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  1. Article ; Online: Polly: An R package for genotyping microsatellites and detecting highly polymorphic DNA markers from short-read data.

    Perry, Annabel / Eddelbuettel, Dirk / Rosenthal, Gil / Blackmon, Heath

    Molecular ecology resources

    2024  Volume 24, Issue 4, Page(s) e13933

    Abstract: ... that impede their efficiency. We created Polly, an R package with C++ source code that uses Illumina short ...

    Abstract Highly polymorphic markers, such as microsatellites, are invaluable for the study of natural populations. However, contemporary methods for genotyping highly polymorphic variants have serious drawbacks that impede their efficiency. We created Polly, an R package with C++ source code that uses Illumina short-read data to genotype microsatellites, detect highly polymorphic variants and identify clusters of highly polymorphic SNPs, indels and microsatellites. We tested Polly on short-read data from Xiphophorus birchmanni (Teleostei: Poeciliidae) and Arabidopsis thaliana, finding it to be efficient and accurate both for microsatellite genotyping and polymorphic marker detection. This program can be applied to any diploid population for which there exists short-read data and at least one scaffolded reference genome.
    MeSH term(s) Genetic Markers ; Genotype ; Genome ; Polymorphism, Single Nucleotide ; Microsatellite Repeats
    Chemical Substances Genetic Markers
    Language English
    Publishing date 2024-02-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 2406833-0
    ISSN 1755-0998 ; 1755-098X
    ISSN (online) 1755-0998
    ISSN 1755-098X
    DOI 10.1111/1755-0998.13933
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  2. Article ; Online: Partial Ribosomal Nontranscribed Spacer Sequences Distinguish Rhagoletis zephyria (Diptera: Tephritidae) From the Apple Maggot, R. pomonella.

    Smith, J J / Brzezinski, P / Dziedziula, J / Rosenthal, E / Klaus, M

    Journal of economic entomology

    2022  Volume 115, Issue 2, Page(s) 647–661

    Abstract: ... spacer (NTS) of the ribosomal RNA gene cistron of R. pomonella and R. zephyria that appear to be ... base-pair difference in PCR amplicon size between R. zephyria and R. pomonella that can be scored using ... agarose gel electrophoresis. PCR amplification and DNA sequencing of 766 bp of the NTS region from 38 R. pomonella individuals ...

    Abstract The apple maggot, Rhagoletis pomonella (Walsh), was introduced into the apple-growing regions of the Pacific Northwest in the U.S.A. during the past 60-100 yr. Apple maggot (larvae, puparia, and adults) is difficult to distinguish from its morphologically similar sister species, Rhagoletis zephyria Snow, which is native and abundant in the Pacific Northwest. While morphological identifications are common practice, a simple, inexpensive assay based on genetic differences would be very useful when morphological traits are unclear. Here we report nucleotide substitution and insertion-deletion mutations in the nontranscribed spacer (NTS) of the ribosomal RNA gene cistron of R. pomonella and R. zephyria that appear to be diagnostic for these two fly species. Insertion-deletion variation is substantial and results in a 49 base-pair difference in PCR amplicon size between R. zephyria and R. pomonella that can be scored using agarose gel electrophoresis. PCR amplification and DNA sequencing of 766 bp of the NTS region from 38 R. pomonella individuals and 35 R. zephyria individuals from across their geographic ranges led to the expected PCR fragments of approx. 840 bp and 790 bp, respectively, as did amplification and sequencing of a smaller set of 26 R. pomonella and 16 R. zephyria flies from a sympatric site in Washington State. Conversely, 633 bp mitochondrial COI barcode sequences from this set of flies were polyphyletic with respect to R. pomonella and R. zephyria. Thus, differences in NTS PCR products on agarose gels potentially provide a simple way to distinguish between R. pomonella and R. zephyria.
    MeSH term(s) Animals ; Diptera ; Larva ; Malus ; Tephritidae/genetics ; Washington
    Language English
    Publishing date 2022-01-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3031-4
    ISSN 1938-291X ; 0022-0493
    ISSN (online) 1938-291X
    ISSN 0022-0493
    DOI 10.1093/jee/toab264
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    Zs.B 1118: Show issues Location:
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  3. Article: Longitudinal diffusion and volumetric kinetics of head and neck cancer magnetic resonance on a 1.5T MR-Linear accelerator hybrid system: A prospective R-IDEAL Stage 2a imaging biomarker characterization/ pre-qualification study.

    El-Habashy, Dina M / Wahid, Kareem A / He, Renjie / McDonald, Brigid / Rigert, Jillian / Mulder, Samuel J / Lim, Tze Yee / Wang, Xin / Yang, Jinzhong / Ding, Yao / Naser, Mohamed A / Ng, Sweet Ping / Bahig, Houda / Salzillo, Travis C / Preston, Kathryn E / Abobakr, Moamen / Shehata, Mohamed A / Elkhouly, Enas A / Alagizy, Hagar A /
    Hegazy, Amira H / Mohammadseid, Mustefa / Terhaard, Chris / Philippens, Marielle / Rosenthal, David I / Wang, Jihong / Lai, Stephen Y / Dresner, Alex / Christodouleas, John C / Mohamed, Abdallah Sherif Radwan / Fuller, Clifton D

    medRxiv : the preprint server for health sciences

    2023  

    Abstract: ... for head and neck squamous cell carcinoma (HNSCC) patients as part of a programmatic R-IDEAL biomarker ...

    Abstract Objectives: We aim to characterize the serial quantitative apparent diffusion coefficient (ADC) changes of the target disease volume using diffusion-weighted imaging (DWI) acquired weekly during radiation therapy (RT) on a 1.5T MR-Linac and correlate these changes with tumor response and oncologic outcomes for head and neck squamous cell carcinoma (HNSCC) patients as part of a programmatic R-IDEAL biomarker characterization effort.
    Methods: Thirty patients with pathologically confirmed HNSCC who received curative-intent RT at the University of Texas MD Anderson Cancer Center, were included in this prospective study. Baseline and weekly Magnetic resonance imaging (MRI) (weeks 1-6) were obtained, and various ADC parameters (mean, 5
    Results: There was an overall significant rise in all ADC parameters during different time points of RT compared to baseline values for both gross primary disease volume (GTV-P) and gross nodal disease volumes (GTV-N). The increased ADC values for GTV-P were statistically significant only for primary tumors achieving complete remission (CR) during RT. RPA identified GTV-P ΔADC 5
    Conclusion: Assessment of ADC kinetics at regular intervals throughout RT seems to be correlated with RT response. Further studies with larger cohorts and multi-institutional data are needed for validation of ΔADC as a model for prediction of response to RT.
    Language English
    Publishing date 2023-05-05
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.04.23289527
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  4. Article: Partial Ribosomal Nontranscribed Spacer Sequences Distinguish Rhagoletis zephyria (Diptera: Tephritidae) From the Apple Maggot, R. pomonella

    Smith, J. J. / Brzezinski, P. / Dziedziula, J. / Rosenthal, E. / Klaus, M.

    Journal of economic entomology. 2022 Jan. 20, v. 115, no. 2

    2022  

    Abstract: ... spacer (NTS) of the ribosomal RNA gene cistron of R. pomonella and R. zephyria that appear to be ... base-pair difference in PCR amplicon size between R. zephyria and R. pomonella that can be scored using ... agarose gel electrophoresis. PCR amplification and DNA sequencing of 766 bp of the NTS region from 38 R. pomonella individuals ...

    Abstract The apple maggot, Rhagoletis pomonella (Walsh), was introduced into the apple-growing regions of the Pacific Northwest in the U.S.A. during the past 60–100 yr. Apple maggot (larvae, puparia, and adults) is difficult to distinguish from its morphologically similar sister species, Rhagoletis zephyria Snow, which is native and abundant in the Pacific Northwest. While morphological identifications are common practice, a simple, inexpensive assay based on genetic differences would be very useful when morphological traits are unclear. Here we report nucleotide substitution and insertion–deletion mutations in the nontranscribed spacer (NTS) of the ribosomal RNA gene cistron of R. pomonella and R. zephyria that appear to be diagnostic for these two fly species. Insertion–deletion variation is substantial and results in a 49 base-pair difference in PCR amplicon size between R. zephyria and R. pomonella that can be scored using agarose gel electrophoresis. PCR amplification and DNA sequencing of 766 bp of the NTS region from 38 R. pomonella individuals and 35 R. zephyria individuals from across their geographic ranges led to the expected PCR fragments of approx. 840 bp and 790 bp, respectively, as did amplification and sequencing of a smaller set of 26 R. pomonella and 16 R. zephyria flies from a sympatric site in Washington State. Conversely, 633 bp mitochondrial COI barcode sequences from this set of flies were polyphyletic with respect to R. pomonella and R. zephyria. Thus, differences in NTS PCR products on agarose gels potentially provide a simple way to distinguish between R. pomonella and R. zephyria.
    Keywords DNA ; Rhagoletis pomonella ; Rhagoletis zephyria ; Washington (state) ; agar gel electrophoresis ; agarose ; entomology ; genes ; mitochondria ; polyphyly ; puparium ; ribosomal RNA ; sympatry
    Language English
    Dates of publication 2022-0120
    Size p. 647-661.
    Publishing place Entomological Society of America
    Document type Article
    ZDB-ID 3031-4
    ISSN 0022-0493
    ISSN 0022-0493
    DOI 10.1093/jee/toab264
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Optimizing the analysis strategy for the CANVAS Program: A prespecified plan for the integrated analyses of the CANVAS and CANVAS-R trials.

    Neal, Bruce / Perkovic, Vlado / Mahaffey, Kenneth W / Fulcher, Greg / Erondu, Ngozi / Desai, Mehul / Shaw, Wayne / Law, Gordon / Walton, Marc K / Rosenthal, Norm / de Zeeuw, Dick / Matthews, David R

    Diabetes, obesity & metabolism

    2017  Volume 19, Issue 7, Page(s) 926–935

    Abstract: ... cardioVascular Assessment Study-Renal (CANVAS-R). Accruing data for the sodium glucose co-transporter 2 (SGLT2 ...

    Abstract Two large cardiovascular outcome trials of canagliflozin, comprising the CANVAS Program, will complete in early 2017: the CANagliflozin cardioVascular Assessment Study (CANVAS) and the CANagliflozin cardioVascular Assessment Study-Renal (CANVAS-R). Accruing data for the sodium glucose co-transporter 2 (SGLT2) inhibitor class has identified questions and opportunities that were not apparent when the trials were designed. Accordingly, a series of modifications have been made to the planned analyses. These updates will ensure that the data from the CANVAS Program will maximize advances in scientific knowledge and patient care. The specification of the analysis strategy prior to knowledge of the trial results, their design by the independent scientific trial Steering Committee, the detailed a priori definition of the analysis plans, and the external review provided by the US Food and Drug Administration all provide maximally efficient and robust utilization of the data. The CANVAS Program should significantly advance our understanding of the effects of canagliflozin, and the broader SGLT2 inhibitor class, on a range of important efficacy and safety outcomes.
    MeSH term(s) Aged ; Biomarkers/blood ; Canagliflozin/administration & dosage ; Canagliflozin/adverse effects ; Canagliflozin/therapeutic use ; Cardiovascular Diseases/complications ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/mortality ; Cardiovascular Diseases/prevention & control ; Cohort Studies ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/mortality ; Diabetic Angiopathies/epidemiology ; Diabetic Angiopathies/mortality ; Diabetic Angiopathies/prevention & control ; Diabetic Cardiomyopathies/epidemiology ; Diabetic Cardiomyopathies/mortality ; Diabetic Cardiomyopathies/prevention & control ; Dose-Response Relationship, Drug ; Double-Blind Method ; Drug Monitoring ; Equivalence Trials as Topic ; Female ; Follow-Up Studies ; Humans ; Hypoglycemic Agents/administration & dosage ; Hypoglycemic Agents/adverse effects ; Hypoglycemic Agents/therapeutic use ; Male ; Middle Aged ; Mortality ; Reproducibility of Results ; Risk Factors ; Sodium-Glucose Transporter 2/metabolism ; Sodium-Glucose Transporter 2 Inhibitors
    Chemical Substances Biomarkers ; Hypoglycemic Agents ; Sodium-Glucose Transporter 2 ; Sodium-Glucose Transporter 2 Inhibitors ; Canagliflozin (0SAC974Z85)
    Language English
    Publishing date 2017-04-03
    Publishing country England
    Document type Comparative Study ; Journal Article ; Multicenter Study ; Randomized Controlled Trial
    ZDB-ID 1454944-x
    ISSN 1463-1326 ; 1462-8902
    ISSN (online) 1463-1326
    ISSN 1462-8902
    DOI 10.1111/dom.12924
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    Zs.A 5442: Show issues Location:
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  6. Article ; Online: A phase 2 study of rituximab, cyclophosphamide, bortezomib and dexamethasone (R-CyBorD) in relapsed low grade and mantle cell lymphoma.

    Sonbol, Mohamad Bassam / Hilal, Talal / Dueck, Amylou C / Rosenthal, Allison C / Conley, Christopher R / Kosiorek, Heidi E / Ginos, Brenda F / Gano, Katherine M / Nichols, Craig S / Leis, Jose F / Johnston, Patrick B / Habermann, Thomas M / Northfelt, Donald W / Bergsagel, Peter Leif / Inwards, David J / Witzig, Thomas E / Ansell, Stephen M / Reeder, Craig B

    Leukemia & lymphoma

    2018  Volume 59, Issue 9, Page(s) 2128–2134

    Abstract: ... bortezomib, and dexamethasone (R-CyBorD) in patients with low-grade NHL. The regimen included rituximab ...

    Abstract In this phase 2 trial, we sought to evaluate the efficacy and safety of rituximab, cyclophosphamide, bortezomib, and dexamethasone (R-CyBorD) in patients with low-grade NHL. The regimen included rituximab on day 1 with weekly cyclophosphamide, dexamethasone, and bortezomib 1.3 mg/m
    MeSH term(s) Aged ; Aged, 80 and over ; Anemia/chemically induced ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bortezomib/administration & dosage ; Bortezomib/adverse effects ; Cyclophosphamide/administration & dosage ; Cyclophosphamide/adverse effects ; Dexamethasone/administration & dosage ; Dexamethasone/adverse effects ; Fatigue/chemically induced ; Female ; Humans ; Lymphoma, Mantle-Cell/drug therapy ; Lymphoma, Mantle-Cell/pathology ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local ; Rituximab/administration & dosage ; Rituximab/adverse effects ; Survival Analysis ; Thrombocytopenia/chemically induced
    Chemical Substances Rituximab (4F4X42SYQ6) ; Bortezomib (69G8BD63PP) ; Dexamethasone (7S5I7G3JQL) ; Cyclophosphamide (8N3DW7272P)
    Language English
    Publishing date 2018-01-10
    Publishing country United States
    Document type Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1042374-6
    ISSN 1029-2403 ; 1042-8194
    ISSN (online) 1029-2403
    ISSN 1042-8194
    DOI 10.1080/10428194.2017.1416368
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    Zs.A 2997: Show issues Location:
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  7. Article ; Online: Posttransplant metabolic syndrome in the withdrawal of immunosuppression in Pediatric Liver Transplant Recipients (WISP-R) pilot trial.

    Perito, E R / Mohammad, S / Rosenthal, P / Alonso, E M / Ekong, U D / Lobritto, S J / Feng, S

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2015  Volume 15, Issue 3, Page(s) 779–785

    Abstract: ... of Immunosuppression in Pediatric Liver Transplant Recipients (WISP-R) pilot trial is the first prospective study ... of PTMS after pediatric liver transplant. Twenty children were enrolled in WISP-R, at median age 8.5 years ... of WISP-R subjects and 58% of controls had at least one component of PTMS. Calcineurin-inhibitor ...

    Abstract Posttransplant metabolic syndrome (PTMS)-obesity, hypertension, elevated triglycerides, low HDL and glucose intolerance-is a major contributor to morbidity after adult liver transplant. This analysis of the Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients (WISP-R) pilot trial is the first prospective study of PTMS after pediatric liver transplant. Twenty children were enrolled in WISP-R, at median age 8.5 years (IQR 6.4-10.8), and weaned from calcineurin-inhibitor monotherapy. The 12 children who tolerated complete immunosuppression withdrawal were compared to matched historical controls. At baseline, 45% of WISP-R subjects and 58% of controls had at least one component of PTMS. Calcineurin-inhibitor withdrawal in the WISP-R subjects did not impact the prevalence of PTMS components compared to controls. At 5 years, despite weaning off of immunosuppression, 92% of the 12 tolerant WISP-R subjects had at least one PTMS component and 58% had at least two; 33% were overweight or obese, 50% had dyslipidemia, 33% glucose intolerance and 42% systolic hypertension. Overweight/obesity increased the risk of hypertension in all children. Compared to controls, WISP-R tolerant subjects had similar GFR at baseline but did have higher GFR at 2, 3 and 4 years. Further study of PTMS and immunosuppression withdrawal after pediatric liver transplant is warranted.
    MeSH term(s) Child ; Follow-Up Studies ; Humans ; Immunosuppressive Agents/administration & dosage ; Liver Transplantation/adverse effects ; Metabolic Syndrome/etiology ; Retrospective Studies
    Chemical Substances Immunosuppressive Agents
    Language English
    Publishing date 2015-02-03
    Publishing country United States
    Document type Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1111/ajt.13024
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    Zs.A 5542: Show issues Location:
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  8. Article ; Online: Magnetic Resonance-based Response Assessment and Dose Adaptation in Human Papilloma Virus Positive Tumors of the Oropharynx treated with Radiotherapy (MR-ADAPTOR): An R-IDEAL stage 2a-2b/Bayesian phase II trial.

    Bahig, Houda / Yuan, Ying / Mohamed, Abdallah S R / Brock, Kristy K / Ng, Sweet Ping / Wang, Jihong / Ding, Yao / Hutcheson, Kate / McCulloch, Molly / Balter, Peter A / Lai, Stephen Y / Al-Mamgani, Abrahim / Sonke, Jan-Jakob / van der Heide, Uulke A / Nutting, Christopher / Li, X Allen / Robbins, Jared / Awan, Mussadiq / Karam, Irene /
    Newbold, Katherine / Harrington, Kevin / Oelfke, Uwe / Bhide, Shreerang / Philippens, Marielle E P / Terhaard, Chris H J / McPartlin, Andrew J / Blanchard, Pierre / Garden, Adam S / Rosenthal, David I / Gunn, Gary B / Phan, Jack / Cazoulat, Guillaume / Aristophanous, Michalis / McSpadden, Kelli K / Garcia, John A / van den Berg, Cornelis A T / Raaijmakers, Cornelis P J / Kerkmeijer, Linda / Doornaert, Patricia / Blinde, Sanne / Frank, Steven J / Fuller, Clifton D

    Clinical and translational radiation oncology

    2018  Volume 13, Page(s) 19–23

    Abstract: Background: Current standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients' quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and ... ...

    Abstract Background: Current standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients' quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and long-term survival of these typically young patients, treatment de-intensification aimed at improving survivorship while maintaining excellent disease control is now a central concern. The recent implementation of magnetic resonance image - guided radiotherapy (MRgRT) systems allows for individual tumor response assessment during treatment and offers possibility of personalized dose-reduction. In this 2-stage Bayesian phase II study, we propose to examine weekly radiotherapy dose-adaptation based on magnetic resonance imaging (MRI) evaluated tumor response. Individual patient's plan will be designed to optimize dose reduction to organs at risk and minimize locoregional failure probability based on serial MRI during RT. Our primary aim is to assess the non-inferiority of MRgRT dose adaptation for patients with low risk HPV-associated OPC compared to historical control, as measured by Bayesian posterior probability of locoregional control (LRC).
    Methods: Patients with T1-2 N0-2b (as per AJCC 7th Edition) HPV-positive OPC, with lymph node <3 cm and <10 pack-year smoking history planned for curative radiotherapy alone to a dose of 70 Gy in 33 fractions will be eligible. All patients will undergo pre-treatment MRI and at least weekly intra-treatment MRI. Patients undergoing MRgRT will have weekly adaptation of high dose planning target volume based on gross tumor volume response. The stage 1 of this study will enroll 15 patients to MRgRT dose adaptation. If LRC at 6 months with MRgRT dose adaptation is found sufficiently safe as per the Bayesian model, stage 2 of the protocol will expand enrollment to an additional 60 patients, randomized to either MRgRT or standard IMRT.
    Discussion: Multiple methods for safe treatment de-escalation in patients with HPV-positive OPC are currently being studied. By leveraging the ability of advanced MRI techniques to visualize tumor and soft tissues through the course of treatment, this protocol proposes a workflow for safe personalized radiation dose-reduction in good responders with radiosensitive tumors, while ensuring tumoricidal dose to more radioresistant tumors. MRgRT dose adaptation could translate in reduced long term radiation toxicities and improved survivorship while maintaining excellent LRC outcomes in favorable OPC.
    Trial registration: ClinicalTrials.gov ID: NCT03224000; Registration date: 07/21/2017.
    Language English
    Publishing date 2018-08-24
    Publishing country Ireland
    Document type Journal Article
    ISSN 2405-6308
    ISSN (online) 2405-6308
    DOI 10.1016/j.ctro.2018.08.003
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  9. Article ; Online: ADARRI: a novel method to detect spurious R-peaks in the electrocardiogram for heart rate variability analysis in the intensive care unit.

    Rebergen, Dennis J / Nagaraj, Sunil B / Rosenthal, Eric S / Bianchi, Matt T / van Putten, Michel J A M / Westover, M Brandon

    Journal of clinical monitoring and computing

    2017  Volume 32, Issue 1, Page(s) 53–61

    Abstract: We developed a simple and fully automated method for detecting artifacts in the R-R interval (RRI ... adult ICU-subjects we selected 60 epochs with valid R-peak detections and 60 epochs containing artifacts ... leading to missed or false positive R-peak detections. Next, we calculated the absolute value ...

    Abstract We developed a simple and fully automated method for detecting artifacts in the R-R interval (RRI) time series of the ECG that is tailored to the intensive care unit (ICU) setting. From ECG recordings of 50 adult ICU-subjects we selected 60 epochs with valid R-peak detections and 60 epochs containing artifacts leading to missed or false positive R-peak detections. Next, we calculated the absolute value of the difference between two adjacent RRIs (adRRI), and obtained the empirical probability distributions of adRRI values for valid R-peaks and artifacts. From these, we calculated an optimal threshold for separating adRRI values arising from artifact versus non-artefactual data. We compared the performance of our method with the methods of Berntson and Clifford on the same data. We identified 257,458 R-peak detections, of which 235,644 (91.5%) were true detections and 21,814 (8.5%) arose from artifacts. Our method showed superior performance for detecting artifacts with sensitivity 100%, specificity 99%, precision 99%, positive likelihood ratio of 100 and negative likelihood ratio <0.001 compared to Berntson's and Clifford's method with a sensitivity, specificity, precision and positive and negative likelihood ratio of 99%, 78%, 82%, 4.5, 0.013 for Berntson's method and 55%, 98%, 96%, 27.5, 0.460 for Clifford's method, respectively. A novel algorithm using a patient-independent threshold derived from the distribution of adRRI values in ICU ECG data identifies artifacts accurately, and outperforms two other methods in common use. Furthermore, the threshold was calculated based on real data from critically ill patients and the algorithm is easy to implement.
    MeSH term(s) Algorithms ; Artifacts ; Automation ; Critical Illness ; Electrocardiography ; Heart Rate/physiology ; Humans ; Infant, Newborn ; Intensive Care Units, Neonatal ; Intensive Care, Neonatal ; Predictive Value of Tests ; ROC Curve ; Reproducibility of Results ; Sensitivity and Specificity ; Signal Processing, Computer-Assisted ; Software
    Language English
    Publishing date 2017-02-16
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1418733-4
    ISSN 1573-2614 ; 1387-1307 ; 0748-1977
    ISSN (online) 1573-2614
    ISSN 1387-1307 ; 0748-1977
    DOI 10.1007/s10877-017-9999-9
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    Zs.A 2054: Show issues Location:
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  10. Article ; Online: Five-year histological and serological follow-up of operationally tolerant pediatric liver transplant recipients enrolled in WISP-R.

    Feng, Sandy / Demetris, Anthony J / Spain, Katharine M / Kanaparthi, Sai / Burrell, Bryna E / Ekong, Udeme D / Alonso, Estella M / Rosenthal, Philip / Turka, Laurence A / Ikle, David / Tchao, Nadia K

    Hepatology (Baltimore, Md.)

    2017  Volume 65, Issue 2, Page(s) 647–660

    Abstract: ... living donor liver grafts, identified as operationally tolerant through complete IS withdrawal (WISP-R ...

    Abstract Pediatric liver transplant recipients arguably have the most to gain and the most to lose from discontinuing immunosuppression (IS). Whereas IS undoubtedly exerts a cumulative toll, there is concern that insufficient or no IS may contribute to allograft deterioration. Twelve pediatric recipients of parental living donor liver grafts, identified as operationally tolerant through complete IS withdrawal (WISP-R; NCT00320606), were followed for a total of 5 years (1 year of IS withdrawal and 4 years off IS) with serial liver tests and autoantibody and alloantibody assessments. Liver biopsies were performed 2 and 4 years off IS, and, at these time points, immunoglobulin G (IgG) subclass and C1q binding activity for donor-specific antibodies (DSAs) were determined. There were no cases of chronic rejection, graft loss, or death. Allografts did not exhibit progressive increase in inflammation or fibrosis. Smooth-muscle actin expression by stellate cells and CD34 expression by liver sinusoidal endothelial cells remained stable, consistent with the absence of progressive graft injury. Three subjects never exhibited DSA. However, 3 subjects showed intermittent de novo class I DSA, 4 subjects showed persistent de novo class II DSA, and 5 subjects showed persistent preexisting class II DSA. Class II DSA was predominantly against donor DQ antigens, often of high mean fluorescence intensity, rarely of the IgG3 subclass, and often capable of binding C1q.
    Conclusion: Operationally tolerant pediatric liver transplant recipients maintain generally stable allograft histology in spite of apparently active humoral allo-immune responses. The absence of increased inflammation or progressive fibrosis suggests that a subset of liver allografts seem resistant to the chronic injury that is characteristic of antibody-mediated damage. (Hepatology 2017;65:647-660).
    MeSH term(s) Allografts ; Biopsy, Needle ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Graft Rejection ; Graft Survival ; Humans ; Immunoglobulin G/immunology ; Immunohistochemistry ; Immunosuppressive Agents/administration & dosage ; Isoantibodies/immunology ; Liver Diseases/congenital ; Liver Diseases/pathology ; Liver Diseases/surgery ; Liver Transplantation/adverse effects ; Liver Transplantation/methods ; Living Donors ; Male ; Prospective Studies ; Risk Assessment ; Time Factors ; Transplantation Immunology ; Treatment Outcome
    Chemical Substances Immunoglobulin G ; Immunosuppressive Agents ; Isoantibodies
    Language English
    Publishing date 2017-02
    Publishing country United States
    Document type Journal Article ; Multicenter Study ; Randomized Controlled Trial
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1002/hep.28681
    Database MEDical Literature Analysis and Retrieval System OnLINE

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