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Genetics in Medicine Open 2024年第Suppl 2期2卷 101854-101854页

作者： Valverde, Kathleen D. Hartman, Tiffiney R. Reichert, Sara L. Bennett, Robin L. Dudek, Martha Duquette, Debra Riconda, Daniel Cox, Nancy J. Jarvik, Gail P. Elsea, Sarah H. McNally, Elizabeth M. Worley, Kim C. Rader, Daniel J. Master of Science in Genetic Counseling Program Department of Genetics Perelman School of Medicine University of Pennsylvania Philadelphia PA United States Department of Pathology Division of Genomic Diagnostics The Children's Hospital of Philadelphia Philadelphia PA United States Division of Medical Genetics Department of Medicine University of Washington Seattle WA United States Master of Genetic Counseling Program Vanderbilt University School of Medicine Department of Obstetrics and Gynecology Division of Maternal-Fetal Medicine Vanderbilt University Medical Center Nashville TN United States Feinberg School of Medicine Chicago IL United States Department of Molecular and Human Genetics and the School of Health Professions Baylor College of Medicine Houston TX United States Division of Genetic Medicine Vanderbilt University Nashville TN United States Department of Molecular and Human Genetics Baylor College of Medicine Houston TX United States Center for Genetic Medicine Northwestern University Chicago IL United States Departments of Genetics Medicine and Pediatrics Perelman School of Medicine at the University of Pennsylvania Philadelphia PA United States

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RBC-Enhance: A Randomized Pilot Feasibility Trial of Red Cell Transfusion Thresholds in Myelodysplastic Syndromes

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BLOOD 2020年 136卷 3-4页

作者： Buckstein, Rena J. Prica, Anca Leber, Brian Heddle, Nancy Yee, Karen W. L. Stanworth, Simon J. Bowen, David Chodirker, Lisa Gallagher, Jennifer Parmentier, Anne Zhang, Liying Mamedov, Alexandre Lin, Yulia Callum, Jeannie L. Sunnybrook Odette Cancer Center Toronto Canada Division of Medical Oncology and Hematology Princess Margaret Cancer Centre Toronto Canada Division of Hematology Juravinski Cancer Centre McMaster University Hamilton Canada McMaster Centre for Transfusion Research McMaster University Hamilton Canada Leukemia Program Division of Medical Oncology and Hematology Princess Margaret Cancer Centre University Health Network Toronto Canada Oxford University Oxford United Kingdom Department of Haematology Leeds Teaching Hospitals Leeds United Kingdom Odette Cancer Centre Sunnybrook Health Sciences Centre Toronto Canada Odette Cancer Center Toronto Canada Odette Cancer Centre Toronto CAN Department of Laboratory Medicine and Molecular Diagnostics Sunnybrook Health Sciences Center Toronto Canada Department of Laboratory Medicine and Molecular Diagnostics Sunnybrook Health Sciences Centre Toronto Canada

Background Red blood cell (RBC) transfusion dependence (TD) and anemia are associated with inferior quality of life (QOL) and survival in myelodysplastic syndromes (MDS). As part of a research programme to identify the optimal transfusion hemoglobin (Hb) threshold that translates into significantly improved QOL, we conducted a pilot randomized study of two transfusion algorithms (liberal versus restrictive) to determine the feasibility of a larger study. This trial was aligned with the REDDS study (ISRCTN26088319, Stanworth et al., BJH 2019) and followed the same pre-defined statistical analysis plan. Methods The study was undertaken at 3 cancer centers (NCT02099669). We included patients with MDS, CMML, low blast AML (20-30%) or myeloproliferative neoplasms who were TD (> 1 RBC/8 weeks x 16 weeks). Patients on disease modifying therapy for > 6 months were permitted only if they had remained stably RBC-TD with a life expectancy of > 3 months. Central randomization was to one of two RBC transfusion strategies over a 12-week period: 1. Restrictive strategy to maintain Hb between 85 and 105g/L. To achieve this, 2 RBC units were transfused when Hb < 85 g/L 2. Liberal strategy to maintain Hb between 110 and 120 g/L. To achieve this, 2 RBC units were transfused when Hb < 105 g/L and 1 unit for Hb 105-110 g/L. The first 4 weeks were considered a run-in period to achieve the target Hb. The primary outcomes of this feasibility study were 1. The percentage compliance of Hb being within or abov e the target range of the assigned transfusion threshold (after the 4 week run-in). Feasibility was set at 70%. 2. Achievement of at least a 15 g/L difference between the mean pre-transfusion Hb of the liberal and restrictive strategy groups. Secondary outcomes included changes and differences in QOL scores, rates of transfusion reactions and alloimmunizations, overall blood utilization and visit numbers and impact on serum ferritin. The primary analysis was intention to treat. The stud

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CANTRK

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Journal of molecular diagnostics, The 2023年第3期25卷 168-174页

作者： Stockley, Tracy L. Lo, Bryan Box, Adrian Corredor, Andrea Gomez DeCoteau, John Desmeules, Patrice Feilotter, Harriet Grafodatskaya, Daria Greer, Wenda Hawkins, Cynthia Huang, Weei Yuarn Izevbaye, Iyare Lépine, Guylaine Martins Filho, Sebastiao N. Papadakis, Andreas I. Park, Paul C. Riviere, Jean-Baptiste Sheffield, Brandon S. Spatz, Alan Spriggs, Elizabeth Tran-Thanh, Danh Yip, Stephen Zhang, Tong Torlakovic, Emina Tsao, Ming Sound Laboratory Medicine Program University Health Network Toronto Ontario Canada Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Ontario Canada Advanced Molecular Diagnostics Laboratory Princess Margaret Cancer Centre Toronto Ontario Canada Department of Pathology and Laboratory Medicine The Ottawa Hospital Ottawa Ontario Canada Alberta Precision Labs Calgary Alberta Canada McGill University Health Center Montreal Quebec Canada Department of Pathology and Laboratory Medicine College of Medicine University of Saskatchewan Saskatoon Saskatchewan Canada IUCPQ-UL Quebec Heart and Lung Institute Quebec City Quebec Canada Kingston Health Sciences Centre Kingston Ontario Canada Department of Pathology and Molecular Medicine Queen’s University Kingston Ontario Canada Hamilton Health Sciences Centre Hamilton Ontario Canada Department of Pathology and Molecular Medicine McMaster University Hamilton Ontario Canada Nova Scotia Health Authority Halifax Nova Scotia Canada The Hospital for Sick Children Toronto Ontario Canada Sunnybrook Health Sciences Centre Toronto Ontario Canada Department of Laboratory Medicine and Pathology University of Alberta Edmonton Alberta Canada Hôpital Maisonneuve-Rosemont Montreal Quebec Canada Lady Davis Institute Jewish General Hospital Montreal Quebec Canada Shared Health Manitoba Winnipeg Manitoba Canada William Osler Health System Brampton Ontario Canada

The Canadian NTRK (CANTRK) study is an interlaboratory comparison ring study to optimize testing for neurotrophic receptor tyrosine kinase ( NTRK) fusions in Canadian laboratories. Sixteen diagnostic laboratories used next-generation sequencing (NGS) for NTRK1, NTRK2, or NTRK3 fusions. Each laboratory received 12 formalin-fixed, paraffin-embedded tumor samples with unique NTRK fusions and two control non- NTRK fusion samples (one ALK and one ROS1). Laboratories used validated protocols for NGS fusion detection. Panels included Oncomine Comprehensive Assay v3, Oncomine Focus Assay, Oncomine Precision Assay, AmpliSeq for Illumina Focus, TruSight RNA Pan-Cancer Panel, FusionPlex Lung, and QIAseq Multimodal Lung. One sample was withdrawn from analysis because of sample quality issues. Of the remaining 13 samples, 6 of 11 NTRK fusions and both control fusions were detected by all laboratories. Two fusions, WNK2::NTRK2 and STRN3::NTRK2, were not detected by 10 laboratories using the Oncomine Comprehensive or Focus panels, due to absence of WNK2 and STRN3 in panel designs. Two fusions, TPM3::NTRK1 and LMNA::NTRK1, were challenging to detect on the AmpliSeq for Illumina Focus panel because of bioinformatics issues. One ETV6::NTRK3 fusion at low levels was not detected by two laboratories using the TruSight Pan-Cancer Panel. Panels detecting all fusions included FusionPlex Lung, Oncomine Precision, and QIAseq Multimodal Lung. The CANTRK study showed competency in detection of NTRK fusions by NGS across different panels in 16 Canadian laboratories and identified key test issues as targets for improvements.

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Development of a sensitive, quantitative assay with broad subtype specificity for detection of total HIV-1 nucleic acids in plasma and PBMC (vol 12, 1550, 2022)

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SCIENTIFIC REPORTS 2022年第1期12卷 1-16页

作者： Kibirige, C. N. Manak, M. King, D. Abel, B. Hack, H. Wooding, D. Liu, Y. Fernandez, N. Dalel, J. Kaye, Steve Imami, N. Jagodzinski, L. Gilmour, J. IAVI Human Immunology Laboratory Imperial College London Chelsea and Westminster NHS Foundation Trust 369 Fulham Road London SW10 9NH UK Henry M. Jackson Foundation for the Advancement of Military Medicine Bethesda MD USA U.S. Military HIV Research Program Walter Reed Army Institute of Research 503 Robert Grant Ave. Silver Spring MD 20910 USA Diagnostics and Countermeasures Branch Walter Reed Army Institute of Research 503 Robert Grant Ave Silver Spring MD 20910 USA Molecular Diagnostics Unit Imperial College London Jefferiss Trust Laboratory St. Mary’s Campus Norfolk Place London W2 1PG UK Centre for Immunology and Vaccinology Imperial College London Chelsea and Westminster NHS Foundation Trust 369 Fulham Road London SW10 9NH UK

An LTR-based quantitative PCR (qPCR) assay was modified and optimized for the quantification of total HIV-1 nucleic acids in plasma and PBMC. TaqMan qPCR primers and probes were designed against the NCBI/LANL HIV-1 compendium database by analyzing sequences used in assays for sensitive cross-clade detection of HIV-1 as reported in the literature and elucidating regions of improved cross-subtype specificity. Inosine and mixed nucleotide bases were included at polymorphic sites. Real-time RT-qPCR and qPCR were performed on plasma viral RNA and cellular lysates. A step-up amplification approach to allow binding of primers across polymorphic regions showed improved sensitivity compared to universal cycling. Unlike a lead competing laboratory-developed assay, all major HIV-1 subtypes, and a wide range of recombinants from a 127-member diversity panel were detected and accurately quantified in spiked plasmas. Semi-nested PCR increased detection sensitivity even further. The assay was able to detect down to 88 copies/mL of HIV-1 in plasma with 95% efficiency or the equivalent of a single infected cell. The PCR assay will be valuable in studies that monitor very low viral levels including residual or break through HIV-1 in patients receiving antiretroviral therapy, in HIV-1 cure, and in other research studies.

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Extracellular rna in systemic lupus erythematosus

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ExRNA 2019年第October-November-December期1卷 1-7页

作者： Liu, Shanshan Wang, Dandan Liu, Yuan Department of Rheumatology and Immunology the Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008 China Program of Immunology & Molecular Cellular Biology Department of Biology Center for Diagnostics & Therapeutics Center of Inflammation Immunity & Infection Georgia State University Atlanta 30302 GA United States

Since the discovery of extracellular RNA (exRNA), it has been shown that exRNAs play a significant role as a transducer in intercellular communication and biomarkers in various diseases. Systemic lupus erythematosus (SLE) is a kind of autoimmune disease that has protean manifestations. The survival and long-term prognosis of patients with SLE has improved in these 5–10 years, while disease pathogenesis is still not clear. Many researchers found the changes in exRNA profile, and exRNAs are likely participating in the process of SLE. In this review, we summarize the current profile and function of exRNA in SLE. Circulating miRNAs, in particular, have been identified as biomarkers for SLE diagnosis. We also explore the function of lncRNA in SLE and the potential correlation with disease progression and activity. These studies show that exRNAs may take parts in the process of SLE and some of them can be used as diagnostic tool for SLE. © The Author(s).

关键词： ExRNAs LncRNAs MiRNAs Systemic lupus erythematosus

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Ultra-Sensitive Point of Care Biosensor for Detecting Pathogeneses

Ultra-Sensitive Point of Care Biosensor for Detecting Pathog...

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作者： Farzad, Negin Cui, Chengde Senejani, Ali Sinha, Saion Biomedical Engineering Program University of New Haven West HavenCT06516 United States 12-15 Molecular Diagnostics BranfordCT06405 United States Department of Biology and Environmental Sciences University of New Haven West HavenCT United States

Pathogen diseases cause considerable loses in production of food which impact human health from diverse bacterial/viral infections. Precise spotting and diagnosis of such infectious disease is significant to prevent it from further outbreak issues. Moreover, to detect this kind of diseases at an early stage with highly sensitive and selective basis is necessary to avoid the spread of invasive pathogens. The conventional methods such as ELISA, PCR techniques are currently in use to diagnose bacterial/viral disease with high throughput. Though these diagnostic techniques assist in detect and identify the diseases, there are few modern challenges to be meet in order to make this diagnostic more effective in recent days. In this paper, our designed device consists of Bionanosensor works on nucleic acid-based testing provides result with high specificity and selectivity which is vital for early stage identification in a rapid real-time effective manner. © 2019 World Scientific Publishing Company.

关键词： Biosensors

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Surgeon-dependent histopathological variations in minor alloantigen-mismatched mouse lung transplantation

JHLT open

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JHLT open 2024年 4卷 100050页

作者： Mitsuaki Kawashima Jillian D Oliver Tatsuaki Watanabe Hisashi Oishi Ning Huang Chihiro Konoeda Shin Hirayama David M Hwang Qixuan Li Ella Huszti Mingyao Liu Shaf Keshavjee Stephen Juvet Tereza Martinu Latner Thoracic Research Laboratories Toronto Lung Transplant Program Ajmera Transplant Centre Toronto General Hospital Research Institute University Health Network Toronto Ontario Canada. Department of Laboratory Medicine and Molecular Diagnostics Sunnybrook Hospital Toronto Ontario Canada. Biostatistics Research Unit University Health Network Toronto Ontario Canada. Division of Respirology Department of Medicine University of Toronto Toronto Ontario Canada.

Background:The mouse orthotopic single lung transplant (LTx) model is an important scientific tool to explore LTx immunology. C57BL/10J (B10, H-2b) to C57BL/6J (B6, H-2b) minor alloantigen-mismatched LTx exhibits mild acute rejection and chronic fibrosis, mimicking human LTx, where acute rejection is dampened by immunosuppressants and chronic lung allograft dysfunction (CLAD) develops over time. However, we have observed variations in allograft histology across experiments, which were not explained by animal vendor or experimental conditions. The purpose of this study was to evaluate those variations objectively. Methods:We performed a retrospective review of B10-to-B6 LTx performed in our laboratory 2012-2019. Only LTx without experimental interventions (eg, immunomodulatory agents or genetic modifications) examined at day 28 was eligible for this study. Mice from each surgeon were selected and divided into 3 groups to represent early, middle, and late timepoints in their mouse LTx experience (143 LTx from 5 surgeons). Histology from these LTx was graded in a randomized and blinded manner. Pathological variations and trajectories were graphed; logistic regression analyses were performed for statistical assessment. Results:Distribution and trajectories of pathological outcomes were significantly different across surgeons. In multivariable logistic regression analyses, surgeon was associated with pathological outcomes whereas case number was not. Longer warm ischemia time was associated with more severe pleural fibrosis. Conclusions:The B10 to B6 single LTx model can be a powerful tool to recapitulate CLAD-like histology. However, this is a challenging operation and surgeon-dependent variability in histopathological findings needs to be taken into account when designing experimental protocols.

关键词： fibrosis graft rejection lung transplantation mice transplantation immunology

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Development of a spray disinfection mechanism for baths in homes in the city of Cuenca

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AIP Conference Proceedings 2022年第1期2574卷

作者： Jorge Luis Arias Duy Jonnathan Gerardo Ortiz Pablo Ramírez Reyes Lorena Eulalia Enderica Izquierdo 1Catholic University of Cuenca Master’s Program in Construction with a major in Sustainable Construction Management Camino a Patamarca y Cojimíes – Uncovía Cuenca Ecuador 2Catholic University of Cuenca Master’s Program in Clinical and Molecular Laboratory Diagnostics Camino a Patamarca y Cojimíes – Uncovía Cuenca Ecuador 3University of Cuenca Av Huayna Capac entre Juan José Flores y la Republica. Cuenca Ecuador

The outbreak and spread of infectious and contagious diseases such as Covid-19, which is currently affecting the world population, especially Ecuador, highlights the inadequate handling of regulations regarding biosafety measures such as personal and object disinfection everyday use in a home. The objective of the research is to develop a mechanism that allows the continuous disinfection of a bathroom, through the application by spraying of disinfectant chemicals that are not harmful to health and thus guarantee a healthy home for the occupants, reducing the risk of contagion of diseases. intestinal and respiratory; and at the same time offering a comfortable method of disinfection. Methodologically, the sampling was carried out on surfaces of 6 houses of interest at the level of the home bathrooms in Cuenca - Ecuador, using swabs. Stuart medium was used to transport the samples. Bacterial identification was carried out using the semi-automatic RapID one method and conventional biochemical tests to determine the existence of pathogens. In addition to conducting a review of the state of the art for the selection of the best disinfectant and in turn the appropriate disinfection mechanism. Among the results obtained, the presence of pathogens is observed in the following percentages, 55% Escherichia coli, 18% Proteus mirabilis, 15% Enterococcus faecalis, 5% Klebsiella aerogenes, 5% Staphylococcus coagulase negative and 2.5% Morganella morganii in the different areas of the bathrooms where the samples were collected. The best disinfectant is determined to be quaternary ammonium used by means of a mist disinfection mechanism. The presence of microorganisms in areas that are used on a daily basis has consequences for the health of the inhabitants, for this reason, it is advisable to use quaternary ammonium to carry out the disinfection mechanism by nebulization, which is capable of eliminating 99.9% of these agents, guaranteeing a healthy environment without causing damag

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An Overview of molecular Genetic Diagnosis Techniques

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Current Protocols in Human Genetics 2020年第1期105卷 e97页

作者： Goswami, Rashmi S. Harada, Shuko Department of Laboratory Medicine and Molecular Diagnostics Sunnybrook Health Sciences Centre Toronto ON Canada Sunnybrook Research Institute Biological Sciences Odette Cancer Research Program Toronto ON Canada Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON Canada Department of Pathology University of Alabama at Birmingham Birmingham AL United States

Our understanding of genetic disease(s) has increased exponentially since the completion of human genome sequencing and the development of numerous techniques to detect genetic variants. These techniques have not only allowed us to diagnose genetic disease, but in so doing, also provide increased understanding of the pathogenesis of these diseases to aid in developing appropriate therapeutic options. Additionally, the advent of next-generation or massively parallel sequencing (NGS/MPS) is increasingly being used in the clinical setting, as it can detect a number of abnormalities from point mutations to chromosomal rearrangements as well as aberrations within the transcriptome. In this article, we will discuss the use of multiple techniques that are used in genetic diagnosis. © 2020 by John Wiley & Sons, Inc. © 2020 John Wiley & Sons, Inc.

关键词： chromosomal structural variants gene mutations linkage analysis next generation sequencing

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Seroepidemiology and Risk Factors for SARS-CoV-2 Infection Among Household Members of Food Processing and Farm Workers in North Carolina

SSRN

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SSRN 2023年

作者： Sciaudone, Michael Cutshaw, Melissa K. McClean, Colleen M. Lacayo, Roberto Kharabora, Oksana Murray, Katherine Strohminger, Stephen Zivanovich, Miriana Moreno Gurnett, Rachel Markmann, Alena J. Salgado, Emperatriz Morales Bhowmik, D. Ryan Castro-Arroyo, Edwin Boyce, Ross M. Aiello, Allison E. Richardson, David Juliano, Jonathan J. Bowman, Natalie M. Department of Medicine Section of Infectious Diseases Tulane University School of Medicine New OrleansLA United States Center for Intelligent Molecular Diagnostics Tulane University School of Medicine New OrleansLA United States Department of Medicine Duke University DurhamNC United States Duke University School of Medicine DurhamNC United States Infectious Disease Epidemiology and Ecology Laboratory University of North Carolina School of Medicine Chapel HillNC United States Department of Medicine Division of Infectious Diseases University of North Carolina School of Medicine Chapel HillNC United States Department of Microbiology and Immunology University of North Carolina School of Medicine Chapel HillNC United States Institute for Global Health and Infectious Diseases University of North Carolina Chapel HillNC United States Department of Epidemiology Gillings School of Global Public Health University of North Carolina Chapel HillNC United States Carolina Population Center University of North Carolina Chapel HillNC United States Department of Epidemiology Mailman School of Public Health Columbia University New YorkNY United States Robert N Butler Columbia Aging Center Mailman School of Public Health Columbia University New YorkNY United States Department of Environmental and Occupational Health Program in Public Health University of California IrvineCA United States Curriculum in Genetics and Molecular Biology University of North Carolina Chapel HillNC United States

Background: Racial and ethnic minorities have borne a disproportionate burden from COVID-19. Certain essential occupations, including food processing and farm work, employ large numbers of Hispanic migrant workers and have been shown to carry an especially high risk of ***: We conducted an observational cohort study measuring the seroprevalence of SARS-CoV-2 and assessing risk factors for seropositivity among North Carolina (NC) food processing and farm workers and members of their households. Participants completed questionnaires and we collected blood samples and used an enzyme-linked immunosorbent assay to assess SARS-CoV-2 seropositivity. Univariate and multivariate analyses were carried out to identify risk factors associated with seropositivity, using generalized estimating equations to account for household ***: Among the 218 participants, 94.5% were Hispanic, and SARS-CoV-2 seropositivity was 50.0%. Most seropositive individuals did not report a history of illness compatible with COVID-19. Attending church, having a prior history of COVID-19, having a seropositive household member, and speaking Spanish as one’s primary language were associated with SARS-CoV-2 seropositivity, while preventive behaviors were ***: These findings underscore the substantial burden of COVID-19 among a population of mostly Hispanic essential workers and their households in rural NC. Our study contributes to a large body of evidence showing that Hispanic Americans have suffered a disproportionate COVID-19 burden. We also highlight the epidemiologic importance of viral transmission within the ***: North Carolina Collaboratory, National Center for Advancing Translational Sciences (2KR27005 and 550KR242003), National Institutes of Health (UL1TR002489), SeroNet Serocenter of Excellence Award (U54 CA260543).Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Institutional Review Board at the

关键词： Coronavirus

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