Publications by authors named "Yajun Zhu"

50 Publications

A novel free-standing metal organic frameworks-derived cobalt sulfide polyhedron array for shuttle effect suppressive lithium-sulfur batteries.

Nanotechnology 2021 Nov 24. Epub 2021 Nov 24.

Chinese Academy of Sciences - Intelligent Machines Institute, Science Island 1130 M B, Hefei 230026, Hefei, 230031, CHINA.

Metal-organic-foams (MOFs)-derived nanostructures have received broad attention for secondary batteries. However, common strategies are focusing on the preparation of dispersive materials, which need complicated steps and some additives for making electrodes of batteries. Here, we develop a novel free-standing Co9S8 polyhedron array derived from ZIF-67, which grows on a three-dimensional carbon cloth for lithium-sulfur (Li-S) battery. The polar Co9S8 provides strong chemical binding to immobilize polysulfides, which enables efficiently suppressing of the shuttle effect. The free-standing [email protected] polyhedron array-based cathode exhibits ultrahigh capacity of 1079 mAh g-1 after cycling 100 times at 0.1C, and long cycling life of 500 cycles at 1C, recoverable rate-performance and good temperature tolerance. Furthermore, the adsorption energies towards polysulfides are investigated by using density functional theory (DFT) calculations, which display a strong binding with polysulfides.
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http://dx.doi.org/10.1088/1361-6528/ac3ce5DOI Listing
November 2021

Health care resource utilization and treatment variability in the care of patients with advanced or metastatic colorectal or gastric cancer.

J Med Econ 2021 Jan-Dec;24(1):930-938

Eli Lilly and Company, Indianapolis, IN, USA.

Aims: This study was designed to describe health care resource utilization (HCRU) of patients with metastatic colorectal cancer (CRC) or gastric cancer to test the hypothesis that greater treatment variability would be associated with increased HCRU.

Methods: A retrospective observational study using Marketscan claims data was conducted. Eligible patients had a first diagnosis of metastatic CRC or gastric cancer between 2004 and 2015 and must have received systemic anti-cancer therapy after diagnosis. Treatment variability was measured using the Herfindahl-Hirschman Index (HHI). HHI scores were stratified by quartile. HCRU variables were evaluated throughout the follow-up period and described by 6-month periods. Chi-square test was used for categorical variables and ANOVA for continuous variables.

Results: A total of 55,403 CRC and 9,073 gastric cancer patients were eligible. First-line HHI scores ranged from 0.1304-0.2778 for CRC and 0.0383-0.1778 for gastric cancer by state of residence. Statistically significant differences by HHI quartiles for HCRU in CRC included hospitalizations ( = 0.0003), ER visits ( < 0.0001), ER visits leading to hospitalization ( < 0.0001), and supportive care (all agents studied,  < 0.01). For gastric cancer, significant differences by HHI quartile were observed for ER visits ( = 0.002) and selected supportive care (G-CSF, erythropoiesis-stimulating agents, bisphosphonates, nutritional support, and antiemetics, each  < 0.05). No consistent increasing or decreasing trends were observed across the quartiles for either cohort.

Limitations: Large sample sizes could lead to statistical significance without being clinically meaningful. High treatment heterogeneity in the gastric cancer cohort and lack of a homogeneous quartile for comparisons limited the ability to evaluate HCRU by different levels of treatment variability.

Conclusions: Statistically significant relationships were observed between treatment variability as measured by HHI and increased HCRU, but no consistent directional trends in HCRU variables were observed. Therefore, this study failed to reject the null hypothesis of equivalent HCRU by level of treatment variability.
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http://dx.doi.org/10.1080/13696998.2021.1958607DOI Listing
September 2021

Efficacy of immune checkpoint inhibitor therapy in patients with fusion-positive non-small-cell lung cancer.

Immunotherapy 2021 08 18;13(11):893-904. Epub 2021 Jun 18.

Loxo Oncology, a wholly owned subsidiary of Eli Lilly & Company, Stamford, CT 06901, USA.

To describe outcomes of patients with rearraned during transfection () fusion-positive non-small-cell lung cancer (NSCLC) who received immune checkpoint inhibitor (ICI)-based treatments in the US. Using de-identified Flatiron Health-Foundation Medicine NSCLC Clinico-Genomic and Guardant Health databases, treatment patterns and outcomes of 69 patients with advanced/metastatic fusion-positive NSCLC who received ICI-based treatment were described. Median real-world progression-free survival and overall survival months were 4.2 (95% CI: 1.4-8.4) and 19.1 (6.9-not reached), respectively, among patients in Clinico-Genomic database (n = 17) receiving first-line ICI-based therapy. In the Guardant Health database, progression-free survival was unavailable, and the median overall survival was not reached (n = 29). Outcomes associated with ICI-based treatments in the first-line setting among patients with fusion-positive NSCLC are consistent with unselected populations reported in literature.
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http://dx.doi.org/10.2217/imt-2021-0035DOI Listing
August 2021

Relationship between cigarette smoking and hearing loss in China: A cross-sectional study in Zhejiang province.

Tob Induc Dis 2021 26;19:40. Epub 2021 May 26.

Department of Medicine, Hangzhou Normal University, Hangzhou City, China.

Introduction: Hearing loss and cigarette smoking are major challenges that affect public health in China. Revealing the effect of smoking on hearing loss in the Chinese general population is critical for hearing health protection. We investigated the relationship between smoking status and hearing loss in China, especially in stratified sex and age groups.

Methods: A cross-sectional study was conducted on 4685 individuals aged 20- 80 years in Zhejiang province from 2016 to 2018, with audiometric testing for hearing loss and a structured questionnaire for collecting smoking status and covariates. Logistic regression was used to estimate the association between smoking and hearing loss.

Results: Cigarette smoking was not significantly associated with hearing loss in females and young males. In middle-aged males, after adjusting for covariates, current smokers and past smokers had a significantly higher prevalence of speech-frequency loss (OR=1.65; 95% CI: 1.17-2.33 and OR=1.88; 95% CI: 1.11-3.17; respectively) and high-frequency hearing loss (OR=2.01; 95% CI: 1.43-2.84 and OR=2.64; 95% CI: 1.50-4.66; respectively). In older males, only past smokers had a significantly higher prevalence of speech-frequency hearing loss than never smokers (OR=2.58; 95% CI: 1.38-4.85). Regarding middle-aged and older current smokers, a dose-dependent relationship between smoking intensity and hearing loss was found. Passive smoking was not significantly associated with an increased hearing loss risk in all the three male groups.

Conclusions: The relationship between cigarette smoking and hearing loss varied according to gender and age. Therefore, the interventions for smoking need to be tailored according to age in males.
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http://dx.doi.org/10.18332/tid/135440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152310PMC
May 2021

Real-world treatment patterns and outcomes of abemaciclib for the treatment of HR+, HER2- metastatic breast cancer.

Curr Med Res Opin 2021 07 20;37(7):1179-1187. Epub 2021 May 20.

Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Objective: This retrospective observational study described baseline characteristics, real-world treatment patterns, and outcomes among patients with metastatic breast cancer treated with abemaciclib in the United States.

Methods: De-identified electronic health record-derived data were used to describe patients who began abemaciclib treatment on or after 30 June 2016 and ≥4 months before data cutoff (31 December 2018). Real-world response (rwR) and real-world progression assessments were abstracted from clinical documentation. Descriptive statistics were used to calculate the real-world best response. The Kaplan-Meier method estimated real-world time to first response (rwTTFR) and real-world progression-free survival (rwPFS).

Results: The median age of 118 female patients at abemaciclib initiation was 66.5 years (interquartile range, 57.0, 73.0). The breakdown of patients who received abemaciclib in first, second, third, or later lines was 28.8%, 21.2%, 20.3%, and 29.7%, respectively. Patients received abemaciclib as monotherapy (12.7%) or in combination with endocrine therapy: fulvestrant (59.3%); aromatase inhibitor (22.9%); aromatase inhibitor and fulvestrant (5.1%). There were 68 patients (57.6%) with ≥1 rwR assessment: 41.2% with a real-world complete response or real-world partial response. Median rwTTFR was 3.6 months (95% confidence interval, 3.5, 5.2). Twelve-month rwPFS probability was 61.7%.

Conclusions: This study represents utilization and outcomes associated with abemaciclib approximately 1 year following FDA approval. Treatment patterns demonstrated heterogeneity and, as in clinical trials, patients appeared to benefit from abemaciclib treatment in the real world. More research investigating outcomes associated with abemaciclib treatment is needed, with larger samples and longer follow-up to enable closer evaluation by subgroup, regimen, and line of therapy.
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http://dx.doi.org/10.1080/03007995.2021.1923468DOI Listing
July 2021

A yolk-shell [email protected]@carbon nanochain as shuttle effect suppressive and volume-change accommodating sulfur host for long-life lithium-sulfur batteries.

Nanoscale 2021 Apr;13(16):7744-7750

Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Provincial Engineering Laboratory for New-Energy Vehicle Battery Energy-Storage Materials, College of Chemistry and Materials Science, Anhui Normal University, Wuhu, Anhui 241002, P.R. China.

A lithium-sulfur (Li-S) battery is considered a promising next-generation secondary battery owing to its high theoretical capacity and energy density. However, the volume change and poor conductivity of sulfur, and the shuttle effect, restrict its practical applications. Herein, we develop a yolk-shell [email protected]@C nanochain as the Li-S battery cathode in which sulfur is encapsulated between the Fe3O4 core and the carbon shell. After cycling 500 times at 0.2C, the [email protected]@C nanochains exhibit a stable capacity of 625 mA h g-1 and a coulombic efficiency exceeding 99.8%. When measuring at temperatures of -5 and 45 °C, the capacities remain stable, and a well-reversible rate performance under repeated testing for three rounds is also achieved. Furthermore, density functional theory (DFT) calculations show large adsorption energies of Fe3O4 towards polysulfides, indicating the capability of suppressing the shuttle effect during long-term charge and discharge.
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http://dx.doi.org/10.1039/d1nr00658dDOI Listing
April 2021

QTL Mapping and Favorable Allele Mining of Nitrogen Deficiency Tolerance Using an Interconnected Breeding Population in Rice.

Front Genet 2021 6;12:616428. Epub 2021 Apr 6.

Institute of Crop Sciences, National Key Facility for Crop Gene Resources and Genetic Improvement, Chinese Academy of Agricultural Sciences, Beijing, China.

Nitrogen is one of the most important nutrients for rice growth and development. Breeding of nitrogen deficiency tolerance (NDT) variety is considered to be the most economic measure to solve the constrain of low nitrogen stress on grain yield in rice. An interconnected breeding (IB) population of 497 lines developed using Huanghuazhan (HHZ) as the recurrent parent and eight elite lines as the donor parents were tested for five traits including grain yield, biomass, harvest index, thousand grain weight, and spikelet fertility under two nitrogen treatments in three growing seasons. Association analysis using 7,388 bins generated by sequencing identified a total of 14, 14, and 12 QTLs for the five traits under low nitrogen (LN), normal nitrogen (NN), and LN/NN conditions, respectively, across three seasons. Favorable alleles were dissected for the 40 QTLs at the 10 NDT regions, and OM1723 was considered as the most important parent with the highest frequency of favorable alleles contributing to NDT-related traits. Six superior lines all showed significantly higher GY in LN environments and similar GY under NN environments except for H10. Substitution mapping using near-isogenic introgression lines delimited the , which was identified on chromosome 2 under LN, NN, and LN/NN conditions into two QTLs, which were located in the two regions of about 200 and 350 kb with different favorable alleles. The bins 16, 1301, 1465, 1486, 3464, and 6249 harbored the QTLs for NDT detected in this study, and the QTLs/genes previously identified for NDT or nitrogen use efficiency (NUE) could be used for enhancing NDT and NUE by marker-assisted selection (MAS).
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http://dx.doi.org/10.3389/fgene.2021.616428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056011PMC
April 2021

Treatment patterns for patients with advanced/metastatic cancers by site of care.

Am J Manag Care 2021 04 1;27(4):e105-e113. Epub 2021 Apr 1.

Humana Healthcare Research Inc, 515 W Market St, Louisville, KY 40202. Email:

Objectives: To compare treatments, overall survival (OS), and total costs among patients receiving anticancer therapy in hospital outpatient vs physician office settings.

Study Design: This retrospective observational study utilized claims data from a large national health plan to identify patients with advanced/metastatic non-small cell lung cancer (aNSCLC), metastatic colorectal cancer (mCRC), or metastatic breast cancer (mBC) treated in hospital outpatient or physician office settings.

Methods: Patients enrolled in Medicare Advantage Prescription Drug or commercial plans for at least 180 days prior to and at least 30 days after start of first-line (1L) therapy were included. Treatments by lines of therapy, OS, and total costs were evaluated by site of care.

Results: Eligible patients included 4618 with aNSCLC, 2304 with mCRC, and 1411 with mBC. There were no major differences in 1L, second-line, or third-line therapy by site of care. Patients with aNSCLC in physician office had longer 1L duration (hospital outpatient, 96 days vs physician office, 102 days; P < .01), but there were no differences in duration of therapy by site of care for mBC or mCRC. Costs were higher in the hospital outpatient setting for mCRC and mBC, but there were no differences in OS for any of the cancers.

Conclusions: Although patients received similar care in hospital outpatient and physician office settings, the differences in duration of treatment and costs warrant further evaluation.
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http://dx.doi.org/10.37765/ajmc.2021.88619DOI Listing
April 2021

Development of a Prognostic Factor Index Among Women With HR/HER2 Metastatic Breast Cancer in a Community Oncology Setting.

Clin Breast Cancer 2021 08 1;21(4):317-328.e7. Epub 2021 Jan 1.

West Cancer Center and Research Institute, Germantown, TN.

Background: This study explored the impact of multiple prognostic factors on patient overall survival (OS) and real-world progression-free survival (rwPFS) for patients with hormone receptor-positive (HR)/human epidermal growth factor 2 negative (HER2) metastatic breast cancer (MBC).

Materials And Methods: This retrospective study used electronic health record data of patients in the United States from community oncology practices from January 1, 2008 to April 30, 2017. Eligibility included HR/HER2 MBC diagnosis in 2008 or later and prior systemic therapy for MBC. An index variable was created to assess the effect of multiple clinical prognostic factors collectively, including liver metastases (LM), primary endocrine resistance (PER), negative progesterone receptor (PR) status, and high tumor grade (TG). Patients were grouped based on the number of prognostic factors present at MBC diagnosis: 0, 1, and 2+. Differences in rwPFS and OS from start of first-line therapy were evaluated by the Kaplan-Meier method and multivariable Cox proportional hazards regression.

Results: Approximately 29.1% of the 378 eligible patient sample had 0, 36.0% had 1, and 34.9% had 2+ prognostic factors. For the patients with 1 of the prognostic factors, 24.3% had high TG, 14.7% were LM+, 39.7% had PER, and 21.3% were PR. Univariate and multivariate results showed that rwPFS and OS were significantly (P < .05) shorter in patients with 1 and 2+ prognostic factors compared with patients with 0.

Conclusions: The individual prognostic factors and the prognostic factor index may enable early identification of patients with a less favorable prognosis across the HR/HER2 MBC population and help inform treatment decisions in difficult-to-treat populations.
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http://dx.doi.org/10.1016/j.clbc.2020.12.012DOI Listing
August 2021

Characteristics and outcomes of patients with RET-fusion positive non-small lung cancer in real-world practice in the United States.

BMC Cancer 2021 Jan 5;21(1):28. Epub 2021 Jan 5.

Loxo Oncology at Lilly, a wholly owned subsidiary of Eli Lilly and Company, Stamford, CT, USA.

Background: Contradictory and limited data are available about the presentation and outcomes of patients with RET-fusion positive metastatic NSCLC as compared to patients without RET fusions. This observational study utilizing a linked electronic health records (EHR) database to genomics testing results was designed to compare characteristics, tumor response, progression-free (PFS) and overall survival (OS) outcomes by RET fusion status among patients with metastatic NSCLC treated with standard therapies.

Methods: Adult patients with metastatic NSCLC with linked EHR and genomics data were eligible who received systemic anti-cancer therapy on or after January 1, 2011. Adjusted, using all available baseline covariates, and unadjusted analyses were conducted to compare tumor response, PFS and OS between patients with RET-fusion positive and RET-fusion negative disease as detected by next-generation sequencing. Tumor response outcomes were analysed using Fisher's exact test, and time-to-event analyses were conducted using Cox proportional hazards model.

Results: There were 5807 eligible patients identified (RET+ cohort, N = 46; RET- cohort, N = 5761). Patients with RET fusions were younger, more likely to have non-squamous disease and be non-smokers and had better performance status (all p < 0.01). In unadjusted analyses, there were no significant differences in tumor response (p = 0.17) or PFS (p = 0.06) but OS was significantly different by RET status (hazard ratio, HR = 1.91, 95% CI:1.22-3.0, p = 0.005). There were no statistically significant differences by RET fusion status in adjusted analyses of either PFS or OS (PFS HR = 1.24, 95% CI:0.86-1.78, p = 0.25; OS HR = 1.52, 95% CI: 0.95-2.43, p = 0.08).

Conclusions: Patients with RET fusions have different baseline characteristics that contribute to favorable OS in unadjusted analysis. However, after adjusting for baseline covariates, there were no significant differences in either OS or PFS by RET status among patients treated with standard therapy prior to the availability of selective RET inhibitors.
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http://dx.doi.org/10.1186/s12885-020-07714-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786962PMC
January 2021

Genome-Wide Association Study on Resistance to Rice Black-Streaked Dwarf Disease Caused by .

Plant Dis 2021 Mar 20;105(3):607-615. Epub 2021 Jan 20.

Institute of Crop Sciences, National Key Facility for Crop Gene Resources and Genetic Improvement, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Rice black-streaked dwarf disease caused by (RBSDV) is one of the most destructive viral diseases of rice. Thus, it is imperative that resistant rice germplasms are screened for novel RBSDV-resistant genes. RBSDV resistance of a diverse global collection comprising 1,953 rice accessions was evaluated under natural conditions across 3 years. The average disease incidences of the / () subgroup were significantly lower than those of the / () subgroup. Interestingly, most accessions in the subgroup were significantly more susceptible than accessions, even though and have a close phylogenetic relationship. Four accessions stably and highly resistant to RBSDV were consistently identified in 2 years. Ten genomic regions (GRs) with 147 single nucleotide polymorphisms associated with RBSDV resistance were detected by a single-locus genome-wide association study (GWAS), of which five were repeatedly identified in a multilocus GWAS. Two previously reported GRs, and , which were repeatedly detected as stably and highly associated with RBSDV resistance, contained 17 and seven genes, respectively, with significant differences of resistance among haplotypes. Haplotype analyses of the candidate genes in and in suggested that the former gene is mainly associated with the differentiation of resistance within the subgroup and the latter gene mainly explains the difference in the resistance between and . Another three novel resistance GRs (, , and ) were identified. Our findings may enhance the application of disease-resistant rice germplasms for breeding RBSDV-resistant varieties.
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http://dx.doi.org/10.1094/PDIS-10-19-2263-REDOI Listing
March 2021

Thermally stable monolithic Doppler asymmetric spatial heterodyne interferometer: optical design and laboratory performance.

Opt Express 2020 Jul;28(14):19887-19900

We report on a thermally stable monolithic Doppler asymmetric spatial heterodyne (DASH) interferometer with field-widening prisms for thermospheric wind measurements by observing the Doppler shift of the airglow emission. Analytical deduction and numerical simulation are applied to determine the central optical path difference, the thermal compensation condition and the field-widening design. A monolithic interferometer with optimized configuration was built and tested in the laboratory. Laboratory tests show that the best visibility of 0.94 was realized with the 9 field-of-view illumination, while the thermal responses of the spatial frequency and the optical phase offset are 0.0154 cm/C and 0.469 rad/C, respectively.
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http://dx.doi.org/10.1364/OE.394101DOI Listing
July 2020

Debunking Myths While Understanding Limitations.

Am J Public Health 2020 05;110(5):e2

Lisa M. Hess, Katherine B. Winfree, Catherine E. Muehlenbein, Yajun E. Zhu, Ana B. Oton, and Himani Aggarwal are with Eli Lilly and Company, Indianapolis, IN. Nicole Princic is with IBM Watson Health, Cambridge, MA.

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http://dx.doi.org/10.2105/AJPH.2020.305603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144428PMC
May 2020

A Multicenter, Comparative Study of Two Pressure-Redistribution Mattresses with Repositioning Intervals for Critical Care Patients.

Adv Skin Wound Care 2020 Mar;33(3):1-9

In Jinling Hospital, Nanjing University School of Medicine, China, Qixia Jiang, MSN, RN, ET, is Head Nurse, Outpatient Department; and Yuxiu Liu, MM, is Director, Department of Medical Administration. Hui Yu, MSN, RN, is Nurse, Wuxi No. 3 People's Hospital, Jiangnan University. Siping Song, BSN, RN, is a master's degree candidate, Medical School of Nanjing University. Guohong Li, MPH, RN, is Director, Department of Nursing Administration, Zhongda Hospital, Southeast University, Nanjing. Haiying Liu, BSN, RN, is Associate Director, Department of Nursing Administration, Wuxi No. 2 People's Hospital, Nanjing Medical University. Yi Zhou, BSN, RN, is Director, Department of Nursing Administration, Changshu No. 2 People's Hospital, Yangzhou University. Yajun Zhu, BSN, RN, ET, is Associate Director, Department of Nursing Administration, Jingjiang People's Hospital, Yangzhou University. Jing Jia, BSN, RN, ET, is a head nurse of Department of Nursing Administration, Zhenjiang People's Hospital, Jiangsu University. Yunjuan Huang, MSN, RN, is Director, Department of Nursing Administration, Wuxi People's Hospital, Nanjing Medical University. Jiandong Wang, PhD, MD, is Associate Professor, Department of Pathology, Jinling Hospital, Nanjing University of Medicine. Acknowledgments: The authors thank Andrea Baird, MD, and Jennifer Barrett, PhD, from Liwen Bianji, Edanz Editing China, for editing a draft of this manuscript. This study was sponsored by the Jinling Hospital Science Research Fund (no. 2010M012 and no. 2013NYL014; partly supported by 20WQ027, WZGF 20200101) and Taica Shanghai Co, Ltd (Shanghai, China), manufacturer of pressure redistribution mattresses. The authors have disclosed no other financial relationships related to this article. Submitted May 13, 2019; accepted in revised form July 3, 2019.

Objective: To compare the effectiveness of two protocols for preventing pressure injuries (PIs) in Chinese hospitals.

Design And Setting: A multicenter, open-label, comparative study conducted in seven Chinese acute care hospitals.

Patients And Intervention: In total, 1,654 eligible patients were identified, and 1,204 were enrolled in the study. Enrolled patients were randomly assigned into the trial group (4-hour repositioning combined with a viscoelastic foam mattress; n = 602) or the control group (2-hour repositioning combined with a powered air pressure redistribution mattress; n = 602). Participants received their respective protocols until they were discharged, died, or for at least 7 days.

Main Outcome Measures: The incidence of PIs, Braden Scale scores, and the time to development of PIs.

Main Results: Ultimately, 596 trial group patients and 598 control group patients were analyzed. Thirteen patients had single new stage 2 or worse PIs. The total incidence of PIs was 1.1%. The difference between the two groups was significant (0.3% vs 1.8%). However, the difference between the groups' Braden Scale score median during the intervention was not significant (13 vs 13.5).

Conclusions: The 4-hour repositioning interval combined with a viscoelastic foam mattress did not increase PI incidence or risk. These findings could help providers select the right pressure redistribution mattresses and repositioning intervals for critical care patients.
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http://dx.doi.org/10.1097/01.ASW.0000653160.13611.5dDOI Listing
March 2020

Safety outcomes in advanced non-small-cell lung cancer patients treated with first-line platinum-based regimens in the United States.

J Thorac Dis 2019 Nov;11(11):4474-4483

Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.

Background: We analyzed the treatment patterns and safety outcomes of the most common first-line platinum-based regimens initiated on or after non-small cell lung cancer (NSCLC) diagnosis in a real-world setting.

Methods: Based on a United States oncology electronic medical record (EMR) database, patients treated with first-line platinum-based regimens after advanced NSCLC diagnosis from September 2008 to November 2014 were analyzed. Baseline characteristics and selected adverse events during treatment [incidence proportions and incidence rates (IRs)] were described by regimen. Propensity score stratification was used to adjust for baseline characteristics differences. Hazard ratios (HRs) were estimated using Cox proportional hazards model, with paclitaxel (Pac)/carboplatin (Carbo) as reference. Subgroup analysis was conducted for elderly patients (≥70 years old).

Results: The most common five regimens for the eligible patients were as follows: Pac/Carbo (n=3,009), pemetrexed (Pem)/Carbo (n=1,625), Pem/Carbo/bevacizumab (Bev) (n=735), Pac/Carbo/Bev (n=531), Pem/cisplatin (Cis) (n=357), and docetaxel (Doc)/Carbo (n=355). Highest IRs were reported for anemia, neutropenia, nausea, and vomiting across these regimens in patients of all ages. After propensity score stratification, compared with Pac/Carbo, risk of anemia was significantly lower with Pac/Carbo/Bev (HR =0.67), Pem/Cis (HR =0.68), and Pem/Carbo/Bev (HR =0.82); risk of neutropenia was comparable among all regimens except Doc/Carbo (significantly lower risk; HR =0.72); and risk of nausea (HR =1.45) and vomiting (HR =1.50) was significantly higher with Pem/Cis. Safety outcomes in elderly patients were consistent with the overall population.

Conclusions: While EMR data have limitations, the real-world safety outcome with individual chemotherapy regimen could be considered for the better selection of platinum-based therapies in NSCLC.
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http://dx.doi.org/10.21037/jtd.2019.11.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940240PMC
November 2019

New insights into amylose and amylopectin biosynthesis in rice endosperm.

Carbohydr Polym 2020 Feb 22;230:115656. Epub 2019 Nov 22.

Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding, Key Laboratory of Plant Functional Genomics of the Ministry of Education, College of Agriculture, Yangzhou University, Yangzhou, Jiangsu, 225009, China; Jiangsu Key Laboratory of Crop Genetics and Physiology, Joint International Research Laboratory of Agriculture and Agri-Product Safety, Co-Innovation Center for Modern Production Technology of Grain Crops of Jiangsu, Yangzhou University, Yangzhou, Jiangsu, 225009, China. Electronic address:

How various isoforms of rice-starch biosynthesis enzymes interact during amylose and amylopectin synthesis is explored. The chain-length distributions of amylopectin and amylose from 95 varieties with different environmental and genetic backgrounds were obtained using size- exclusion chromatography, and fitted with biosynthesis-derived models based on isoforms of starch synthase (SSI-SSIV), starch branching enzyme (SBE, including SBEI and SBEII) and granule-bound starch synthase (GBSS) that are involved in amylose and amylopectin synthesis. It is usually thought that these are synthesized by separate enzymes. However, the amount of longer amylopectin chains correlated with that of shorter amylose chains, indicating that GBSS, SBE and SS affect both amylose and amylopectin synthesis. Further, the activity of GBSS in amylose correlated with that of SS in amylopectin. This new understanding of which enzymes are suggested by the statistics to be involved in both amylose and amylopectin synthesis could help rice breeders develop cereals with targeted properties.
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http://dx.doi.org/10.1016/j.carbpol.2019.115656DOI Listing
February 2020

Identification of genes for salt tolerance and yield-related traits in rice plants grown hydroponically and under saline field conditions by genome-wide association study.

Rice (N Y) 2019 Dec 2;12(1):88. Epub 2019 Dec 2.

Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.

Background: Soil salinity is one of the main environmental conditions that affects rice production. Identifying the genetic loci that affect rice salt tolerance (ST)-related traits at the seedling stage, especially under saline field conditions, is crucial for ST rice breeding by pyramiding ST genes that act at different developmental stages.

Results: Large phenotypic variations were observed in 708 rice accessions, and yield and its related traits were considerably limited when exposed to salt stress. In a genome-wide association study (GWAS), 2255 marker-trait association signals were detected for all measured traits, and the significant SNPs were distributed in 903 genes. Of these, 43 genes processed same functional annotation, and the gene ontology terms "biological processes" and "molecular function" with the known genes responsive to salt stress in rice. Further haplotype analysis detected 15 promising candidates significantly associated with the target traits, including five known genes and 10 novel genes. We identified seven accessions carrying favorable haplotypes of four genes significantly associated with grain yield that performed well under saline stress conditions.

Conclusions: Using high density SNPs within genes to conduct GWAS is an effective way to identify candidate genes for salt tolerance in rice. Five known genes (OsMYB6, OsGAMYB, OsHKT1;4, OsCTR3, and OsSUT1) and two newly identified genes (LOC_Os02g49700, LOC_Os03g28300) significantly associated with grain yield and its related traits under saline stress conditions were identified. These promising candidates provide valuable resources for validating potential ST-related genes and will facilitate rice breeding for salt tolerance through marker-assisted selection.
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http://dx.doi.org/10.1186/s12284-019-0349-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889114PMC
December 2019

Sciapodinae from the Himalayan region with description of nine new species from Tibet (Diptera: Dolichopodidae).

Zootaxa 2019 Apr 4;4577(1):zootaxa.4577.1.1. Epub 2019 Apr 4.

Department of Entomology, China Agricultural University, Beijing 100193, China..

The Himalayan region now includes 67 species in seven genera of Sciapodinae, including nine new species (Amblypsilopus acuminatus sp. nov., A. liangi sp. nov., A. liratus sp. nov., A. marginatus sp. nov., A. medogensis sp. nov., A. quinquepetalus sp. nov., Plagiozopelma fornicata sp. nov., P. trilobata sp. nov., Sciapus zewoiensus sp. nov.). Six species are reported from the Himalayan region for the first time: A. baoshanus Yang, A. didymus Yang, A. hubeiensis Yang Yang, A. imitans (Becker), A. liui Zhu Yang, and P. medivittatum Bickel Wei. Chrysosoma insensibile Yang is re-assessed and transferred to Amblypsilopus, new combination. Amblypsilopus sinensis Yang Yang, 2003 is proposed as a new synonym of A. subabruptus Bickel Wei, 1996. This is the first time Sciapus Zeller is reported from the Himalayan region. Keys to genera and species of Sciapodinae occurring in the Himalayas are provided. The distribution of Sciapodinae in the Himalayas is discussed.
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http://dx.doi.org/10.11646/zootaxa.4577.1.1DOI Listing
April 2019

Real-World Outcomes and Factors Associated With the Second-Line Treatment of Patients With Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma.

Cancer Control 2019 Jan-Dec;26(1):1073274819847642

4 City of Hope Comprehensive Cancer Center, Duarte, CA, USA.

This retrospective observational study was designed to evaluate overall survival in a real-world patient population and to identify predictive factors associated with receipt of second-line therapy. A retrospective analysis of electronic medical records (Flatiron Health, New York) was conducted among patients initiating first-line therapy from January 1, 2013, through April 30, 2018. Eligible patients were diagnosed with advanced gastric, gastroesophageal junction, or esophageal adenocarcinoma and ≥18 years of age at the time of treatment initiation. Patients alive 45 days after discontinuation of first-line therapy were considered potentially eligible for continued therapy and were categorized into those who received and those who did not receive second-line therapy. Survival analyses were conducted using Kaplan-Meier method and log-rank test without adjusting for any baseline covariates. Factors associated with further treatment were evaluated using logistic regression. A total of 3850 patients met eligibility criteria. Among the 2516 patients available to receive second-line therapy, 1515 (60.2%) received second-line therapy and 1001 (39.8%) did not receive further therapy. Among those potentially eligible to receive second-line therapy, median survival was 15.4 months (95% confidence interval [CI]: 14.6-16.0) from initiation of first-line therapy for those who received second-line therapy and 10.0 months (95% CI: 9.3-10.7) for those who did not. Longer duration of first-line therapy (≥169 vs ≤84 days), HER2-positive tumors, initially diagnosed with stage IV disease, less weight loss during first-line therapy, and younger age were associated with receipt of second-line therapy (all P < .001). Longer survival was associated with multiple lines of therapy; however, these results should be interpreted with caution, and no causal relationship can be inferred.
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http://dx.doi.org/10.1177/1073274819847642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503607PMC
November 2019

Challenges of Using ICD-9-CM and ICD-10-CM Codes for Soft-Tissue Sarcoma in Databases for Health Services Research.

Perspect Health Inf Manag 2019 1;16(Spring):1a. Epub 2019 Apr 1.

Eli Lilly and Company in Indianapolis, IN.

Objectives: Soft-tissue sarcoma (STS) is a heterogeneous group of rare solid tumors that arise from various soft tissues in the body, such as muscle, fat, nerves, and blood vessels. Current International Classification of Diseases (ICD) coding systems include a set of nonspecific codes for malignancies of connective and soft tissue (ICD-9-CM code 171 and ICD-10-CM code C49). The goal of this study was to evaluate the use of these codes for health services research involving patients with a diagnosis of this rare malignancy.

Methods: Two databases were utilized to explore ICD coding for STS: claims data from Truven MarketScan and electronic medical records (EMRs) from Flatiron Health. Eligible patients from claims data were those with at least two ICD-9-CM codes of 171.x on two different days between July 1, 2004, and March 30, 2014. The treatment patterns of these cases were evaluated for consistency with known therapeutic approaches for STS. Eligible patients from the Flatiron EMR system were those who received olaratumab (a drug indicated only for use in patients diagnosed with STS) after its US Food and Drug Administration approval in October 2016 through the end of the data set (November 2017). ICD-10-CM codes were evaluated for this known STS cohort.

Results: In claims data, 4,159 patients were eligible for inclusion. Although national treatment guidelines include only a limited number of drugs used to treat STS, 98 unique anticancer drugs were identified as being used to treat patients in a claims data cohort. Only 7.7 percent of patients had claims for doxorubicin-based therapy and 3.8 percent had claims for ifosfamide-based therapy as initial treatment for STS, despite these being a standard of care. In the EMR data, 350 patients were eligible; only 170 patients (48.6 percent) had any evidence in the database of a connective or soft-tissue ICD-10-CM malignancy code within 60 days before or after initiation of olaratumab.

Conclusions: ICD coding for STS using the "Malignant neoplasm of connective and soft tissue" code is not reliable as a method to identify patients diagnosed with STS. Although codes reflecting the primary site of disease may have clinical relevance, lack of consistency in ICD coding for the diagnosis and treatment of this disease is a limiting factor in the ability to conduct real-world observational research of this rare disease. In the absence of consistent use of this code, an algorithm needs to be developed and validated to accurately identify patients with STS in these databases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462881PMC
March 2020

Upregulation of the long non-coding RNA CBR3-AS1 predicts tumor prognosis and contributes to breast cancer progression.

Gene X 2019 Jun 25;2:100014. Epub 2019 Mar 25.

Department of Radiotherapy, Jiangyin People's Hospital, Affiliated Hospital of Southeast University, Jiangyin, 214400, China.

Breast cancer is the most common female malignancy and the major cause of cancer-related death in women. Long non-coding RNAs (lncRNAs), as oncogenic or tumor suppressor factor, involved in the development and progression of various cancers. In this study, we sought to investigate the function of lncRNA CBR3-AS1 in breast cancer. We evaluated the expression pattern of CBR3-AS1 in breast cancer tissues and cell lines, explored the correlation between CBR3-AS1 expression and the survival time of breast cancer patients, and probed the effect of CBR3-AS1 on tumor progression of breast cancer through loss-of-function and gain-of-function strategies. Our results showed that CBR3-AS1 was overexpressed in breast cancer tissues and cell lines and predicted the prognosis of breast cancer patients. And CBR3-AS1 exerted biological function as an oncogenic lncRNA, involved in the regulation of cell proliferation, colony formation, apoptosis and tumor growth in breast cancer. Taken together, CBR3-AS1 was up-regulated in breast cancer and promoted the risk of breast cancer. It may be a novel therapeutic target and potential prognostic marker for breast cancer.
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http://dx.doi.org/10.1016/j.gene.2019.100014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285981PMC
June 2019

Patient and Oncologist Preferences for the Treatment of Adults with Advanced Soft Tissue Sarcoma: A Discrete Choice Experiment.

Patient 2019 08;12(4):393-404

Eli Lilly and Company, Indianapolis, IN, USA.

Background: There has been no single standard-of-care treatment of patients with advanced/metastatic soft tissue sarcoma (STS). This study was designed to understand patient and oncologist preferences in the advanced/metastatic setting.

Methods: Adult patients diagnosed with STS and oncologists treating patients with STS completed discrete choice experiment surveys. Study participants chose between pairs of hypothetical treatment profiles for advanced STS characterized by varying levels of overall survival (14, 20, or 26 months), progression-free survival (3, 5, or 7 months), objective tumor response rate (12, 18, or 26%), risk of hospitalization due to side effects (12, 30, or 46%), and days/month to administer treatment (1, 2, or 4 days). A hierarchical Bayes model was used to estimate preferences and relative importance of attributes.

Results: Seventy-six patients (23.7% male, mean age 52.8 years) and 160 oncologists (73.8% male, mean 16.9 years in practice) completed the surveys. Among patients, overall survival had the highest relative importance (39.5%, standard deviation [SD] 18.2%), followed by response rate (21.2%, SD 10.4%), and hospitalization (19.8%, SD 12.5%). Among oncologists, overall survival had the highest relative importance (44.6%, SD 16.0%), followed by hospitalization (18.4%, SD 8.3%).

Conclusions: Both patients with STS and oncologists preferred a treatment that maximizes the life of patients while avoiding hospitalizations.
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http://dx.doi.org/10.1007/s40271-019-00355-0DOI Listing
August 2019

Upregulation of the long non-coding RNA CBR3-AS1 predicts tumor prognosis and contributes to breast cancer progression.

Gene 2019 25;721S:100014. Epub 2019 Mar 25.

Department of Radiotherapy, Jiangyin People's Hospital, Affiliated Hospital of Southeast University, Jiangyin, 214400, China. Electronic address:

Breast cancer is the most common female malignancy and the major cause of cancer-related death in women. Long non-coding RNAs (lncRNAs), as oncogenic or tumor suppressor factor, involved in the development and progression of various cancers. In this study, we sought to investigate the function of lncRNA CBR3-AS1 in breast cancer. We evaluated the expression pattern of CBR3-AS1 in breast cancer tissues and cell lines, explored the correlation between CBR3-AS1 expression and the survival time of breast cancer patients, and probed the effect of CBR3-AS1 on tumor progression of breast cancer through loss-of-function and gain-of-function strategies. Our results showed that CBR3-AS1 was overexpressed in breast cancer tissues and cell lines and predicted the prognosis of breast cancer patients. And CBR3-AS1 exerted biological function as an oncogenic lncRNA, involved in the regulation of cell proliferation, colony formation, apoptosis and tumor growth in breast cancer. Taken together, CBR3-AS1 was up-regulated in breast cancer and promoted the risk of breast cancer. It may be a novel therapeutic target and potential prognostic marker for breast cancer.
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http://dx.doi.org/10.1016/j.gene.2019.100014DOI Listing
March 2019

Effective wind and temperature retrieval from Doppler asymmetric spatial heterodyne spectrometer interferograms.

Appl Opt 2018 Oct;57(30):8829-8835

This paper presents a method for wind velocity and Doppler temperature retrieval from interferograms of a Doppler asymmetric spatial heterodyne spectrometer. This method is based on the analytic representation of the signal and the subsequent algorithms. It turns out to be more robust than the conventional Fourier transform method at low SNR. The influence of optical dispersion on the accuracy of the retrieved parameters is also characterized. The effective optical path difference is suggested for use in wind and temperature retrieval routines. Computer simulations are used to characterize the accuracy of the proposed method, in particular regarding the influence of optical dispersion.
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http://dx.doi.org/10.1364/AO.57.008829DOI Listing
October 2018

Treatment patterns, duration and outcomes of pemetrexed maintenance therapy in patients with advanced NSCLC in a real-world setting.

Curr Med Res Opin 2019 05 10;35(5):817-827. Epub 2018 Dec 10.

b Flatiron Health , New York , NY , USA.

Objectives: In patients with non-squamous non-small-cell lung cancer (NSCLC), maintenance therapy regimens, including pemetrexed, have been shown to prolong overall survival (OS) and progression-free survival (PFS). The purpose of this study was to describe real-world maintenance use of pemetrexed and associated outcomes in patients with advanced NSCLC.

Methods: This was a retrospective, observational study that used longitudinal, demographically and geographically diverse electronic health record data in the United States. Eligible patients were adults with advanced non-squamous NSCLC who had received maintenance treatment with pemetrexed monotherapy or pemetrexed plus bevacizumab. Descriptive statistics were used to describe the patient population and multivariable logistic regression was used to identify the factors associated with duration of maintenance therapy. Kaplan-Meier curves and Cox regression models were used for time-to-event analysis.

Results: Patients receiving pemetrexed maintenance therapy were treated with either pemetrexed monotherapy (66.0%) or pemetrexed plus bevacizumab (34.0%). Carboplatin and pemetrexed (37.9%) or carboplatin, pemetrexed and bevacizumab (36.1%) were the most commonly used first-line therapies observed. The majority (84.9%) of these maintenance patients responded to first-line therapy. The median duration of maintenance therapy was 6.0 months for pemetrexed and bevacizumab and 4.1 months for pemetrexed monotherapy. The median OS from the start of first-line therapy of the total study cohort was 21.5 months (95% CI 20.0, 22.9).

Conclusion: Real-world effectiveness of pemetrexed maintenance therapy is similar to that observed in published randomized controlled trials, confirming a role for pemetrexed maintenance in eligible patients in clinical practice.
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http://dx.doi.org/10.1080/03007995.2018.1547273DOI Listing
May 2019

Treatment Patterns by EGFR Mutation Status in Non-Small Cell Lung Cancer Patients in the USA: A Retrospective Database Analysis.

Adv Ther 2018 11 19;35(11):1905-1919. Epub 2018 Oct 19.

Texas Oncology, Baylor University Medical Center, Dallas, TX, USA.

Introduction: Targeted therapies, including tyrosine kinase inhibitors (TKIs) that target the sensitizing epidermal growth factor receptor (EGFR) gene are recommended for patients with non-small cell lung cancer (NSCLC). Most patients with NSCLC who test positive for the EGFR mutation and receive TKIs develop resistance to these drugs. Questions remain regarding which treatment sequence is optimal for patients with EGFR-mutant NSCLC, and few studies have evaluated patterns of TKI treatment use in NSCLC, irrespective of EGFR mutation status, in a real-world setting. This population-based study aimed to evaluate treatment patterns at a national level in the USA.

Methods: This retrospective observational study used data from the US Oncology Network's iKnowMed database. Patients with advanced NSCLC who initiated first-line therapy with erlotinib and/or intravenous chemotherapy between January 1, 2012 and June 30, 2015 and met all other study criteria were included. Descriptive analyses assessed demographic and clinical characteristics and treatment patterns among the overall study cohort, as well as for specific erlotinib treatment subgroups, stratified by EGFR status.

Results: Among the 3108 patients identified, 18.5% were EGFR positive, 49.8% were EGFR negative, and 31.7% were EGFR documented unknown. For the overall cohort, 18.4% received first-line erlotinib monotherapy, fewer than 1% received first-line combination therapy (erlotinib plus chemotherapy), 4.7% received second-line erlotinib monotherapy, and 3.3% received second-line combination therapy. First-line erlotinib monotherapy was used in 77.8% of all EGFR positive patients. Almost two-thirds of the overall cohort were not observed to have advanced to second-line therapy.

Conclusions: As treatment options evolve, this study provides real-world treatment patterns that suggest concordance with NCCN guidelines and confirm the remaining need to understand sequencing of therapies and related outcomes.

Funding: Eli Lilly and Company.
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http://dx.doi.org/10.1007/s12325-018-0811-0DOI Listing
November 2018

Treatment Decisions for Advanced Non-Squamous Non-Small Cell Lung Cancer: Patient and Physician Perspectives on Maintenance Therapy.

Patient 2019 04;12(2):223-233

Eli Lilly and Company, Indianapolis, IN, USA.

Introduction: Advanced non-small cell lung cancer (NSCLC) is a severe disease with burdensome symptoms and traditionally poor outcomes. The treatment of advance disease is based on chemotherapy, with the recent addition of immunotherapy. Patients who respond to initial treatment can opt to receive maintenance therapy (MT). It is important to understand why patients with advanced NSCLC choose to accept or refuse therapy, and how physician recommendations play into this decision-making process. This study characterized patient and physician decision-making regarding treatment for patients with advanced non-squamous NSCLC in the USA using the example of MT.

Methods And Materials: This study employed multiple approaches: patient interviews, a patient survey, and a physician survey. Qualitative interviews were conducted among patients who had been offered MT to identify factors influencing treatment decision-making. The patient survey explored the decision-making process and quantified challenges and motivators for receiving MT. The physician survey included a discrete choice experiment to understand the relationship between physician treatment recommendations and patient characteristics.

Results: Interviewed patients (n = 10) were motivated to receive MT in the hope of extending their lives and being proactive against their cancer, and they anticipated reduced adverse effects compared with first-line therapy. Surveyed patients (n = 77) described several deterrents to receiving therapy; the most prominent was severity of adverse effects, which was an influencing factor for 34% of patients. The major motivator for receiving therapy was the potential to extend life, which influenced 97% of patients. A total of 100 oncologists participated in the physician survey. Patients' lack of treatment motivation/inconvenience, disease progression, presence of severe renal co-morbidities, and older age decreased the likelihood of physicians recommending the use of MT.

Conclusion: This study identified challenges and motivators influencing advanced NSCLC patients' decisions to accept or refuse therapy, as well as patient and disease characteristics associated with physician's treatment recommendations for MT.
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http://dx.doi.org/10.1007/s40271-018-0327-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397138PMC
April 2019

Genetic Dissection and Simultaneous Improvement of Drought and Low Nitrogen Tolerances by Designed QTL Pyramiding in Rice.

Front Plant Sci 2018 9;9:306. Epub 2018 Mar 9.

Institute of Crop Sciences, National Key Facility for Crop Gene Resources and Genetic Improvement, Chinese Academy of Agricultural Sciences, Beijing, China.

Drought and low nitrogen are the most common abiotic stresses limiting rice productivity in the rainfed rice areas of Asia and Africa. Development and adoption of green super rice (GSR) varieties with greatly improved drought tolerance (DT) and low nitrogen tolerance (LNT) are the most efficient way to resolve this problem. In this study, using three sets of trait-specific introgression lines (ILs) in a variety Huanghuazhan (HHZ) background, we identified nine DT-QTL and seven LNT-QTL by a segregation distortion approach and a genome-wide association study, respectively. Based on performances of DT and LNT and genotypes at the detected QTL, two ILs M79 and M387 with DT and LNT were selected for cross-making to validate the identified QTL and to develop DT and LNT rice lines by pyramiding two DT-QTL ( and and two LNT-QTL and ). Using four pairs of kompetitive allele specific PCR (KASP) SNP markers, we selected 66 F individuals with different combinations of the target DT- and LNT-QTL favorable alleles and they showed expected improvement in DT and/or LNT, which were further validated by the significant improvement in DT and/or LNT of their F progeny testing. Based on evaluation of pyramiding lines in F lines under drought, low nitrogen (LN) and normal conditions, four promising pyramiding lines having different QTL favorable alleles were selected, which showed significantly improved tolerances to drought and/or LN than HHZ and their IL parents. Our results demonstrated that trait-specific ILs could effectively connect QTL mapping and QTL pyramiding breeding, and designed QTL pyramiding (DQP) using ILs could be more effective in molecular rice breeding for complex quantitative traits.
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http://dx.doi.org/10.3389/fpls.2018.00306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855007PMC
March 2018

Predictors of heterogeneity in the first-line treatment of patients with advanced/metastatic gastric cancer in the U.S.

Gastric Cancer 2018 09 1;21(5):738-744. Epub 2018 Feb 1.

Yale Cancer Center, New Haven, CT, USA.

Background: Patients with metastatic gastric cancer have a poor prognosis (5-year survival of less than 10%). This study was designed to describe the treatment patterns of patients with gastric cancer and to understand the factors associated with treatment choices to inform evidence-based care.

Methods: A retrospective observational study was conducted using two real-world databases to describe treatment trends and to quantify variability in treatment patterns of patients diagnosed with advanced/metastatic gastric cancer between 1/1/2007 and 9/30/2014 in the U.S. Heterogeneity was measured by the Herfindahl-Hirschman Index (HHI). Predictors (baseline clinical, treatment, and demographic variables) of treatment regimen choice were evaluated using logistic regression.

Results: A total of 5772 patients with advanced/metastatic gastric cancer were included in this study [5044 from claims data and 728 from electronic medical records (EMR)]. Of the 5044 from claims data, 2457 had evidence of metastatic disease at diagnosis. Only the fluorouracil + oxaliplatin regimen exceeded 10% utilization in the first-line setting [claims metastatic (12.1%), claims advanced (8.2%), and EMR metastatic (16.6%) cohorts]. The HHI demonstrated extreme heterogeneity (0.14 for first-line therapy and 0.13 for second-line therapy). Patient age and geographic region of residence were significantly associated with treatment choice across all three cohorts in the first-line setting (p < 0.05).

Conclusion: Treatment of patients with gastric cancer was highly variable. Despite the availability of treatment guidelines, there is a lack of consistent treatment patterns. There is a need to improve evidence-based care for patients with gastric cancer.
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http://dx.doi.org/10.1007/s10120-018-0802-5DOI Listing
September 2018

One-Year Clinical Effectiveness Comparison of Prasugrel with Ticagrelor: Results from a Retrospective Observational Study using an Integrated Claims Database.

Am J Cardiovasc Drugs 2018 Apr;18(2):129-141

Allied Health Professions School, Virginia Commonwealth University, Richmond, VA, 23219, USA.

Background: No direct comparisons of ticagrelor and prasugrel with 1-year clinical follow-up have been reported.

Objectives: Our objective was to compare 1-year clinical outcomes among patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with either ticagrelor or prasugrel in a real-world setting.

Methods: This retrospective study included patients from a payer database who were aged ≥18 years and had ACS managed with PCI with no history of transient ischemic attack (TIA)/stroke. Data were propensity matched for prasugrel use with a 3:1 prasugrel:ticagrelor ratio. Post-discharge net adverse clinical event (NACE) rate at 1 year was evaluated for noninferiority using a pre-defined 20% margin. NACE was a composite of major adverse cardiovascular events (MACE) or rehospitalization for bleeding.

Results: In total, 15,788 ACS-PCI patients were included (prasugrel 12,797; ticagrelor 2991). Prasugrel-treated patients were younger; less likely to be female, have prior myocardial infarction (MI), diabetes, or non-ST-segment elevation MI (NSTEMI); and more likely to have unstable angina (UA) than ticagrelor-treated patients. Prior to matching, NACE and MACE (P < 0.01) were lower, with no difference in bleeding with prasugrel compared with ticagrelor. After matching, there was no significant difference in baseline characteristics. Noninferiority was demonstrated for NACE, MACE, and bleeding between prasugrel and ticagrelor. NACE and MACE were significantly lower with prasugrel use, primarily driven by heart failure, with no significant difference in all-cause death, MI, UA, revascularization, TIA/stroke, or bleeding.

Conclusions: In this retrospective study, physicians preferentially used prasugrel rather than ticagrelor in younger ACS-PCI patients with lower risk of bleeding or comorbidities. After propensity matching, clinical outcomes associated with prasugrel were noninferior to those with ticagrelor.
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http://dx.doi.org/10.1007/s40256-017-0255-yDOI Listing
April 2018
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