2820 Journal article (peer-reviewed)abstract While TKI are the preferred first-line treatment for chronic phase (CP) CML, alloHCT remains an important consideration. The aim is to estimate residual life expectancy (RLE) for patients initially diagnosed with CP CML based on timing of alloHCT or continuation of TKI in various settings: CP1 CML, CP2 + [after transformation to accelerated phase (AP) or blast phase (BP)], AP, or BP. Non-transplant cohort included single-institution patients initiating TKI and switched TKI due to failure. CIBMTR transplant cohort included CML patients who underwent HLA sibling matched (MRD) or unrelated donor (MUD) alloHCT. AlloHCT appeared to shorten survival in CP1 CML with overall mortality hazard ratio (HR) for alloHCT of 2.4 (95% CI 1.2-4.9;p = .02). In BP CML, there was a trend toward higher survival with alloHCT; HR = 0.7 (0.5-1.1;p = .099). AlloHCT in CP2 + [HR = 2.0 (0.8-4.9),p = .13] and AP [HR = 1.1 (0.6-2.1);p = .80] is less clear and should be determined on a case-by-case basis.
11.	Kim, Haesook T., et al. (author) Prognostic Score and Cytogenetic Risk Classification for Chronic Lymphocytic Leukemia Patients : Center for International Blood and Marrow Transplant Research Report 2019 In: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 25:16, s. 5143-5155 Journal article (peer-reviewed)abstract Purpose: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT).Experimental Design: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research.Results: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or >= 5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years).Conclusions: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.
12.	Menghrajani, Kamal, et al. (author) Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML 2022 In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:3, s. 828-847 Journal article (peer-reviewed)abstract Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.
13.	Metheny, Leland, et al. (author) Allogeneic Transplantation to Treat Therapy-Related Myelodysplastic Syndrome and Acute Myelogenous Leukemia in Adults 2021 In: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 27:11, s. 923.e1-923.e12 Journal article (peer-reviewed)abstract Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myelogenous leukemia (t-AML), have a poor prognosis. An earlier Center for International Blood and Marrow Transplant Research (CIBMTR) analysis of 868 allogeneic hematopoietic cell transplantations (allo-HCTs) performed between 1990 and 2004 showed a 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%, respectively. Modern supportive care, graft-versus-host disease prophylaxis, and reduced-intensity conditioning (RIC) regimens have led to improved outcomes. Therefore, the CIBMTR analyzed 1531 allo-HCTs performed in adults with t-MDS (n = 759) or t-AML (n = 772) between and 2000 and 2014. The median age was 59 years (range, 18 to 74 years) for the patients with t-MDS and 52 years (range, 18 to 77 years) for those with tAML. Twenty-four percent of patients with t-MDS and 11% of those with t-AML had undergone a previous autologous (auto-) HCT. A myeloablative conditioning (MAC) regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Nonrelapse mortality at 5 years was 34% (95% confidence interval [CI], 30% to 37%) for patients with t-MDS and 34% (95% CI, 30% to 37%) for those with t-AML. Relapse rates at 5 years in the 2 groups were 46% (95% CI, 43% to 50%) and 43% (95% CI, 40% to 47%). Five-year OS and DFS were 27% (95% CI, 23% to 31%) and 19% (95% CI, 16% to 23%), respectively, for patients with t-MDS and 25% (95% CI, 22% to 28%) and 23% (95% CI, 20% to 26%), respectively, for those with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low-risk t-MDS and those with t-AML undergoing HCT with MAC while in first complete remission, but worse for those with previous auto-HCT, higher-risk cytogenetics or Revised International Prognostic Scoring System score, and a partially matched unrelated donor. Relapse remains the major cause of treatment failure, with little improvement seen over the past 2 decades. These data mandate caution when recommending allo-HCT in these conditions and indicate the need for more effective antineoplastic approaches before and after allo-HCT.
14.	Oran, Betul, et al. (author) Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes 2021 In: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 27:11, s. 921.e1-921.e10 Journal article (peer-reviewed)abstract Reduced-intensity conditioning (RIC) regimens developed to extend the use of allogeneic hematopoietic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the 2 most commonly used RIC regimens, i.v. fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in patients with myelodysplastic syndrome (MDS). Through the Center for International Blood and Marrow Transplant Research (CIBMTR), we identified 1045 MDS patients age >= 60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using an RIC regimen. The CIBMTR's definition of RIC was used: a regimen that incorporated an i.v. busulfan total dose <= 7.2 mg/kg or a low-dose melphalan total dose <= 150 mg/m(2). The 2 groups, recipients of FluBu (n = 697) and recipients of FluMel (n = 448), were comparable in terms of disease- and transplantation-related characteristics except for the more frequent use of antithymocyte globulin or alemtuzumab in the FluBu group (39% versus 31%). The median age was 67 years in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% versus 44% (P <=.0001). Transplantation-related mortality (TRM) was higher in the FluMel group (26% versus 16%; P <= .0001). Because the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was better at 1 year and beyond with FluMel compared with FluBu (48% versus 40% at 1 year [P =.02] and 35% versus 27% at 3 years [P =.01]). Overall survival was comparable in the 2 groups at 1 year (63% versus 61%; P =.4) but was significantly improved with FluMel compared with FluBu at 3 years (46% versus 39%; P =.03). Our results suggest that FluMel is associated with superior DFS compared with FluBu owing to reduced RI in older patients with MDS patients.
15.	Petrescu, Ana Maria Roxana, et al. (author) The uncertain climate footprint of wetlands under human pressure 2015 In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 112:15, s. 4594-4599 Journal article (peer-reviewed)abstract Significant climate risks are associated with a positive carbon-temperature feedback in northern latitude carbon-rich ecosystems, making an accurate analysis of human impacts on the net greenhouse gas balance of wetlands a priority. Here, we provide a coherent assessment of the climate footprint of a network of wetland sites based on simultaneous and quasi-continuous ecosystem observations of CO2 and CH4 fluxes. Experimental areas are located both in natural and in managed wetlands and cover a wide range of climatic regions, ecosystem types, and management practices. Based on direct observations we predict that sustained CH4 emissions in natural ecosystems are in the long term (i.e., several centuries) typically offset by CO2 uptake, although with large spatiotemporal variability. Using a space-for-time analogy across ecological and climatic gradients, we represent the chronosequence from natural to managed conditions to quantify the "cost" of CH4 emissions for the benefit of net carbon sequestration. With a sustained pulse-response radiative forcing model, we found a significant increase in atmospheric forcing due to land management, in particular for wetland converted to cropland. Our results quantify the role of human activities on the climate footprint of northern wetlands and call for development of active mitigation strategies for managed wetlands and new guidelines of the Intergovernmental Panel on Climate Change (IPCC) accounting for both sustained CH4 emissions and cumulative CO2 exchange.
16.	Pisek, Jan, et al. (author) Retrieval and validation of forest background reflectivity from daily Moderate Resolution Imaging Spectroradiometer (MODIS) bidirectional reflectance distribution function (BRDF) data across European forests 2021 In: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 18:2, s. 621-635 Journal article (peer-reviewed)abstract Information about forest background reflectance is needed for accurate biophysical parameter retrieval from forest canopies (overstory) with remote sensing. Separating under- and overstory signals would enable more accurate modeling of forest carbon and energy fluxes. We retrieved values of the normalized difference vegetation index (NDVI) of the forest understory with the multi-angular Moderate Resolution Imaging Spectroradiometer (MODIS) bidirectional reflectance distribution function (BRDF)/albedo data (gridded 500 m daily Collection 6 product), using a method originally developed for boreal forests. The forest floor background reflectance estimates from the MODIS data were compared with in situ understory reflectance measurements carried out at an extensive set of forest ecosystem experimental sites across Europe. The reflectance estimates from MODIS data were, hence, tested across diverse forest conditions and phenological phases during the growing season to examine their applicability for ecosystems other than boreal forests. Here we report that the method can deliver good retrievals, especially over different forest types with open canopies (low foliage cover). The performance of the method was found to be limited over forests with closed canopies (high foliage cover), where the signal from understory becomes too attenuated. The spatial heterogeneity of individual field sites and the limitations and documented quality of the MODIS BRDF product are shown to be important for the correct assessment and validation of the retrievals obtained with remote sensing.
17.	Qiu, Chunjing, et al. (author) ORCHIDEE-PEAT (revision 4596), a model for northern peatland CO2, water, and energy fluxes on daily to annual scales 2018 In: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 11:2, s. 497-519 Journal article (peer-reviewed)abstract Peatlands store substantial amounts of carbon and are vulnerable to climate change. We present a modified version of the Organising Carbon and Hydrology In Dynamic Ecosystems (ORCHIDEE) land surface model for simulating the hydrology, surface energy, and CO2 fluxes of peatlands on daily to annual timescales. The model includes a separate soil tile in each 0.5° grid cell, defined from a global peatland map and identified with peat-specific soil hydraulic properties. Runoff from non-peat vegetation within a grid cell containing a fraction of peat is routed to this peat soil tile, which maintains shallow water tables. The water table position separates oxic from anoxic decomposition. The model was evaluated against eddy-covariance (EC) observations from 30 northern peatland sites, with the maximum rate of carboxylation (Vcmax) being optimized at each site. Regarding short-term day-to-day variations, the model performance was good for gross primary production (GPP) (r2 Combining double low line 0.76; Nash-Sutcliffe modeling efficiency, MEF Combining double low line 0.76) and ecosystem respiration (ER, r2 Combining double low line 0.78, MEF Combining double low line 0.75), with lesser accuracy for latent heat fluxes (LE, r2 Combining double low line 0.42, MEF Combining double low line 0.14) and and net ecosystem CO2 exchange (NEE, r2 Combining double low line 0.38, MEF Combining double low line 0.26). Seasonal variations in GPP, ER, NEE, and energy fluxes on monthly scales showed moderate to high r2 values (0.57-0.86). For spatial across-site gradients of annual mean GPP, ER, NEE, and LE, r2 values of 0.93, 0.89, 0.27, and 0.71 were achieved, respectively. Water table (WT) variation was not well predicted (r2<0.1), likely due to the uncertain water input to the peat from surrounding areas. However, the poor performance of WT simulation did not greatly affect predictions of ER and NEE. We found a significant relationship between optimized Vcmax and latitude (temperature), which better reflects the spatial gradients of annual NEE than using an average Vcmax value.
18.	Scholz, Roland W., et al. (author) Unintended Side Effects of the Digital Transition : European Scientists' Messages from a Proposition-Based Expert Round Table 2018 In: Sustainability. - : MDPI. - 2071-1050. ; 10:6 Journal article (peer-reviewed)abstract We present the main messages of a European Expert Round Table (ERT) on the unintended side effects (unseens) of the digital transition. Seventeen experts provided 42 propositions from ten different perspectives as input for the ERT. A full-day ERT deliberated communalities and relationships among these unseens and provided suggestions on (i) what the major unseens are; (ii) how rebound effects of digital transitioning may become the subject of overarching research; and (iii) what unseens should become subjects of transdisciplinary theory and practice processes for developing socially robust orientations. With respect to the latter, the experts suggested that the ownership, economic value, use and access of data and, related to this, algorithmic decision-making call for transdisciplinary processes that may provide guidelines for key stakeholder groups on how the responsible use of digital data can be developed. A cluster-based content analysis of the propositions, the discussion and inputs of the ERT, and a theoretical analysis of major changes to levels of human systems and the human-environment relationship resulted in the following greater picture: The digital transition calls for redefining economy, labor, democracy, and humanity. Artificial Intelligence (AI)-based machines may take over major domains of human labor, reorganize supply chains, induce platform economics, and reshape the participation of economic actors in the value chain. (Digital) Knowledge and data supplement capital, labor, and natural resources as major economic variables. Digital data and technologies lead to a post-fuel industry (post-) capitalism. Traditional democratic processes can be (intentionally or unintentionally) altered by digital technologies. The unseens in this field call for special attention, research and management. Related to the conditions of ontogenetic and phylogenetic development (humanity), the ubiquitous, global, increasingly AI-shaped interlinkage of almost every human personal, social, and economic activity and the exposure to indirect, digital, artificial, fragmented, electronically mediated data affect behavioral, cognitive, psycho-neuro-endocrinological processes on the level of the individual and thus social relations (of groups and families) and culture, and thereby, the essential quality and character of the human being (i.e., humanity). The findings suggest a need for a new field of research, i.e., focusing on sustainable digital societies and environments, in which the identification, analysis, and management of vulnerabilities and unseens emerging in the sociotechnical digital transition play an important role.
19.	Weil, Tatjana, et al. (author) Advanced Molecular Tweezers with Lipid Anchors against SARS-CoV-2 and Other Respiratory Viruses 2022 In: JACS Au. - : American Chemical Society (ACS). - 2691-3704. ; 2:9, s. 2187-2202 Journal article (peer-reviewed)abstract The COVID-19 pandemic caused by SARS-CoV-2 presents a global health emergency. Therapeutic options against SARS-CoV-2 are still very limited but urgently required. Molecular tweezers are supramolecular agents that destabilize the envelope of viruses resulting in a loss of viral infectivity. Here, we show that first-generation tweezers, CLR01 and CLR05, disrupt the SARS-CoV-2 envelope and abrogate viral infectivity. To increase the antiviral activity, a series of 34 advanced molecular tweezers were synthesized by insertion of aliphatic or aromatic ester groups on the phosphate moieties of the parent molecule CLR01. A structure-activity relationship study enabled the identification of tweezers with a markedly enhanced ability to destroy lipid bilayers and to suppress SARS-CoV-2 infection. Selected tweezer derivatives retain activity in airway mucus and inactivate the SARS-CoV-2 wildtype and variants of concern as well as respiratory syncytial, influenza, and measles viruses. Moreover, inhibitory activity of advanced tweezers against respiratory syncytial virus and SARS-CoV-2 was confirmed in mice. Thus, potentiated tweezers are broad-spectrum antiviral agents with great prospects for clinical development to combat highly pathogenic viruses.
20.	Wieduwilt, Matthew J., et al. (author) Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia 2022 In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:1, s. 339-357 Journal article (peer-reviewed)abstract The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLAmatched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P <_ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P <_ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (<_18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.
21.	Zhou, Zheng, et al. (author) Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens : a CIBMTR report 2020 In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 4:13, s. 3180-3190 Journal article (peer-reviewed)abstract There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.

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