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1.  An Adaptive Weighting Algorithm for Interpolating the Soil Potassium Content 
Scientific Reports  2016;6:23889.
The concept of spatial interpolation is important in the soil sciences. However, the use of a single global interpolation model is often limited by certain conditions (e.g., terrain complexity), which leads to distorted interpolation results. Here we present a method of adaptive weighting combined environmental variables for soil properties interpolation (AW-SP) to improve accuracy. Using various environmental variables, AW-SP was used to interpolate soil potassium content in Qinghai Lake Basin. To evaluate AW-SP performance, we compared it with that of inverse distance weighting (IDW), ordinary kriging, and OK combined with different environmental variables. The experimental results showed that the methods combined with environmental variables did not always improve prediction accuracy even if there was a strong correlation between the soil properties and environmental variables. However, compared with IDW, OK, and OK combined with different environmental variables, AW-SP is more stable and has lower mean absolute and root mean square errors. Furthermore, the AW-SP maps provided improved details of soil potassium content and provided clearer boundaries to its spatial distribution. In conclusion, AW-SP can not only reduce prediction errors, it also accounts for the distribution and contributions of environmental variables, making the spatial interpolation of soil potassium content more reasonable.
PMCID: PMC4823722  PMID: 27051998
2.  The influence of body composition on the N-terminal pro-B-type natriuretic peptide level and its prognostic performance in patients with acute coronary syndrome: a cohort study 
Whether body composition is associated with the N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and its prognostic performance in acute coronary syndrome (ACS) remains unknown. We aimed to investigate the influence of body composition on the NT-proBNP level and its prognostic performance among ACS patients.
In total, 1623 ACS patients with NT-proBNP data were enrolled. Percent body fat and lean mass index were estimated using the Clínica Universidad de Navarra—Body Adiposity Estimator equation. Patients were divided into three groups according to the tertiles of sex-specific body mass index, percent body fat, or lean mass index. The endpoints were death from any cause and cardiovascular death.
Body mass index was inversely correlated with NT-proBNP levels (β = −0.036, P = 0.003). Lean mass index, but not percent body fat, was inversely associated with NT-proBNP levels (β of lean mass index = −0.692, P = 0.002). During a median follow-up of 23 months, 161 all-cause deaths occurred, and of these, 93 (57.8 %) were attributed to cardiovascular causes. Multivariate Cox analysis showed that the NT-proBNP level independently predicted all-cause mortality or cardiovascular death in the lower body mass index, lean mass index, and percent body fat groups. However, the prognostic performance of NT-proBNP was attenuated in patients with high body mass index, lean mass index, and percent body fat. In the subgroup of patients with diabetes, inverse associations between NT-proBNP levels and body mass index or body composition were not observed. In addition, the negative influence of high body mass index and body composition on the prognostic performance of the NT-proBNP level appeared to be attenuated.
Body mass index and lean mass index, but not percent body fat, are inversely associated with NT-proBNP levels. The prognostic performance of this biomarker may be compromised in patients with high body mass index, percent body fat, or lean mass index. Additionally, the influence of body composition on the NT-proBNP level and its prognostic performance might be attenuated in diabetic patients with ACS.
PMCID: PMC4822263  PMID: 27048159
Prognostic performance; N-terminal pro-B-type natriuretic peptide; Acute coronary syndrome; Body composition; Diabetes mellitus
3.  Transplantation of bone marrow-derived mesenchymal stem cells expressing elastin alleviates pelvic floor dysfunction 
Pelvic floor dysfunction (PFD) is a group of clinical conditions including stress urinary incontinence (SUI) and pelvic organ prolapse (POP). The abnormality of collagen and elastin metabolism in pelvic connective tissues is implicated in SUI and POP.
To reconstitute the connective tissues with normal distribution of collagen and elastin, we transduced elastin to bone marrow-derived mesenchymal stem cells (BMSC). Elastin-expressing BMSCs were then differentiated to fibroblasts using bFGF, which produced collagen and elastin. To achieve the sustained release of bFGF, we formulated bFGF in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP).
In an in vitro cell culture system of 7 days, when no additional bFGF was administrated, the initial PLGA-loaded bFGF NP induced prolonged production of collagen and elastin from elastin-expressing BMSCs. In vivo, co-injection of PLGA-loaded bFGF NP and elastin-expressing BMSCs into the PFD rats significantly improved the outcome of urodynamic tests. Together, these results provided an efficient model of connective tissue engineering using BMSC and injectable PLGA-loaded growth factors.
Our results provided the first instance of a multidisciplinary approach, combining both stem cell and nanoparticle technologies, for the treatment of PFD.
PMCID: PMC4822266  PMID: 27048404
Pelvic floor dysfunction; Bone marrow-derived mesenchymal stem cells; Basic fibroblast growth factor; Stress urinary incontinence
4.  Keep Eyes on Integrins 
Journal of immunobiology  2016;1(1):106.
PMCID: PMC4819984  PMID: 27054197
5.  Efficacy of a tobacco quitline among adult cancer survivors 
Preventive medicine  2015;73:22-27.
The purpose of the study (conducted 2010–2013) was to determine the efficacy of two common types of tobacco quitlines in adult cancer survivors who regularly smoked cigarettes.
Adult onset cancer survivors in Memphis, Tennessee (n = 427, 67% female, 60% Caucasian) were randomized either to a Proactive (i.e., counselor-initiated calls) or Reactive (i.e., participant-initiated calls) quitline. Both conditions also received nicotine replacement therapy. The primary outcome was biochemically-verified (i.e., salivary cotinine) smoking cessation.
While 12-month self-reported abstinence was consistent with other published studies of smoking cessation (22% and 26% point prevalence abstinence for Proactive and Reactive conditions, respectively), 48% of participants who were tested for cotinine failed biochemical verification, indicating a considerable falsification of self-reported cessation. Adjusted cessation rates were less than 5% in both intervention conditions.
Our results are consistent with other studies indicating that traditional smoking cessation interventions are ineffective among cancer survivors. Moreover, self-reports of cessation were unreliable in cancer survivors participating in a quitline intervention, indicating that future studies should include biochemical verification. Given the importance of smoking cessation among cancer survivors and low cessation rates in the current study, it may be necessary to design alternative interventions for this population.
PMCID: PMC4355239  PMID: 25572620
Smoking cessation; Adults; Cancer; Survivors; Intervention studies
6.  Dietary patterns associated with HbA1c and LDL cholesterol among individuals with type 1 diabetes in China 
To identify dietary patterns that influence cardiometabolic risk among individuals with type 1 diabetes (T1D) in China.
Data are from a cross-sectional study of T1D in China (n=99). Dietary intake was assessed using three 24-hour recalls. Reduced rank regression was used to identify dietary patterns from a set of 20 food groups that maximized the explained variation in glycated hemoglobin A1c (HbA1c) and low-density lipoprotein (LDL) cholesterol.
Dietary pattern 1 was characterized by low intakes of wheat products and high-fat cakes, and high intakes of beans and pickled vegetables. Dietary pattern 2 was characterized by low intakes of high-fat cakes, nuts/seeds, fish/shellfish, and teas/coffee, and high intakes of rice and eggs. Participants in the highest tertile of dietary pattern 1 had significantly (p<0.05) higher HbA1c and LDL cholesterol compared to participants in the lowest tertile: mean difference in HbA1c was 1.0 percentage point (11mmol/mol) and in LDL cholesterol was 0.36 mmol/L after adjustment for age and household income. Dietary pattern 2 was not associated with HbA1c or LDL cholesterol.
We identified a dietary pattern that is significantly related to HbA1c and LDL cholesterol. These findings provide support for behavioral strategies to prevent complications in individuals with T1D in China.
PMCID: PMC4369414  PMID: 25630525
reduced rank regression; dietary patterns; glycemic control; type 1 diabetes; China
7.  Risk Factors for Haemorrhagic Cystitis in Paediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients 
Haemorrrhagic cystitis (HC) results in significant morbidity among hematopoietic stem cell transplant (HSCT) recipients. Several potential causes for HC have been postulated, including viral infection, but definitive evidence is lacking, particularly in paediatric HSCT patients. Ninety paediatric HSCT recipients were prospectively tested on a weekly basis for adenovirus and BK virus by quantitative real-time PCR in blood and urine samples. Results were correlated with the occurrence of grade II-IV HC. The odds ratio (OR) of HC (95% CI) for BK virus ≥ 1× 109 copies/mL of urine was 7.39 (1.52, 35.99), with a p-value of 0.013. Those with aGvHD also had higher odds of developing HC, with an OR of 5.34. Given a 20% prevalence rate of HC, positive and negative predictive values of 29% and 95% were seen with a cutoff of 109 copies/mL. BK viremia did not reach significance as a risk factor for development of HC (p=0.06). Only 8 patients showed adenoviruria and 7 showed adenoviremia; all had low viral loads and four had no evidence of HC. HC in paediatric HSCT is correlated most strongly to elevated urinary viral load of BK virus and to aGVHD, but less strongly to BK viremia.
PMCID: PMC4648238  PMID: 25648430
BK virus; Bone Marrow Transplant; Hematopoietic Stem Cell Transplant; Haemorrhagic Cystitis
8.  Tracking ocean heat uptake during the surface warming hiatus 
Nature Communications  2016;7:10926.
Ocean heat uptake is observed to penetrate deep into the Atlantic and Southern Oceans during the recent hiatus of global warming. Here we show that the deep heat penetration in these two basins is not unique to the hiatus but is characteristic of anthropogenic warming and merely reflects the depth of the mean meridional overturning circulation in the basin. We find, however, that heat redistribution in the upper 350 m between the Pacific and Indian Oceans is closely tied to the surface warming hiatus. The Indian Ocean shows an anomalous warming below 50 m during hiatus events due to an enhanced heat transport by the Indonesian throughflow in response to the intensified trade winds in the equatorial Pacific. Thus, the Pacific and Indian Oceans are the key regions to track ocean heat uptake during the surface warming hiatus.
Mechanisms for the warming hiatus are inferred by tracking regional ocean heat uptake in different regions. Here, the authors show that the Indo-Pacific heat redistribution holds the key while the abyssal heat uptake in the Atlantic and Southern Oceans primarily reflects the downward penetration of anthropogenic heat.
PMCID: PMC4821003  PMID: 27025666
9.  Energetic and kinetic dataset on interaction of the vacancy and self-interstitial atom with the grain boundary in α-iron 
Data in Brief  2016;7:798-813.
We provide the dataset of the vacancy (interstitial) formation energy, segregation energy, diffusion barrier, vacancy-interstitial annihilation barrier near the grain boundary (GB) in bcc-iron and also the corresponding interactive range. The vacancy-interstitial annihilation mechanisms in the bulk, near the GB and at the GB at across scales were given.
PMCID: PMC4816880  PMID: 27077081
10.  Simultaneous Determination of Glass Transition Temperatures of Several Polymers 
PLoS ONE  2016;11(3):e0151454.
A simple and easy optical method is proposed for the determination of glass transition temperature (Tg) of polymers.
Methods & Results
Tg was determined using the technique of microsphere imaging to monitor the variation of the refractive index of polymer microsphere as a function of temperature. It was demonstrated that the method can eliminate most thermal lag and has sensitivity about six fold higher than the conventional method in Tg determination. So the determined Tg is more accurate and varies less with cooling/heating rate than that obtained by conventional methods. The most attractive character of the method is that it can simultaneously determine the Tg of several polymers in a single experiment, so it can greatly save experimental time and heating energy.
The method is not only applicable for polymer microspheres, but also for the materials with arbitrary shapes. Therefore, it is expected to be broadly applied to different fundamental researches and practical applications of polymers.
PMCID: PMC4795599  PMID: 26985670
11.  Lead Optimization of Spiropyrazolopyridones: A New and Potent Class of Dengue Virus Inhibitors 
ACS Medicinal Chemistry Letters  2015;6(3):344-348.
Spiropyrazolopyridone 1 was identified, as a novel dengue virus (DENV) inhibitor, from a DENV serotype 2 (DENV-2) high-throughput phenotypic screen. As a general trend within this chemical class, chiral resolution of the racemate revealed that R enantiomer was significantly more potent than the S. Cell-based lead optimization of the spiropyrazolopyridones focusing on improving the physicochemical properties is described. As a result, an optimal compound 14a, with balanced in vitro potency and pharmacokinetic profile, achieved about 1.9 log viremia reduction at 3 × 50 mg/kg (bid) or 3 × 100 mg/kg (QD) oral doses in the dengue in vivo mouse efficacy model.
PMCID: PMC4360157  PMID: 25878766
Dengue virus (DENV); spiropyrazolopyridones; structure−activity relationship; lead optimization
12.  Pharmacological inhibition of LSD1 for the treatment of MLL-rearranged leukemia 
Mixed lineage leukemia (MLL) gene translocations are found in ~75 % infant and 10 % adult acute leukemia, showing a poor prognosis. Lysine-specific demethylase 1 (LSD1) has recently been implicated to be a drug target for this subtype of leukemia. More studies using potent LSD1 inhibitors against MLL-rearranged leukemia are needed.
LSD1 inhibitors were examined for their biochemical and biological activities against LSD1 and MLL-rearranged leukemia as well as other cancer cells.
Potent LSD1 inhibitors with biochemical IC50 values of 9.8–77 nM were found to strongly inhibit proliferation of MLL-rearranged leukemia cells with EC50 of 10–320 nM, while these compounds are generally non-cytotoxic to several other tumor cells. LSD1 inhibition increased histone H3 lysine 4 (H3K4) methylation, downregulated expression of several leukemia-relevant genes, induced apoptosis and differentiation, and inhibited self-renewal of stem-like leukemia cells. Moreover, LSD1 inhibitors worked synergistically with inhibition of DOT1L, a histone H3 lysine 79 (H3K79) methyltransferase, against MLL-rearranged leukemia. The most potent LSD1 inhibitor showed significant in vivo activity in a systemic mouse model of MLL-rearranged leukemia without overt toxicities. Mechanistically, LSD1 inhibitors caused significant upregulation of several pathways that promote hematopoietic differentiation and apoptosis.
LSD1 is a drug target for MLL-rearranged leukemia, and LSD1 inhibitors are potential therapeutics for the malignancy.
Electronic supplementary material
The online version of this article (doi:10.1186/s13045-016-0252-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4789278  PMID: 26970896
MLL-rearranged leukemia; Lysine-specific demethylase 1; Enzyme inhibitor; Drug discovery; Leukemia therapeutics
13.  miR-434-3p and DNA hypomethylation co-regulate eIF5A1 to increase AChRs and to improve plasticity in SCT rat skeletal muscle 
Scientific Reports  2016;6:22884.
Acetylcholine receptors (AChRs) serve as connections between motor neurons and skeletal muscle and are essential for recovery from spinal cord transection (SCT). Recently, microRNAs have emerged as important potential biotherapeutics for several diseases; however, whether miRNAs operate in the modulation of AChRs remains unknown. We found increased AChRs numbers and function scores in rats with SCT; these increases were reduced following the injection of a eukaryotic translation initiation factor 5A1 (eIF5A1) shRNA lentivirus into the hindlimb muscle. Then, high-throughput screening for microRNAs targeting eIF5A1 was performed, and miR-434-3p was found to be robustly depleted in SCT rat skeletal muscle. Furthermore, a highly conserved miR-434-3p binding site was identified within the mRNA encoding eIF5A1 through bioinformatics analysis and dual-luciferase assay. Overexpression or knockdown of miR-434-3p in vivo demonstrated it was a negative post-transcriptional regulator of eIF5A1 expression and influenced AChRs expression. The microarray-enriched Gene Ontology (GO) terms regulated by miR-434-3p were muscle development terms. Using a lentivirus, one functional gene (map2k6) was confirmed to have a similar function to that of miR-434-3p in GO terms. Finally, HRM and MeDIP-PCR analyses revealed that DNA demethylation also up-regulated eIF5A1 after SCT. Consequently, miR-434-3p/eIF5A1 in muscle is a promising potential biotherapy for SCI repair.
PMCID: PMC4786822  PMID: 26964899
14.  Multiple Brain Abscesses Due to Aspergillus Fumigatus in a Patient With Liver Cirrhosis 
Medicine  2016;95(9):e2813.
Invasive cerebral aspergillosis always developed in immunocompromised host. Early diagnosis may save life in this critical condition; however, it is difficult to reach. Herein, we presented an unusual case of invasive cerebral aspergillosis in a cirrhotic patient.
A 47-year-old man presented with progressive deterioration of consciousness for three days. The patient had a history of alcoholic liver cirrhosis, Child-Pugh class C. Magnetic resonance imaging (MRI) of brain showed multi-focal parenchymal lesions, which was consistent with multiple brain abscesses. The diagnosis of invasive cerebral aspergillosis was made by molecular based laboratory methods including Aspergillus galactomannan antigen assay and oligonucleotide array. Despite treatment with the antifungal agent, Amphotericin B, the patient died at the ninth day of hospitalization.
Our findings suggest that liver cirrhosis can be one of risk factors of invasive cerebral aspergillosis, and support the diagnosing usefulness of MRI, Aspergillus galactomannan antigen assay, and oligonucleotide array.
PMCID: PMC4782847  PMID: 26945363
15.  The Severe Fever with Thrombocytopenia Syndrome Bunyavirus (SFTSV) Antibody in a Highly Endemic Region from 2011 to 2013: A Comparative Serological Study 
A seropositive rate of 6.59% was determined in the highly endemic region for severe fever with thrombocytopenia syndrome. A significant correlation was observed between case incidence and seroprevalence on temporal and geographic levels. Seroprevalence was comparable in the last 3 years, indicating a stable and ongoing circulation of the infection.
PMCID: PMC4350533  PMID: 25624404
16.  Hepatic resection provided long-term survival for patients with intermediate and advanced-stage resectable hepatocellular carcinoma 
Hepatic resection has the highest local controllability that results in long-term survival for hepatocellular carcinoma (HCC). This study aimed to investigate the role of hepatic resection in selected patients of intermediate and advanced stage.
Clinical, pathological, and outcome data of 542 consecutive patients were retrospectively analyzed from a single center. The Kaplan-Meier method was used to estimate survival. Postoperative prognostic factors were evaluated using univariate and multivariate analyses.
The 1-, 3-, and 5-year overall survival rates were 89.0, 64.3, and 53.0 %, respectively. The 1-, 3-, and 5-year disease-free survival rates were 72.2, 44.5, and 34.2 %, respectively. Preoperative α-fetoprotein level >400 ng/mL, macroscopic vascular invasion, microscopic portal vein thrombosis, multiple tumor nodules, and the largest tumor size >5 cm were significantly correlated with overall survival. When these clinical risk factors were used in a postoperative staging system, assigning one point for each factor, the total score was precisely predictive of long-term survival. For patients with surgery plus adjuvant TACE (transarterial chemoembolization), the median overall survival was 56 months (range 1–110 months) and the 5-year OS rate was 48.5 %.
Hepatic resection is efficient and safe for HCC patients of intermediate and advanced stage. The adjuvant TACE should be recommended for HCC patients with poor risk factors.
Electronic supplementary material
The online version of this article (doi:10.1186/s12957-016-0811-y) contains supplementary material, which is available to authorized users.
PMCID: PMC4776356  PMID: 26936459
Hepatocellular; Hepatic resection; Prognosis; Large; Multinodular
17.  Pneumothorax, pneumomediastinum, pneumoperitoneum and extensive subcutaneous emphysema resulting from endoscopic mucosal resection secondary to colonoscopy: A case report 
Oncology Letters  2016;11(4):2763-2767.
Rectal perforation is an unusual complication of therapeutic colonoscopy. The present study reports the case of a patient with a rare manifestation of pneumothorax, pneumomediastinum, pneumoperitoneum and extensive subcutaneous emphysema that resulted from an endoscopic mucosal resection following a colonoscopy of the rectum. Only 3 cases of colonic perforation and 1 case of rectal perforation have been described previously, of which the clinical diagnoses and treatments were varied, and no results of follow-up studies were reported. In the present study, dyspnea and neck swelling were acute signs of extraluminal air that resulted from rectal perforation. Computed axial tomography was an effective diagnosis method, and is recommended for the early recognition of colorectal perforation. Appropriate management and a close follow-up are crucial for optimal results.
PMCID: PMC4812224  PMID: 27073549
endoscopic mucosal resection; rectal perforation; early recognition; appropriate management; close follow-up
18.  TNF-α-induced NF-κB activation upregulates microRNA-150-3p and inhibits osteogenesis of mesenchymal stem cells by targeting β-catenin 
Open Biology  2016;6(3):150258.
Although systemic or local inflammation, commonly featured by cytokine activation, is implicated in patients with bone loss, the underlying mechanisms are still elusive. As microRNAs (miR), a class of small non-coding RNAs involved in essential physiological processes, have been found in bone cells, we aimed to investigate the role of miR for modulating osteogenesis in inflammatory milieu using human bone marrow mesenchymal stem cells (hBM-MSCs). Induced by proinflammatory cytokine TNF-α, miR-150-3p was identified as a key player in suppressing osteogenic differentiation through downregulating β-catenin, a transcriptional co-activator promoting bone formation. TNF-α treatment increased the levels of miR-150-3p, which directly targeted the 3′-UTR of β-catenin mRNA and in turn repressed its expression. In addition, we observed that miR-150-3p expression was increased by TNF-α via IKK-dependent NF-κB signalling. There are three putative NF-κB binding sites in the promoter region of miR-150, and we identified −686 region as the major NF-κB binding site for stimulation of miR-150 expression by TNF-α. Finally, the osteogenic differentiation of hBM-MSCs was inhibited by either miR-150-3p overexpression or TNF-α treatment, which was prevented by anti-miR-150-3p oligonucleotides. Taken together, our data suggested that miR-150-3p integrated inflammation signalling and osteogenic differentiation and may contribute to the inhibition effects of inflammation on bone formation, thus expanding the pathophysiological functions of microRNAs in bone diseases.
PMCID: PMC4821240  PMID: 26935950
mesenchymal stem cells; β-catenin; TNF-α; microRNA; osteogenesis
19.  Immunization with Recombinant SFTSV/NSs Protein Does Not Promote Virus Clearance in SFTSV-Infected C57BL/6J Mice 
Viral Immunology  2015;28(2):113-122.
The severe fever with thrombocytopenia syndrome (SFTS), caused by a novel Phlebovirus in the Bunyaviridae family named SFTS virus (SFTSV), is an emerging hemorrhagic fever with a wide distribution and high case-fatality rate. Neither effective treatment nor vaccines are available to treat and prevent this disease to date. It was recently reported that SFTSV nonstructural protein in S segment (SFTSV/NSs) functioned as the interferon (IFN) antagonist targeting for suppressing host's innate immunity. This study was designed to investigate the potential of recombinant SFTSV (rSFTSV)/NSs protein for inducing anti-NSs antibodies by pre-exposure vaccination to block SFTSV/NSs in the SFTSV-infected C57BL/6J mice. All mice in the rSFTSV/NSs-vaccinated group, negative control group, and blank control group survived with no visible clinical abnormities throughout the experiment, except for their sacrifice for sampling at each observation point. However, unexpectedly, a negative effect on the bodyweight of rSFTSV/NSs-vaccinated mice was observed after 21 days postinoculation. Pre-exposure vaccination with rSFTSV/NSs did not accelerate virus removal in mice though high titer of anti-NSs antibodies and elevated IFN-γ were detected in sera. Before virus challenge, the rSFTSV/NSs-vaccinated mice and negative control mice had a larger amount of platelets (PLT) than the blank control mice, which indicated that Freund's adjuvants could stimulate PLT production. In the aspect of cytokines, the rSFTSV/NSs-vaccinated mice had a 5- to 10-fold increase in interleukin (IL)-2, IL-5, IL-6, IFN-γ, and tumor necrosis factor-α, which probably just had a negative effect on the bodyweight of mice. In general, therefore, previous vaccination with rSFTSV/NSs did not accelerate virus clearance in the SFTSV-infected mice.
PMCID: PMC4334103  PMID: 25594805
20.  Impact of Respiratory Motion on Worst-Case-Scenario Optimized Intensity-Modulated Proton Therapy for Lung Cancers 
Practical radiation oncology  2014;5(2):e77-e86.
We compared conventionally optimized intensity-modulated proton therapy (IMPT) treatment plans against the worst-case scenario optimized treatment plans for lung cancer. The comparison of the two IMPT optimization strategies focused on the resulting plans’ ability to retain dose objectives under the influence of patient set-up, inherent proton range uncertainty, and dose perturbation caused by respiratory motion.
For each of the 9 lung cancer cases two treatment plans were created accounting for treatment uncertainties in two different ways: the first used the conventional method: delivery of prescribed dose to the planning target volume (PTV) that is geometrically expanded from the internal target volume (ITV). The second employed the worst-case scenario optimization scheme that addressed set-up and range uncertainties through beamlet optimization. The plan optimality and plan robustness were calculated and compared. Furthermore, the effects on dose distributions of the changes in patient anatomy due to respiratory motion was investigated for both strategies by comparing the corresponding plan evaluation metrics at the end-inspiration and end-expiration phase and absolute differences between these phases. The mean plan evaluation metrics of the two groups were compared using two-sided paired t-tests.
Without respiratory motion considered, we affirmed that worst-case scenario optimization is superior to PTV-based conventional optimization in terms of plan robustness and optimality. With respiratory motion considered, worst-case-scenario optimization still achieved more robust dose distributions to respiratory motion for targets and comparable or even better plan optimality [D95% ITV: 96.6% versus 96.1% (p=0.26), D5% − D95% ITV: 10.0% versus 12.3% (p=0.082), D1% spinal cord: 31.8% versus 36.5% (p =0.035)].
Worst-case scenario optimization led to superior solutions for lung IMPT. Despite of the fact that worst-case-scenario optimization did not explicitly account for respiratory motion it produced motion-resistant treatment plans. However, further research is needed to incorporate respiratory motion into IMPT robust optimization.
PMCID: PMC4355168  PMID: 25413400
intensity-modulated proton therapy; lung cancer; respiratory motion; robust optimization; root-mean-square dose; treatment planning
21.  Robust optimization in intensity-modulated proton therapy to account for anatomy changes in lung cancer patients 
Background and Purpose
Robust optimization for IMPT takes setup and range uncertainties into account during plan optimization. However, anatomical changes were not prospectively included. The purpose of this study was to examine robustness and dose variation due to setup uncertainty and anatomical change in IMPT of lung cancer.
Material and Methods
Plans were generated with multi-field optimization based on planning target volume (MFO-PTV) and worst-case robust optimization (MFO-RO) on simulation computed tomography scans (CT0) for nine patients. Robustness was evaluated on the CT0 by computing the standard deviation of DVH (SD-DVH). Dose variations calculated on weekly CTs were compared with SD-DVH. Equivalent uniform dose (EUD) change from the original plan on weekly dose was also calculated for both plans.
SD-DVH and dose variation on weekly CTs were both significantly lower in the MFO-RO plans than in the MFO-PTV plans for targets, lungs, and the esophagus (p < 0.05). When comparing EUD for ITV between weekly and planned dose distributions, three patients and 28% of repeated CTs for MFO-RO plans, and six patients and 44% of repeated CTs for MFO-PTV plans, respectively, showed an EUD change of > 5%.
RO in IMPT reduces the dose variation due to setup uncertainty and anatomy changes during treatment compared with PTV-based planning. However, dose variation could still be substantial; repeated imaging and adaptive planning as needed are highly recommended for IMPT of lung tumors.
PMCID: PMC4400219  PMID: 25708992
robust optimization; robustness evaluation; adaptive planning; IMPT
22.  Type III Secretion System Translocon Component EseB Forms Filaments on and Mediates Autoaggregation of and Biofilm Formation by Edwardsiella tarda 
Applied and Environmental Microbiology  2015;81(17):6078-6087.
The type III secretion system (T3SS) of Edwardsiella tarda plays an important role in infection by translocating effector proteins into host cells. EseB, a component required for effector translocation, is reported to mediate autoaggregation of E. tarda. In this study, we demonstrate that EseB forms filamentous appendages on the surface of E. tarda and is required for biofilm formation by E. tarda in Dulbecco's modified Eagle's medium (DMEM). Biofilm formation by E. tarda in DMEM does not require FlhB, an essential component for assembling flagella. Dynamic analysis of EseB filament formation, autoaggregation, and biofilm formation shows that the formation of EseB filaments occurs prior to autoaggregation and biofilm formation. The addition of an EseB antibody to E. tarda cultures before bacterial autoaggregation prevents autoaggregation and biofilm formation in a dose-dependent manner, whereas the addition of the EseB antibody to E. tarda cultures in which biofilm is already formed does not destroy the biofilm. Therefore, EseB filament-mediated bacterial cell-cell interaction is a prerequisite for autoaggregation and biofilm formation.
PMCID: PMC4551241  PMID: 26116669
23.  Discovering communities in complex networks by edge label propagation 
Scientific Reports  2016;6:22470.
The discovery of the community structure of real-world networks is still an open problem. Many methods have been proposed to shed light on this problem, and most of these have focused on discovering node community. However, link community is also a powerful framework for discovering overlapping communities. Here we present a novel edge label propagation algorithm (ELPA), which combines the natural advantage of link communities with the efficiency of the label propagation algorithm (LPA). ELPA can discover both link communities and node communities. We evaluated ELPA on both synthetic and real-world networks, and compared it with five state-of-the-art methods. The results demonstrate that ELPA performs competitively with other algorithms.
PMCID: PMC4772381  PMID: 26926830
24.  A Novel General Imaging Formation Algorithm for GNSS-Based Bistatic SAR 
Global Navigation Satellite System (GNSS)-based bistatic Synthetic Aperture Radar (SAR) recently plays a more and more significant role in remote sensing applications for its low-cost and real-time global coverage capability. In this paper, a general imaging formation algorithm was proposed for accurately and efficiently focusing GNSS-based bistatic SAR data, which avoids the interpolation processing in traditional back projection algorithms (BPAs). A two-dimensional point target spectrum model was firstly presented, and the bulk range cell migration correction (RCMC) was consequently derived for reducing range cell migration (RCM) and coarse focusing. As the bulk RCMC seriously changes the range history of the radar signal, a modified and much more efficient hybrid correlation operation was introduced for compensating residual phase errors. Simulation results were presented based on a general geometric topology with non-parallel trajectories and unequal velocities for both transmitter and receiver platforms, showing a satisfactory performance by the proposed method.
PMCID: PMC4813869  PMID: 26927117
bistatic SAR; GNSS; bulk RCMC; modified hybrid correlation
25.  Mortality attributable to carbapenem-resistant Pseudomonas aeruginosa bacteremia: a meta-analysis of cohort studies 
Whether carbapenem resistance is associated with mortality in patients with Pseudomonas aeruginosa bacteremia is controversial. To address this issue, we conducted a systematic review and meta-analysis based on cohort studies. We searched PubMed and Embase databases to identify articles (up to April 2015). The DerSimonian and Laird random-effect model was used to generate a summary estimate of effect. Associations were evaluated in subgroups based on different patient characteristics and study quality criteria. Seven studies with a total of 1613 patients were finally included, of which 1 study had a prospective design, and the other 6 were retrospective. Our meta-analysis showed patients with carbapenem-resistant P. aeruginosa bacteremia were at a higher risk of death compared with those with carbapenem-susceptible P. aeruginosa bloodstream infections (pooled odds ratio (OR) from three studies reporting adjusted ORs: 3.07, 95% confidence interval (CI), 1.60–5.89; pooled OR from 4 studies only reporting crude ORs: 1.46, 95% CI, 1.10–1.94). The results were robust across a number of stratified analyses and a sensitivity analysis. We also calculated that 8%–18.4% of deaths were attributable to carbapenem resistance in four studies assessing the outcome with 30-day mortality, and these were 3% and 14.6%, respectively, in two studies using 7-day mortality or mortality during bacteremia as an outcome of interest. Carbapenem resistance had a deleterious impact on the mortality of P. aeruginosa bacteremia; however, the results should be interpreted cautiously because only three studies reporting adjusted ORs were included. More large-scale, well-designed prospective cohorts, as well as mechanistic studies, are urgently needed in the future.
PMCID: PMC4820673  PMID: 27004762
carbapenem resistance; cohort; meta-analysis; mortality; P. aeruginosa bacteremia

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