Hydrothermal Synthesis Of Graphene Supported Pd/Fe 3 O 4 Nanoparticles As Efficient Magnetic Catalysts For Suzuki Cross – Coupling

This research reports a reproducible, reliable, and efficient method for preparing palladium nanoparticles dispersed on a composite of Fe3O4 and graphene as an active catalyst with high efficiency for being used in Suzuki cross – coupling reactions. Graphene supported Pd/Fe3O4 nanoparticles (Pd/Fe3O4 /G) exhibit a remarkable catalytic performance towards Suzuki coupling reactions. Moreover, the prepared catalyst recyclability was up to nine times without losing its high catalytic activity. The catalyst was prepared using hydrothermal synthesis; the prepared catalyst is magnetic in order to facilitate catalyst separation out of the reaction medium after reaction completion simply through using a strong magnet. This approach offers unique advantages including recyclability, mild reaction conditions, and reproducibility. Furthermore, the magnetic properties of the prepared catalyst made a huge enhancement to the ability to purify the reaction products from catalyst and other side products. The high catalytic performance and recyclability of the prepared catalyst are due to the strong interaction between the catalyst and the support. Moreover, the reduced GO nanosheets have defect sites acting as nucleation centers to anchor the Pd and Fe3O4 nanoparticles and hence minimize the harmful effect of potential agglomeration and subsequently the anticipated decrease in the catalyst catalytic activity as a direct impact for this unfavorable agglomeration

Method comparison studies of telomere length measurement using qPCR approaches:A critical appraisal of the literature

Use of telomere length (TL) as a biomarker for various environmental exposures and diseases has increased in recent years. Various methods have been developed to measure telomere length. Polymerase chain reaction (PCR)-based methods remain wide-spread for population-based studies due to the high-throughput capability. While several studies have evaluated the repeatability and reproducibility of different TL measurement methods, the results have been variable. We conducted a literature review of TL measurement cross-method comparison studies that included a PCR-based method published between January 1, 2002 and May 25, 2020. A total of 25 articles were found that matched the inclusion criteria. Papers were reviewed for quality of methodologic reporting of sample and DNA quality, PCR assay characteristics, sample blinding, and analytic approaches to determine final TL. Overall, methodologic reporting was low as assessed by two different reporting guidelines for qPCR-based TL measurement. There was a wide range in the reported correlation between methods (as assessed by Pearson's r) and few studies utilized the recommended intra-class correlation coefficient (ICC) for assessment of assay repeatability and methodologic comparisons. The sample size for nearly all studies was less than 100, raising concerns about statistical power. Overall, this review found that the current literature on the relation between TL measurement methods is lacking in validity and scientific rigor. In light of these findings, we present reporting guidelines for PCR-based TL measurement methods and results of analyses of the effect of assay repeatability (ICC) on statistical power of cross-sectional and longitudinal studies. Additional cross-laboratory studies with rigorous methodologic and statistical reporting, adequate sample size, and blinding are essential to accurately determine assay repeatability and replicability as well as the relation between TL measurement methods

Epidemiology of Subpatent Plasmodium Falciparum Infection: Implications for Detection of Hotspots with Imperfect Diagnostics.

At the local level, malaria transmission clusters in hotspots, which may be a group of households that experience higher than average exposure to infectious mosquitoes. Active case detection often relying on rapid diagnostic tests for mass screen and treat campaigns has been proposed as a method to detect and treat individuals in hotspots. Data from a cross-sectional survey conducted in north-western Tanzania were used to examine the spatial distribution of Plasmodium falciparum and the relationship between household exposure and parasite density. Dried blood spots were collected from consenting individuals from four villages during a survey conducted in 2010. These were analysed by PCR for the presence of P. falciparum, with the parasite density of positive samples being estimated by quantitative PCR. Household exposure was estimated using the distance-weighted PCR prevalence of infection. Parasite density simulations were used to estimate the proportion of infections that would be treated using a screen and treat approach with rapid diagnostic tests (RDT) compared to targeted mass drug administration (tMDA) and Mass Drug Administration (MDA). Polymerase chain reaction PCR analysis revealed that of the 3,057 blood samples analysed, 1,078 were positive. Mean distance-weighted PCR prevalence per household was 34.5%. Parasite density was negatively associated with transmission intensity with the odds of an infection being subpatent increasing with household exposure (OR 1.09 per 1% increase in exposure). Parasite density was also related to age, being highest in children five to ten years old and lowest in those > 40 years. Simulations of different tMDA strategies showed that treating all individuals in households where RDT prevalence was above 20% increased the number of infections that would have been treated from 43 to 55%. However, even with this strategy, 45% of infections remained untreated. The negative relationship between household exposure and parasite density suggests that DNA-based detection of parasites is needed to provide adequate sensitivity in hotspots. Targeting MDA only to households with RDT-positive individuals may allow a larger fraction of infections to be treated. These results suggest that community-wide MDA, instead of screen and treat strategies, may be needed to successfully treat the asymptomatic, subpatent parasite reservoir and reduce transmission in similar settings

Impact of Previously Unrecognized HLA Mismatches Using Ultrahigh Resolution Typing in Unrelated Donor Hematopoietic Cell Transplantation

PURPOSE: Ultrahigh resolution (UHR) HLA matching is reported to result in better outcomes following unrelated donor hematopoietic cell transplantation, improving survival and reducing post-transplant complications. However, most studies included relatively small numbers of patients. Here we report the findings from a large, multicenter validation study. METHODS: UHR HLA typing was available on 5,140 conventionally 10 out of 10 HLA-matched patients with malignant disease transplanted between 2008 and 2017. RESULTS: After UHR HLA typing, 82% of pairs remained 10 out of 10 UHR-matched; 12.3% of patients were 12 out of 12 UHR HLA-matched. Compared with 12 out of 12 UHR-matched patients, probabilities of grade 2-4 acute graft-versus-host disease (aGVHD) were significantly increased with UHR mismatches (overall P = .0019) and in those patients who were HLA-DPB1 T-cell epitope permissively mismatched or nonpermissively mismatched (overall P = .0011). In the T-cell-depleted subset, the degree of UHR HLA mismatch was only associated with increased transplant-related mortality (TRM) (overall P = .0068). In the T-cell-replete subset, UHR HLA matching was associated with a lower probability of aGVHD (overall P = .0020); 12 out of 12 UHR matching was associated with reduced TRM risk when compared with HLA-DPB1 T-cell epitope permissively mismatched patients, whereas nonpermissive mismatching resulted in a greater risk (overall P = .0003). CONCLUSION: This study did not confirm that UHR 12 out of 12 HLA matching increases the probability of overall survival but does demonstrate that aGVHD risk, and in certain settings TRM, is lowest in UHR HLA-matched pairs and thus warrants consideration when multiple 10 out of 10 HLA-matched donors of equivalent age are available

Specific Class I HLA Supertypes but Not HLA Zygosity or Expression Are Associated with Outcomes following HLA-Matched Allogeneic Hematopoietic Cell Transplant: HLA Supertypes Impact Allogeneic HCT Outcomes

Maximizing the probability of antigen presentation to T cells through diversity in HLAs can enhance immune responsiveness and translate into improved clinical outcomes, as evidenced by the association of heterozygosity and supertypes at HLA class I loci with improved survival in patients with advanced solid tumors treated with immune checkpoint inhibitors. We investigated the impact of HLA heterozygosity, supertypes, and surface expression on outcomes in adult and pediatric patients with acute myeloid leukemia (AML), myelodysplastic syndrome, acute lymphoblastic leukemia, and non-Hodgkin lymphoma who underwent 8/8 HLA-matched, T cell replete, unrelated, allogeneic hematopoietic cell transplant (HCT) from 2000 to 2015 using patient data reported to the Center for International Blood and Marrow Transplant Research. HLA class I heterozygosity and HLA expression were not associated with overall survival, relapse, transplant-related mortality (TRM), disease-free survival (DFS), and acute graft-versus-host disease following HCT. The HLA-B62 supertype was associated with decreased TRM in the entire patient cohort (hazard ratio [HR], 0.79; 95% CI, 0.69 to 0.90; P = .00053). The HLA-B27 supertype was associated with worse DFS in patients with AML (HR = 1.21; 95% CI, 1.10 to 1.32; P = .00005). These findings suggest that the survival benefit of HLA heterozygosity seen in solid tumor patients receiving immune checkpoint inhibitors does not extend to patients undergoing allogeneic HCT. Certain HLA supertypes, however, are associated with TRM and DFS, suggesting that similarities in peptide presentation between supertype members play a role in these outcomes. Beyond implications for prognosis following HCT, these findings support the further investigation of these HLA supertypes and the specific immune peptides important for transplant outcomes

GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia.

We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P \u3c .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P \u3c .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors. © 2019 American Society of Hematology. All rights reserved

Drug-resistant genotypes and multi-clonality in Plasmodium falciparum analysed by direct genome sequencing from peripheral blood of malaria patients.

Naturally acquired blood-stage infections of the malaria parasite Plasmodium falciparum typically harbour multiple haploid clones. The apparent number of clones observed in any single infection depends on the diversity of the polymorphic markers used for the analysis, and the relative abundance of rare clones, which frequently fail to be detected among PCR products derived from numerically dominant clones. However, minority clones are of clinical interest as they may harbour genes conferring drug resistance, leading to enhanced survival after treatment and the possibility of subsequent therapeutic failure. We deployed new generation sequencing to derive genome data for five non-propagated parasite isolates taken directly from 4 different patients treated for clinical malaria in a UK hospital. Analysis of depth of coverage and length of sequence intervals between paired reads identified both previously described and novel gene deletions and amplifications. Full-length sequence data was extracted for 6 loci considered to be under selection by antimalarial drugs, and both known and previously unknown amino acid substitutions were identified. Full mitochondrial genomes were extracted from the sequencing data for each isolate, and these are compared against a panel of polymorphic sites derived from published or unpublished but publicly available data. Finally, genome-wide analysis of clone multiplicity was performed, and the number of infecting parasite clones estimated for each isolate. Each patient harboured at least 3 clones of P. falciparum by this analysis, consistent with results obtained with conventional PCR analysis of polymorphic merozoite antigen loci. We conclude that genome sequencing of peripheral blood P. falciparum taken directly from malaria patients provides high quality data useful for drug resistance studies, genomic structural analyses and population genetics, and also robustly represents clonal multiplicity

Metaverse-Retail Service Quality: A Future Framework for Retail Service Quality in the 3D Internet

This paper argues that service quality in retailing in 3D Collaborative Virtual Environments (aka Metaverses) is distinct from service quality in the more familiar 2D mainly menu-driven web internet store (e-SQ). The study identifies and conceptualises the determinants of Metaverse Retailing service quality (MR-SQ) through a combination of focus groups and Critical Incident Technique. A set of four overarching determining elements of MR-SQ was revealed including customer service, product dimension, store dimension and 3D platform dimension. These incorporate some of the features found in 2D e-SQ but importantly the study indicated new characteristics, unique to MR-SQ. The CVE context presents opportunities for retailers in enhancing social experience, responsive service and creative co-production opportunities. It is within these gaps that respondents identified in 2D retailing that current CVEs and the future Web 3.0 hold appealing prospects for enhancing and producing creative and co-operative online retailing service quality (MR-SQ). The study provides a framework for guidance for retailers as well as for future research. Summary Statement of Contribution: The paper establishes new understanding of the determinants of Metaverse Retailing-Service Quality (MR-SQ). For virtual worlds in general and for service quality in particular, this study shows new MR-SQ dimensions, overlapping dimensions with different meanings to MR-SQ compares to e-SQ, and similar dimensions in both MR-SQ and e-SQ

High resolution 3D imaging of living cells with sub-optical wavelength phonons

Label-free imaging of living cells below the optical diffraction limit poses great challenges for optical microscopy. Biologically relevant structural information remains below the Rayleigh limit and beyond the reach of conventional microscopes. Super-resolution techniques are typically based on the nonlinear and stochastic response of fluorescent labels which can be toxic and interfere with cell function. In this paper we present, for the first time, imaging of live cells using sub-optical wavelength phonons. The axial imaging resolution of our system is determined by the acoustic wavelength (λa = λprobe/2n) and not on the NA of the optics allowing sub-optical wavelength acoustic sectioning of samples using the time of flight. The transverse resolution is currently limited to the optical spot size. The contrast mechanism is significantly determined by the mechanical properties of the cells and requires no additional contrast agent, stain or label to image the cell structure. The ability to breach the optical diffraction limit to image living cells acoustically promises to bring a new suite of imaging technologies to bear in answering exigent questions in cell biology and biomedicine