A comprehensive microarray-based DNA methylation study of 367 hematological neoplasms

Background: Alterations in the DNA methylation pattern are a hallmark of leukemias and lymphomas. However, most epigenetic studies in hematologic neoplasms (HNs) have focused either on the analysis of few candidate genes or many genes and few HN entities, and comprehensive studies are required. Methodology/Principal Findings: Here, we report for the first time a microarray-based DNA methylation study of 767 genes in 367 HNs diagnosed with 16 of the most representative B-cell (n = 203), T-cell (n = 30), and myeloid (n = 134) neoplasias, as well as 37 samples from different cell types of the hematopoietic system. Using appropriate controls of B-, T-, or myeloid cellular origin, we identified a total of 220 genes hypermethylated in at least one HN entity. In general, promoter hypermethylation was more frequent in lymphoid malignancies than in myeloid malignancies, being germinal center mature B-cell lymphomas as well as B and T precursor lymphoid neoplasias those entities with highest frequency of gene-associated DNA hypermethylation. We also observed a significant correlation between the number of hypermethylated and hypomethylated genes in several mature B-cell neoplasias, but not in precursor B- and T-cell leukemias. Most of the genes becoming hypermethylated contained promoters with high CpG content, and a significant fraction of them are targets of the polycomb repressor complex. Interestingly, T-cell prolymphocytic leukemias show low levels of DNA hypermethylation and a comparatively large number of hypomethylated genes, many of them showing an increased gene expression. Conclusions/Significance: We have characterized the DNA methylation profile of a wide range of different HNs entities. As well as identifying genes showing aberrant DNA methylation in certain HN subtypes, we also detected six genes—DBC1, DIO3, FZD9, HS3ST2, MOS, and MYOD1—that were significantly hypermethylated in B-cell, T-cell, and myeloid malignancies. These might therefore play an important role in the development of different HNs

On the NASA GEDI and ESA CCI biomass maps: aligning for uptake in the UNFCCC global stocktake

Earth Observation data are uniquely positioned to estimate forest aboveground biomass density (AGBD) in accordance with the United Nations Framework Convention on Climate Change (UNFCCC) principles of 'transparency, accuracy, completeness, consistency and comparability'. However, the use of space-based AGBD maps for national-level reporting to the UNFCCC is nearly non-existent as of 2023, the end of the first global stocktake (GST). We conduct an evidence-based comparison of AGBD estimates from the NASA Global Ecosystem Dynamics Investigation and ESA Climate Change Initiative, describing differences between the products and National Forest Inventories (NFIs), and suggesting how science teams must align efforts to inform the next GST. Between the products, in the tropics, the largest differences in estimated AGBD are primarily in the Congolese lowlands and east/southeast Asia. Where NFI data were acquired (Peru, Mexico, Lao PDR and 30 regions of Spain), both products show strong correlation to NFI-estimated AGBD, with no systematic deviations. The AGBD-richest stratum of these, the Peruvian Amazon, is accurately estimated in both. These results are remarkably promising, and to support the operational use of AGB map products for policy reporting, we describe targeted ways to align products with Intergovernmental Panel on Climate Change (IPCC) guidelines. We recommend moving towards consistent statistical terminology, and aligning on a rigorous framework for uncertainty estimation, supported by the provision of open-science codes for large-area assessments that comprehensively report uncertainty. Further, we suggest the provision of objective and open-source guidance to integrate NFIs with multiple AGBD products, aiming to enhance the precision of national estimates. Finally, we describe and encourage the release of user-friendly product documentation, with tools that produce AGBD estimates directly applicable to the IPCC guideline methodologies. With these steps, space agencies can convey a comparable, reliable and consistent message on global biomass estimates to have actionable policy impact

How dusty is <i>α</i> Centauri? Excess or non-excess over the infrared photospheres of main-sequence stars

Context. Debris discs around main-sequence stars indicate the presence of larger rocky bodies. The components of the nearby, solar-type binary α Centauri have metallicities that are higher than solar, which is thought to promote giant planet formation. Aims. We aim to determine the level of emission from debris around the stars in the α Cen system. This requires knowledge of their photospheres. Having already detected the temperature minimum, Tmin, of α Cen A at far-infrared wavelengths, we here attempt to do the same for the more active companion α Cen B. Using the α Cen stars as templates, we study the possible effects that Tmin may have on the detectability of unresolved dust discs around other stars. Methods. We used Herschel-PACS, Herschel-SPIRE, and APEX-LABOCA photometry to determine the stellar spectral energy distributions in the far infrared and submillimetre. In addition, we used APEX-SHeFI observations for spectral line mapping to study the complex background around α Cen seen in the photometric images. Models of stellar atmospheres and of particulate discs, based on particle simulations and in conjunction with radiative transfer calculations, were used to estimate the amount of debris around these stars. Results. For solar-type stars more distant than α Cen, a fractional dust luminosity fd ≡ Ldust/Lstar ~ 2 × 10-7 could account for SEDs that do not exhibit the Tmin effect. This is comparable to estimates of fd for the Edgeworth-Kuiper belt of the solar system. In contrast to the far infrared, slight excesses at the 2.5σ level are observed at 24 μm for both α Cen A and B, which, if interpreted as due to zodiacal-type dust emission, would correspond to fd ~ (1-3) × 10-5, i.e. some 102 times that of the local zodiacal cloud. Assuming simple power-law size distributions of the dust grains, dynamical disc modelling leads to rough mass estimates of the putative Zodi belts around the α Cen stars, viz. ≲4 × 10-6 M☾of 4 to 1000 μm size grains, distributed according to n(a) ∝ a-3.5. Similarly, for filled-in Tmin emission, corresponding Edgeworth-Kuiper belts could account for ~ 10-3 M☾ of dust. Conclusions Our far-infrared observations lead to estimates of upper limits to the amount of circumstellar dust around the stars α Cen A and B. Light scattered and/or thermally emitted by exo-Zodi discs will have profound implications for future spectroscopic missions designed to search for biomarkers in the atmospheres of Earth-like planets. The far-infrared spectral energy distribution of α Cen B is marginally consistent with the presence of a minimum temperature region in the upper atmosphere of the star. We also show that an α Cen A-like temperature minimum may result in an erroneous apprehension about the presence of dust around other, more distant stars. Based on observations with Herschel which is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA. Also based on observations with APEX, which is a 12 m diameter submillimetre telescope at 5100 m altitude on Llano Chajnantor in Chile. The telescope is operated by Onsala Space Observatory, Max-Planck-Institut für Radioastronomie (MPIfR), and European Southern Observatory (ESO)

A Comprehensive Microarray-Based DNA Methylation Study of 367 Hematological Neoplasms

Background: Alterations in the DNA methylation pattern are a hallmark of leukemias and lymphomas. However, most epigenetic studies in hematologic neoplasms (HNs) have focused either on the analysis of few candidate genes or many genes and few HN entities, and comprehensive studies are required. Methodology/Principal Findings: Here, we report for the first time a microarray-based DNA methylation study of 767 genes in 367 HNs diagnosed with 16 of the most representative B-cell (n = 203), T-cell (n = 30), and myeloid (n = 134) neoplasias, as well as 37 samples from different cell types of the hematopoietic system. Using appropriate controls of B-, T-, or myeloid cellular origin, we identified a total of 220 genes hypermethylated in at least one HN entity. In general, promoter hypermethylation was more frequent in lymphoid malignancies than in myeloid malignancies, being germinal center mature B-cell lymphomas as well as B and T precursor lymphoid neoplasias those entities with highest frequency of gene-associated DNA hypermethylation. We also observed a significant correlation between the number of hypermethylated and hypomethylated genes in several mature B-cell neoplasias, but not in precursor B- and T-cell leukemias. Most of the genes becoming hypermethylated contained promoters with high CpG content, and a significant fraction of them are targets of the polycomb repressor complex. Interestingly, T-cell prolymphocytic leukemias show low levels of DNA hypermethylation and a comparatively large number of hypomethylated genes, many of them showing an increased gene expression. Conclusions/Significance: We have characterized the DNA methylation profile of a wide range of different HNs entities. As well as identifying genes showing aberrant DNA methylation in certain HN subtypes, we also detected six genes DBC1, DIO3, FZD9, HS3ST2, MOS, and MYOD1 that were significantly hypermethylated in B-cell, T-cell, and myeloid malignancies. These might therefore play an important role in the development of different HNs

HE-LHC: The High-Energy Large Hadron Collider – Future Circular Collider Conceptual Design Report Volume 4

In response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100 km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100 TeV. Its unprecedented centre-of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

HE-LHC: The High-Energy Large Hadron Collider: Future Circular Collider Conceptual Design Report Volume 4

In response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100 km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100 TeV. Its unprecedented centre-of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries