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Single atoms of platinum group metals on CeO2 represent a potential approach to lower precious metal requirements for automobile exhaust treatment catalysts. Here we show the dynamic evolution of two types of single-atom Pt (Pt1) on CeO2, i.e., adsorbed Pt1 in Pt/CeO2 and square planar Pt1 in PtATCeO2, fabricated at 500 °C and by atom-trapping method at 800 °C, respectively. Adsorbed Pt1 in Pt/CeO2 is mobile with the in situ formation of few-atom Pt clusters during CO oxidation, contributing to high reactivity with near-zero reaction order in CO. In contrast, square planar Pt1 in PtATCeO2 is strongly anchored to the support during CO oxidation leading to relatively low reactivity with a positive reaction order in CO. Reduction of both Pt/CeO2 and PtATCeO2 in CO transforms Pt1 to Pt nanoparticles. However, both catalysts retain the memory of their initial Pt1 state after reoxidative treatments, which illustrates the importance of the initial single-atom structure in practical applications.

Methotrexate is used in the treatment of many malignancies, rheumatological diseases, and inflammatory bowel disease. Toxicity from use is associated with severe morbidity and mortality. Rescue treatments include intravenous hydration, folinic acid, and, in some centers, glucarpidase. We conducted systematic reviews of the literature following published EXtracorporeal TReatments In Poisoning (EXTRIP) methods to determine the utility of extracorporeal treatments in the management of methotrexate toxicity. The quality of the evidence and the strength of recommendations (either “strong” or “weak/conditional”) were graded according to the GRADE approach. A formal voting process using a modified Delphi method assessed the level of agreement between panelists on the final recommendations. A total of 92 articles met inclusion criteria. Toxicokinetic data were available on 90 patients (89 with impaired kidney function). Methotrexate was considered to be moderately dialyzable by intermittent hemodialysis. Data were available for clinical analysis on 109 patients (high-dose methotrexate [>0.5 g/m(2)]: 91 patients; low-dose [≤0.5 g/m(2)]: 18). Overall mortality in these publications was 19.5% and 26.7% in those with high-dose and low-dose methotrexate–related toxicity, respectively. Although one observational study reported lower mortality in patients treated with glucarpidase compared with those treated with hemodialysis, there were important limitations in the study. For patients with severe methotrexate toxicity receiving standard care, the EXTRIP workgroup: (1) suggested against extracorporeal treatments when glucarpidase is not administered; (2) recommended against extracorporeal treatments when glucarpidase is administered; and (3) recommended against extracorporeal treatments instead of administering glucarpidase. The quality of evidence for these recommendations was very low. Rationales for these recommendations included: (1) extracorporeal treatments mainly remove drugs in the intravascular compartment, whereas methotrexate rapidly distributes into cells; (2) extracorporeal treatments remove folinic acid; (3) in rare cases where fast removal of methotrexate is required, glucarpidase will outperform any extracorporeal treatment; and (4) extracorporeal treatments do not appear to reduce the incidence and magnitude of methotrexate toxicity.

Supplementary Figure 2 from Intravesical Immunotherapy of Superficial Bladder Cancer with Chitosan/Interleukin-12

Supplementary Figure 1 from Intravesical Immunotherapy of Superficial Bladder Cancer with Chitosan/Interleukin-12

Supplementary Figure Legends 1-2 from Intravesical Immunotherapy of Superficial Bladder Cancer with Chitosan/Interleukin-12

Intravesical BCG has been used successfully to treat superficial bladder cancer for three decades. However, 20% to 30% of patients will fail initial BCG therapy and 30% to 50% of patients will develop recurrent tumors within 5 years. Alternative or complementary strategies for the management of superficial bladder cancer are needed. Interleukin-12 (IL-12) is a potent TH1 cytokine with robust antitumor activity and the ability to potentiate immunologic memory. Unfortunately, intravesical IL-12 did not show antitumor efficacy in a recent clinical study of patients with recurrent superficial bladder cancer. We hypothesized that coformulation of IL-12 with chitosan, a biocompatible, mucoadhesive polysaccharide, could improve intravesical IL-12 delivery and provide an effective and durable alternative for the treatment of superficial bladder cancer. In antitumor studies, 88% to 100% of mice bearing orthotopic bladder tumors were cured after four intravesical treatments with chitosan/IL-12. In contrast, only 38% to 60% of mice treated with IL-12 alone and 0% treated with BCG were cured. Antitumor responses following chitosan/IL-12 treatments were durable and provided complete protection from intravesical tumor rechallenge. Urinary cytokine analysis showed that chitosan/IL-12 induced multiple TH1 cytokines at levels significantly higher than either IL-12 alone or BCG. Immunohistochemistry revealed moderate to intense tumor infiltration by T cells and macrophages following chitosan/IL-12 treatments. Bladder submucosa from cured mice contained residual populations of immune cells that returned to baseline levels after several months. Intravesical chitosan/IL-12 is a well-tolerated, effective immunotherapy that deserves further consideration for testing in humans for the management of superficial bladder cancer. [Cancer Res 2009;69(15):6192–9]

Introduction Although decisions about breast reconstruction surgery include patients’ perspectives, little is known about which options patients recall discussing and how their psychosocial factors influence their recall. The purpose of this study was to explore whether psychosocial factors were associated with the breast reconstruction options a patient remembers discussing with their reconstructive surgeon, controlling for medical factors that impact surgical decision-making. Material and methods From 2011 to 2014, we recruited English-speaking adults whose legal sex was female who had an appointment at The University of Texas MD Anderson Cancer Center to discuss breast reconstruction. After the clinical consultation, participants indicated which reconstruction procedures they remembered discussing with their reconstructive surgeon (choose all that apply): (1) implant-based, (2) tissue-based, (3) combination of implant and tissue. Analyses focused on three groups: participants who remembered (a) only an implant-based option being discussed; (b) only a tissue-based option being discussed; and (c) implant-based, tissue-based, and combination options being discussed. We investigated the association between which reconstruction option(s) a participant remembered discussing with her reconstructive surgeon and her body image investment (Appearance Schemas Inventory-Revised (ASI-R)), body image (Body Image Scale (BIS)), and overall psychological distress (Brief Symptom Inventory-18 (BSI-18)), considering participant age and Body Mass Index (BMI). Multiple multinomial logistic regression models were used to investigate the associations of participant factors with the reconstruction options they remembered discussing with their surgeon. Akaike information criterion (AIC) was applied to select the best-fitting multivariable model. Results Out of 306 participants,138 participants remembered discussing only implant-based reconstruction; 118 participants remembered discussing only tissue-based reconstruction; and 50 participants remembered discussing implant-based, tissue-based, and combination options. The majority of participants were Caucasian (74.8%) and non-Hispanic (75.2%). BMI, body image investment, and body image were identified as associated with remembering different reconstruction options being discussed and were included in the multiple multinomial logistic regression model. Greater body image investment (i.e., higher ASI-R composite score) was significantly associated with higher odds of remembering discussing only implant-based reconstruction as compared to remembering discussing only tissue-based reconstruction, adjusted for the other factors in the model (adjusted odds ratio [OR] = 1.70, 95% CI = 1.04-2.79, p-value = 0.035). Greater body image dissatisfaction or concerns (i.e., higher BIS score) was associated with higher odds of remembering discussing only tissue-based reconstruction compared to remembering discussing only implant-based reconstruction, adjusted for the other factors in the model (adjusted OR = 1.04, 95% CI = 1.00-1.08, p-value = 0.045). Conclusion Our findings indicate that even when adjusted for BMI, patients with higher body image investment may be more likely to remember discussions about implant-based reconstruction, and patients with greater body image dissatisfaction may be more likely to remember discussions about tissue-based reconstruction. Tailored counseling approaches may be recommended to ensure all patients equally attend to and consider all medically-relevant options when discussing breast reconstruction surgery. Citation Format: Haoqi Wang, Jun Liu, Mary Catherine Bordes, Deepti Chopra, Gregory P Reece, Mia K Markey, Aubri S Hoffman. When discussing breast reconstruction, do psychosocial characteristics influence which surgical options patients remember? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-09-04.

Atomically dispersed noble metal catalysts have drawn wide attention as candidates to replace supported metal clusters and metal nanoparticles. Atomic dispersion can offer unique chemical properties as well as maximum utilization of the expensive metals. Addition of a second metal has been found to help reduce the size of Pt ensembles in bimetallic clusters; however, the stabilization of isolated Pt atoms in small nests of nonprecious metal atoms remains challenging. We now report a novel strategy for the design, synthesis, and characterization of a zeolite-supported propane dehydrogenation catalyst that incorporates predominantly isolated Pt atoms stably bonded within nests of Zn atoms located within the nanoscale pores of dealuminated zeolite Beta. The catalyst is stable in long-term operation and exhibits high activity and high selectivity to propene. Atomic resolution images, bolstered by X-ray absorption spectra, demonstrate predominantly atomic dispersion of the Pt in the nests and, with complementary infrared and nuclear magnetic resonance spectra, determine a structural model of the nested Pt.

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

The conversion of syngas to higher oxygenates is an important step in the pathway towards the long-term sustainable production of fuels and chemicals. Mixed Cu/Fe catalysts combine metals with different CO activation characteristics, a property that makes them promising candidates for higher oxygenate production. However, Cu/Fe catalysts suffer from instability due to sintering and phase separation, and the active sites for higher oxygenate formation on these materials are not well understood. In this work, we use atomic layer deposition (ALD) to modify silica-supported Cu nanoparticles with monolayer precise amounts of Fe2O3 and study the effects on catalyst structure, reactivity, and stability. We demonstrate that the Fe2O3 ALD process is inherently selective towards deposition on the SiO2 surface versus the Cu nanoparticles. As a result, a sufficiently thick Fe2O3 layer surrounding the Cu nanoparticles acts as a barrier against Cu migration, preventing catalyst deactivation through sintering without covering the Cu. In syngas conversion reactions, we find that higher oxygenate selectivity increases with Fe2O3 loading at low and intermediate ALD cycle numbers. Furthermore, using in situ X-ray absorption spectroscopy, we demonstrate that the Fe near the Cu nanoparticles is reduced to a metallic state under reaction conditions. From these measurements, we identify these metallic Cu/Fe interfaces as the active sites for higher oxygenate formation, which are most abundant at intermediate Fe2O3 ALD cycle numbers. As the Fe2O3 loading increases, higher oxygenate selectivity falls, resulting from encapsulation of the Cu nanoparticles by thick Fe2O3 layers. The results demonstrate how thickness-controlled ALD Fe2O3 can be used as both a promoter and stabilizer of Cu-based higher oxygenate synthesis catalysts.

Purpose Fertility preservation is an increasingly important topic in adolescent and young adult cancer survivorship, yet treatments remain under-utilized, possibly due to lack of awareness and understanding. The internet is widely used by adolescents and young adults and has been proposed to fill knowledge gaps and advance high-quality, more equitable care. As a first step, this study analyzed the quality of current fertility preservation resources online and identified opportunities for improvement. Methods We conducted a systematic analysis of 500 websites to assess the quality, readability, and desirability of website features, and the inclusion of clinically relevant topics. Results The majority of the 68 eligible websites were low quality, written at college reading levels, and included few features that younger patients find desirable. Websites mentioned more common fertility preservation treatments than promising experimental treatments, and could be improved with cost information, socioemotional impacts, and other equity-related fertility topics. Conclusions Currently, the majority of fertility preservation websites are about, but not for, adolescent and young adult patients. High-quality educational websites are needed that address outcomes that matter to teens and young adults, with a priority on solutions that prioritize equity. Implications for Cancer Survivors: Adolescent and young adult survivors have limited access to high-quality fertility preservation websites that are designed for their needs. There is a need for the development of fertility preservation websites that are clinically comprehensive, written at appropriate reading levels, inclusive, and desirable. We include specific recommendations that future researchers can use to develop websites that could better address AYA populations and improve the fertility preservation decision making process.

The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup defined criteria for extracorporeal toxin removal in patients with metformin poisoning. The primary objective of this study was to determine the benefit of extracorporeal toxin removal in patients meeting EXTRIP criteria. The secondary objective was to determine the performance characteristics of the EXTRIP criteria. This was a single-center retrospective analysis of metformin poisoned patients. Inclusion criteria were: suspicion of metformin poisoning with at least one of the following present: lactate concentration >5 mmol/L; pH < 7.35; or impaired kidney function. Patient data were extracted by reviewers who were unaware of the study hypothesis. Cases were analyzed based on EXTRIP criteria, whether extracorporeal toxin removal was performed, and survival. Sensitivity, specificity, negative predictive value and positive predictive value were calculated with respect to the EXTRIP criteria and survival. Of 201 patients studied, 145 patients met recommended EXTRIP criteria (EXTRIP positive) and 56 patients did not (EXTRIP negative). Among patients who met recommended EXTRIP criteria, 96 received extracorporeal toxin removal and 49 did not. There was no difference in survival between these groups: 75.0% versus 73.5%, respectively (P >0.05). All 56 patients who did not meet EXTRIP criteria, survived (negative predictive value = 100%). The study did not demonstrate a survival benefit for extracorporeal toxin removal in those meeting EXTRIP criteria. In this retrospective analysis, the recommended EXTRIP criteria had a negative predictive value for death of 100%. Further study is needed to evaluate the benefit of extracorporeal toxin removal in patients meeting EXTRIP criteria for metformin poisoning.

Compositionally versatile, nonstoichiometric, mixed ionic–electronic conducting metal oxides of the form An+1BnO3n+1 (n = 1 → ∞; A = rare-earth-/alkaline-earth-metal cation; B = transition-metal (TM) cation) remain a highly attractive class of electrocatalysts for catalyzing the energy-intensive oxygen evolution reaction (OER). The current design strategies for describing their OER activities are largely derived assuming a static, unchanged view of their surfaces, despite reports of dynamic structural changes to 3d TM-based perovskites during OER. Herein, through variations in the A- and B-site compositions of An+1BnO3n+1 oxides (n = 1 (A2BO4) or n = ∞ (ABO3); A = La, Sr, Ca; B = Mn, Fe, Co, Ni), we show that, in the absence of electrolyte impurities, surface restructuring is universally the source of high OER activity in these oxides and is dependent on the initial oxide composition. Oxide surface restructuring is induced by irreversible A-site cation dissolution, resulting in in situ formation of a TM oxyhydroxide shell on top of the parent oxide core that serves as the active surface for OER. The rate of surface restructuring is found to depend on (i) composition of A-site cations, with alkaline-earth-metal cations dominating lanthanide cation dissolution, (ii) oxide crystal phase, with n = 1 A2BO4 oxides exhibiting higher rates of A-site dissolution in comparison to n = ∞ ABO3 perovskites, (iii) lattice strain in the oxide induced by mixed rare-earth- and alkaline-earth-metal cations in the A-site, and (iv) oxide reducibility. Among the in situ generated 3d TM oxyhydroxide structures from An+1BnO3n+1 oxides, Co-based structures are characterized by superior OER activity and stability, even in comparison to as-synthesized Co-oxyhydroxide, pointing to the generation of high active surface area structures through oxide restructuring. These insights are critical toward the development of revised design criteria to include surface dynamics for effectively describing the OER activity of nonstoichiometric mixed-metal oxides.

Food acquisition is an important modulator of animal behavior and habitat selection that can affect fitness. Optimal foraging theory predicts that predators should select habitat patches to maximize their foraging success and net energy gain, likely achieved by targeting areas with high prey availability. However, it is debated whether prey availability drives fine‐scale habitat selection for predators. We assessed whether an ambush predator, the timber rattlesnake (Crotalus horridus), exhibits optimal foraging site selection based on the spatial distribution and availability of prey. We used passive infrared camera trap detections of potential small mammal prey (Peromyscus spp., Tamias striatus, and Sciurus spp.) to generate variables of prey availability across the study area and used whether a snake was observed in a foraging location or not to model optimal foraging in timber rattlesnakes. Our models of small mammal spatial distributions broadly predicted that prey availability was greatest in mature deciduous forests, but T. striatus and Sciurus spp. exhibited greater spatial heterogeneity compared with Peromyscus spp. We found the spatial distribution of cumulative small mammal encounters (i.e., overall prey availability), rather than the distribution of any one species, to be highly predictive of snake foraging. Timber rattlesnakes appear to forage where the probability of encountering prey is greatest. Our study provides evidence for fine‐scale optimal foraging in a low‐energy, ambush predator and offers new insights into drivers of snake foraging and habitat selection., We assessed whether the spatial distribution and availability of potential prey influence foraging site selection in a low‐energy ambush predator, the timber rattlesnake. We found the spatial distribution of cumulative small mammal encounters (i.e. overall prey availability), rather than the distribution of any one prey species, to be highly predictive of snake foraging. We demonstrate that optimal foraging theory may be applicable to the habitat selection of low‐energy ambush predators.

Catch data from bottom trawl surveys are used in various ways (e.g. stock assessments, fisheries management, and ecosystem studies) to represent trends in fish populations across space, time, season, or size. Relative abundance indices assume constant capture efficiency, and area-swept abundance requires an estimate of capture efficiency. Therefore, it is important to develop a predictive understanding of the interaction between fish and survey gear. We conducted experiments to test two primary factors that influence the efficiency of survey trawls at capturing demersal groundfish: (1) footrope escapement—estimated by attaching a collection bag beneath the primary trawl, and (2) herding of the sweeps/doors—estimated by varying sweep length. Random forest models were used to disentangle the herding effect from patterns caused by environmental variables. Contrary to common assumptions, footrope efficiency was incomplete (< 100%) and herding was non-trivial (> 0%), which introduces a bias in population metrics that rely on such assumptions. This bias varied by species and depended upon the relative strength of the counteracting effects of footrope escapement and herding. Our findings suggest that trawl efficiency should be estimated (not assumed) to derive area-swept abundance, and relative abundance indices should account for size-based efficiency and changing size compositions.

Transcriptional regulation, a pivotal biological process by which cells adapt to environmental fluctuations, is achieved by the binding of transcription factors to target sequences in a sequence-specific manner. However, how transcription factors recognize the correct target from amongst the numerous candidates in a genome has not been fully elucidated. We here show that, in the fission-yeast fbp1 gene, when transcription factors bind to target sequences in close proximity, their binding is reciprocally stabilized, thereby integrating distinct signal transduction pathways. The fbp1 gene is massively induced upon glucose starvation by the activation of two transcription factors, Atf1 and Rst2, mediated via distinct signal transduction pathways. Atf1 and Rst2 bind to the upstream-activating sequence 1 region, carrying two binding sites located 45 bp apart. Their binding is reciprocally stabilized due to the close proximity of the two target sites, which destabilizes the independent binding of Atf1 or Rst2. Tup11/12 (Tup-family co-repressors) suppress independent binding. These data demonstrate a previously unappreciated mechanism by which two transcription-factor binding sites, in close proximity, integrate two independent-signal pathways, thereby behaving as a hub for signal integration.

Background Multiple studies have described acute effects of the Covid-19 infection on the heart, but little is known about the long-term cardiac and pulmonary effects and complications after recovery. The aim of this analysis was to deliver a comprehensive report of symptoms and possible long-term impairments after hospitalization because of Covid-19 infection as well as to try to identify predictors for Long-Covid. Methods This was a prospective, multicenter registry study. Patients with verified Covid-19 infection, who were treated as in-patients at our dedicated Covid hospital (Clinic Favoriten), have been included in this study. In all patients, testing was performed approximately 6 months post discharge. During the study visit the following tests and investigations were performed: detailed patient history and clinical examination, transthoracic echocardiography, electrocardiography, cardiac magnetic resonance imaging (MRI), chest computed tomography (CT) scan, lung function test and a comprehensive list of laboratory parameters including cardiac bio markers. Results Between July 2020 and October 2021, 150 patients were recruited. Sixty patients (40%) were female and the average age was 53.5±14.5 years. Of all patients, 92% had been admitted to our general ward and 8% had a severe course of disease, requiring admission to our intensive care unit. Six months after discharge the majority of patients still experienced symptoms and 75% fulfilled the criteria for Long-Covid. Only 24% were completely asymptomatic (figure 1). Echocardiography detected reduced global longitudinal strain (GLS) in 11%. Cardiac MRI revealed pericardial effusion in 18%. Furthermore, cardiac MRI showed signs of former peri- or myocarditis in 4%. Pulmonary CT scans identified post-infectious residues, such as bilateral ground glass opacities and fibrosis in 22%. Exertional dyspnea was associated with either reduced forced vital capacity measured during pulmonary function tests in 11%, with reduced GLS and/or diastolic dysfunction, thus providing evidence for a cardiac and/or pulmonary cause. Independent predictors for Long-Covid were markers of a more severe disease course like length of in-hospital stay, admission to an intensive care unit, type of ventilation as well as higher NT-proBNP and/or troponin levels. Conclusion Even 6 months after recovery from Covid-19 infection, the majority of previously hospitalized patients still suffer from at least one symptom, such as chronic fatigue and/or exertional dyspnea. While there was no association between fatigue and cardiopulmonary abnormalities, impaired lung function, reduced GLS and/or diastolic dysfunction were significantly more prevalent in patients presenting with exertional dyspnea. On chest CT approximately one fifth of all patients showed post infectious changes in chest CT including evidence for myo- and pericarditis as well as accumulation of pericardial effusions. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Major fund

OBJECTIVE: Exposure to sex hormones is important in the pathogenesis of breast cancer and inability to tolerate such exposure may be reflected in increased asymmetrical growth of the breasts. This study aims to characterize, for the first time, asymmetry in breast volume (BV) and radiodense volume (DV) in a large ethnically diverse population. METHODS: Automated measurements from digital raw mammographic images of 54,591 cancer-free participants (aged 47–73) in a UK breast screening programme were used to calculate absolute (cm(3)) and relative asymmetry in BV and DV. Logistic regression models were fitted to assess asymmetry associations with age and ethnicity. RESULTS: BV and DV absolute asymmetry were positively correlated with the corresponding volumetric dimension (BV or DV). BV absolute asymmetry increased, whilst DV absolute asymmetry decreased, with increasing age (P-for-linear-trend

Hypoxemia, a medical condition that occurs when the blood is not carrying enough oxygen to adequately supply the tissues, is a leading indicator for dangerous complications of respiratory diseases like asthma, COPD, and COVID-19. While purpose-built pulse oximeters can provide accurate blood-oxygen saturation (SpO2) readings that allow for diagnosis of hypoxemia, enabling this capability in unmodified smartphone cameras via a software update could give more people access to important information about their health. Towards this goal, we performed the first clinical development validation on a smartphone camera-based SpO2 sensing system using a varied fraction of inspired oxygen (FiO2) protocol, creating a clinically relevant validation dataset for solely smartphone-based contact PPG methods on a wider range of SpO2 values (70–100%) than prior studies (85–100%). We built a deep learning model using this data to demonstrate an overall MAE = 5.00% SpO2 while identifying positive cases of low SpO2

Single-atom catalysts (SACs) often exhibit dynamic responses to the reaction and pretreatment environment that affect their activity. The lack of understanding of these behaviors hinders the development of effective, stable SACs, and makes their investigations rather difficult. Here we report a reduction-oxidation cycle that induces nearly 5-fold activity enhancement on Pt/TiO2 SACs for the reverse water-gas shift (rWGS) reaction. We combine microscopy (STEM) and spectroscopy (XAS and IR) studies with kinetic measurements, to convincingly show that the low activity on the fresh SAC is a result of limited accessibility of Pt single atoms (Pt1) due to high Pt-O coordination. The reduction step mobilizes Pt1, forming small, amorphous, and unstable Pt aggregates. The reoxidation step redisperses Pt into Pt1, but in a new, less O-coordinated chemical environment that makes the single metal atoms more accessible and, consequently, more active. After the cycle, the SAC exhibits superior rWGS activity to nonatomically dispersed Pt/TiO2. During the rWGS, the activated Pt1 experience slow deactivation, but can be reactivated by mild oxidation. This work demonstrates a clear picture of how the structural evolution of Pt/TiO2 SACs leads to ultimate catalytic efficiency, offering desired understanding on the rarely explored dynamic chemical environment of supported single metal atoms and its catalytic consequences.

AIMS Two guidelines for haemodialysis in lithium poisoning, one from the Extracorporeal TReatments in Poisoning (EXTRIP) workgroup and a single centre retrospective one (Paris) differ. We compared outcomes in lithium poisoning based on these criteria with a primary outcome of worsening neurological symptoms in patients for whom EXTRIP and Paris criteria were discordant. METHODS Poison centre data were queried for lithium poisoned patients for whom haemodialysis was either recommended or performed. Patients were categorized according to EXTRIP and Paris criteria and excluded if the peak lithium concentration was

The atomic scale structure of the active sites in heterogeneous catalysts is central to their reactivity and selectivity. Therefore, understanding active site stability and evolution under different reaction conditions is key to the design of efficient and robust catalysts. Herein we describe theoretical calculations which predict that carbon monoxide can be used to stabilize different active site geometries in bimetallic alloys and then demonstrate experimentally that the same PdAu bimetallic catalyst can be transitioned between a single-atom alloy and a Pd cluster phase. Each state of the catalyst exhibits distinct selectivity for the dehydrogenation of ethanol reaction with the single-atom alloy phase exhibiting high selectivity to acetaldehyde and hydrogen versus a range of products from Pd clusters. First-principles based Monte Carlo calculations explain the origin of this active site ensemble size tuning effect, and this work serves as a demonstration of what should be a general phenomenon that enables in situ control over catalyst selectivity., Single-atom alloys are promising catalysts for a number of different reactions. Here, the authors demonstrate that carbon monoxide can be used to transition a PdAu catalyst between a single atom and a cluster phase which exhibit distinct selectivities for ethanol dehydrogenation.

MotivationWith the rapidly growing volume of knowledge and data in biomedical databases, improved methods for knowledge-graph-based computational reasoning are needed in order to answer translational questions. Previous efforts to solve such challenging computational reasoning problems have contributed tools and approaches, but progress has been hindered by the lack of an expressive analysis workflow language for translational reasoning and by the lack of a reasoning engine—supporting that language—that federates semantically integrated knowledge-bases.ResultsWe introduce ARAX, a new reasoning system for translational biomedicine that provides a web browser user interface and an application programming interface. ARAX enables users to encode translational biomedical questions and to integrate knowledge across sources to answer the user’s query and facilitate exploration of results. For ARAX, we developed new approaches to query planning, knowledge-gathering, reasoning, and result ranking and dynamically integrate knowledge providers for answering biomedical questions. To illustrate ARAX’s application and utility in specific disease contexts, we present several use-case examples.Availability and ImplementationThe source code and technical documentation for building the ARAX server-side software and its built-in knowledge database are freely available online (https://github.com/RTXteam/RTX). We provide a hosted ARAX service with a web browser interface at arax.rtx.ai and a web application programming interface (API) endpoint at arax.rtx.ai/api/arax/v1.3/ui/.Contactdmk333@psu.edu

Vesicular disease caused by Senecavirus A (SVA) is clinically indistinguishable from foot-and-mouth disease (FMD) and other vesicular diseases of swine. When a vesicle is observed in FMD-free countries, a costly and time-consuming foreign animal disease investigation (FADI) is performed to rule out FMD. Recently, there has been an increase in the number of FADIs and SVA positive samples at slaughter plants in the U.S. The objectives of this investigation were to: (1) describe the environmental burden of SVA in sow slaughter plants; (2) determine whether there was a correlation between PCR diagnostics, virus isolation (VI), and swine bioassay results; and (3) phylogenetically characterize the genetic diversity of contemporary SVA isolates. Environmental swabs were collected from three sow slaughter plants (Plants 1-3) and one market-weight slaughter plant (Plant 4) between June to December 2020. Of the 426 samples taken from Plants 1-3, 304 samples were PCR positive and 107 were VI positive. There was no detection of SVA by PCR or VI at Plant 4. SVA positive samples were most frequently found in the summer (78.3% June-September, vs. 59.4% October-December), with a peak at 85% in August. Eighteen PCR positive environmental samples with a range of Ct values were selected for a swine bioassay: a single sample infected piglets (n = 2). A random subset of the PCR positive samples was sequenced; and phylogenetic analysis demonstrated co-circulation and divergence of two genetically distinct groups of SVA. These data demonstrate that SVA was frequently found in the environment of sow slaughter plants, but environmental persistence and diagnostic detection was not indicative of whether a sampled was infectious to swine. Consequently, a more detailed understanding of the epidemiology of SVA and its environmental persistence in the marketing chain is necessary to reduce the number of FADIs and aide in the development of control measures to reduce the spread of SVA.

Dyslipidemia is a common co-morbidity of insulin resistance, where chronic elevations in hepatic and intestinal lipoproteins are linked to cardiovascular disease. Postprandial production is regulated in-part by gut-derived hormones such as glucagon-like peptide (GLP) -1. Although degradation-resistant analogs of GLP-1 continue to work in diabetic individuals, none have examined whether GLP-1s endogenous neuroendocrine signalling pathways are affected by diet-induced dyslipidemia. Thus, we sought to test whether native GLP-1 could modulate postprandial lipids in a fructose-fed hamster model.Hamsters were fed either a chow or fructose-enriched (FF) diet for 14 days, then received a portal vein injection of either GLP-1 (7-36) or vehicle control to examine if they remained responsive to portal GLP-1. Separately, in hamsters fed either chow or a fat/fructose/cholesterol enriched (FFC) diet we performed nodose ganglia (NG) injections with GLP-1 (7-36) or vehicle. To recapitulate the loss of vagal GLP-1R signalling in the absence of dietary intervention we selectively deafferented GLP-1R containing NG neurons via injection of the cytotoxin saporin conjugated to exendin-4. After treatment, animals received a gavage of olive oil and an intraperitoneal injection of poloxamer to prevent lipoprotein clearance. Postprandial triglyceride-rich lipoproteins isolated via density ultracentrifugation were assessed via blood draws over a 6-hour period.Chow-fed hamsters saw significant reductions in post-prandial lipids after portal GLP-1 injection, whereas FF-fed hamsters were unaffected. Chow-fed hamsters were similarly responsive to GLP-1 (7-36) injection into the NG, displaying reduced postprandial lipids; however, FFC-fed hamsters showed no reduction in plasma lipids. Finally, selective deafferentation of NG GLP-1R-containing neurons caused significant rises in postprandial TG and TRL, underscoring the importance of GLP-1R insensitivity in states of metabolic disease. Disclosure S.S.Hoffman: None. D.C.Alvares: None. K.Adeli: None. Funding CIHR Foundation Grant

Fasting dyslipidemia is characterized by a lipid profile with elevated triglycerides, increased small dense LDL and low HDL-cholesterol, and is a commonly comorbid with insulin resistance. Bile acid (BA) signalling has been suggested to improve hepatic insulin sensitivity and lipid accumulation through activation of the Takeda G protein-coupled receptor 5 (TGR5) . As the role of TGR5 in regulating hepatic lipid and lipoprotein metabolism has not been explored, the present study was performed to characterize the role of bile acid signaling via TGR5 in hepatic lipid and lipoprotein metabolism. We have recently developed novel Tgr5-/- and GLP1R-/- hamster models. Tgr5+/+ and Tgr5-/ - hamsters were fed a high fat, high fructose, and low cholesterol (FFLC) diet for 6 weeks. Glucose tolerance, insulin tolerance, and fasting plasma lipids were examined at baseline, and following 6-weeks on diet. Loss of TGR5 signalling appeared to be initially protective against diet induced hypertriglyceridemia, however this effect was lost with prolonged feeding. Following 6 weeks of diet, Tgr5-/ - hamsters were less glucose tolerant, with similar insulin sensitivity. Fasting plasma deoxycholic acid (DCA) and taurocholic acid (TCA) compositions differed under chow fed conditions, with additional changes in postprandial DCA, TCA and cholic acid (CA) . Finally, chow fed Tgr5+/+ and Tgr5-/ - hamsters received intraduodenal injections (IDI) of DCA or TCA. Both DCA and TCA administration were associated with reduced VLDL-triglyceride secretion in Tgr5+/+ hamsters, an effect that was blunted in Tgr5-/ -hamsters. The lipid lowering effects of DCA were similarly blunted in GLP1R-/- hamsters, suggesting this effect is dependent on GLP-1R signalling. The present research will set a framework to expand our knowledge of the role of BA signaling through TGR5 in hepatic lipogenesis. Disclosure D.C.L.Alvares: None. S.S.Hoffman: None. K.Adeli: None.

Calcium channel blockers (CCBs) are commonly used to treat conditions such as arterial hypertension and supraventricular dysrhythmias. Poisoning from these drugs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in the management of CCB poisoning.We conducted systematic reviews of the literature, screened studies, extracted data, summarized findings, and formulated recommendations following published EXTRIP methods.A total of 83 publications (6Both dialyzability and clinical data do not support a clinical benefit from ECTRs for CCB poisoning. The EXTRIP workgroup recommends against using extracorporeal methods to enhance the elimination of amlodipine, diltiazem, and verapamil in patients with severe poisoning.

Anion gap metabolic acidosis (AGMA) is common in patients presenting for emergency care. While some disease processes and ingestions are easily excluded, diagnosing toxic alcohol (TA) ingestion can be challenging. This is especially true if drug concentrations are not readily available, which forces clinicians to rely on surrogate markers. Like TA ingestion, alcoholic ketoacidosis (AKA) produces an elevated osmol gap and an AGMA. The aim of this study was to identify risk factors suggestive of AKA when TA ingestion was the primary alternative differential diagnosis. We hypothesized that the odds of an AKA diagnosis would increase as ethanol concentration increased.This was a retrospective analysis of data from 2000 through 2019 from a single US Poison Control Center. Records were reviewed to identify cases coded as "methanol" or "ethylene glycol"; or coded as "alcohol" or "ethanol with acidosis." The case definition for AKA required: (1) documented alcohol use disorder; (2) urine or serum ketones or elevated blood beta-hydroxybutyrate concentration; (3) anion gap ≥ 14 mmol/L. The inclusion criterion for TAs was a detectable methanol or ethylene glycol concentration.Of 699 patients screened, 86 were diagnosed with AKA and 36 were diagnosed with TA ingestion. As ethanol concentration increased, the odds of an AKA diagnosis significantly increased (OR = 1.016, 95% CI 1.002-1.031,In this retrospective analysis, the odds of diagnosing AKA instead of TA ingestion increased as ethanol concentration increased. The limited ability of common clinical factors to differentiate these diagnoses highlights the need to obtain quantitative TA concentrations in real time. Until prospective validation, interpretation of ketone concentrations and toxic alcohol concentrations (when available) will continue to guide decision making.

Recently metal carbide catalysts have attracted attention as alternatives to pure metals for the conversion of syngas to higher oxygenates, a process which could enable the sustainable production of fuels, polymers, and chemicals. Although Mo and Co carbides have both shown promise for higher oxygenate production, they have not achieved the requisite activity and selectivity for practical implementation. In this work we synthesize and characterize a binary Mo and Co carbide catalyst that exhibits improved activity and oxygenate selectivity relative to either pure metal carbide. We apply a combination of advanced electron microscopy and X-ray diffraction to show that the binary Mo/Co carbide catalyst forms uniformly mixed amorphous nanoparticles. Through in situ X-ray absorption spectroscopy studies, we determine that the structure of the mixed metal carbide catalyst under reaction conditions consists of both carbidic and bimetallic components. By testing the catalytic properties of a series of Mo/Co carbide catalysts prepared by different synthesis methods, we find that the Mo and Co sites must be in close contact to achieve improved syngas conversion to higher alcohols. Through in situ DRIFTS measurements, both Mo and Co atoms at the surface of the catalyst are identified as adsorption sites for reactive species.

An understanding of the fundamentals of the reaction between CuO with trace amounts of H2S to form CuS products is critical for the optimal utilization of this process in sulfur removal applications. Unfortunately, CuS is a complex material, featuring various Cu2-xS compounds (with 0 ≤ x ≤ 1), distorted crystal phases, and varying electronic structures and coordination environments of Cu and S ions. In this work, we combine ex situ and in situ X-ray absorption spectroscopy (XAS) at S and Cu K edges, fixed bed sorption experiments, DFT simulations, and other characterization techniques to speciate the CuS products formed at different temperatures (298-383 K) and from CuO sorbents with different crystallite sizes (2.8-40 nm). The results of our analysis identify the formation of a distorted CuS layer at the surface of CuO crystals with disulfide groups with shorter Cu-S bonds and higher delocalization of the positive charge of the Cu center into (S1-)2. This distorted CuS layer dominates the XAS signal at lower temperatures (298-323 K) and at the initial stages of sulfidation at higher temperatures (353 and 383 K) where conversion is low (