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"Li, George"
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Deploying vaccine distribution sites for improved accessibility and equity to support pandemic response
In response to COVID-19, many countries have mandated social distancing and banned large group gatherings in order to slow down the spread of SARS-CoV-2. These social interventions along with vaccines remain the best way forward to reduce the spread of SARS CoV-2. In order to increase vaccine accessibility, states such as Virginia have deployed mobile vaccination centers to distribute vaccines across the state. When choosing where to place these sites, there are two important factors to take into account: accessibility and equity. We formulate a combinatorial problem that captures these factors and then develop efficient algorithms with theoretical guarantees on both of these aspects. Furthermore, we study the inherent hardness of the problem, and demonstrate strong impossibility results. Finally, we run computational experiments on real-world data to show the efficacy of our methods.
Journal Article
Use of Neoadjuvant Imatinib to Facilitate Minimally Invasive Resection of Gastric Gastrointestinal Stromal Tumors
BackgroundNeoadjuvant imatinib is used to downstage surgery for large and/or unfavorably located gastric gastrointestinal stromal tumors (GISTs), but data regarding minimally invasive surgery (MIS) after neoadjuvant imatinib are limited.Patients and MethodsWe analyzed patients undergoing resection of nonmetastatic primary gastric GISTs larger than or equal to 4.5 cm in diameter at our institution between 2009 and 2020, as no tumors below this size received neoadjuvant imatinib.ResultsWe identified 71 patients, 43 of whom (61%) received neoadjuvant imatinib. Patients receiving neoadjuvant imatinib had larger tumors at diagnosis [median diameter 8.6 cm (range 4.5–25 cm) versus 5.9 cm (range 4.5–11 cm), p < 0.01]. After a median 7.2 months of imatinib, tumors shrank by a median 34% in diameter, such that there was no longer a significant size difference at time of surgery between groups (median 6.3 cm versus 5.9 cm, p = 0.69). Of 29 patients for whom neoadjuvant imatinib was used to facilitate MIS, 21 (72%) underwent successful MIS, which accounted for 49% of the entire neoadjuvant cohort. In a multivariable regression model, smaller tumor size at time of surgery was predictive of successful MIS, but tumor location was not.ConclusionsNeoadjuvant imatinib caused significant tumor shrinkage, and MIS was successful in 72% of cases for which neoadjuvant imatinib was intended to facilitate it. Smaller tumor size at time of surgery, but not tumor location, was associated with successful MIS, which may help inform patient selection for neoadjuvant imatinib.
Journal Article
Grouping, Spectrum–Effect Relationship and Antioxidant Compounds of Chinese Propolis from Different Regions Using Multivariate Analyses and Off-Line Anti-DPPH Assay
49 samples of propolis from different regions in China were collected and analyzed for their chemical compositions, contents of total flavonoids (TFC), total phenolic acid (TPC) and antioxidant activity. High-performance liquid chromatography (HPLC) analysis identified 15 common components, including key marker compounds pinocembrin, 3-O-acetylpinobanksin, galangin, chrysin, benzyl p-coumarate, pinobanksin and caffeic acid phenethyl ester (CAPE). Cluster analysis (CA) and correlation coefficients (CC) analysis showed that these propolis could be divided into three distinct groups. Principal component analysis (PCA) and multiple linear regression analysis (MLRA) revealed that the contents of isoferulic acid, caffeic acid, CAPE, 3,4-dimethoxycinnamic acid, chrysin and apigenin are closely related to the antioxidant properties of propolis. In addition, eight peak areas decreased after reacting with 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radicals, indicating that these compounds have antioxidant activity. The results indicate that the grouping and spectrum–effect relationship of Chinese propolis are related to their chemical compositions, and several compounds may serve as a better marker for the antioxidant activity of Chinese propolis than TFC and TPC. The findings may help to develop better methods to evaluate the quality of propolis from different geographic origins.
Journal Article
The Symptom Cluster of Fatigue, Pain, Anxiety, and Depression and the Effect on the Quality of Life of Women Receiving Treatment for Breast Cancer: A Multicenter Study
To examine the symptom cluster of fatigue, pain, anxiety, and depression and its effect on the quality of life (QOL) of women receiving chemotherapy or radiotherapy for breast cancer.
Descriptive.
Oncology outpatient sections of four public hospitals in Hong Kong.
215 ethnic Chinese women who were midway through treatment for breast cancer.
Chinese versions of the Brief Fatigue Inventory, Hospital Anxiety and Depression Scale, Brief Pain Inventory, Functional Assessment of Chronic Illness Therapy for Breast Cancer, and Medical Outcomes Study Social Support Survey were used. Spearman rho correlation and structural equation modeling were used to examine the relationships among the study variables.
Breast cancer, fatigue, pain, anxiety, depression, and QOL.
Most participants reported mild-to-moderate levels of fatigue and pain. Twenty-one percent and 36% of patients might have had an anxiety or depression disorder, respectively. Significant correlations among the four symptoms supported the existence of the symptom cluster. The participants receiving chemotherapy had inadequate social support, experienced higher levels of symptoms, and were more likely to have a poorer QOL.
The findings supported the existence of the symptom cluster that had detrimental effects on QOL.
This study shed light on a contemporary approach of grouping several related symptoms together. The findings enhance nurses' clinical sensitivity when identifying patients in high-risk groups and provide useful information for designing and prioritizing symptom-management strategies to meet patients' needs.
Journal Article
Targeted therapy and personalized medicine in gastrointestinal stromal tumors: drug resistance, mechanisms, and treatment strategies
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Since the discovery that the KIT and PDGFRA receptor tyrosine kinases are the primary oncogenic drivers in the vast majority of GISTs, targeted therapy with tyrosine kinase inhibitors has been the mainstay of treatment for this disease. Using molecular profiling of tumor specimens, researchers also discovered that
and
mutations are non-random and occur in specific regions of the receptors, and furthermore, that particular genotypes predicted response or resistance to targeted therapy. Imatinib, the first tyrosine kinase inhibitor used to treat GIST, remains the first-line therapy in advanced GIST and the only therapy confirmed through clinical trials in the adjuvant or neoadjuvant setting for resectable disease. Resistance to imatinib is well described and is either primary or secondary. Primary resistance is associated with specific tumor genotypes, so genotyping of individual patient tumors helps guide decision-making into whether to offer imatinib and at what dose. Secondary resistance occurs due to the acquisition of secondary mutations during therapy. Currently, the main strategy to combat imatinib resistance is to switch to another tyrosine kinase inhibitor, because imatinib-resistant GIST is usually still oncogenically addicted to KIT/PDGFRA signaling. Surgery can also be used to combat resistant disease in select settings. Unfortunately, progression-free and overall survival remains dismal for patients who develop imatinib-resistant disease, and further research into alternative strategies is still needed.
Journal Article
A tannin compound from Sanguisorba officinalis blocks Wnt/β-catenin signaling pathway and induces apoptosis of colorectal cancer cells
Background
Sanguisorba officinalis
, a popular Chinese herb, called DiYu, has been shown to inhibit the growth of many human cancer cell lines, including colorectal cancer cells. The aims of this study were to discover the active compound and molecular mechanism of
S. officinalis
against Wnt/β-catenin signaling pathway and develop Wnt inhibitors from natural products as anti-colorectal cancer agents.
Methods
1,4,6-Tri-
O
-galloyl-β-
d
-glucopyranose (TGG) was obtained by the preparative HPLC. The effect of DiYu on proliferation of NIH3T3 and HT29 was detected by MTT assay. Luciferase reporter assay was applied to investigate the activity of Wnt/β-catenin signaling in NIH3T3. The expression levels of mRNA and protein were detected by RT-PCR and western blot. Immunofluorescence assay was used to measure the level of β-catenin in cytoplasm and nucleus. Transcriptomic profiling study was performed to investigate the molecular mechanism of DiYu on the Wnt/β-catenin signaling pathway.
Results
TGG significantly inhibited the Wnt/β-catenin signaling pathway, down-regulated the expression of β-catenin and Wnt target genes (Dkk1, c-Myc, FGF20, NKD1, Survivin), up-regulated the levels of cleaved caspase3, cleaved PARP and ratio of Bax/Bcl-2, which may explain the apoptosis of HT29.
Conclusions
Our study enhanced the discovery of the materials and elucidation of mechanisms that account for the anti-Wnt activity of natural inhibitor (DiYu) and identified the potential of TGG to be developed as anti-colorectal cancer drugs.
Journal Article
Differentiation of Three Centella Species in Australia as Inferred from Morphological Characteristics, ISSR Molecular Fingerprinting and Phytochemical Composition
is one of the popular herbs used for inflammatory and neural conditions. Its differentiation from similar species is currently lacking. The aims of this study were to differentiate the three closely related
species using methods based on morphological characters, genetic biodiversity, phytochemical compositions and antioxidant activities. According to the morphological characteristics, the collected samples were identified as three species:
and
and clustered into three groups based on their morphometric variability. Dendogram constructed on the basis of the intersimple sequence repeats (ISSR) analyses were consistent with the morphological grouping.
had the highest triterpene glycosides, phenolics and antioxidant capacity, followed by
, then
, therefore, was genetically and chemically closer to
, while
was distinctively different from them. The results confirm the occurrence of the closely related three species of
in Australia, and the differentiation among them can be achieved via the combination of morphometric, molecular and phytochemical methods. This first comparative botanical study on
species provides a foundation for further systematic study and medicinal development of
.
Journal Article