Stable chalcogenide Ge-Sb-Te heterostructures with minimal Ge segregation.

Matching of various chalcogenide films shows the advantage of delivering multilayer heterostructures whose physical properties can be tuned with respect to the ones of the constituent single films. In this work, (Ge-Sb-Te)-based heterostructures were deposited by radio frequency sputtering on Si(100) substrates and annealed up to 400 °C. The as-deposited and annealed samples were studied by means of X-ray fluorescence, X-ray diffraction, scanning transmission electron microscopy, electron energy loss spectroscopy and Raman spectroscopy. The heterostructures, combining thermally stable thin layers (i. e. Ge-rich Ge5.5Sb2Te5, Ge) and films exhibiting fast switching dynamics (i. e. Sb2Te3), show, on the one side, higher crystallization-onset temperatures than the standard Ge2Sb2Te5 alloy and, on the other side, none to minimal Ge-segregation.

Synthesis and Properties of the Helium Clathrate and Defect Perovskite [He2-x □ x ][CaNb]F6.

The defect double perovskite [He2-x □ x ][CaNb]F6, with helium on its A-site, can be prepared by the insertion of helium into ReO3-type CaNbF6 at high pressure. Upon cooling from 300 to 100 K under 0.4 GPa helium, ∼60% of the A-sites become occupied. Helium uptake was quantified by both neutron powder diffraction and gas insertion and release measurements. After the conversion of gauge pressure to fugacity, the uptake of helium by CaNbF6 can be described by a Langmuir isotherm. The enthalpy of absorption for helium in [He2-x □ x ][CaNb]F6 is estimated to be ∼+3(1) kJ mol-1, implying that its formation is entropically favored. Helium is able to diffuse through the material on a time scale of minutes at temperatures down to ∼150 K but is trapped at 100 K and below. The insertion of helium into CaNbF6 reduces the magnitude of its negative thermal expansion, increases the bulk modulus, and modifies its phase behavior. On compressing pristine CaNbF6, at 50 and 100 K, a cubic (Fm3̅m) to rhombohedral (R3̅) phase transition was observed at <0.20 GPa. However, a helium-containing sample remained cubic at 0.4 GPa and 50 K. CaNbF6, compressed in helium at room temperature, remained cubic to >3.7 GPa, the limit of our X-ray diffraction measurements, in contrast to prior reports that upon compression in a nonpenetrating medium, a phase transition is detected at ∼0.4 GPa.

Three-Component Gold(I)-Catalyzed Alkoxyvinylation.

Acetylene has been underexploited despite being a highly valuable feedstock for chemical synthesis. We have developed the first true gold(I)-catalyzed intermolecular three-component reaction between acetylene, alkenes, and alcohols to afford ß-vinyl hemiaminal scaffolds from N-vinyl amides. Unusual biscyclopropyl and 3-vinyl N-heterocyclic scaffolds were obtained through the incorporation of a second N-vinyl unit or tethered alkene into the starting material.

Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis Attenuates Disparity in Outcomes Between Use of Matched or Mismatched Unrelated Donors.

PURPOSE: Access to allogeneic hematopoietic cell transplantation (HCT) remains limited among persons of non-European ancestry if human leukocyte antigen (HLA) matching is required. We evaluated whether post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis improved HCT outcomes with HLA-matched unrelated donor (MUD) and mismatched unrelated donor (MMUD) HCT when compared with calcineurin inhibitor (CNI)-based prophylaxis. METHODS: Three-year overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were compared between adult recipients undergoing initial MUD or single HLA locus MMUD HCT with either PTCy- or CNI-based prophylaxis who were reported to the Center for International Blood and Marrow Transplant Research between 2017 and 2021. RESULTS: Included were 10,025 HCT recipients (7,272 recipients of MUD with CNI, 1,681 MUD with PTCy, 613 MMUD with CNI, and 459 MMUD with PTCy) who underwent HCT for acute leukemia (70.9%) or myelodysplastic syndromes (29.2%). Median patient age was 60.7 years (range, 18.0-82.7) and median follow-up was 36.6 (range, 3.0-77.8) months. When compared with MUD HCT with PTCy, MMUD HCT with PTCy had similar OS (hazard ratio [HR], 0.96 [95% CI, 0.823 to 1.11]; P = .60) and GRFS (HR, 0.90 [0.79 to 1.02]; P = .1). When compared with MUD HCT with CNI, OS was improved after MUD HCT with PTCy (HR, 0.88 [0.80 to 0.96]; P = .004) and GRFS was improved with PTCy after either MUD (HR, 0.61 [0.57 to 0.66]; P < .0001) or MMUD (HR, 0.68 [0.60 to 0.76]; P < .0001) HCT. Benefit from PTCy was independent of patient ancestry. Global registry level analysis demonstrated that inclusion of MMUD increased donor availability regardless of recipient ancestry. CONCLUSION: Use of PTCy results in comparable OS and GRFS using either MUD or MMUD HCT, expanding access to HCT for patients from all racial and ethnic ancestry groups.

Southern marsh deer (Blastocerus dichotomus) populations assessed using Amplicon Sequencing on fecal samples.

Populations in isolated and small fragments lose genetic variability very fast and are usually of conservation concern because they are at greater risk of local extinction. The largest native deer in South America, Blastocerus dichotomus (Illiger, 1815), is a Vulnerable species according to the IUCN categorization, which inhabits tropical and subtropical swampy areas. In Argentina, its presence has been restricted to four isolated fragments. Here we examine the genetic diversity and differentiation among three of them, including the three different patches that form the southernmost population, using 18 microsatellite markers genotyped by Amplicon Sequencing of DNA extracted from fecal samples. Genetic diversity was low (HE < 0.45) in all three populations studied. We found three genetic clusters compatible with the geographic location of the samples. We also found a metapopulation dynamics that involves the patches that make up the southernmost population, with evidence of a barrier to gene flow between two of them. Our results point to the creation of a corridor as a necessary and urgent management action. This is the first study, at the population level, employing microsatellite genotyping by Amplicon Sequencing with non-invasive samples in an endangered species.

The role of microbial communities in biogeochemical cycles and greenhouse gas emissions within tropical soda lakes.

Although anthropogenic activities are the primary drivers of increased greenhouse gas (GHG) emissions, it is crucial to acknowledge that wetlands are a significant source of these gases. Brazil's Pantanal, the largest tropical inland wetland, includes numerous lacustrine systems with freshwater and soda lakes. This study focuses on soda lakes to explore potential biogeochemical cycling and the contribution of biogenic GHG emissions from the water column, particularly methane. Both seasonal variations and the eutrophic status of each examined lake significantly influenced GHG emissions. Eutrophic turbid lakes (ET) showed remarkable methane emissions, likely due to cyanobacterial blooms. The decomposition of cyanobacterial cells, along with the influx of organic carbon through photosynthesis, accelerated the degradation of high organic matter content in the water column by the heterotrophic community. This process released byproducts that were subsequently metabolized in the sediment leading to methane production, more pronounced during periods of increased drought. In contrast, oligotrophic turbid lakes (OT) avoided methane emissions due to high sulfate levels in the water, though they did emit CO2 and N2O. Clear vegetated oligotrophic turbid lakes (CVO) also emitted methane, possibly from organic matter input during plant detritus decomposition, albeit at lower levels than ET. Over the years, a concerning trend has emerged in the Nhecolândia subregion of Brazil's Pantanal, where the prevalence of lakes with cyanobacterial blooms is increasing. This indicates the potential for these areas to become significant GHG emitters in the future. The study highlights the critical role of microbial communities in regulating GHG emissions in soda lakes, emphasizing their broader implications for global GHG inventories. Thus, it advocates for sustained research efforts and conservation initiatives in this environmentally critical habitat.

Genomic Characterization of Piscicolin CM22 Produced by Carnobacterium maltaromaticum CM22 Strain Isolated from Salmon (Salmo salar).

Carnobacterium maltaromaticum is a species of lactic acid bacteria (LAB) that has been isolated from various natural environments. It is well-known for producing a diverse spectrum of bacteriocins with potential biotechnological applications. In the present study, a new psychrotolerant strain of C. maltaromaticum CM22 is reported, isolated from a salmon gut sample and producing a variant of the bacteriocin piscicolin 126 that has been named piscicolin CM22. After identification by 16S rRNA gene, this strain has been genomically characterized by sequencing and assembling its complete genome. Moreover, its bacteriocin was purified and characterized. In vitro tests demonstrated that both the strain and its bacteriocin possess antimicrobial activity against several Gram-positive bacteria of interest in human and animal health, such as Listeria monocytogenes, Clostridium perfringens, or Enterococcus faecalis. However, this bacteriocin did not produce any antimicrobial effect on Gram-negative species. The study of its genome showed the genetic structure of the gene cluster that encodes the bacteriocin, showing a high degree of homology to the gene cluster of piscicolin 126 described in other C. maltaromaticum. Although more studies are necessary concerning its functional properties, this new psychrotolerant strain C. maltaromaticum CM22 and its bacteriocin could be considered an interesting candidate with potential application in agri-food industry.

Biallelic variants in POPDC2 cause a novel autosomal recessive syndrome presenting with cardiac conduction defects and variable hypertrophic cardiomyopathy.

POPDC2 encodes for the Popeye domain-containing protein 2 which has an important role in cardiac pacemaking and conduction, due in part to its cAMP-dependent binding and regulation of TREK-1 potassium channels. Loss of Popdc2 in mice results in sinus pauses and bradycardia and morpholino knockdown of popdc2 in zebrafish results in atrioventricular (AV) block. We identified bi-allelic variants in POPDC2 in 4 families that presented with a phenotypic spectrum consisting of sinus node dysfunction, AV conduction defects and hypertrophic cardiomyopathy. Using homology modelling we show that the identified POPDC2 variants are predicted to diminish the ability of POPDC2 to bind cAMP. In in vitro electrophysiological studies we demonstrated that, while co-expression of wild-type POPDC2 with TREK-1 increased TREK-1 current density, POPDC2 variants found in the patients failed to increase TREK-1 current density. While patient muscle biopsy did not show clear myopathic disease, it showed significant reduction of the expression of both POPDC1 and POPDC2, suggesting that stability and/or membrane trafficking of the POPDC1-POPDC2 complex is impaired by pathogenic variants in any of the two proteins. Single-cell RNA sequencing from human hearts demonstrated that co-expression of POPDC1 and 2 was most prevalent in AV node, AV node pacemaker and AV bundle cells. Sinoatrial node cells expressed POPDC2 abundantly, but expression of POPDC1 was sparse. Together, these results concur with predisposition to AV node disease in humans with loss-of-function variants in POPDC1 and POPDC2 and presence of sinus node disease in POPDC2, but not in POPDC1 related disease in human. Using population-level genetic data of more than 1 million individuals we showed that none of the familial variants were associated with clinical outcomes in heterozygous state, suggesting that heterozygous family members are unlikely to develop clinical manifestations and therefore might not necessitate clinical follow-up. Our findings provide evidence for POPDC2 as the cause of a novel Mendelian autosomal recessive cardiac syndrome, consistent with previous work showing that mice and zebrafish deficient in functional POPDC2 display sinus and AV node dysfunction.

Re-assessing thermal response of schistosomiasis transmission risk: Evidence for a higher thermal optimum than previously predicted.

The geographical range of schistosomiasis is affected by the ecology of schistosome parasites and their obligate host snails, including their response to temperature. Previous models predicted schistosomiasis' thermal optimum at 21.7°C, which is not compatible with the temperature in sub-Saharan Africa (SSA) regions where schistosomiasis is hyperendemic. We performed an extensive literature search for empirical data on the effect of temperature on physiological and epidemiological parameters regulating the free-living stages of S. mansoni and S. haematobium and their obligate host snails, i.e., Biomphalaria spp. and Bulinus spp., respectively. We derived nonlinear thermal responses fitted on these data to parameterize a mechanistic, process-based model of schistosomiasis. We then re-cast the basic reproduction number and the prevalence of schistosome infection as functions of temperature. We found that the thermal optima for transmission of S. mansoni and S. haematobium range between 23.1-27.3°C and 23.6-27.9°C (95% CI) respectively. We also found that the thermal optimum shifts toward higher temperatures as the human water contact rate increases with temperature. Our findings align with an extensive dataset of schistosomiasis prevalence in SSA. The refined nonlinear thermal-response model developed here suggests a more suitable current climate and a greater risk of increased transmission with future warming for more than half of the schistosomiasis suitable regions with mean annual temperature below the thermal optimum.

Radiotherapy Plan Quality Assurance in NRG Oncology Trials for Brain and Head/Neck Cancers: An AI-Enhanced Knowledge-Based Approach.

The quality of radiation therapy (RT) treatment plans directly affects the outcomes of clinical trials. KBP solutions have been utilized in RT plan quality assurance (QA). In this study, we evaluated the quality of RT plans for brain and head/neck cancers enrolled in multi-institutional clinical trials utilizing a KBP approach. The evaluation was conducted on 203 glioblastoma (GBM) patients enrolled in NRG-BN001 and 70 nasopharyngeal carcinoma (NPC) patients enrolled in NRG-HN001. For each trial, fifty high-quality photon plans were utilized to build a KBP photon model. A KBP proton model was generated using intensity-modulated proton therapy (IMPT) plans generated on 50 patients originally treated with photon RT. These models were then applied to generate KBP plans for the remaining patients, which were compared against the submitted plans for quality evaluation, including in terms of protocol compliance, target coverage, and organ-at-risk (OAR) doses. RT plans generated by the KBP models were demonstrated to have superior quality compared to the submitted plans. KBP IMPT plans can decrease the variation of proton plan quality and could possibly be used as a tool for developing improved plans in the future. Additionally, the KBP tool proved to be an effective instrument for RT plan QA in multi-center clinical trials.

Structural characterization of cholesterol-rich nanoemulsion (LDE).

Cholesterol-rich nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and can concentrate those agents in the neoplastic and inflammatory tissues. This method improves the biodistribution of the drug and reduces toxicity. However, the structural stability of LDE particles, without or with associated drugs, has not been extensively investigated. The aim of the present study is to investigate the structural stability of LDE and LDE associated to paclitaxel, etoposide or methotrexate in aqueous solution over time by small-angle X-ray scattering (SAXS and Ultra SAXS) and dynamic light scattering (DLS). The results show that LDE and LDE associated with those chemotherapeutic agents had reproducible and stable particle diameter, physical structure, and aggregation behavior over 3-month observation period. As estimated from both DLS and Ultra-SAXS methods, performed at pre-established intervals, the average particle diameter of LDE alone was approx. 32 nm, of LDE-paclitaxel was 31 nm, of LDE-methotrexate was 35 nm and of LDE-etoposide was 36 nm. Ultra-SAXS analysis showed that LDE nanoparticles were quasi-spherical, and SAXS showed that drug molecules inside the particles showed a layered-like organization. Formulations of LDE with associated PTX, ETO or MTX were successfully tested in animal experiments and in patients with cancer or with cardiovascular disease, showing markedly low toxicity, good tolerability and possible superior pharmacological action. Our results may be useful for ensuing clinical trials of this novel Nanomedicine tool, by strengthening the knowledge of the structural aspects of those LDE formulations.

Arrhythmic Mitral Valve Prolapse Phenotype: An Unsupervised Machine Learning Analysis Using a Multicenter Cardiac MRI Registry.

Purpose To use unsupervised machine learning to identify phenotypic clusters with increased risk of arrhythmic mitral valve prolapse (MVP). Materials and Methods This retrospective study included patients with MVP without hemodynamically significant mitral regurgitation or left ventricular (LV) dysfunction undergoing late gadolinium enhancement (LGE) cardiac MRI between October 2007 and June 2020 in 15 European tertiary centers. The study end point was a composite of sustained ventricular tachycardia, (aborted) sudden cardiac death, or unexplained syncope. Unsupervised data-driven hierarchical k-mean algorithm was utilized to identify phenotypic clusters. The association between clusters and the study end point was assessed by Cox proportional hazards model. Results A total of 474 patients (mean age, 47 years ± 16 [SD]; 244 female, 230 male) with two phenotypic clusters were identified. Patients in cluster 2 (199 of 474, 42%) had more severe mitral valve degeneration (ie, bileaflet MVP and leaflet displacement), left and right heart chamber remodeling, and myocardial fibrosis as assessed with LGE cardiac MRI than those in cluster 1. Demographic and clinical features (ie, symptoms, arrhythmias at Holter monitoring) had negligible contribution in differentiating the two clusters. Compared with cluster 1, the risk of developing the study end point over a median follow-up of 39 months was significantly higher in cluster 2 patients (hazard ratio: 3.79 [95% CI: 1.19, 12.12], P = .02) after adjustment for LGE extent. Conclusion Among patients with MVP without significant mitral regurgitation or LV dysfunction, unsupervised machine learning enabled the identification of two phenotypic clusters with distinct arrhythmic outcomes based primarily on cardiac MRI features. These results encourage the use of in-depth imaging-based phenotyping for implementing arrhythmic risk prediction in MVP. Keywords: MR Imaging, Cardiac, Cardiac MRI, Mitral Valve Prolapse, Cluster Analysis, Ventricular Arrhythmia, Sudden Cardiac Death, Unsupervised Machine Learning Supplemental material is available for this article. © RSNA, 2024.

Re-assessing thermal response of schistosomiasis transmission risk: evidence for a higher thermal optimum than previously predicted.

The geographical range of schistosomiasis is affected by the ecology of schistosome parasites and their obligate host snails, including their response to temperature. Previous models predicted schistosomiasis' thermal optimum at 21.7 °C, which is not compatible with the temperature in sub-Saharan Africa (SSA) regions where schistosomiasis is hyperendemic. We performed an extensive literature search for empirical data on the effect of temperature on physiological and epidemiological parameters regulating the free-living stages of S. mansoni and S. haematobium and their obligate host snails, i.e., Biomphalaria spp. and Bulinus spp., respectively. We derived nonlinear thermal responses fitted on these data to parameterize a mechanistic, process-based model of schistosomiasis. We then re-cast the basic reproduction number and the prevalence of schistosome infection as functions of temperature. We found that the thermal optima for transmission of S. mansoni and S. haematobium range between 23.1-27.3 °C and 23.6-27.9 °C (95 % CI) respectively. We also found that the thermal optimum shifts toward higher temperatures as the human water contact rate increases with temperature. Our findings align with an extensive dataset of schistosomiasis prevalence in SSA. The refined nonlinear thermal-response model developed here suggests a more suitable current climate and a greater risk of increased transmission with future warming for more than half of the schistosomiasis suitable regions with mean annual temperature below the thermal optimum.

In vitro antiproliferative effects of Vatairea macrocarpa (Benth.) Ducke lectin on human tumor cell lines and in vivo evaluation of its toxicity in Drosophila melanogaster.

Tumor cells may develop alterations in glycosylation patterns during the initial phase of carcinogenesis. These alterations may be important therapeutic targets for lectins with antitumor action. This work aimed to evaluate the in vitro cytotoxicity of VML on tumor and non-tumor cells (concentration of 25 µg/mL and then microdiluted) and evaluate its in vivo toxicity at different concentrations (1.8, 3.5 and 7.0 µg/mL), using Drosophila melanogaster. Toxicity in D. melanogaster evaluated mortality rate, as well as oxidative stress markers (TBARS, iron levels, nitric oxide levels, protein and non-protein thiols). The cytotoxicity assay showed that VML had cytotoxic effect on leukemic lines HL-60 (IC50 = 3.5 µg/mL), KG1 (IC50 = 18.6 µg/mL) and K562 (102.0 µg/mL). In the toxicity assay, VML showed no reduction in survival at concentrations of 3.5 and 7.0 µg/mL and did not alter oxidative stress markers at any concentrations tested. Cytotoxicity of VML from HL-60, KG1 and K562 cells could arise from the interaction between the lectin and specific carbohydrates of tumor cells. In contrast, effective concentrations of VML against no-tumor cells human keratinocyte - HaCat and in the D. melanogaster model did not show toxicity, suggesting that VML is a promising molecule in vivo studies involving leukemic cells.

Cognitive, behavioral and socio-communication skills as predictors of response to Early Start Denver Model: a prospective study in 32 young children with Autism Spectrum Disorder.

Introduction: The effectiveness of early interventions in young autistic children is well established, but there is great interindividual variability in treatment response. Predictors of response to naturalistic developmental behavioral interventions (NDBI), like the Early Start Denver Model (ESDM), are needed. Methods: We conducted an exploratory study to prospectively seek predictors of response in 32 young children treated with ESDM after receiving an ASD diagnosis. All children were less than 39 months old (mean age: 29.7 mo), and received individualized ESDM for nine months. Tests were administered at the beginning, after 4 months, and at the end of treatment. Results: Four children (12.5%) were "strong responders", 8 children (25.0%) were "moderate responders", and 20 children (62.5%) were "poor responders". A more favorable response to ESDM was significantly predicted by higher PEP-3 Expressive Language, Receptive Language, Cognitive Verbal/Preverbal, Visuo-Motor Imitation scores, higher GMDS-ER Personal/Social, and VABS-II Communication scores, by lower ADI-R C restricted/stereotypic behaviors, and by joint attention level. Discussion: Most predictors showed a linear association with increasing response to ESDM, but GMDS-ER Personal-Social and joint attention level predicted strong response, while PEP-3 receptive language equally predicted moderate or strong response. Although larger samples will be necessary to reach definitive conclusions, in conjunction with prior reports our findings begin providing information able to assist clinicians in choosing the most appropriate treatment program for young autistic children.

Theoretical Investigation of the Lattice Thermal Conductivities of II-IV-V2 Pnictide Semiconductors.

Ternary pnictide semiconductors with II-IV-V2 stoichiometry hold potential as cost-effective thermoelectric materials with suitable electronic transport properties, but their lattice thermal conductivities (κ) are typically too high. Insights into their vibrational properties are therefore crucial to finding strategies to reduce κ and achieve improved thermoelectric performance. We present a theoretical exploration of the lattice thermal conductivities for a set of pnictide semiconductors with ABX2 composition (A = Zn, Cd; B = Si, Ge, Sn; and X = P, As) using machine-learning-based regression algorithms to extract force constants from a reduced number of density functional theory simulations and then solving the Boltzmann transport equation for phonons. Our results align well with available experimental data, decreasing the mean absolute error by ∼3 W m-1 K-1 with respect to the best previous set of theoretical predictions. Zn-based ternary pnictides have, on average, more than double the thermal conductivity of the Cd-based compounds. Anisotropic behavior increases with the mass difference between A and B cations, but while the nature of the anion does not affect the structural anisotropy, the thermal conductivity anisotropy is typically higher for arsenides than for phosphides. We identify compounds such as CdGeAs2, for which nanostructuring to an affordable range of particle sizes could lead to κ values low enough for thermoelectric applications.

Comparative Analysis of Atherogenic Lipoproteins L5 and Lp(a) in Atherosclerotic Cardiovascular Disease.

PURPOSE OF REVIEW: Low-density lipoprotein (LDL) poses a risk for atherosclerotic cardiovascular disease (ASCVD). As LDL comprises various subtypes differing in charge, density, and size, understanding their specific impact on ASCVD is crucial. Two highly atherogenic LDL subtypes-electronegative LDL (L5) and Lp(a)-induce vascular cell apoptosis and atherosclerotic changes independent of plasma cholesterol levels, and their mechanisms warrant further investigation. Here, we have compared the roles of L5 and Lp(a) in the development of ASCVD. RECENT FINDINGS: Lp(a) tends to accumulate in artery walls, promoting plaque formation and potentially triggering atherosclerosis progression through prothrombotic or antifibrinolytic effects. High Lp(a) levels correlate with calcific aortic stenosis and atherothrombosis risk. L5 can induce endothelial cell apoptosis and increase vascular permeability, inflammation, and atherogenesis, playing a key role in initiating atherosclerosis. Elevated L5 levels in certain high-risk populations may serve as a distinctive predictor of ASCVD. L5 and Lp(a) are both atherogenic lipoproteins contributing to ASCVD through distinct mechanisms. Lp(a) has garnered attention, but equal consideration should be given to L5.