Third‐party vessel allografts in kidney and pancreas transplantation: Utilization, de novo DSAs, and outcomes

2020 ◽  
Vol 20 (12) ◽  
pp. 3443-3450 ◽  
Author(s):  
Neetika Garg ◽  
Luis G. Hidalgo ◽  
Tom M. Ellis ◽  
Robert R. Redfield ◽  
Sandesh Parajuli ◽  
...  
Keyword(s):  
Pancreas Transplantation ◽  
De Novo ◽  
Third Party

scholarly journals multiPhATE: bioinformatics pipeline for functional annotation of phage isolates

2019 ◽  
Vol 35 (21) ◽  
pp. 4402-4404 ◽  
Author(s):  
Carol L Ecale Zhou ◽  
Stephanie Malfatti ◽  
Jeffrey Kimbrel ◽  
Casandra Philipson ◽  
Katelyn McNair ◽  
...  
Keyword(s):  
De Novo ◽  
Third Party ◽  
Supplementary Information ◽  
Modular Construction ◽  
Bioinformatics Pipeline ◽  
Annotation Pipeline ◽  
Phage Gene ◽  
Software Documentation ◽  
Multiple Processors ◽  
Calling Algorithm

Abstract Summary To address the need for improved phage annotation tools that scale, we created an automated throughput annotation pipeline: multiple-genome Phage Annotation Toolkit and Evaluator (multiPhATE). multiPhATE is a throughput pipeline driver that invokes an annotation pipeline (PhATE) across a user-specified set of phage genomes. This tool incorporates a de novo phage gene calling algorithm and assigns putative functions to gene calls using protein-, virus- and phage-centric databases. multiPhATE’s modular construction allows the user to implement all or any portion of the analyses by acquiring local instances of the desired databases and specifying the desired analyses in a configuration file. We demonstrate multiPhATE by annotating two newly sequenced Yersinia pestis phage genomes. Within multiPhATE, the PhATE processing pipeline can be readily implemented across multiple processors, making it adaptable for throughput sequencing projects. Software documentation assists the user in configuring the system. Availability and implementation multiPhATE was implemented in Python 3.7, and runs as a command-line code under Linux or Unix. multiPhATE is freely available under an open-source BSD3 license from https://github.com/carolzhou/multiPhATE. Instructions for acquiring the databases and third-party codes used by multiPhATE are included in the distribution README file. Users may report bugs by submitting to the github issues page associated with the multiPhATE distribution. Supplementary information Supplementary data are available at Bioinformatics online.

Third-Party BK Virus-Specific Cytotoxic T Lymphocyte Therapy for Hemorrhagic Cystitis Following Allotransplantation

2021 ◽  
pp. JCO.20.02608
Author(s):  
Amanda Olson ◽  
Ruitao Lin ◽  
David Marin ◽  
Hind Rafei ◽  
Mustafa H. Bdaiwi ◽  
...  
Keyword(s):  
De Novo ◽  
Cytotoxic T Lymphocyte ◽  
Therapeutic Option ◽  
Hemorrhagic Cystitis ◽  
Standard Of Care ◽  
Bk Virus ◽  
Third Party ◽  
Matched Pair ◽  
Hematopoietic Stem

PURPOSE BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of alternative donor transplants, which are being performed in increasing numbers. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option. METHODS We performed a clinical trial (ClinicalTrials.gov identifier: NCT02479698 ) to assess the feasibility, safety, and efficacy of administering most closely HLA-matched third-party BKV-specific cytotoxic T lymphocytes (CTLs), generated from 26 healthy donors and banked for off-the-shelf use. The cells were infused into 59 patients who developed BKV-HC following AHSCT. Comprehensive clinical assessments and correlative studies were performed. RESULTS Response to BKV-CTL infusion was rapid; the day 14 overall response rate was 67.7% (40 of 59 evaluable patients), which increased to 81.6% among evaluable patients at day 45 (40 of 49 evaluable patients). No patient lost a previously achieved response. There were no cases of de novo grade 3 or 4 graft-versus-host disease, graft failure, or infusion-related toxicities. BKV-CTLs were identified in patient blood samples up to 3 months postinfusion and their in vivo expansion predicted for clinical response. A matched-pair analysis revealed that, compared with standard of care, after accounting for prognostic covariate effects, treatment with BKV-CTLs resulted in higher probabilities of response at all follow-up timepoints as well as significantly lower transfusion requirement. CONCLUSION Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BKV-HC after AHSCT.

Efficacy of ‘Off-the-Shelf’, Commercially-Available, Third-Party Mesenchymal Stem Cells (MSC) in Ex Vivo Cord Blood (CB) Co-Culture Expansion.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4106-4106
Author(s):  
Simon N. Robinson ◽  
Paul J. Simmons ◽  
Nathalie Brouard ◽  
Shannon Kidd ◽  
Hong Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cord Blood ◽  
Mononuclear Cells ◽  
De Novo ◽  
Ex Vivo ◽  
Third Party ◽  
Clinical Grade ◽  
Hematopoietic Stem ◽  
Research Grade

Abstract INTRODUCTION: Our previous studies have shown that clinically-relevant levels of hematopoietic stem and progenitor cell (HSPC) expansion are possible by ex vivo co-culture of cord blood (CB) mononuclear cells (MNC) with third-party bone marrow (BM)-derived mesenchymal stem cells (MSC) and growth factors.1 A recently activated M. D. Anderson protocol requires that BM from a haplo-identical family member be used for the de novo generation of sufficient MSC for subsequent co-culture, a process requiring ∼3 weeks. Time constraints, uncertainties associated with the identification of a suitable BM donor and potential variation in MSC performance make logistical execution of this strategy difficult. We therefore investigated the potential efficacy of ‘off-the-shelf’ commercially-available sources of MSC. Since MSC do not express HLA-II (DR) they are non-immunogenic, suggesting that this might be a valuable alternative strategy. We compared ex vivo CB HSPC expansion obtained following CB MNC co-culture with 2 commercially-available research-grade MSC isolated by density separation and plastic adherence (MSC#1, Cambrex, Walkersville, MD and MSC#2, Allcells, Emeryville, CA). A third MSC, isolated by Stro-12 selection (MSC#3, supplied by PJS) was also evaluated. METHODS: Two MDACC frozen CB units (CB#1&2) were thawed, washed and co-cultured with adherent monolayers from each MSC. Total nucleated cell (TNC) and HSPC (CD34+ cells and colony-forming units, CFU) numbers were measured at input (Day 0) and output (Day 14). RESULTS: TNC and HSPC numbers revealed that the 2 commercially-available research-grade MSC (MSC#1&2) supported ex vivo CB HSPC expansion. MSC TNC CB34+ CFU n/a - not available CB#1 #1 x 6 x23 n/a #2 x 3 x 8 x15 #3 x 6 x16 x23 CB#2 #1 x 7 x20 x31 #2 x 5 x10 x20 #3 x10 x16 x34 1 Robinson et al. x13 x14 x25 MSC#2 performed less well than MSC#1 for both CB units suggesting that variation may exist between individual MSC. These data suggest that the screening of clinical-grade MSC that perform optimally during ex vivo expansion co-culture might be warranted to best utilize this ‘off-the-shelf’ strategy. Data were similar to previous reports where TNC, CD34+ and CFU numbers were shown to increase approximately 13, 14 and 25-fold, respectively.1 Data were also similar for MSC#3, suggesting that the method used to isolate MSC does not appear to be an important variable for effective CB MNC/MSC co-culture. CONCLUSION: Although research-grade MSC were compared from different commercial sources, these data suggest that, in principle, commercially-available clinical-grade MSC might prove a valuable ‘off-the-shelf’ option, potentially reducing the time to therapy and addressing concerns associated with identifying a BM donor and variation in MSC performance. Future studies will evaluate FDA-compliant MSC that could be used clinically.

De Novo Malignancy After Pancreas Transplantation in Japan

2015 ◽  
Vol 47 (3) ◽  
pp. 742-745 ◽  
Author(s):  
Y. Tomimaru ◽  
T. Ito ◽  
S. Marubashi ◽  
K. Kawamoto ◽  
A. Tomokuni ◽  
...  
Keyword(s):  
Pancreas Transplantation ◽  
De Novo ◽  
De Novo Malignancy

scholarly journals NovoGraph: Human genome graph construction from multiple long-read de novo assemblies

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1391
Author(s):  
Evan Biederstedt ◽  
Jeffrey C. Oliver ◽  
Nancy F. Hansen ◽  
Aarti Jajoo ◽  
Nathan Dunn ◽  
...  
Keyword(s):  
Human Genome ◽  
De Novo ◽  
Wide Spectrum ◽  
Third Party ◽  
Sequencing Data ◽  
Multiple Sequence ◽  
Human Genomes ◽  
A Genome ◽  
Long Read ◽  
Genome Graph

Genome graphs are emerging as an important novel approach to the analysis of high-throughput human sequencing data. By explicitly representing genetic variants and alternative haplotypes in a mappable data structure, they can enable the improved analysis of structurally variable and hyperpolymorphic regions of the genome. In most existing approaches, graphs are constructed from variant call sets derived from short-read sequencing. As long-read sequencing becomes more cost-effective and enables de novo assembly for increasing numbers of whole genomes, a method for the direct construction of a genome graph from sets of assembled human genomes would be desirable. Such assembly-based genome graphs would encompass the wide spectrum of genetic variation accessible to long-read-based de novo assembly, including large structural variants and divergent haplotypes. Here we present NovoGraph, a method for the construction of a human genome graph directly from a set of de novo assemblies. NovoGraph constructs a genome-wide multiple sequence alignment of all input contigs and creates a graph by merging the input sequences at positions that are both homologous and sequence-identical. NovoGraph outputs resulting graphs in VCF format that can be loaded into third-party genome graph toolkits. To demonstrate NovoGraph, we construct a genome graph with 23,478,835 variant sites and 30,582,795 variant alleles from de novo assemblies of seven ethnically diverse human genomes (AK1, CHM1, CHM13, HG003, HG004, HX1, NA19240). Initial evaluations show that mapping against the constructed graph reduces the average mismatch rate of reads from sample NA12878 by approximately 0.2%, albeit at a slightly increased rate of reads that remain unmapped.

scholarly journals Fast Confirmation of Antibody Identity by MALDI-TOF MS Fingerprints

Antibodies ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 8 ◽  
Author(s):  
Georg Tscheuschner ◽  
Timm Schwaar ◽  
Michael G. Weller
Keyword(s):  
De Novo ◽  
Scientific Progress ◽  
Recombinant Antibodies ◽  
Enzymatic Digestion ◽  
Third Party ◽  
Research Activity ◽  
Open Communication ◽  
Maldi Tof Ms ◽  
Maldi Tof ◽  
Tof Ms

Thousands of antibodies for diagnostic and other analytical purposes are on the market. However, it is often difficult to identify duplicates, reagent changes, and to assign the correct original publications to an antibody. This slows down scientific progress and might even be a cause of irreproducible research and a waste of resources. Recently, activities were started to suggest the sole use of recombinant antibodies in combination with the open communication of their sequence. In this case, such uncertainties should be eliminated. Unfortunately, this approach seems to be rather a long-term vision since the development and manufacturing of recombinant antibodies remain quite expensive in the foreseeable future. Nearly all commercial antibody suppliers also may be reluctant to publish the sequence of their antibodies, since they fear counterfeiting. De novo sequencing of antibodies is also not feasible today for a reagent user without access to the hybridoma clone. Nevertheless, it seems to be crucial for any scientist to have the opportunity to identify an antibody undoubtedly to guarantee the traceability of any research activity using antibodies from a third party as a tool. For this purpose, we developed a method for the identification of antibodies based on a MALDI-TOF MS fingerprint. To circumvent lengthy denaturation, reduction, alkylation, and enzymatic digestion steps, the fragmentation was performed with a simple formic acid hydrolysis step. Eighty-nine unknown monoclonal antibodies were used for this study to examine the feasibility of this approach. Although the molecular assignment of peaks was rarely possible, antibodies could be easily recognized in a blinded test, simply from their mass-spectral fingerprint. A general protocol is given, which could be used without any optimization to generate fingerprints for a database. We want to propose that, in most scientific projects relying critically on antibody reagents, such a fingerprint should be established to prove and document the identity of the used antibodies, as well as to assign a specific reagent to a datasheet of a commercial supplier, public database record, or antibody ID.

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