Publications by authors named "D Michael Nelson"

5,453 Publications

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Simultaneous screening of the FRAXA and FRAXE loci for rapid detection of FMR1 CGG and/or AFF2 CCG repeat expansions by triplet-primed PCR.

J Mol Diagn 2021 Jun 7. Epub 2021 Jun 7.

Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 119228, SINGAPORE; Khoo Teck Puat - National University Children's Medical Institute, National University Health System, 119228, SINGAPORE; Department of Laboratory Medicine, National University Hospital, 119074, SINGAPORE; Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, 119228, SINGAPORE. Electronic address:

Moderate to hyper expansion of trinucleotide repeats at the FRAXA and FRAXE fragile sites, with or without concomitant hypermethylation are associated with intellectual disability and other conditions. Unlike molecular diagnosis of FMR1 CGG repeat expansions in FRAXA, current detection of AFF2 CCG repeat expansions in FRAXE relies on low-throughput and inefficient techniques combining Southern blot and PCR. A novel triplet-primed PCR assay was developed to simultaneously screen for trinucleotide repeat expansions at the FRAXA and FRAXE fragile sites, and validated using archived clinical samples of known FMR1 and AFF2 genotypes. Sequencing of population samples and FRAXE-affected samples was performed to evaluate variation of the AFF2 CCG repeat structure. The duplex assay accurately identified expansions at the FMR1 and AFF2 trinucleotide repeat loci. Sanger sequencing of the AFF2 CCG repeat revealed that the SNP variant rs868914124(C), which effectively adds two CCG repeats at the 5' end, is enriched in the Malay population and with short repeats (<11 CCGs), and was present in all six expanded AFF2 alleles of this study. All expanded AFF2 alleles contained multiple non-CCG interruptions towards the 5' end of the repeat. We have developed a sensitive, robust and rapid assay to simultaneously detect expansion mutations at the FMR1 and AFF2 trinucleotide repeat loci, simplifying the screening of FRAXA and FRAXE associated disorders.
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http://dx.doi.org/10.1016/j.jmoldx.2021.04.015DOI Listing
June 2021

Anisotropic satellite galaxy quenching modulated by black hole activity.

Nature 2021 Jun 9;594(7862):187-190. Epub 2021 Jun 9.

Max-Planck-Institut für Astrophysik, Garching, Germany.

The evolution of satellite galaxies is shaped by their constant interaction with the circumgalactic medium surrounding central galaxies, which in turn may be affected by gas and energy ejected from the central supermassive black hole. The nature of such a coupling between black holes and galaxies is, however, much debated and observational evidence remains scarce. Here we report an analysis of archival data on 124,163 satellite galaxies in the potential wells of 29,631 dark matter halos with masses between 10 and 10 solar masses. We find that quenched satellite galaxies are relatively less frequent along the minor axis of their central galaxies. This observation might appear counterintuitive given that black hole activity is expected to eject mass and energy preferentially in the direction of the minor axis of the host galaxy. We show, however, that the observed anisotropic signal results precisely from the ejective nature of black hole feedback in massive halos, as outflows powered by active galactic nuclei clear out the circumgalactic medium, reducing the ram pressure and thus preserving star formation in satellite galaxies. This interpretation is supported by the IllustrisTNG suite of cosmological numerical simulations, even though the model's sub-grid implementation of black hole feedback is effectively isotropic.
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http://dx.doi.org/10.1038/s41586-021-03545-9DOI Listing
June 2021

An investigation of sickle cell trait, body mass index, and fitness in relation to venous thromboembolism among African American adults.

J Thromb Haemost 2021 Jun 9. Epub 2021 Jun 9.

Department of Medicine, Division of Primary Care and Population Health, Stanford University School of Medicine, USA.

Background: The relationships of sickle cell trait (SCT), body mass index, and physical fitness to venous thromboembolism (VTE) in young adults have received little attention.

Objectives: To test for associations between SCT, BMI, fitness and VTE.

Patients/methods: We conducted a retrospective cohort study of 48,316 SCT-tested, African American individuals in the US Army during 2011-14. We used Cox proportional hazards models to compute adjusted hazards of deep vein thrombosis (DVT) and pulmonary embolism (PE) associated with selected factors.

Results: Incidence rates of DVT and PE were 1.09 and 0.91 cases per 1000 person-years, respectively. Adjusted hazard ratios (aHRs) for DVT for men and women with SCT were 0.9 (95% confidence interval [CI]: 0.4 - 2.0; P = 0.711) and 1.51 (CI: 0.7 - 3.2; P = 0.274), respectively. aHRs for PE for SCT+ men and women were 1.1 (CI: 0.5 - 2.4; P = 0.773) and 1.2 (CI: 0.5 - 3.1; P = 0.650), respectively. Low physical fitness was associated with DVT and PE in women (DVT aHR = 3.1; CI: 1.4 - 6.5; P = 0.004; PE aHR = 4.6; CI: 2.1 - 9.9; P < 0.001) and DVT in men (aHR = 2.2; CI: 1.0 - 4.6; P = 0.048). A one BMI point increase was associated with DVT in men (aHR = 1.8; CI: 1.1 - 2.8; P = 0.017).

Conclusions: We found no evidence of increased VTE risk associated with SCT in this population. However, lower fitness levels and BMI increases were so associated.
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http://dx.doi.org/10.1111/jth.15422DOI Listing
June 2021

Near Complete Pathologic Response to PD-1 Inhibitor and Radiotherapy in a Patient with Locally Advanced Pancreatic Ductal Adenocarcinoma.

Onco Targets Ther 2021 1;14:3537-3544. Epub 2021 Jun 1.

Department of Surgery, Brooke Army Medical Center, San Antonio, TX, USA.

Pancreatic ductal adenocarcinoma (PDAC) remains deadly despite advances in systemic therapies and surgical techniques. While there is increasing utilization of immune therapies across diverse cancer types, PDAC remains generally resistant to these treatments. We report a case of locally advanced PDAC treated with preoperative radiation and anti-PD-1 immunotherapy guided by preoperative PD-L1 tumor analysis. After 4 months of preoperative therapy, the patient was submitted to resection, demonstrating a near-complete pathologic response on final tumor analysis. We will discuss the relevant literature and current state of immunotherapeutics for PDAC.
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http://dx.doi.org/10.2147/OTT.S311661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179799PMC
June 2021