Expression of the plasma membrane citrate carrier (pmCiC) in human cancerous tissues—correlation with tumour aggressiveness

We have recently shown that cancer cells of various origins take up extracellular citrate through the plasma membrane citrate carrier (pmCiC), a specific plasma membrane citrate transporter. Extracellular citrate is required to support cancer cell metabolism, in particular fatty acid synthesis, mitochondrial activity, protein synthesis and histone acetylation. In addition, cancer cells tend to acquire a metastatic phenotype in the presence of extracellular citrate. Our recent study also showed that cancer-associated stromal cells synthesise and release citrate and that this process is controlled by cancer cells. In the present study, we evaluated the expression of pmCiC, fibroblast activation protein-α (FAP) and the angiogenesis marker cluster of differentiation 31 (CD31) in human cancer tissues of different origins. In the cohort studied, we found no correlation between disease stage and the expression of FAP or CD31. However, we have identified a clear correlation between pmCiC expression in cancer cells and cancer-associated stroma with tumour stage. It can be concluded that pmCiC is increased in cancer cells and in cancer-supporting cells in the tumour microenvironment at the later stages of cancer development, particularly at the metastatic sites. Therefore, pmCiC expression has the potential to serve as a prognostic marker, although further studies are needed

Impact of Hyponatremia after Renal Transplantation on Decline of Renal Function, Graft Loss and Patient Survival: A Prospective Cohort Study.

Hyponatremia is one of the most common electrolyte disorders observed in hospitalized and ambulatory patients. Hyponatremia is associated with increased falls, fractures, prolonged hospitalisation and mortality. The clinical importance of hyponatremia in the renal transplant field is not well established, so the aim of this study was to determine the relationships between hyponatremia and mortality as main outcome and renal function decline and graft loss as secondary outcome among a prospective cohort of renal transplant recipients. This prospective cohort study included 1315 patients between 1 May 2008 and 31 December 2014. Hyponatremia was defined as sodium concentration below 136 mmol/L at 6 months after transplantation. The main endpoint was mortality. A secondary composite endpoint was also defined as: rapid decline in renal function (≥5 mL/min/1.73 m <sup>2</sup> drop of the eGFR/year), graft loss or mortality. Mean sodium was 140 ± 3.08 mmol/L. 97 patients displayed hyponatremia with a mean of 132.9 ± 3.05 mmol/L. Hyponatremia at 6 months after transplantation was associated neither with mortality (HR: 1.02; p = 0.97, 95% CI: 0.47-2.19), nor with the composite outcome defined as rapid decline in renal function, graft loss or mortality (logrank test p = 0.9). Hyponatremia 6 months after transplantation is not associated with mortality in kidney allograft patients

Climate Change and Weather Extremes in the Eastern Mediterranean and Middle East

Observation‐based and modeling studies have identified the Eastern Mediterranean and Middle East (EMME) region as a prominent climate change hotspot. While several initiatives have addressed the impacts of climate change in parts of the EMME, here we present an updated assessment, covering a wide range of timescales, phenomena and future pathways. Our assessment is based on a revised analysis of recent observations and projections and an extensive overview of the recent scientific literature on the causes and effects of regional climate change. Greenhouse gas emissions in the EMME are growing rapidly, surpassing those of the European Union, hence contributing significantly to climate change. Over the past half‐century and especially during recent decades, the EMME has warmed significantly faster than other inhabited regions. At the same time, changes in the hydrological cycle have become evident. The observed recent temperature increase of about 0.45°C per decade is projected to continue, although strong global greenhouse gas emission reductions could moderate this trend. In addition to projected changes in mean climate conditions, we call attention to extreme weather events with potentially disruptive societal impacts. These include the strongly increasing severity and duration of heatwaves, droughts and dust storms, as well as torrential rain events that can trigger flash floods. Our review is complemented by a discussion of atmospheric pollution and land‐use change in the region, including urbanization, desertification and forest fires. Finally, we identify sectors that may be critically affected and formulate adaptation and research recommendations toward greater resilience of the EMME region to climate change. The Eastern Mediterranean and Middle East is warming almost two times faster than the global average and other inhabited parts of the world Climate projections indicate a future warming, strongest in summers. Precipitation will likely decrease, particularly in the Mediterranean Virtually all socio‐economic sectors will be critically affected by the projected changes The Eastern Mediterranean and Middle East is warming almost two times faster than the global average and other inhabited parts of the world Climate projections indicate a future warming, strongest in summers. Precipitation will likely decrease, particularly in the Mediterranean Virtually all socio‐economic sectors will be critically affected by the projected change

Climate Change and Weather Extremes in the Eastern Mediterranean and Middle East

Observation-based and modeling studies have identified the Eastern Mediterranean and Middle East (EMME) region as a prominent climate change hotspot. While several initiatives have addressed the impacts of climate change in parts of the EMME, here we present an updated assessment, covering a wide range of timescales, phenomena and future pathways. Our assessment is based on a revised analysis of recent observations and projections and an extensive overview of the recent scientific literature on the causes and effects of regional climate change. Greenhouse gas emissions in the EMME are growing rapidly, surpassing those of the European Union, hence contributing significantly to climate change. Over the past half-century and especially during recent decades, the EMME has warmed significantly faster than other inhabited regions. At the same time, changes in the hydrological cycle have become evident. The observed recent temperature increase of about 0.45 degrees C per decade is projected to continue, although strong global greenhouse gas emission reductions could moderate this trend. In addition to projected changes in mean climate conditions, we call attention to extreme weather events with potentially disruptive societal impacts. These include the strongly increasing severity and duration of heatwaves, droughts and dust storms, as well as torrential rain events that can trigger flash floods. Our review is complemented by a discussion of atmospheric pollution and land-use change in the region, including urbanization, desertification and forest fires. Finally, we identify sectors that may be critically affected and formulate adaptation and research recommendations toward greater resilience of the EMME region to climate change.Peer reviewe

Governing Artificial Intelligence to benefit the UN Sustainable Development Goals

Big Tech's unregulated roll-out out of experimental AI poses risks to the achievement of the UN Sustainable Development Goals (SDGs), with particular vulnerability for developing countries. The goal of financial inclusion is threatened by the imperfect and ungoverned design and implementation of AI decision-making software making important financial decisions affecting customers. Automated decision-making algorithms have displayed evidence of bias, lack ethical governance, and limit transparency in the basis for their decisions, causing unfair outcomes and amplify unequal access to finance. Poverty reduction and sustainable development targets are risked by Big Tech's potential exploitation of developing countries by using AI to harvest data and profits. Stakeholder progress toward preventing financial crime and corruption is further threatened by potential misuse of AI. In the light of such risks, Big Tech's unscrupulous history means it cannot be trusted to operate without regulatory oversight. The article proposes effective pre-emptive regulatory options to minimize scenarios of AI damaging the SDGs. It explores internationally accepted principles of AI governance, and argues for their implementation as regulatory requirements governing AI developers and coders, with compliance verified through algorithmic auditing. Furthermore, it argues that AI governance frameworks must require a benefit to the SDGs. The article argues that proactively predicting such problems can enable continued AI innovation through well-designed regulations adhering to international principles. It highlights risks of unregulated AI causing harm to human interests, where a public and regulatory backlash may result in over-regulation that could damage the otherwise beneficial development of AI.Qatar National Research Fund, Grant/Award Number: NPRP 11S-1119-17001

Validation of resting full-cycle ratio and diastolic pressure ratio with [15O]H2O positron emission tomography myocardial perfusion

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min−1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD

Grand Challenges in global eye health: a global prioritisation process using Delphi method

Background: We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods: Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings: Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation: This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenges. Funding: The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity, National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The Seva Foundation, British Council for the Prevention of Blindness, and Christian Blind Mission. Translations: For the French, Spanish, Chinese, Portuguese, Arabic and Persian translations of the abstract see Supplementary Materials section

The Circadian Neuropeptide PDF Signals Preferentially through a Specific Adenylate Cyclase Isoform AC3 in M Pacemakers of Drosophila

To synchronize a network of pacemakers in the Drosophila brain, a neuropeptide receptor specifically associates with adenylate cyclase 3 to create a “circadian signalosome.

Recognizing animal personhood in compassionate conservation

Compassionate conservation is based on the ethical position that actions taken to protect biodiversity should be guided by compassion for all sentient beings. Critics argue that there are 3 core reasons harming animals is acceptable in conservation programs: the primary purpose of conservation is biodiversity protection; conservation is already compassionate to animals; and conservation should prioritize compassion to humans. We used argument analysis to clarify the values and logics underlying the debate around compassionate conservation. We found that objections to compassionate conservation are expressions of human exceptionalism, the view that humans are of a categorically separate and higher moral status than all other species. In contrast, compassionate conservationists believe that conservation should expand its moral community by recognizing all sentient beings as persons. Personhood, in an ethical sense, implies the individual is owed respect and should not be treated merely as a means to other ends. On scientific and ethical grounds, there are good reasons to extend personhood to sentient animals, particularly in conservation. The moral exclusion or subordination of members of other species legitimates the ongoing manipulation and exploitation of the living worlds, the very reason conservation was needed in the first place. Embracing compassion can help dismantle human exceptionalism, recognize nonhuman personhood, and navigate a more expansive moral space

Grand Challenges in global eye health: a global prioritisation process using Delphi method

Background We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenge