Publications by authors named "M Lam"

1,691 Publications

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Reforms to the Radiation Oncology Model: Prioritizing Health Equity.

Int J Radiat Oncol Biol Phys 2021 Jun;110(2):328-330

Department of Health Policy & Management, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Radiation Oncology, Brigham and Women's Hospital, Dana Farber Cancer Institute, Boston, Massachusetts. Electronic address:

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http://dx.doi.org/10.1016/j.ijrobp.2021.01.029DOI Listing
June 2021

Increased peripheral blood neutrophil activation phenotypes and NETosis in critically ill COVID-19 patients: a case series and review of the literature.

Clin Infect Dis 2021 May 14. Epub 2021 May 14.

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego (UCSD), La Jolla, CA 92093, USA.

Background: Increased inflammation has been well defined in COVID-19, while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases and acute respiratory distress syndrome (ARDS), a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets.

Methods: Blood was obtained serially from critically ill COVID-19 patients for eleven days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis and cytokine levels were assessed. Lung tissue was obtained immediately post-mortem for immunostaining. Pubmed searches for neutrophils, lung and COVID-19 yielded ten peer-reviewed research articles in English.

Results: Elevations in neutrophil-associated cytokines IL-8 and IL-6, and general inflammatory cytokines IP-10, GM-CSF, IL-1b, IL-10 and TNF, were identified both at first measurement and across hospitalization (p<0.0001). COVID neutrophils had exaggerated oxidative burst (p<0.0001), NETosis (p<0.0001) and phagocytosis (p<0.0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of SARS-CoV-2 infected lungs available for examination (2 out of 5). While elevations in IL-8 and ANC correlated with disease severity, plasma IL-8 levels alone correlated with death.

Conclusions: Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data shows that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.
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http://dx.doi.org/10.1093/cid/ciab437DOI Listing
May 2021

An artificial intelligence that increases simulated brain-computer interface performance.

J Neural Eng 2021 May 13;18(4). Epub 2021 May 13.

Department of Electrical and Computer Engineering, University of California, Los Angeles, CA 90024, United States of America.

Brain-computer interfaces (BCIs) translate neural activity into control signals for assistive devices in order to help people with motor disabilities communicate effectively. In this work, we introduce a new BCI architecture that improves control of a BCI computer cursor to type on a virtual keyboard.Our BCI architecture incorporates an external artificial intelligence (AI) that beneficially augments the movement trajectories of the BCI. This AI-BCI leverages past user actions, at both long (100 s of seconds ago) and short (100 s of milliseconds ago) timescales, to modify the BCI's trajectories.We tested our AI-BCI in a closed-loop BCI simulator with nine human subjects performing a typing task. We demonstrate that our AI-BCI achieves: (1) categorically higher information communication rates, (2) quicker ballistic movements between targets, (3) improved precision control to 'dial in' on targets, and (4) more efficient movement trajectories. We further show that our AI-BCI increases performance across a wide control quality spectrum from poor to proficient control.This AI-BCI architecture, by increasing BCI performance across all key metrics evaluated, may increase the clinical viability of BCI systems.
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http://dx.doi.org/10.1088/1741-2552/abfaaaDOI Listing
May 2021

Comprehensive interactome profiling of the human Hsp70 network highlights functional differentiation of J domains.

Mol Cell 2021 Apr 27. Epub 2021 Apr 27.

Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada. Electronic address:

Hsp70s comprise a deeply conserved chaperone family that has a central role in maintaining protein homeostasis. In humans, Hsp70 client specificity is provided by 49 different co-factors known as J domain proteins (JDPs). However, the cellular function and client specificity of JDPs have largely remained elusive. We have combined affinity purification-mass spectrometry (AP-MS) and proximity-dependent biotinylation (BioID) to characterize the interactome of all human JDPs and Hsp70s. The resulting network suggests specific functions for many uncharacterized JDPs, and we establish a role of conserved JDPs DNAJC9 and DNAJC27 in histone chaperoning and ciliogenesis, respectively. Unexpectedly, we find that the J domain of DNAJC27 but not of other JDPs can fully replace the function of endogenous DNAJC27, suggesting a previously unappreciated role for J domains themselves in JDP specificity. More broadly, our work expands the role of the Hsp70-regulated proteostasis network and provides a platform for further discovery of JDP-dependent functions.
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http://dx.doi.org/10.1016/j.molcel.2021.04.012DOI Listing
April 2021

Association of Medicaid expansion and insurance status, cancer stage, treatment and mortality among patients with cervical cancer.

Cancer Rep (Hoboken) 2021 May 2:e1407. Epub 2021 May 2.

Harvard Medical School, Boston, Massachusetts, USA.

Background: Currently, little is known about the effect of the Patient Protection and Affordable Care Act's Medicaid expansion on care delivery and outcomes in cervical cancer.

Aim: We evaluated whether Medicaid expansion was associated with changes in insurance status, stage at diagnosis, timely treatment, and survival outcomes in cervical cancer.

Methods And Results: Using the National Cancer Database, we performed a difference-in-differences (DID) cross-sectional analysis to compare insurance status, stage at diagnosis, timely treatment, and survival outcomes among cervical cancer patients residing in Medicaid expansion and nonexpansion states before (2011-2013) and after (2014-2015) Medicaid expansion. January 1, 2014 was used as the timepoint for Medicaid expansion. The primary outcomes of interest were insurance status, stage at diagnosis, treatment within 30 and 90 days of diagnosis, and overall survival. Fifteen thousand two hundred sixty-five patients (median age 50) were included: 42% from Medicaid expansion and 58% from nonexpansion states. Medicaid expansion was significantly associated with increased Medicaid coverage (adjusted DID = 11.0%, 95%CI = 8.2, 13.8, p < .01) and decreased rates of uninsured (adjusted DID = -3.0%, 95%CI = -5.2, -0.8, p < .01) among patients in expansion states compared with non-expansion states. However, Medicaid expansion was not associated with any significant changes in cancer stage at diagnosis or timely treatment. There was no significant change in survival from the pre- to post-expansion period in either expansion or nonexpansion states, and no significant differences between the two (DID-HR = 0.95, 95%CI = 0.83, 1.09, p = .48).

Conclusion: Although Medicaid expansion was associated with an increase in Medicaid coverage and decrease in uninsured among patients with cervical cancer, the effects of increased coverage on diagnosis and treatment outcomes may have yet to unfold. Future studies, including longer follow-up are necessary to understand the effects of Medicaid expansion.
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http://dx.doi.org/10.1002/cnr2.1407DOI Listing
May 2021