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This booklet presents 18 experiments in the chemistry of food, suitable for elementary and secondary school science classes. Experiments deal with an analysis of milk, determinations of the amounts of sulfur dioxide, iron, and fat in foods, and the concentration of vitamin C in fruit juice and iodine in salt. Tests are provided for fats, carbohydrates, sugars, starches and proteins in various foods, and the presence of calcium propionate in bread. Other experiments include the identification of colors in food and factors involved in the discoloration of fresh fruit, the conversion of molasses into granulated sugar, the recovery of iodine from seaweed and caffeine from tea, and investigations relating to toasting bread and popping corn. (JR)

Layer 3 (L3) pyramidal neurons in aged rhesus monkey lateral prefrontal cortex (LPFC) exhibit significantly elevated excitability in vitro and reduced spine density compared to neurons in young subjects. The time-course of these alterations, and whether they can be ameliorated in middle age by the powerful anti-oxidant curcumin is unknown. We compared the properties of L3 pyramidal neurons from the LPFC of behaviorally characterized rhesus monkeys over the adult lifespan using whole-cell patch clamp recordings and neuronal reconstructions. Working memory (WM) impairment, neuronal hyperexcitability, and spine loss began in middle age. There was no significant relationship between neuronal properties and WM performance. Middle-aged subjects given curcumin exhibited better WM performance and less neuronal excitability compared to control subjects. These findings suggest that the appropriate time frame for intervention for age-related cognitive changes is early middle age, and points to the efficacy of curcumin in delaying WM decline. Because there was no relationship between excitability and behavior, the effects of curcumin on these measures appear to be independent.

Cholesterol-mediated perturbations of membrane structural integrity are key early events in the molecular pathogenesis of Alzheimer’s disease (AD). In AD, protein misfolding (proteopathy) and pro-inflammatory conditions (immunopathy) culminate in neuronal death, a process enabled by altered membrane biophysical properties which render neurons more susceptible to proteopathic and immunopathic cytotoxicities. Since cholesterol is a principal neuronal membrane lipid, normal cholesterol homeostasis is central to membrane health; also, since increased cholesterol composition is especially present in neuronal myelin sheath (i.e. brain “white matter”), recent studies have not surprisingly revealed that white matter atrophy precedes the conventional biomarkers of AD (amyloid plaques, tau tangles). Employing extensive microsecond all-atom molecular dynamics simulations, we investigated biophysical and mechanical properties of myelin sheath membrane as a function of cholesterol mole fraction (χ_CHL). Impaired χ_CHL modulates multiple membrane properties including surface area per lipid, chain order, area compressibility and bending moduli, bilayer thickness, lipid tilt angles and tail interdigitation. High χ_CHL condenses and stiffens the membrane, changing permeability and altering interfacial water density; low χ_CHL increases membrane fluidity and disorder, modulating lipid tilt angles and enhancing bilayer leaflet interdigitation. These calculations provide a molecular-level understanding of myelin sheath susceptibility to pathology as an early event in the pathogenesis of AD.

Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a “shift” of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis.

Above average precipitation from October 2018 through July 2019 in the Maumee River (R.) Basin resulted in 29% of cropland left fallow, providing a glimpse of potential effects from decreased nutrient application. Ongoing monitoring at 15 water-quality sites on the Maumee R. upstream from Defiance enabled comparison with 2017, which was hydrologically similar to 2019 in precipitation and streamflow. In 2019, nitrate (as nitrogen; NO3-N) for March-July was significantly less than previous years (2015–2018), but the response for phosphorus (P) was more complicated. Relative to 2017, total P (TP) was lower at 7 of 15 sites, but higher at 7, reflecting higher suspended sediment (SS). Dissolved P (DP) was generally lower, but less different than NO3; DP was higher at 3 sites. DP-P:NO3-N was generally higher in 2019, DP-P:TP was lower, and there was less TP relative to SS. Overall, less P was in the system in 2019. However smaller streams showed a large range of difference between 2019 and 2017 for all constituents, indicating variability in land management and physiography. In contrast, all constituents were lower in 2019 in larger (>5000 km2) streams, including the Maumee R. near Defiance, where the difference in NO3 (−37%) exceeded that for TP (−16%), DP (−10%), and SS (−20%). Differences in these relations among N, P, and SS indicate that P was available from legacy sources that are more difficult to distinguish during typical agricultural production years and that some material from 2019 was stored in the system upstream from the largest sites.

Delays between soil sampling and processing for analysis are common in both research and agronomy, but the effects of storage conditions on measurements of plant-available nitrogen (N) are rarely considered. With increasing recognition of organic N pools in soils, such as amino acids and peptides, it is necessary to determine how sample handling impacts the outcomes of soil N quantification. In this study, we used in situ microdialysis to approximate plant availability of amino acids, ammonium and nitrate, then compared to both potassium chloride (KCl) extract and microdialysis samples taken from excavated soil samples when in the field, after 24 h refrigerated storage, and after storage for 1 month, either refrigerated or air-dried. Nitrate levels measured with microdialysis and KCl extracts increased immediately after soil sampling and continued to accumulate in the next day and 1 month stored samples. Amino acid and ammonium measurements remained more constant; however, microdialysis showed a decline in amino acid-N between in situ and next day samples. The proportional representation of N pools in the in-field extracts was most similar to in situ microdialysis. Soil samples should be processed for N analysis as close to sampling as possible, and the storage duration and conditions reported. The influence of storage must be considered in interpreting soil test results.

The electrochemical synthesis of metal-organic frameworks (MOFs) has been widely explored but has involved indirect routes, including anodic dissolution of solid metal electrodes or the use of interfacial redox chemistry to generate base equivalents and drive MOF assembly. These methods are limited in scope, as the former relies on the use of an anode consisting of the metal ion to be incorporated into the MOF, and the latter relies on the compatibility of the metal/ligand solution with the probase that is subsequently oxidized or reduced. We report the facile, direct electrochemical syntheses of four iron-based MOFs via controlled potential oxidation of dissolved metal cations. Oxidation of Fe(II) at +0.75 V (vs Ag/Ag+) in a solution containing 2,6-lutidine and terephthalic acid affords highly crystalline Fe-MIL-101. Controlled potential electrolysis with carboxy-functionalized ITO affords Fe-MIL-101 grown directly on the surface of modified electrodes. The methods we report herein represent the first general routes that employ interfacial electrochemistry to alter the oxidation state of metal ions dissolved in solution to directly trigger MOF formation. The reported method is functional group tolerant and will be broadly applicable to the bulk synthesis or surface growth of a range of MOFs based on metal ions with accessible oxidation states.

BACKGROUND Urine albumin-to-creatinine ratio (ACR) and protein-to-creatinine ratio (PCR) are used to measure urine protein. Recent guidelines endorse ACR use, and equations have been developed incorporating ACR to predict risk of kidney failure. For situations in which PCR only is available, having a method to estimate ACR from PCR as accurately as possible would be useful. METHODS We used data from a population-based cohort of 47,714 adults in Alberta, Canada, who had simultaneous assessments of urine ACR and PCR. After log-transforming ACR and PCR, we used cubic splines and quantile regression to estimate the median ACR from a PCR, allowing for modification by specified covariates. On the basis of the cubic splines, we created models using linear splines to develop equations to estimate ACR from PCR. In a subcohort with eGFR

Efficacious treatments against Acanthamoeba Keratitis (AK) is challenging, often ineffective and linked to the intragenotype variation in the drug efficacy. Increased oxygen can facilitate host response and can inhibit some organisms. Herein, we report the effect of increased oxygen concentrations on Acanthamoeba spp. growth and its effect on ROS (reactive oxygen species) production. The exposition to pure oxygen could reduce cell growth by at least 60% for Acanthamoeba castellanii Neff, Acanthamoeba polyphaga, and Acanthamoeba griffini. The increase in ROS production confirming that oxygen cell’s growth inhibition was due to oxidative stress. Further studies are needed to determine oxygen saturation level, time of oxygen exposition, and number of sessions needed to eliminate the parasite.

In Gulu area, geothermal waters show a high concentration of alkali metals (Li, Rb and Cs) and some other typical pollution elements, e.g. As, Sb and Tl. They are also enriched in the geothermal deposits during the phase separation of silica sinter and residual geothermal water. A comprehensive sequential extraction was carried out on the Gulu silica sinter. The results indicated that significant Li and K amount is bound to the Fe-Mn oxide and the residual fractions of sinter while, the elements (B, Cs, Rb, As, Sb and Tl) are predominantly concentrated in the sinter crystal lattices. In addition, the elemental distribution law during phase separation of the residual geothermal water and associated evapoconcentrated deposits is also uncovered in this study. With the respect to the system of the natural silica sinters precipitated from the mother geothermal water, complex variations occur during the trace elements partition between the mother water and associated deposits under evapoconcentration. Thus, the miscellaneous minerals (Li, Rb, K, Cs and B) are also distributed in the solid phases when special minerals such as opal, borax or sylvite precipitate from the residual fluids. This confirms that the valuable minerals of K, B, Cs, Rb or Li can precipitate when the geothermal water is evapoconcentrated to a certain degree and within a very concentrative stage of density. However, these elements are remarkably depleted in the residual geothermal fluid at the stages corresponding to the precipitation of these minerals while they are highly enriched in the mother fluid during the late stages of the evapoconcentration. Thus, it can be stated for the first time that the high concentration of these elements in the residual waters at the final stages will be certainly used in the future. In contrast, the concentration of pollution elements (As, Sb and Tl) of the geothermal solids is higher in the early stage of the opal precipitation, while it is lower in the later stages. The concentration of these elements (As, Sb and Tl) in residual geothermal fluids distinctly increases and is very high at the final stages of the evapoconcentration. This scenario indicates that large quantities of toxic elements such as As, Tl and Sb may degrade the surface and ground waters resources located at or near the geothermal water by mixing process making them unsuitable for drinking or irrigation. Thus, in addition to the thermal energy provided, the geothermal area are very important prospect for exploration and extraction of the mineral resources of the elements such as K, Li, B, Rb or Cs that have very significant economic value. However, percentages of trace elements such as Li, Tl, Rb and K in the exchangeable and carbonates fractions of this sinter suggested that they could become rapidly bioavailable in the geothermal environment.

Hemorrhagic stroke is a leading cause of death. The causes of intracerebral hemorrhage (ICH)-induced brain damage are thought to include lysis of red blood cells, hemin release and iron overload. These mechanisms, however, have not proven very amenable to therapeutic intervention, and so other mechanistic targets are being sought. Here we report that accumulation of endogenously formed zinc protoporphyrin (ZnPP) also critically contributes to ICH-induced brain damage. ICH caused a significant accumulation of ZnPP in brain tissue surrounding hematoma, as evidenced by fluorescence microscopy of ZnPP, and further confirmed by fluorescence spectroscopy and supercritical fluid chromatography-mass spectrometry. ZnPP formation was dependent upon both ICH-induced hypoxia and an increase in free zinc accumulation. Notably, inhibiting ferrochelatase, which catalyzes insertion of zinc into protoporphyrin, greatly decreased ICH-induced endogenous ZnPP generation. Moreover, a significant decrease in brain damage was observed upon ferrochelatase inhibition, suggesting that endogenous ZnPP contributes to the damage in ICH. Our findings reveal a novel mechanism of ICH-induced brain damage through ferrochelatase-mediated formation of ZnPP in ICH tissue. Since ferrochelatase can be readily inhibited by small molecules, such as protein kinase inhibitors, this may provide a promising new and druggable target for ICH therapy.

The Peel–Harvey estuarine system in Western Australia's south-west is affected by poor water quality, algal blooms, and fish kills. Phosphorus (P) discharge from agricultural activities is the main source of poor water quality. The catchment’s soils are naturally infertile, but P application has increased P fertility. This paper draws on and undertakes a meta-analysis of 20 200 surface (0–10 cm) and profile (to 100 cm depth) soil samples collected in the period 1983–2018. Soil P content was high, with 70% of samples with Colwell P content in excess of agronomic requirements; Production is more likely limited by low soil pH(CaCl2) and low K (92% and 67% of paddocks respectively). Strong P stratification in the soil is evident, particularly topsoil; sandy soils are saturated to depth; and clay soils show signs of P saturation in the topsoil. Management of P in sandy soil near the estuary is a high priority as is P stratification in highly P retentive soil. Soil P stocks increased since clearing compared with uncleared soils (1221 kg ha–1 m–1 and 285–694 kg ha–1 m–1, respectively). Thirteen percent of samples had P content in excess of agronomic requirements in 1983, rising slowly to 69% in 2018. Landholder practices need to be analysed in detail to confirm if this accumulation occurs everywhere or is only confined to actively farmed land.

Supplemental Table 1. Five mice lacking intestinal SMAD4 expression ("KO") and five littermate control mice ("WT") had their colon microbiome composition compared. 16S targeted sequencing was performed on mouse stool pellets ("Pellet") and colon mucosal scrapings ("Scraping") and compared at the phylum, class, order, family, genus, and species levels. Values represent proportion of organisms detected per sample. Genotypes were split evenly between sexes. The five female mice were co-housed and the five male mice were co-housed, with bedding mixed between cages weekly., This research was funded in part by National Cancer Institute grants (F32 CA236309; T32 CA106183; R01 CA235016), the Burroughs Wellcome Fund Physician-Scientist Institutional Award #1018894/Vanderbilt Supporting Careers in Research for Interventional Physicians and Surgeons (SCRIPS), the Vanderbilt Ingram Cancer Center (VICC) grant (P30 CA068485), the Vanderbilt Digestive Diseases Research Center Grant (P30 DK058404), and the Department of Veterans Affairs Career Development Award (IK2BX004648).

Phosphatic fertilisers have made grazing in the south-west of Western Australia (WA) viable. However, there is evidence that a large proportion of pasture paddocks exceed soil test critical values at which 95% of maximum yield is achieved as identified in the national Better Fertiliser Decisions for Pasture (BFDP) project. Of 22 000 soil samples collected between 2009 and 2020, 56% exceeded the critical value for phosphorus (P), although there were constraints to potassium (K) and sulfur (S) and from soil acidity. Soils with available P exceeding the critical value are expected to lead to excessive losses of P to waterways, resulting in eutrophication. A trial program was established to validate the critical P values from BFDP so that concerns can be addressed about the relevance of these critical P values to WA conditions and to contemporary pasture varieties. Measured relative yields for 19 trials in the first year were mostly within 10% of that predicted from BFDP for soils with a P buffering index (PBI) >10. Soils with PBI

Indoleamine 2,3-dioxygenase 1 (IDO1) is a promising therapeutic target in cancer immunotherapy and neurological disease. Thus, searching for highly active inhibitors for use in human cancers is now a focus of widespread research and development efforts. In this study, we report the structure-based design of 2-(5-imidazolyl)indole derivatives, a series of novel IDO1 inhibitors which have been designed and synthesized based on our previous study using N1-substituted 5-indoleimidazoles. Among these, we have identified one with a strong IDO1 inhibitory activity (IC50 =0.16 μM, EC50 =0.3 μM). Structural-activity relationship (SAR) and computational docking simulations suggest that a hydroxyl group favorably interacts with a proximal Ser167 residue in Pocket A, improving IDO1 inhibitory potency. The brain penetrance of potent compounds was estimated by calculation of the Blood Brain Barrier (BBB) Score and Brain Exposure Efficiency (BEE) Score. Many compounds had favorable scores and the two most promising compounds were advanced to a pharmacokinetic study which demonstrated that both compounds were brain penetrant. We have thus discovered a flexible scaffold for brain penetrant IDO1 inhibitors, exemplified by several potent, brain penetrant, agents. With this promising scaffold, we provide herein a basis for further development of brain penetrant IDO1 inhibitors.

Side-arm hydrogenation (SAH) by homogeneous catalysis has extended the reach of the parahydrogen enhanced NMR technique to key metabolites such as pyruvate. However, homogeneous hydrogenation requires rapid separation of the dissolved catalyst and purification of the hyperpolarised species with a purity sufficient for safe in-vivo use. An alternate approach is to employ heterogeneous hydrogenation in a continuous-flow reactor, where separation from the solid catalysts is straightforward. Using a TiO2 -nanorod supported Rh catalyst, we demonstrate continuous-flow parahydrogen enhanced NMR by heterogeneous hydrogenation of a model SAH precursor, propargyl acetate, at a flow rate of 1.5 mL/min. Parahydrogen gas was introduced into the flowing solution phase using a novel tube-in-tube membrane dissolution device. Without much optimization, proton NMR signal enhancements of up to 297 (relative to the thermal equilibrium signals) at 9.4 Tesla were shown to be feasible on allyl-acetate at a continuous total yield of 33 %. The results are compared to those obtained with the standard batch-mode technique of parahydrogen bubbling through a suspension of the same catalyst.

Cancer stem-like cells (CSC) contribute to therapy resistance and recurrence. Focal adhesion kinase (FAK) has a role in CSC regulation. We determined the effect of FAK inhibition on breast CSC activity alone and in combination with adjuvant therapies. FAK inhibition reduced CSC activity and self-renewal across all molecular subtypes in primary human breast cancer samples. Combined FAK and paclitaxel reduced self-renewal in triple negative cell lines. An invasive breast cancer cohort confirmed high FAK expression correlated with increased risk of recurrence and reduced survival. Co-expression of FAK and CSC markers was associated with the poorest prognosis, identifying a high-risk patient population. Combined FAK and paclitaxel treatment reduced tumour size, Ki67, ex-vivo mammospheres and ALDH+ expression in two triple negative patient derived Xenograft (PDX) models. Combined treatment reduced tumour initiation in a limiting dilution re-implantation PDX model. Combined FAK inhibition with adjuvant therapy has the potential to improve breast cancer survival.

Many patients with obstructive sleep apnea (OSA) experience excessive daytime sleepiness (EDS), which can negatively affect daily functioning, cognition, mood, and other aspects of well-being. Although EDS can be reduced with primary OSA treatment, such as continuous positive airway pressure (CPAP) therapy, a significant proportion of patients continue to experience EDS despite receiving optimized therapy for OSA. This article reviews the pathophysiology and clinical evaluation and management of EDS in patients with OSA. The mechanisms underlying EDS in CPAP-treated patients remain unclear. Experimental risk factors include chronic intermittent hypoxia and sleep fragmentation, which lead to oxidative injury and changes in neurons and brain circuit connectedness involving noradrenergic and dopaminergic neurotransmission in wake-promoting regions of the brain. In addition, neuroimaging studies have shown alterations in the brain's white matter and gray matter in patients with OSA and EDS. Clinical management of EDS begins with ruling out other potential causes of EDS and evaluating its severity. Tools to evaluate EDS include objective and self-reported assessments of sleepiness, as well as cognitive assessments. Patients who experience residual EDS despite primary OSA therapy may benefit from wake-promoting pharmacotherapy. Agents that inhibit reuptake of dopamine or of dopamine and norepinephrine (modafinil/armodafinil and solriamfetol, respectively) have demonstrated efficacy in reducing EDS and improving quality of life in patients with OSA. Additional research is needed on the effects of wake-promoting treatments on cognition in these patients and to identify individual or disorder-specific responses.

Rev1 is a translesion DNA synthesis (TLS) polymerase involved in the bypass of adducted-guanine bases and abasic sites during DNA replication. During damage bypass, Rev1 utilizes a protein-template mechanism of DNA synthesis, where the templating DNA base is evicted from the Rev1 active site and replaced by an arginine side chain that preferentially binds incoming dCTP. Here, we utilize X-ray crystallography and molecular dynamics simulations to obtain structural insight into the dCTP specificity of Rev1. We show the Rev1 R324 protein-template forms sub-optimal hydrogen bonds with incoming dTTP, dGTP, and dATP that prevents Rev1 from adopting a catalytically competent conformation. Additionally, we show the Rev1 R324 protein-template forms optimal hydrogen bonds with incoming rCTP. However, the incoming rCTP adopts an altered sugar pucker, which prevents the formation of a catalytically competent Rev1 active site. This work provides novel insight into the mechanisms for nucleotide discrimination by the TLS polymerase Rev1.

Continuous exposure to methane causes IrO2(110) films on Ir(100) to undergo extensive reduction at temperatures from 500 to 650 K. Measurements using in situ X-ray photoelectron spectroscopy (XPS) confirm that CH4 oxidation on IrO2(110) converts so-called bridging oxygen atoms (Obr) at the surface to HObr groups while concurrently removing oxygen from the oxide film. Reduction of the IrO2(110) film by methane is mildly activated as evidenced by an increase in the initial reduction rate as the temperature is increased from 500 to 650 K. The XPS results show that subsurface oxygen efficiently replaces Obr atoms at the IrO2(110) surface during CH4 oxidation, even after the reduction of multiple layers of the oxide film, and that metallic Ir gradually forms at the surface as well. The isothermal rate of IrO2(110) reduction by methane decreases continuously as metallic Ir replaces surface IrO2(110) domains, demonstrating that IrO2(110) is the active phase for CH4 oxidation under the conditions studied. A key finding is that the replacement of Obr atoms with oxygen from the subsurface is efficient enough to preserve IrO2(110) domains at the surface and enable CH4 to reduce the ∼10-layer IrO2(110) films nearly to completion. In agreement with these observations, density functional theory calculations predict that oxygen atoms in the subsurface layer can replace Obr atoms at rates that are comparable to or higher than the rates at which Obr atoms are abstracted during CH4 oxidation. The efficacy with which oxygen in the bulk reservoir replenishes surface oxygen atoms has implications for understanding and modeling catalytic oxidation processes promoted by IrO2(110). (Less)

Bile acids are lipid-emulsifying metabolites synthesized in hepatocytes and maintained in vivo through enterohepatic circulation between the liver and small intestine1. As detergents, bile acids can cause toxicity and inflammation in enterohepatic tissues2. Nuclear receptors maintain bile acid homeostasis in hepatocytes and enterocytes3, but it is unclear how mucosal immune cells tolerate high concentrations of bile acids in the small intestine lamina propria (siLP). CD4+ T effector (Teff) cells upregulate expression of the xenobiotic transporter MDR1 (encoded by Abcb1a) in the siLP to prevent bile acid toxicity and suppress Crohn’s disease-like small bowel inflammation4. Here we identify the nuclear xenobiotic receptor CAR (encoded by Nr1i3) as a regulator of MDR1 expression in T cells that can safeguard against bile acid toxicity and inflammation in the mouse small intestine. Activation of CAR induced large-scale transcriptional reprogramming in Teff cells that infiltrated the siLP, but not the colon. CAR induced the expression of not only detoxifying enzymes and transporters in siLP Teff cells, as in hepatocytes, but also the key anti-inflammatory cytokine IL-10. Accordingly, CAR deficiency in T cells exacerbated bile acid-driven ileitis in T cell-reconstituted Rag1−/− or Rag2−/− mice, whereas pharmacological activation of CAR suppressed it. These data suggest that CAR acts locally in T cells that infiltrate the small intestine to detoxify bile acids and resolve inflammation. Activation of this program offers an unexpected strategy to treat small bowel Crohn’s disease and defines lymphocyte sub-specialization in the small intestine. Activation of the nuclear hormone receptor CAR in T cells protects the small intestine against bile acid-driven inflammation.

Late-transition-metal oxides have emerged as promising materials for enabling direct catalytic conversions of light alkanes to value-added products due to the ability of certain facets of these oxi...

Purpose:A randomized phase III study evaluated the efficacy of eribulin versus dacarbazine in patients with advanced liposarcoma and leiomyosarcoma. Improved overall survival (OS) led to approval of eribulin for liposarcoma, but not for leiomyosarcoma.Experimental Design:We explored the molecular profile of 77 archival leiomyosarcoma samples from this trial to identify potential predictive biomarkers, utilizing low-coverage whole-genome and whole-exome sequencing. Tumor molecular profiles were correlated with clinical data, and disease control was defined as complete/partial response or stable disease (RECIST v1.1).Results:Overall, 111 focal copy-number alterations were observed in leiomyosarcoma. Gain of chromosome 17q12 was the most common event, present in 43 of 77 cases (56%). In the eribulin-treated group, gains of 4q26, 20p12.2, 13q13.3, 8q22.2, and 8q13.2 and loss of 1q44 had a negative impact on progression-free survival (PFS), while loss of 2p12 correlated with better prognosis. Gains of 4q22.1 and losses of 3q14.2, 2q14.1, and 11q25 had a negative impact on OS in patients with leiomyosarcoma receiving eribulin. The most commonly mutated genes were TP53 (38%), MUC16 (32%), and ATRX (17%). The presence of ATRX mutations had a negative impact on PFS in both treatment arms; however, the correlation with worse OS was observed only in the eribulin-treated patients. TP53 mutations were associated with longer PFS on eribulin.Conclusions:Leiomyosarcoma has a complex genetic background, with multiple copy-number alterations and mutations affecting genes implicated in tumorigenesis. We identified several molecular changes with potential impact on survival of patients with leiomyosarcoma when treated with eribulin.