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A new international agreement on the conservation and sustainable use of marine biodiversity of areas beyond national jurisdiction (BBNJ) was adopted and subsequently opened for signature in September 2023. Yet on average, recent multilateral environmental agreements (MEAs) have taken over four years to move from signature to entry into force, while ocean-focused MEAs have taken nearly twice as long. Rapid ratification of the BBNJ Agreement is crucial for multiple reasons, not least to achieve the Kunming-Montreal Biodiversity Framework target for 30% of the marine environment to be protected by 2030. It is also vital to fulfill the Agreement’s stated ambition to contribute to a just and equitable future for humankind, considering today’s unprecedented expansion of commercial activities into the ocean.

Abstract Glycemic variability remains frequent in patients with type 1 diabetes treated with insulin pumps. Heterogeneous spreads of insulin infused by pump in the subcutaneous (SC) tissue are suspected but were barely studied. We propose a new real-time ex-vivo method built by combining high-precision imaging with simultaneous pressure measurements, to obtain a real-time follow-up of insulin subcutaneous propagation. Human skin explants from post-bariatric surgery are imaged in a micro-computed tomography scanner, with optimised parameters to reach one 3D image every 5 min during 3 h of 1UI/h infusion. Pressure inside the tubing is recorded. A new index of dispersion (IoD) is introduced and computed upon the segmented 3D insulin depot per time-step. Infusions were hypodermal in 58.3% among 24 assays, others being intradermal or extradermal. Several minor bubbles and one occlusion were observed. IoD increases with time for all injections. Inter-assay variability is the smallest for hypodermal infusions. Pressure elevations were observed, synchronised with air bubbles arrivals in the tissue. Results encourage the use of this method to compare infusion parameters such as pump model, basal rate, catheter characteristics, infusion site characteristics or patient phenotype.

In this work, three commercially available Membrane Electrode Assemblies (MEAs) from Advent Technology Inc. and Danish Power Systems, developed for a use in High Temperature Proton Exchange Membrane Fuel Cell (HT-PEMFC), were tested under various Operating Conditions (OCs): over-stoichiometry of hydrogen gas (1.05, 1.2, 1.35), over-stoichiometry of air gas (1.5, 2, 2.5), gas oxidant (O2 or air) and temperature (140 °C, 160 °C, 180 °C). For each set of operating conditions, a polarization curve (V–I curve) was performed. A semi-empirical and macroscopic (0D) model of the fuel cell voltage was established in steady state conditions in order to model some of these experimental data. The proposed parameterization approach for this model (called here the “multi-VI” approach) is based on the sensitivity to the operating conditions specific to each involved physicochemical phenomenon. According to this method, only one set of parameters is used in order to model all the experimental curves (optimization is performed simultaneously on all curves). A model depending on air over-stoichiometry was developed. The main objective is to validate a simple (0D) and fast-running model that considers the impact of air over-stoichiometry on cell voltage regarding all commercially available MEAs. The obtained results are satisfying with AdventPBI MEA and Danish Power Systems MEA: an average error less than 1.5% and a maximum error around 15% between modelled and measured voltages with only nine parameters to identify. However, the model was not as adapted to Advent TPS® MEA: average error and maximum error around 4% and 21%, respectively. Most of the obtained parameters appear consistent regardless of the OCs. The predictability of the model was also validated in the explored domain during the sensibility study with an interesting accuracy for 27 OCs after being trained on only nine curves. This is attractive for industrial application, since it reduces the number of experiments, hence the cost of model development, and is potentially applicable to all commercial HT-PEMFC MEAs.

In the present work, we studied whether the exposure of synthetic seawater with anaerobic sulphate-reducing bacteria (SRB) on some steel samples generates a bacterial biofilm in their surfaces. Bare steel belonging to a mooring chain as well as two coating systems applied on the steel surface were studied: polyurethane (PU) and thermally sprayed aluminium (TSA) with and without an epoxy-based sealant. After 30 days of immersion in SRB-inoculated synthetic seawater, a bacterial count was attained, and the samples were observed using scanning electron microscopy (SEM) and locally analysed using X-ray scattered energy spectroscopy (EDS). A biofilm developed on every tested surface (continuous or in the form of pustules), with evidence of metabolic activity of the SRB. Finally, a mechanism of degradation for TSA in the presence of SRB is proposed for environments with a high concentration of bacteria.

The decarbonization of air mobility requires the decarbonization of its energy. While biofuels will play an important role, other low-carbon energy carriers based on electricity are considered, such as battery electrification and liquid hydrogen (LH2) or eFuel, a hydrogen-based energy carrier. Each energy carrier has its own conversion steps and losses and its own integration effects with aircraft. These combinations lead to different energy requirements and must be understood in order to compare their cost and CO2 emissions. Since they are all electricity-based, this study compares these energy carriers using the well-to-rotor methodology when applied to a standard vertical take-off and landing (VTOL) air mobility mission. This novel approach allows one to understand that the choice of energy carrier dictates the propulsive system architecture, leading to integration effects with aircraft, which can significantly change the energy required for the same mission, increasing it from 400 to 2665 kWh. These deviations led to significant differences in CO2 emissions and costs. Battery electrification is impacted by battery manufacturing but has the lowest electricity consumption. This is an optimum solution, but only until the battery weight can be lifted. In all scenarios, eFuel is more efficient than LH2. We conclude that using the most efficient molecule in an aircraft can compensate for the extra energy cost spent on the ground. Finally, we found that, for each of these energy carriers, it is the electricity carbon intensity and price which will dictate the cost and CO2 emissions of an air mobility mission.

BackgroundSudomotor dysfunction is one of the earliest manifestations of small fiber neuropathy (SFN), reflecting the alteration of sympathetic C fiber innervation of the sweat glands. Among other techniques, such innervation can be assessed by measuring electrochemical skin conductance (ESC) in microsiemens (μS). In this study, ESC was measured at the feet to detect distal SFN. For this objective, the performance of a new device, the Body Scan® (Withings, France), intended for home use, was compared with that of a reference device, the Sudoscan® (Impeto Medical, France), which requires a hospital setting.MethodsIn patients with diabetes with or without neuropathy or non-diabetic patients with lower-limb neuropathy, the diagnostic performance of the Body Scan® measurement was assessed by calculating its sensitivity (Se) and specificity (Sp) to detect at least moderate SFN (Se70 and Sp70), defined by a value of feet ESC ≤ 70 μS and > 50 μS on the Sudoscan® measure, or severe SFN (Se50 and Sp50), defined by a value of feet ESC ≤ 50 μS on the Sudoscan® measure. The agreement between the two devices was assessed with the analysis of Bland–Altman plots, mean absolute error (MAE), and root mean squared error (RMSE) calculations. The repeatability of the measurements was also compared between the two devices.ResultsA total of 147 patients (52% men, mean age 59 years old, 76% diabetic) were included in the analysis. The sensitivity and specificity to detect at least moderate or severe SFN were: Se70 = 0.91 ([0.83, 0.96]), Sp70 = 0.97 ([0.88, 0.99]), Se50 = 0.91 ([0.80, 0.98]), and Sp50 = 0.99 ([0.94, 1]), respectively. The bias and 95% limits of agreement were 1.5 [−5.4, 8.4]. The MAE was 2.9 and the RMSE 3.8. The intra-sample variability was 2.0 for the Body Scan® and 2.3 for the Sudoscan®.ConclusionThe ESC measurements provided by the Body Scan® were in almost perfect agreement with those provided by the reference device, the Sudoscan®, which validates the accuracy of the Body Scan® for the detection of SFN. By enabling simple, rapid, and autonomous use by the patient at home, this new technique will facilitate screening and monitoring of SFN in daily practice.Clinical trial registrationClinicalTrials.gov, identifier NCT05178459.

Abstract Mesophotic marine ecosystems are characterized by lower light penetration supporting specialized fish fauna. Due to their depths (−30–−150 m), accessibility is challenging, and the structure of mesophotic fish assemblages is generally less known than either shallow reefs or deep zones with soft bottoms which are generally trawled. Environmental DNA metabarcoding from seawater filtered in situ could improve our ability to monitor the diversity of mesophotic ecosystems. Here, we developed and tested a submersible standalone pumping device allowing targeted marine water filtering to explore the biodiversity of two mesophotic ecosystems, one temperate along the Provence coast in the North‐Western Mediterranean Sea and one tropical at the seamount La Pérouse in the Western Indian Ocean. We filtered water samples from depths ranging between 0 and 200 m in the Mediterranean Sea and between 60 and 140 m in the Indian Ocean and applied a metabarcoding protocol using the teleo primer pair targeting the 12S mitochondrial rDNA (Actinopterygii and Chondrichthyes). For both study regions, our eDNA surveys were able to recover highly diverse fish assemblages, and the compositional analysis of eDNA samples showed both a marked signal of fish compositional turnover and overlapping taxa between depth zones. Further, we observed that a substantial number of species were found in samples collected in depths beyond their reported depth range suggesting an underestimation of species' depth tolerances. eDNA metabarcoding should thus complement existing knowledge of species' geographic distributions across space and depth. Overall, our results demonstrate the potential of eDNA metabarcoding for future mesophotic surveys as it allows fast and broad biodiversity assessment.

Sub/millimeter galaxies are a key population for the study of galaxy evolution because the majority of star formation at high redshifts occurred in galaxies deeply embedded in dust. To search for this population, we have performed an extensive survey with Atacama Large Millimeter/submillimeter Array (ALMA), called the ALMA Lensing Cluster Survey (ALCS). This survey covers 133 arcmin ^2 area and securely detects 180 sources at z ∼ 0.5–6 with a flux limit of ∼0.2 mJy at 1.2 mm. Here, we report the results of multiwavelength spectral energy distribution analysis of the whole ALCS sample, utilizing the observed-frame UV to millimeter photometry. We find that the majority of the ALCS sources lie on the star-forming main sequence, with a smaller fraction showing intense starburst activities. The ALCS sample contains high infrared-excess sources ( $\mathrm{IRX}=\mathrm{log}({L}_{\mathrm{dust}}/{L}_{\mathrm{UV}})\gt 1$ ), including two extremely dust-obscured galaxies (IRX > 5). We also confirm that the ALCS sample probes a broader range in lower dust mass than conventional submillimeter galaxy samples in the same redshift range. We identify six heavily obscured active galactic nucleus (AGN) candidates that are not detected in the archival Chandra data in addition to the three X-ray AGNs reported by Uematsu et al. (2023). The inferred AGN luminosity density shows a possible excess at z = 2–3 compared with that determined from X-ray surveys below 10 keV.

In this work, a commercially available membrane electrode assembly from Advent Technology Inc., developed for use in high-temperature proton exchange membrane fuel cells, was tested under various operating conditions (OCs) according to a sensibility study with three OCs varying on three levels: hydrogen gas over-stoichiometry (1.05, 1.2, 1.35), air gas over-stoichiometry (1.5, 2, 2.5), and temperature (140 °C, 160 °C, 180 °C). A polarization curve (V-I curve) was performed for each set of operating conditions (27 V-I curves in total). A semi-empirical and macroscopic (0D) model of the cell voltage was developed in steady-state conditions to model these experimental data. With the proposed parameterization approach, only one set of parameters is used in order to model all the experimental curves (simultaneous optimization with 27 curves). Thus, an air over-stoichiometry-dependent model was developed. The obtained results are promising between 0.2 and 0.8 A·cm−2: an average error less than 1.5% and a maximum error around 7% between modeled and measured voltages with only 9 parameters to identify. The obtained parameters appear consistent, regardless of the OCs. The proposed approach with only one set of parameters seems to be an interesting way to converge towards the uniqueness of consistent parameters.

Abstract The biosphere crisis requires changes to existing business practices. We ask how corporations can become sustainability leaders, when constrained by multiple barriers to collaboration for biosphere stewardship. We describe how scientists motivated, inspired and engaged with ten of the world’s largest seafood companies, in a collaborative process aimed to enable science-based and systemic transformations (2015–2021). CEOs faced multiple industry crises in 2015 that incentivized novel approaches. New scientific insights, an invitation to collaborate, and a bold vision of transformative change towards ocean stewardship, created new opportunities and direction. Co-creation of solutions resulted in new knowledge and trust, a joint agenda for action, new capacities, international recognition, formalization of an organization, increased policy influence, time-bound goals, and convergence of corporate change. Independently funded scientists helped remove barriers to cooperation, provided means for reflection, and guided corporate strategies and actions toward ocean stewardship. By 2021, multiple individuals exercised leadership and the initiative had transitioned from preliminary and uncomfortable conversations, to a dynamic, operational organization, with capacity to perform global leadership in the seafood industry. Mobilizing transformational agency through learning, collaboration, and innovation represents a cultural evolution with potential to redirect and accelerate corporate action, to the benefit of business, people and the planet.

An inferential approach to compactness/finitude in propositional logic.

Abstract Quantifying fish species diversity in rich tropical marine environments remains challenging. Environmental DNA (eDNA) metabarcoding is a promising tool to face this challenge through the filtering, amplification, and sequencing of DNA traces from water samples. However, because eDNA concentration is low in marine environments, the reliability of eDNA to detect species diversity can be limited. Using an eDNA metabarcoding approach to identify fish Molecular Taxonomic Units (MOTUs) with a single 12S marker, we aimed to assess how the number of sampling replicates and filtered water volume affect biodiversity estimates. We used a paired sampling design of 30 L per replicate on 68 reef transects from 8 sites in 3 tropical regions. We quantified local and regional sampling variability by comparing MOTU richness, compositional turnover, and compositional nestedness. We found strong turnover of MOTUs between replicated pairs of samples undertaken in the same location, time, and conditions. Paired samples contained non‐overlapping assemblages rather than subsets of one another. As a result, non‐saturated localized diversity accumulation curves suggest that even 6 replicates (180 L) in the same location can underestimate local diversity (for an area

In a context of marine biodiversity erosion, the need to better understand the effects of overfishing stands out. New genetic techniques such as environmental DNA (eDNA) metabarcoding have emerged and allow the detection of a wider range of species compared to conventional methods, but still fall short of providing reliable abundance estimations and subsequent ecological indicators. In this paper, we propose a combination of metabarcoding and quantitative polymerase chain reaction to obtain the quantity of eDNA molecules per species. This method was used inside and outside six no-take Mediterranean marine reserves to measure the effect of the protection on fish species and build a new indicator. Even if the total quantity of fish eDNA molecules was not different between the inside and outside of the reserves, we detected that cryptobenthic fish eDNA was significantly associated to the outside of reserves. Based on this observation, we propose a novel ecological indicator, the Demerso-pelagic to Benthic fish eDNA Ratio (DeBRa), taking advantage of the eDNA capacity to detect cryptobenthic reef fishes which are often missed by classical surveys. The DeBRa was significantly higher inside reserves, reflecting a higher relative quantity of eDNA molecules belonging to pelagic and demersal fishes under protection against fishing, therefore it appears to be a reliable eDNA-based indicator of human pressure. Furthermore, the DeBRa was not sensitive to habitat or environmental variations and does not require a complete reference database of eDNA sequences since it can rely on sequences assigned at the genus or family scale if possible and necessary.

Abstract Monitoring large marine mammals is challenging due to their low abundances in general, an ability to move over large distances and wide geographical range sizes. The distribution of the pygmy (Kogia breviceps) and dwarf (Kogia sima) sperm whales is informed by relatively rare sightings, which does not permit accurate estimates of their distribution ranges. Hence, their conservation status has long remained Data Deficient (DD) in the Red list of the International Union for Conservation of Nature (IUCN), which prevent appropriate conservation measures. Environmental DNA (eDNA) metabarcoding uses DNA traces left by organisms in their environments to detect the presence of targeted taxon, and is here proved to be useful to increase our knowledge on the distribution of rare but emblematic megafauna. Retrieving eDNA from filtered surface water provides the first detection of the Dwarf sperm whale (Kogia sima) around the remote Malpelo island (Colombia). Environmental DNA collected during oceanic missions can generate better knowledge on rare but emblematic animals even in regions that are generally well sampled for other taxa.

Abstract Environmental DNA (eDNA) analysis is a revolutionary method to monitor marine biodiversity from animal DNA traces. Examining the capacity of eDNA to provide accurate biodiversity measures in species‐rich ecosystems such as coral reefs is a prerequisite for their application in long‐term monitoring. Here, we surveyed two Colombian tropical marine reefs, the island of Providencia and Gayraca Bay near Santa Marta, using eDNA and underwater visual census (UVC) methods. We collected a large quantity of surface water (30 L per filter) above the reefs and applied a metabarcoding protocol using three different primer sets targeting the 12S mitochondrial DNA, which are specific to the vertebrates Actinopterygii and Elasmobranchii. By assigning eDNA sequences to species using a public reference database, we detected the presence of 107 and 85 fish species, 106 and 92 genera, and 73 and 57 families in Providencia and Gayraca Bay, respectively. Of the species identified using eDNA, 32.7% (Providencia) and 18.8% (Gayraca) were also found in the UVCs. We further found congruence in genus and species richness and abundance between eDNA and UVC approaches in Providencia but not in Gayraca Bay. Mismatches between eDNA and UVC had a phylogenetic and ecological signal, with eDNA detecting a broader phylogenetic diversity and more effectively detecting smaller species, pelagic species and those in deeper habitats. Altogether, eDNA can be used for fast and broad biodiversity surveys and is applicable to species‐rich ecosystems in the tropics, but improved coverage of the reference database is required before this new method could serve as an effective complement to traditional census methods.

Humanity has never benefited more from the ocean as a source of food, livelihoods, and well-being, yet on a global scale this has been accompanied by trajectories of degradation and persistent inequity. Awareness of this has spurred policymakers to develop an expanding network of ocean governance instruments, catalyzed civil society pressure on the public and private sector, and motivated engagement by the general public as consumers and constituents. Among local communities, diverse examples of stewardship have rested on the foundation of care, knowledge and agency. But does an analog for stewardship exist in the context of globally active multinational corporations? Here, we consider the seafood industry and its efforts to navigate this new reality through private governance. We examine paradigmatic events in the history of the sustainable seafood movement, from seafood boycotts in the 1970s through to the emergence of certification measures, benchmarks, and diverse voluntary environmental programs. We note four dimensions of stewardship in which efforts by actors within the seafood industry have aligned with theoretical concepts of stewardship, which we describe as (1) moving beyond compliance, (2) taking a systems perspective, (3) living with uncertainty, and (4) understanding humans as embedded elements of the biosphere. In conclusion, we identify emerging stewardship challenges for the seafood industry and suggest the urgent need to embrace a broader notion of ocean stewardship that extends beyond seafood.

Objectives:. The determinants of decisions to limit life support (withholding or withdrawal) in ventilated stroke patients have been evaluated mainly for patients with intracranial hemorrhages. We aimed to evaluate the frequency of life support limitations in ventilated ischemic and hemorrhagic stroke patients compared with a nonbrain-injured population and to determine factors associated with such decisions. Design:. Multicenter prospective French observational study. Setting:. Fourteen ICUs of the French OutcomeRea network. PATIENTS:. From 2005 to 2016, we included stroke patients and nonbrain-injured patients requiring invasive ventilation within 24 hours of ICU admission. INTERVENTION:. None. MEASUREMENTS AND MAIN RESULTS:. We identified 373 stroke patients (ischemic, n = 167 [45%]; hemorrhagic, n = 206 [55%]) and 5,683 nonbrain-injured patients. Decisions to limit life support were taken in 41% of ischemic stroke cases (vs nonbrain-injured patients, subdistribution hazard ratio, 3.59 [95% CI, 2.78–4.65]) and in 33% of hemorrhagic stroke cases (vs nonbrain-injured patients, subdistribution hazard ratio, 3.9 [95% CI, 2.97–5.11]). Time from ICU admission to the first limitation was longer in ischemic than in hemorrhagic stroke (5 [3–9] vs 2 d [1–6] d; p < 0.01). Limitation of life support preceded ICU death in 70% of ischemic strokes and 45% of hemorrhagic strokes (p < 0.01). Life support limitations in ischemic stroke were increased by a vertebrobasilar location (vs anterior circulation, subdistribution hazard ratio, 1.61 [95% CI, 1.01–2.59]) and a prestroke modified Rankin score greater than 2 (2.38 [1.27–4.55]). In hemorrhagic stroke, an age greater than 70 years (2.29 [1.43–3.69]) and a Glasgow Coma Scale score less than 8 (2.15 [1.08–4.3]) were associated with an increased risk of limitation, whereas a higher nonneurologic admission Sequential Organ Failure Assessment score was associated with a reduced risk (per point, 0.89 [0.82–0.97]). Conclusions:. In ventilated stroke patients, decisions to limit life support are more than three times more frequent than in nonbrain-injured patients, with different timing and associated risk factors between ischemic and hemorrhagic strokes.

Objectives:. About 5% of patients with coronavirus disease-2019 are admitted to the ICU for acute hypoxemic respiratory failure. Opinions differ on whether invasive mechanical ventilation should be used as first-line therapy over noninvasive oxygen support. The aim of the study was to assess the effect of early invasive mechanical ventilation in coronavirus disease-2019 with acute hypoxemic respiratory failure on day-60 mortality. Design:. Multicenter prospective French observational study. Setting:. Eleven ICUs of the French OutcomeRea network. Patients:. Coronavirus disease-2019 patients with acute hypoxemic respiratory failure (Pao2/Fio2 ≤ 300 mm Hg), without shock or neurologic failure on ICU admission, and not referred from another ICU or intermediate care unit were included. Intervention:. We compared day-60 mortality in patients who were on invasive mechanical ventilation within the first 2 calendar days of the ICU stay (early invasive mechanical ventilation group) and those who were not (nonearly invasive mechanical ventilation group). We used a Cox proportional-hazard model weighted by inverse probability of early invasive mechanical ventilation to determine the risk of death at day 60. Measurement and Main Results:. The 245 patients included had a median (interquartile range) age of 61 years (52–69 yr), a Simplified Acute Physiology Score II score of 34 mm Hg (26–44 mm Hg), and a Pao2/Fio2 of 121 mm Hg (90–174 mm Hg). The rates of ICU-acquired pneumonia, bacteremia, and the ICU length of stay were significantly higher in the early (n = 117 [48%]) than in the nonearly invasive mechanical ventilation group (n = 128 [52%]), p < 0.01. Day-60 mortality was 42.7% and 21.9% in the early and nonearly invasive mechanical ventilation groups, respectively. The weighted model showed that early invasive mechanical ventilation increased the risk for day-60 mortality (weighted hazard ratio =1.74; 95% CI, 1.07–2.83, p=0.03). Conclusions:. In ICU patients admitted with coronavirus disease-2019-induced acute hypoxemic respiratory failure, early invasive mechanical ventilation was associated with an increased risk of day-60 mortality. This result needs to be confirmed.

Research on pathways to reducing plastic pollution often concludes that greater action is needed by the private sector. Yet the private sector is not a monolithic or homogeneous entity. We compiled a novel library of 2,317 corporate reports from the world's 200 largest companies, by revenue, over a ten-year period (2010–2019) and used text mining tools to identify pronounced regional and sectoral variability in the extent to which plastic waste and pollution is of material importance to corporate operations. The results show a dominant focus on recycling, with far less attention to the other stages of the life cycle of plastic. While green clubs have emerged in recent years to mobilize voluntary actions by companies seeking to position themselves as leaders in this context, we see regional and sectoral gaps in green club membership, as well as a tendency for members to be those companies that already had a history of reporting on plastics issues. This analysis provides a starting point for a more nuanced consideration of the private sector's role in addressing plastic pollution, and suggests sectors and regions for prioritization by policymakers and civil society actors seeking to broaden the range of committed corporate actors.

Abstract Early in the COVID‐19 pandemic, type 2 diabetes (T2D) was marked as a risk factor for severe disease and mortality. Inflammation is central to the aetiology of both conditions where variations in immune responses can mitigate or aggravate disease course. Identifying at‐risk groups based on immunoinflammatory signatures is valuable in directing personalised care and developing potential targets for precision therapy. This observational study characterised immunophenotypic variation associated with COVID‐19 severity in T2D. Broad‐spectrum immunophenotyping quantified 15 leucocyte populations in peripheral circulation from a cohort of 45 hospitalised COVID‐19 patients with and without T2D. Lymphocytopenia and specific loss of cytotoxic CD8+ lymphocytes were associated with severe COVID‐19 and requirement for intensive care in both non‐diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia restricted to classical CD14Hi CD16− monocytes was specifically associated with severe COVID‐19 in patients with T2D requiring intensive care. Increased expression of inflammatory markers reminiscent of the type 1 interferon pathway (IL6, IL8, CCL2, INFB1) underlaid the immunophenotype associated with T2D. These immunophenotypic and hyperinflammatory changes may contribute to increased voracity of COVID‐19 in T2D. These findings allow precise identification of T2D patients with severe COVID‐19 as well as provide evidence that the type 1 interferon pathway may be an actionable therapeutic target for future studies.