Synthesis, Characterization, and Biological Activity of N1-Methyl-2-(1H-1,2,3-Benzotriazol-1-y1)-3-Oxobutan- ethioamide Complexes with Some Divalent Metal (II) Ions

A new series of Zn2+, Cu2+, Ni2+, and Co2+ complexes of N1-methyl-2-(1H-1,2,3-benzotriazol-1-yl)-3-oxobutanethioamide (MBOBT), HL, has been synthesized and characterized by different spectral and magnetic measurements and elemental analysis. IR spectral data indicates that (MBOBT) exists only in the thione form in the solid state while 13C NMR spectrum indicates its existence in thione and thiole tautomeric forms. The IR spectra of all complexes indicate that (MBOBT) acts as a monobasic bidentate ligand coordinating to the metal(II) ions via the keto-oxygen and thiolato-sulphur atoms. The electronic spectral studies showed that (MBOBT) bonded to all metal ions through sulphur and nitrogen atoms based on the positions and intensity of their charge transfer bands. Furthermore, the spectra reflect four coordinate tetrahedral zinc(II), tetragonally distorted copper(II), square planar nickel(II), and cobalt(II) complexes. Thermal decomposition study of the complexes was monitored by TG and DTG analyses under N2 atmosphere. The decomposition course and steps were analyzed and the activation parameters of the nonisothermal decomposition are determined. The isolated metal chelates have been screened for their antimicrobial activities and the findings have been reported and discussed in relation to their structures

Origin and Global Expansion of Mycobacterium tuberculosis Complex Lineage 3

Tuberculosis still causes 1.5 million deaths annually and is mainly caused by Mycobacterium tuberculosis complex strains belonging to three evolutionary modern lineages (Lineages 2–4). While Lineage 2 and Lineage 4 virtually conquered the world, Lineage 3 is particularly successful in Northern and Eastern Africa, as well as in Southern Asia, the suspected evolutionary origin of these strains. Here, we sought to understand how Lineage 3 strains came to the African continent. To this end, we performed routine genotyping to characterize over 2500 clinical isolates from 38 countries. We then selected a representative collection of 373 isolates for a whole-genome analysis and a modeling approach to infer the geographic origin of different sublineages. In fact, the origin of Lineage 3 could be located in India, and we found evidence for independent introductions of four distinct sublineages into North/East Africa, in line with known ancient exchanges and migrations between both world regions. Our study illustrates that the evolutionary history of humans and their pathogens are closely connected and further provides a systematic understanding of the genomic diversity of Lineage 3, which could be important for the development of new tuberculosis vaccines or new therapeutics.Mycobacterium tuberculosis complex (MTBC) Lineage 3 (L3) strains are abundant in world regions with the highest tuberculosis burden. To investigate the population structure and the global diversity of this major lineage, we analyzed a dataset comprising 2682 L3 strains from 38 countries over 5 continents, by employing 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats genotyping (MIRU-VNTR) and drug susceptibility testing. We further combined whole-genome sequencing (WGS) and phylogeographic analysis for 373 strains representing the global L3 genetic diversity. Ancestral state reconstruction confirmed that the origin of L3 strains is located in Southern Asia and further revealed multiple independent introduction events into North-East and East Africa. This study provides a systematic understanding of the global diversity of L3 strains and reports phylogenetic variations that could inform clinical trials which evaluate the effectivity of new drugs/regimens or vaccine candidates.Peer Reviewe

Ten New Insights in Climate Science 2023/2024

Non-technical summary: We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems. Technical summary The IPCC Assessment Reports offer the scientific foundation for international climate negotiations and constitute an unmatched resource for climate change researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding across diverse climate change research communities, we have streamlined an annual process to identify and synthesise essential research advances. We collected input from experts on different fields using an online questionnaire and prioritised a set of ten key research insights with high policy relevance. This year we focus on: (1) looming overshoot of the 1.5°C warming limit, (2) urgency of phasing-out fossil fuels, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future of natural carbon sinks, (5) need for join governance of biodiversity loss and climate change, (6) advances in the science of compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems. We first present a succinct account of these Insights, reflect on their policy implications, and offer an integrated set of policy relevant messages. This science synthesis and science communication effort is also the basis for a report targeted to policymakers as a contribution to elevate climate science every year, in time for the UNFCCC COP. Social media summary We highlight recent and policy-relevant advances in climate change research - with input from more than 200 experts 1.</p

Ten new insights in climate science 2023

Non-technical summary. We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems. Technical summary. The Intergovernmental Panel on Climate Change Assessment Reports provides the scientific foundation for international climate negotiations and constitutes an unmatched resource for researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding of climate change across diverse research communities, we have streamlined an annual process to identify and synthesize significant research advances. We collected input from experts on various fields using an online questionnaire and prioritized a set of 10 key research insights with high policy relevance. This year, we focus on: (1) the looming overshoot of the 1.5°C warming limit, (2) the urgency of fossil fuel phase-out, (3) challenges to scale-up carbon dioxide removal, (4) uncertainties regarding future natural carbon sinks, (5) the need for joint governance of biodiversity loss and climate change, (6) advances in understanding compound events, (7) accelerated mountain glacier loss, (8) human immobility amidst climate risks, (9) adaptation justice, and (10) just transitions in food systems. We present a succinct account of these insights, reflect on their policy implications, and offer an integrated set of policy-relevant messages. This science synthesis and science communication effort is also the basis for a policy report contributing to elevate climate science every year in time for the United Nations Climate Change Conference. Social media summary. We highlight recent and policy-relevant advances in climate change research – with input from more than 200 experts

Ten New Insights in Climate Science 2023/2024

Non-technical summary: We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems. Technical summary The IPCC Assessment Reports offer the scientific foundation for international climate negotiations and constitute an unmatched resource for climate change researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding across diverse climate change research communities, we have streamlined an annual process to identify and synthesise essential research advances. We collected input from experts on different fields using an online questionnaire and prioritised a set of ten key research insights with high policy relevance. This year we focus on: (1) looming overshoot of the 1.5°C warming limit, (2) urgency of phasing-out fossil fuels, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future of natural carbon sinks, (5) need for join governance of biodiversity loss and climate change, (6) advances in the science of compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems. We first present a succinct account of these Insights, reflect on their policy implications, and offer an integrated set of policy relevant messages. This science synthesis and science communication effort is also the basis for a report targeted to policymakers as a contribution to elevate climate science every year, in time for the UNFCCC COP. Social media summary We highlight recent and policy-relevant advances in climate change research - with input from more than 200 experts 1.</p

Ten new insights in climate science 2023

RESEARCH TRANSPARENCY AND REPRODUCIBILITY : All potential additional resources such as anonymized data and protocols (if not referenced in the manuscript or provided in the Supplementary material) can be requested via e-mail to the corresponding author.NON-TECHNICHAL SUMMARY. We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems. TECHNICHAL SUMMARY. The Intergovernmental Panel on Climate Change Assessment Reports provides the scientific foundation for international climate negotiations and constitutes an unmatched resource for researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding of climate change across diverse research communities, we have streamlined an annual process to identify and synthesize significant research advances. We collected input from experts on various fields using an online questionnaire and prioritized a set of 10 key research insights with high policy relevance. This year, we focus on: (1) the looming overshoot of the 1.5°C warming limit, (2) the urgency of fossil fuel phase-out, (3) challenges to scale-up carbon dioxide removal, (4) uncertainties regarding future natural carbon sinks, (5) the need for joint governance of biodiversity loss and climate change, (6) advances in understanding compound events, (7) accelerated mountain glacier loss, (8) human immobility amidst climate risks, (9) adaptation justice, and (10) just transitions in food systems. We present a succinct account of these insights, reflect on their policy implications, and offer an integrated set of policy-relevant messages. This science synthesis and science communication effort is also the basis for a policy report contributing to elevate climate science every year in time for the United Nations Climate Change Conference. SOCIAL MEDIA SUMMARY. We highlight recent and policy-relevant advances in climate change research – with input from more than 200 experts.FORMAS, a Swedish Research Council for Sustainable Development, European Union’s Horizon 2020 ERC StG, ForExD, Australian National Environmental Science Program – Climate Systems Hub, Australian Research Council, European Research Council, Ramón y Cajal fellowship, Swiss Foundation, European Union’s Horizon 2020 research and innovation program, Ministry for Business, Innovation & Employment of New Zealand, Helmholtz Association, Ministry of the Environment of Japan, Ministry of Education, Culture, Sports, Science and Technology of Japan, Research Institute for Humanity and Nature, the German Federal Ministry of Education and Research, ERA-Net ForestValue, National Aeronautics and Space Administration, CGIAR, Norway’s International Climate and Forest Initiative (NICFI), World Resource Institute, Bilateral program from the Japan Society for the Promotion of Science, and Helmholtz Initiative and Networking Fund.https://www.cambridge.org/core/journals/global-sustainabilityam2024Agricultural Economics, Extension and Rural DevelopmentSDG-13:Climate actio

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation