Histamine dihydrochloride and low-dose interleukin-2 has antileukemic efficacy in NPM1-mutated and myelomonocytic/monocytic acute myeloid leukemia.

Not available.

Rapid Cytokine Release Assays for Analysis of Severe Acute Respiratory Syndrome Coronavirus 2-Specific T Cells in Whole Blood.

BACKGROUND: Waning of immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complicates the diagnosis of past infection. The durability of T-cell memory against SARS-CoV-2 remains unclear, and most current T-cell protocols are unsuited for large-scale automation. METHODS: Whole-blood samples from 31 patients with verified past coronavirus disease 2019 (COVID-19) and 46 controls, of whom 40 received COVID-19 vaccine, were stimulated with peptides spanning the nucleocapsid (NC) or spike 1 (S1) regions of SARS-CoV-2 and analyzed for interferon γ in supernatant plasma. Diagnostic accuracy of these assays was evaluated against serum anti-NC and anti-receptor-binding domain S1-IgG. RESULTS: Induction of interferon γ in whole blood by NC or S1 peptides diagnosed past COVID-19 with high accuracy (area under the receiver operating characteristic curve, 0.93 and 0.95, respectively). In accordance with previous studies, NC-IgG levels rapidly waned with only 5 of 17 patients (29%) remaining seropositive >180 days after infection. By contrast, NC peptide-induced T-cell memory responses remained in 13 of 17 study participants (76%) >180 days after infection (P = .01 for comparison with NC-IgG; McNemar test). After 2 vaccine doses, all 18 donors exhibited S1-specific T-cell memory. CONCLUSIONS: Cytokine release assays for the monitoring of T-cell memory in whole blood may be useful for evaluating complications following unverified past COVID-19 and for long-term assessment of vaccine-induced T-cell immunity. CLINICAL TRIALS REGISTRATION: EudraCT 2021-000349-42.

To embrace and be present: The lived experiences of nurse-led consultations in Sweden from the perspective of pediatric nurses.

PURPOSE: This study describes the lived experiences of nurse-led consultations in pediatric emergency departments from the perspective of pediatric nurses. DESIGN AND METHODS: A descriptive qualitative study with a reflective lifeworld research approach was used to explore nurses' experiences of nurse-led consultations. The study was conducted through meaning-oriented individual interviews with ten pediatric nurses. RESULTS: The results are grouped into four themes: (a) embracing the encounter and being touched by it; (b) having time to be present and committed; (c) having the ability and trusting in one's intuition; and (d) negotiating between families' wishes and the organization's guidelines. CONCLUSIONS: Our study shows that nurse-led consultations conducted in separate nurse-led reception areas promote a positive experience of the consultations from the perspective of pediatric nurses. In a nurse-led consultation, a nurse's confidence in their ability to provide care is connected to time, broad skills and knowledge, and a supportive organization. PRACTICE IMPLICATIONS: As the rising global population increases the demand for healthcare services, pediatric emergency departments must streamline their services to provide patient-safe, high-quality health care. Nurse-led consultations are an effective means of meeting these growing demands. This study contributes to an understanding of pediatric nurses' experiences at both the individual level and a more structured level, namely that families' wishes and an organization's guidelines do not always coincide.

Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases.

Under normal physiological conditions the brain primarily utilizes glucose for ATP generation. However, in situations where glucose is sparse, e.g., during prolonged fasting, ketone bodies become an important energy source for the brain. The brain's utilization of ketones seems to depend mainly on the concentration in the blood, thus many dietary approaches such as ketogenic diets, ingestion of ketogenic medium-chain fatty acids or exogenous ketones, facilitate significant changes in the brain's metabolism. Therefore, these approaches may ameliorate the energy crisis in neurodegenerative diseases, which are characterized by a deterioration of the brain's glucose metabolism, providing a therapeutic advantage in these diseases. Most clinical studies examining the neuroprotective role of ketone bodies have been conducted in patients with Alzheimer's disease, where brain imaging studies support the notion of enhancing brain energy metabolism with ketones. Likewise, a few studies show modest functional improvements in patients with Parkinson's disease and cognitive benefits in patients with-or at risk of-Alzheimer's disease after ketogenic interventions. Here, we summarize current knowledge on how ketogenic interventions support brain metabolism and discuss the therapeutic role of ketones in neurodegenerative disease, emphasizing clinical data.

Experimental non-severe hypoglycaemia substantially impairs cognitive function in type 2 diabetes: a randomised crossover trial.

AIMS/HYPOTHESIS: Previous studies have demonstrated a relationship between cognitive impairment and hypoglycaemia (<3 mmol/l). This study hypothesised that non-severe insulin-induced hypoglycaemia reduces cognitive function in individuals with type 2 diabetes. METHODS: In this randomised crossover study, 25 participants with type 2 diabetes attended two experimental visits with hyperinsulinaemic glucose clamping: one hypoglycaemic clamp (plasma glucose 3.0 ± 0.2 mmol/l) and one euglycaemic clamp (plasma glucose 6.0 ± 0.2 mmol/l). Participants were eligible if their diabetes was treated with diet or glucose-lowering medications (except sulfonylureas or insulin), age was 35-70 years, BMI was 23-35 kg/m2 and HbA1c was below 75 mmol/mol (9%). Cognitive function was assessed with a neurocognitive test battery measuring verbal memory, executive function, sustained attention and psychomotor speed. From the examined cognitive domains, a global cognition score was constructed estimating global cognition. A measurement for psychomotor speed was selected as the primary outcome. Participants and people assessing the outcomes were blinded to group assignment. RESULTS: Cognitive performance was impaired during hypoglycaemia with a mean score in the primary outcome test, Symbol Digit Modalities Test measuring psychomotor speed, of 48.7 ± 9.8 (hypoglycaemia) vs 56.6 ± 12.0 (euglycaemia); i.e. a change of -7.9 points (95% CI -10.9, -4.9; p < 0.0001). In addition, hypoglycaemia reduced global cognitive score by -0.7 (95% CI -0.9, -0.6; p < 0.0001). A stable glucose plateau was achieved during both experimental visits. For the hypoglycaemic clamp, mean plasma glucose concentration (± SD) during neurocognitive testing was 3.1 (± 0.3) mmol/l. Age, sex, fasting C-peptide, counter-regulatory hormones and the severity of hypoglycaemic symptoms did not influence cognitive function. CONCLUSIONS/INTERPRETATION: Acute non-severe hypoglycaemia (mean plasma glucose 3.1 mmol/l) has a substantial negative impact on cognitive function in individuals with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03014011. FUNDING: The study was supported in part by a research grant from the Investigator Initiated Studies Program of Merck Sharp & Dohme Corp (MSD-MA-NORD-007-01). The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme Corp. Funding was also received from Skibsreder Per Henriksen, R. og hustrus Foundation, The Danish Alzheimer Foundation and Savværksejer Jeppe Juhl og hustrus Foundation.

JAK-STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma.

Myxoid liposarcoma (MLS) shows extensive intratumoural heterogeneity with distinct subpopulations of tumour cells. Despite improved survival of MLS patients, existing therapies have shortcomings as they fail to target all tumour cells. The nature of chemotherapy-resistant cells in MLS remains unknown. Here, we show that MLS cell lines contained subpopulations of cells that can form spheres, efflux Hoechst dye and resist doxorubicin, all properties attributed to cancer stem cells (CSCs). By single-cell gene expression, western blot, phospho-kinase array, immunoprecipitation, immunohistochemistry, flow cytometry and microarray analysis we showed that a subset of MLS cells expressed JAK-STAT genes with active signalling. JAK1/2 inhibition via ruxolitinib decreased, while stimulation with LIF increased, phosphorylation of STAT3 and the number of cells with CSC properties indicating that JAK-STAT signalling controlled the number of cells with CSC features. We also show that phosphorylated STAT3 interacted with the SWI/SNF complex. We conclude that MLS contains JAK-STAT-regulated subpopulations of cells with CSC features. Combined doxorubicin and ruxolitinib treatment targeted both proliferating cells as well as cells with CSC features, providing new means to circumvent chemotherapy resistance in treatment of MLS patients.

Histamine targets myeloid-derived suppressor cells and improves the anti-tumor efficacy of PD-1/PD-L1 checkpoint blockade.

Myeloid-derived suppressor cells (MDSCs) are immature monocytes and granulocytes that impede immune-mediated clearance of malignant cells by multiple mechanisms, including the formation of immunosuppressive reactive oxygen species (ROS) via the myeloid cell NADPH oxidase (NOX2). Histamine dihydrochloride (HDC), a NOX2 inhibitor, exerts anti-cancer efficacy in experimental tumor models but the detailed mechanisms are insufficiently understood. To determine effects of HDC on the MDSC compartment we utilized three murine cancer models known to entail accumulation of MDSC, i.e. EL-4 lymphoma, MC-38 colorectal carcinoma, and 4T1 mammary carcinoma. In vivo treatment with HDC delayed EL-4 and 4T1 tumor growth and reduced the ROS formation by intratumoral MDSCs. HDC treatment of EL-4 bearing mice also reduced the accumulation of intratumoral MDSCs and reduced MDSC-induced suppression of T cells ex vivo. Experiments using GR1-depleted and Nox2 knock out mice supported that the anti-tumor efficacy of HDC required presence of NOX2+ GR1+ cells in vivo. In addition, treatment with HDC enhanced the anti-tumor efficacy of programmed cell death receptor 1 (PD-1) and PD-1 ligand checkpoint blockade in EL-4- and MC-38-bearing mice. Immunomodulatory effects of a HDC-containing regimen on MDSCs were further analyzed in a phase IV trial (Re:Mission Trial, ClinicalTrials.gov; NCT01347996) where patients with acute myeloid leukemia received HDC in conjunction with low-dose IL-2 (HDC/IL-2) for relapse prevention. Peripheral CD14+HLA-DR-/low MDSCs (M-MDSCs) were reduced during cycles of HDC/IL-2 therapy and a pronounced reduction of M-MDSCs during HDC/IL-2 treatment heralded favorable clinical outcome. We propose that anti-tumor properties of HDC may comprise the targeting of MDSCs.

Highly symmetric and tunable tunnel couplings in InAs/InP nanowire heterostructure quantum dots.

We present a comprehensive electrical characterization of an InAs/InP nanowire (NW) heterostructure, comprising of two InP barriers forming a quantum dot (QD), two adjacent lead segments and two metallic contacts. We demonstrate how to extract valuable quantitative information of the QD. The QD shows very regular Coulomb blockade resonances over a large gate voltage range. By analyzing the resonance line shapes, we map the evolution of the tunnel couplings from the few to the many electron regime, with electrically tunable tunnel couplings from <1 µeV to >600 µeV, and a transition from the temperature to the lifetime broadened regime. The InP segments form tunnel barriers with almost fully symmetric tunnel couplings and a barrier height of ∼350 meV. All of these findings can be understood in great detail based on the deterministic material composition and geometry. Our results demonstrate that integrated InAs/InP QDs provide a promising platform for electron tunneling spectroscopy in InAs NWs, which can readily be contacted by a variety of superconducting materials to investigate subgap states in proximitized NW regions, or be used to characterize thermoelectric nanoscale devices in the quantum regime.

Tuning the Two-Electron Hybridization and Spin States in Parallel-Coupled InAs Quantum Dots.

We study spin transport in the one- and two-electron regimes of parallel-coupled double quantum dots (DQDs). The DQDs are formed in InAs nanowires by a combination of crystal-phase engineering and electrostatic gating, with an interdot tunnel coupling (t) tunable by one order of magnitude. Large single-particle energy separations (up to 10 meV) and |g^{*}| factors (∼10) enable detailed studies of the B-field-induced transition from a singlet-to-triplet ground state as a function of t. In particular, we investigate how the magnitude of the spin-orbit-induced singlet-triplet anticrossing depends on t. For cases of strong coupling, we find values of 230 µeV for the anticrossing using excited-state spectroscopy. Experimental results are reproduced by calculations based on rate equations and a DQD model including a single orbital in each dot.

A ceramic bone substitute containing gentamicin gives good outcome in trochanteric hip fractures treated with dynamic hip screw and in revision of total hip arthroplasty: a case series.

BACKGROUND: The primary objective was to investigate the clinical and radiological outcome in patients undergoing major hip surgery using a novel antibiotic containing bone substitute for local augmentation in trochanteric fracture fixation or revision of total hip arthroplasty (THA). METHODS: We implanted a novel biphasic bone substitute CERAMENT™|G consisting of hydroxyapatite, calcium sulphate and gentamicin for bone regeneration and local antibiotic delivery in 20 patients treated surgically for trochanteric femoral fracture or uncemented hip revision. Preoperative, postoperative, 3 months and 1 year clinical and radiological assessment were performed including registration of any complications. In one trochanteric fracture patient, histological analyses were performed of bone biopsies taken at removal of hardware. RESULTS: None of the trochanteric fractures or revision of THA showed any large migration. No local wound disturbances were seen and no infection was observed at one year follow-up. All trochanteric fractures healed at 3 months with a minimal sliding screw displacement on average 3 mm. Radiological analysis showed signs of bone remodeling and new bone formation in the substitute, illustrated also by histology in the biopsies taken from one trochanteric fracture at one year post-op. CONCLUSIONS: Local CERAMENT™|G was shown to be safe in a limited prospective major hip surgery study. Remodeling of the bone graft substitute was observed in all patients. TRIAL REGISTRATION: EU-CTR2018-004414-18 Retrospectively registered on November 20, 2018.

Parallel-Coupled Quantum Dots in InAs Nanowires.

We use crystal-phase tuning during epitaxial growth of InAs nanowires to create quantum dots with very strong confinement. A set of gate electrodes are used to reproducibly split the quantum dots into even smaller pairs for which we can control the populations down to the last electron. The double quantum dots, which are parallel-coupled to source and drain, show clear and stable odd-even level pairing due to spin degeneracy and the strong confinement. The combination of hard-wall barriers to source and drain, shallow interdot tunnel barriers, and very high single-particle excitation energies allow an order of magnitude tuning of the strength for the first intramolecular bond. We show examples for nanowires with different facet orientations, and suggest possible mechanisms behind the reproducible double-dot formation.

Conduction Band Offset and Polarization Effects in InAs Nanowire Polytype Junctions.

Although zinc-blende (ZB) and wurtzite (WZ) structures differ only in the atomic stacking sequence, mixing of crystal phases can strongly affect the electronic properties, a problem particularly common to bottom up-grown nanostructures. A lack of understanding of the nature of electronic transport at crystal phase junctions thus severely limits our ability to develop functional nanowire devices. In this work we investigated electron transport in InAs nanowires with designed mixing of crystal structures, ZB/WZ/ZB, by temperature-dependent electrical measurements. The WZ inclusion gives rise to an energy barrier in the conduction band. Interpreting the experimental result in terms of thermionic emission and using a drift-diffusion model, we extracted values for the WZ/ZB band offset, 135 ± 10 meV, and interface sheet polarization charge density on the order of 10-3 C/m2. The extracted polarization charge density is 1-2 orders of magnitude smaller than previous experimental results, but in good agreement with first principle calculation of spontaneous polarization in WZ InAs. When the WZ length is reduced below 20 nm, an effective barrier lowering is observed, indicating the increasing importance of tunneling transport. Finally, we found that band-bending at ZB/WZ junctions can lead to bound electron states within an enclosed WZ segment of sufficient length, evidenced by our observation of Coulomb blockade at low temperature. These findings provide critical input for modeling and designing the electronic properties of novel functional devices, such as nanowire transistors, where crystal polytypes are commonly found.

Role of regulatory T cells in acute myeloid leukemia patients undergoing relapse-preventive immunotherapy.

Regulatory T cells (Tregs) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials.gov ) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase. This study aimed at defining the features, function and dynamics of Foxp3+CD25highCD4+ Tregs during immunotherapy and to determine the potential impact of Tregs on relapse risk and survival. We observed a pronounced increase in Treg counts in peripheral blood during initial cycles of HDC/IL-2. The accumulating Tregs resembled thymic-derived natural Tregs (nTregs), showed augmented expression of CTLA-4 and suppressed the cell cycle proliferation of conventional T cells ex vivo. Relapse of AML was not prognosticated by Treg counts at onset of treatment or after the first cycle of immunotherapy. However, the magnitude of Treg induction was diminished in subsequent treatment cycles. Exploratory analyses implied that a reduced expansion of Tregs in later treatment cycles and a short Treg telomere length were significantly associated with a favorable clinical outcome. Our results suggest that immunotherapy with HDC/IL-2 in AML entails induction of immunosuppressive Tregs that may be targeted for improved anti-leukemic efficiency.

Peripheral Endothelial Function and Coronary Flow Velocity Reserve Are Not Associated in Women with Angina and No Obstructive Coronary Artery Disease: The iPOWER Study.

PURPOSE: We investigated whether impaired flow-mediated dilation (FMD) and plasma biomarkers reflecting endothelial dysfunction are associated with coronary microvascular dysfunction (CMD) in women with angina and no obstructive coronary artery disease (CAD). METHODS: Patients (n = 194) were randomly selected women with angina pectoris and no obstructive CAD (<50% stenosis). A reference population of asymptomatic women without CAD (n = 25) was included. We measured FMD in the brachial artery by high-resolution ultrasound. Coronary flow velocity reserve (CFVR) was assessed by transthoracic Doppler flow echocardiography (TTDE) of the left anterior descending artery during rest and high-dose dipyridamole infusion. CMD was defined as CFVR <2. RESULTS: FMD and CFVR were measured in 128 patients and 21 controls. Mean (SD) age was 64.5 (8.9) years, mean CFVR was 2.3 (2.0-2.7), and mean FMD was 8.4% (4.8%) in angina patients. Angina patients had a higher risk factor burden compared with the reference population. Measures of peripheral endothelial dysfunction and endothelial plasma biomarkers did not differ according to angina or CFVR. CFVR and FMD did not correlate (Spearman ρ = -0.07, p = 0.45). CONCLUSIONS: FMD and biomarkers of endothelial dysfunction did not identify individuals with CMD assessed as impaired CFVR by TTDE in women with angina and no obstructive CAD.

Sn-Seeded GaAs Nanowires as Self-Assembled Radial p-n Junctions.

The widespread use of Au as a seed particle in the fabrication of semiconductor nanowires presents a fundamental limitation to the potential incorporation of such nanostructures into electronic devices. Although several other growth techniques have been demonstrated, the use of alternative seed particle metals remains an underexplored but potentially very promising way to influence the properties of the resulting nanowires while simultaneously avoiding gold. In this Letter, we demonstrate the use of Sn as a seed particle metal for GaAs nanowires grown by metal-organic vapor phase epitaxy. We show that vertically aligned and stacking defect-free GaAs nanowires can be grown with very high yield. The resulting nanowires exhibit Esaki diode behavior, attributed to very high n-doping of the nanowire core with Sn, and simultaneous C-doping of the radial overgrowth. These results demonstrate that the use of alternative seed particle metals is a potentially important area to explore for developing nanowire materials with controlled material properties.

Balance exercise program reduced falls in people with multiple sclerosis: a single-group, pretest-posttest trial.

OBJECTIVE: To evaluate the effects of a balance exercise program on falls in people with mild to moderate multiple sclerosis (MS). DESIGN: Multicenter, single-blinded, single-group, pretest-posttest trial. SETTING: Seven rehabilitation units within 5 county councils. PARTICIPANTS: Community-dwelling adults with MS (N=32) able to walk 100m but unable to maintain 30-second tandem stance with arms alongside the body. INTERVENTION: Seven weeks of twice-weekly, physiotherapist-led 60-minute sessions of group-based balance exercise targeting core stability, dual tasking, and sensory strategies (CoDuSe). MAIN OUTCOME MEASURES: Primary outcomes: number of prospectively reported falls and proportion of participants classified as fallers during 7 preintervention weeks, intervention period, and 7 postintervention weeks. Secondary outcomes: balance performance on the Berg Balance Scale, Four Square Step Test, sit-to-stand test, timed Up and Go test (alone and with cognitive component), and Functional Gait Assessment Scale; perceived limitations in walking on the 12-item MS Walking Scale; and balance confidence on the Activities-specific Balance Confidence Scale rated 7 weeks before intervention, directly after intervention, and 7 weeks later. RESULTS: Number of falls (166 to 43; P≤.001) and proportion of fallers (17/32 to 10/32; P≤.039) decreased significantly between the preintervention and postintervention periods. Balance performance improved significantly. No significant differences were detected for perceived limitations in walking, balance confidence, the timed Up and Go test, or sit-to-stand test. CONCLUSIONS: The CoDuSe program reduced falls and proportion of fallers and improved balance performance in people with mild to moderate MS but did not significantly alter perceived limitations in walking and balance confidence.

Effect of residue combinations on plant uptake of nutrients and potentially toxic elements.

The aim of the plant pot experiment was to evaluate potential environmental impacts of combined industrial residues to be used as soil fertilisers by analysing i) element availability in fly ash and biosolids mixed with soil both individual and in combination, ii) changes in element phytoavailability in soil fertilised with these materials and iii) impact of the fertilisers on plant growth and element uptake. Plant pot experiments were carried out, using soil to which fresh residue mixtures had been added. The results showed that element availability did not correlate with plant growth in the fertilised soil with. The largest concentrations of K (3534 mg/l), Mg (184 mg/l), P (1.8 mg/l), S (760 mg/l), Cu (0.39 mg/l) and Zn (0.58 mg/l) in soil pore water were found in the soil mixture with biosolids and MSWI fly ashes; however plants did not grow at all in mixtures containing the latter, most likely due to the high concentration of chlorides (82 g/kg in the leachate) in this ash. It is known that high salinity of soil can reduce germination by e.g. limiting water absorption by the seeds. The concentrations of As, Cd and Pb in grown plants were negligible in most of the soils and were below the instrument detection limit values. The proportions of biofuel fly ash and biosolids can be adjusted in order to balance the amount and availability of macronutrients, while the possible increase of potentially toxic elements in biomass is negligible seeing as the plant uptake of such elements was low.

Elevated levels of IL-12/IL-23p40 in Nova Scotia Duck Tolling Retrievers with autoimmune disease and lymphoma.

The Nova Scotia Duck Tolling Retriever (NSDTR) is predisposed to immune mediated rheumatic disease (IMRD), steroid-responsive meningitis-arteritis (SRMA) and certain forms of cancer. Cytokines are the main regulators of the immune system. Interleukin 2 is a cytokine involved in activation of T regulatory cells, playing a role in central tolerance and tumor immunity. Interleukin 12 and interleukin 23 share the same subunit, p40, and are both pro-inflammatory cytokines. The aim of this study was to compare levels of IL-2 in healthy NSDTRs to those with cancer or autoimmune disease and to compare levels of IL-12/IL-23p40 in healthy NSDTRs and beagles versus NSDTRs with cancer or autoimmune disease. 62 dogs were included in the analysis of IL-12/IL-23p40; healthy NSDTRs (n = 16), healthy beagles (n = 16), NSDTRs autoimmune (n = 18) and NDSTRs lymphoma/mastocytoma (n = 12) and 68 dogs for IL-2; healthy (n = 20), autoimmune (n = 36) and lymphoma/mastocytoma/adenocarcinoma (n = 12). NSDTRs with autoimmune disease had higher levels of IL-12/IL-23p40 compared to healthy dogs (p = 0.008). NSDTRs with lymphoma also had higher levels of IL-12/IL-23p40 compared to healthy NSDTRs (p = 0.002). There was no difference in levels of IL-2 between healthy and diseased NSDTR. Statistical analysis was performed using Bonferroni corrections for multiple testing. These findings can contribute to the knowledge of autoimmune disease and cancer in dogs.

Glucagon resistance in individuals with obesity and hepatic steatosis can be measured using the GLUSENTIC test and index.

Increased plasma levels of glucagon (hyperglucagonaemia) promote diabetes development but is also observed in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This may reflect hepatic glucagon resistance towards amino acid catabolism. A clinical test for measuring glucagon resistance has not been validated. We evaluated our glucagon sensitivity (GLUSENTIC) test, consisting of two study days: a glucagon injection and measurements of plasma amino acids, and an infusion of mixed amino acids and subsequent calculation of the GLUSENTIC index (primary outcome measure) from measurements of glucagon and amino acids. To distinguish glucagon-dependent from insulin-dependent actions on amino acid metabolism, we also studied patients with type 1 diabetes (T1D). The delta-decline in total amino acids was 49% lower in MASLD following exogenous glucagon (p=0.01), and the calculated GLUSENTIC index was 34% lower in MASLD (p<0.0001), but not T1D (p>0.99). In contrast, glucagon-induced glucose increments were similar in controls and MASLD (p=0.41). The GLUSENTIC test and index may be used to measure glucagon resistance in individuals with obesity and MASLD.