Publications by authors named "S M Saw"

717 Publications

Abnormal B-cell development in TIMP deficient bone marrow.

Blood Adv 2021 Sep 9. Epub 2021 Sep 9.

Princess Margaret Cancer Centre/University Health Network, Toronto, ON, Canada, Torornto, Canada.

Bone marrow (BM) is the primary site of hematopoiesis and is responsible for a lifelong supply of all blood cell lineages. The process of hematopoiesis follows key intrinsic programs that also integrate instructive signals from the BM niche. First identified as an erythropoietin potentiating factor, tissue inhibitor of metalloproteinase (TIMP) protein family has expanded to 4 members and has widely come to be viewed as a classical regulator of tissue homeostasis. By virtue of metalloprotease inhibition, TIMPs not only regulate extracellular matrix turnover but also control growth factor bioavailability. The four mammalian TIMPs possess overlapping enzyme inhibition profiles and have never been studied for their cumulative role in hematopoiesis. Here, we show that TIMPs are critical for post-natal B lymphopoiesis in the BM. TIMP-deficient mice have defective B-cell development arising at the pro-B cell stage. Expression analysis of TIMPless hematopoietic cell subsets pointed to an altered B-cell program in the Lineage-c-Kit+Sca-1+ cell (LSK) fraction. Serial and competitive BM transplants identified a defect in TIMP- deficient HSPCs for B lymphopoiesis. In parallel, reverse BM transplants uncovered the extrinsic role of stromal TIMPs in pro- and pre-B cell development. TIMP-deficiency disrupted CXCL12 localization to LepR+ cells, and increased soluble CXCL12 within the BM niche. It also compromised the number and morphology of LepR+ cells. These data provide new evidence that TIMPs control the cellular and biochemical makeup of the BM niche along with influencing the LSK transcriptional program required for optimal B-lymphopoiesis.
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http://dx.doi.org/10.1182/bloodadvances.2020004101DOI Listing
September 2021

A Review of Biomechanics Analysis of the Umbilical-Placenta System With Regards to Diseases.

Front Physiol 2021 12;12:587635. Epub 2021 Aug 12.

Department of Bioengineering, Imperial College London, London, United Kingdom.

Placenta is an important organ that is crucial for both fetal and maternal health. Abnormalities of the placenta, such as during intrauterine growth restriction (IUGR) and pre-eclampsia (PE) are common, and an improved understanding of these diseases is needed to improve medical care. Biomechanics analysis of the placenta is an under-explored area of investigation, which has demonstrated usefulness in contributing to our understanding of the placenta physiology. In this review, we introduce fundamental biomechanics concepts and discuss the findings of biomechanical analysis of the placenta and umbilical cord, including both tissue biomechanics and biofluid mechanics. The biomechanics of placenta ultrasound elastography and its potential in improving clinical detection of placenta diseases are also discussed. Finally, potential future work is listed.
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http://dx.doi.org/10.3389/fphys.2021.587635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406807PMC
August 2021

Real-world, Multicenter Experience With Meropenem-Vaborbactam for Gram-Negative Bacterial Infections Including Carbapenem-Resistant and .

Open Forum Infect Dis 2021 Aug 14;8(8):ofab371. Epub 2021 Jul 14.

Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.

Background: We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of gram-negative infections (GNIs), primarily including carbapenem-resistant Enterobacterales (CRE).

Methods: This is a real-world, multicenter, retrospective cohort within the United States between 2017 and 2020. Adult patients who received MEV for ≥72 hours were eligible for inclusion. The primary outcome was 30-day mortality. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineated the risk of negative clinical outcomes (NCOs) and was examined by multivariable logistic regression analysis (MLR).

Results: Overall, 126 patients were evaluated from 13 medical centers in 10 states. The most common infection sources were respiratory tract (38.1%) and intra-abdominal (19.0%) origin, while the most common isolated pathogens were CRE (78.6%). Thirty-day mortality and recurrence occurred in 18.3% and 11.9%, respectively. Adverse events occurred in 4 patients: nephrotoxicity (n = 2), hepatoxicity (n = 1), and rash (n = 1). CART-BP between early and delayed treatment was 48 hours ( = .04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (adusted odds ratio, 0.277; 95% CI, 0.081-0.941).

Conclusions: Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNIs, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCOs.
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http://dx.doi.org/10.1093/ofid/ofab371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378588PMC
August 2021

New Polygenic Risk Score to Predict High Myopia in Singapore Chinese Children.

Transl Vis Sci Technol 2021 07;10(8):26

Singapore Eye Research Institute, Singapore.

Purpose: The purpose of this study was to develop an Asian polygenic risk score (PRS) to predict high myopia (HM) in Chinese children in the Singapore Cohort of Risk factors for Myopia (SCORM) cohort.

Methods: We included children followed from 6 to 11 years old until teenage years (12-18 years old). Cycloplegic autorefraction, ultrasound biometry, Illumina HumanHap 550, or 550 Duo Beadarrays, demographics, and environmental factors data were obtained. The PRS was generated from the Consortium for Refractive Error and Myopia genomewide association study (n = 542,934) and the Strabismus, Amblyopia, and Refractive Error in Singapore children Study (n = 500). The Growing Up in Singapore Towards healthy Outcomes Cohort study (n = 339) was the replication cohort. The outcome was teenage HM (≤ -5.00 D) with predictive performance assessed using the area under the curve (AUC).

Results: Mean baseline age ± SD was 7.85 ± 0.84 (n = 1004) and 571 attended the teenage visit; 23.3% had HM. In multivariate analysis, the PRS was associated with a myopic spherical equivalent with an incremental R2 of 0.041 (95% confidence interval [CI] = 0.010, 0.073; P < 0.001). AUC for HM (0.77 [95% CI = 0.71-0.83]) performed better (P = 0.02) with the PRS compared with a model without (0.72 [95% CI = 0.65, 0.78]). Children at the top 25% PRS risk had a 2.34-fold-greater risk of HM (95% CI = 1.53, 3.55; P < 0.001).

Conclusions: The new Asian PRS improved the predictive performance to detect children at risk of HM.

Translational Relevance: Clinicians may use the PRS with other predictive factors to identify high risk children and guide interventions to reduce the risk of HM later in life.
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http://dx.doi.org/10.1167/tvst.10.8.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322707PMC
July 2021

Co-targeting the VEGF axis and immune checkpoints in NSCLC: back to the future.

Authors:
S P L Saw D S W Tan

Ann Oncol 2021 09 6;32(9):1075-1076. Epub 2021 Jul 6.

Division of Medical Oncology, National Cancer Centre Singapore, Singapore. Electronic address:

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http://dx.doi.org/10.1016/j.annonc.2021.06.026DOI Listing
September 2021
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