Publications by authors named "Jing Ning"

350 Publications

Semiparametric isotonic regression modelling and estimation for group testing data.

Can J Stat 2021 Sep 28;49(3):659-677. Epub 2020 Oct 28.

Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Rockville, MD USA.

In the group testing procedure, several individual samples are grouped and the pooled samples, instead of each individual sample, are tested for outcome status (e.g., infectious disease status). Although this cost-effectiveness strategy in data collection is both labor and time efficient, it poses statistical challenges to derive statistically and computationally efficient estimators under semiparametric models. We consider semiparametric isotonic regression models for the simultaneous estimation of the conditional probability curve and covariate effects, in which a parametric form for combining the covariate information is assumed and the monotonic link function is left unspecified. We develop an expectation-maximization algorithm to overcome the computational challenge and embed the pool-adjacent violators algorithm in the M-step to facilitate the computation. We establish the large sample behavior of the proposed estimators and examine their finite sample performance in simulation studies. We apply the proposed method to data from the National Health and Nutrition Examination Survey for illustration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cjs.11581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528191PMC
September 2021

[Bioinformatics analysis of differentially expressed microRNAs in children with bronchial asthma].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Oct;37(10):923-931

Graduate School of Tianjin Medical University, Tianjin 300070; Department of Respiratory Diseases, Tianjin Children's Hospital, Tianjin 300074, China. *Corresponding author, E-mail:

Objective To study important micro-RNAs (miRNAs) and its target genes in children with asthma. Methods Microarray data of pediatric asthma (GSE120172) were downloaded from the GEO database and the differentially expressed miRNAs (DEMs) were analyzed with the R programming language. The potential target genes of DEMs were predicted by miRDB, miRTarBase and Targetscan tools, and annotated by the R software package clusterProfiler. Then the protein-protein interaction (PPI) and miRNA-hub gene network were constructed by the STRING database and Cytoscape software. Finally, the association between the hub gene and asthma was further verified by the CTD database. Results A total of 24 miRNAs were significantly differentially expressed, including 18 up-regulated and 6 down-regulated, and 297 target genes were predicted. The GO analysis showed that the target genes were mainly involved in epithelial cell proliferation and intercellular junction in the biological process, that the cellular components were mainly related to the plasma membrane and membrane components, and that the molecular functions included GTPase activity and receptor binding. KEGG pathway showed that target genes were mainly involved in the PI3K-AKT signal pathway and FoxO signal pathway. According to network analysis, miR-22-3p and miR-625-5p were important down-regulated molecules, while miR-206, miR-200b-3p, miR-548at-5p, miR-193a-3p and miR-935 were significantly up-regulated miRNAs associated with childhood asthma, and 15 potential target genes such as CCND1, SIRT1 and HDAC4 were the key genes selected. Conclusion The study has identified seven DEMs and their target genes that have potential roles in the occurrence and development of childhood asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2021

Single cell T cell landscape and T cell receptor repertoire profiling of AML in context of PD-1 blockade therapy.

Nat Commun 2021 Oct 18;12(1):6071. Epub 2021 Oct 18.

Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

In contrast to the curative effect of allogenic stem cell transplantation in acute myeloid leukemia via T cell activity, only modest responses are achieved with checkpoint-blockade therapy, which might be explained by T cell phenotypes and T cell receptor (TCR) repertoires. Here, we show by paired single-cell RNA analysis and TCR repertoire profiling of bone marrow cells in relapsed/refractory acute myeloid leukemia patients pre/post azacytidine+nivolumab treatment that the disease-related T cell subsets are highly heterogeneous, and their abundance changes following PD-1 blockade-based treatment. TCR repertoires expand and primarily emerge from CD8 cells in patients responding to treatment or having a stable disease, while TCR repertoires contract in therapyresistant patients. Trajectory analysis reveals a continuum of CD8 T cell phenotypes, characterized by differential expression of granzyme B and a bone marrow-residing memory CD8 T cell subset, in which a population with stem-like properties expressing granzyme K is enriched in responders. Chromosome 7/7q loss, on the other hand, is a cancer-intrinsic genomic marker of PD-1 blockade resistance in AML. In summary, our study reveals that adaptive T cell plasticity and genomic alterations determine responses to PD-1 blockade in acute myeloid leukemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-26282-zDOI Listing
October 2021

Flexible High-Stability Self-Variable-Voltage Monolithic Integrated System Achieved by High-Brightness LED for Information Transmission.

Small 2021 Oct 13:e2105207. Epub 2021 Oct 13.

The State Key Discipline Laboratory of Wide Band Gap Semiconductor Technology, Xidian University, Xi'an, Shaanxi Joint Key Laboratory of Graphene, Xidian University, Xi'an, 710071, China.

The emergence of visible light information transmission systems is profoundly affecting the future of the Internet of Things (IoT) technology. The complex sensing and driving circuits of the IoT have become the key factor to hinder signal conversion and processing. Herein, a high-performance self-variable-voltage light information transmission integrated system (SVV-LTS) is reported and its application potential in low-power, self-powered optical communication transmission systems is demonstrated. Diffusion-adsorption regulation growth method and laser induction technology are innovatively used to realize high-brightness light-emitting diode (LED) and flexible micro-supercapacitor (MSC) on graphene. Meanwhile, MSC realizes the dual functions of supplying power to the system, realizing pressure signal response, and converting pressure signals into electrical signals. Finally, the MSC as power, sensor and LED as signal transmitter are integrated into an SVV-LTS. The response time of SVV-LTS is 80 ms and the luminous wavelength fluctuation of the LED is stable at 1.2 nm. This study will provide a new approach to realize low-power optical communication transmission systems affecting the IoT technology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/smll.202105207DOI Listing
October 2021

Mediation model with a categorical exposure and a censored mediator with application to a genetic study.

PLoS One 2021 12;16(10):e0257628. Epub 2021 Oct 12.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

Mediation analysis is a statistical method for evaluating the direct and indirect effects of an exposure on an outcome in the presence of a mediator. Mediation models have been widely used to determine direct and indirect contributions of genetic variants in clinical phenotypes. In genetic studies, the additive genetic model is the most commonly used model because it can detect effects from either recessive or dominant models (or any model in between). However, the existing approaches for mediation model cannot be directly applied when the genetic model is additive (e.g. the most commonly used model for SNPs) or categorical (e.g. polymorphic loci), and thus modification to measures of indirect and direct effects is warranted. In this study, we proposed overall measures of indirect, direct, and total effects for a mediation model with a categorical exposure and a censored mediator, which accounts for the frequency of different values of the categorical exposure. The proposed approach provides the overall contribution of the categorical exposure to the outcome variable. We assessed the empirical performance of the proposed overall measures via simulation studies and applied the measures to evaluate the mediating effect of a women's age at menopause on the association between genetic variants and type 2 diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257628PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509986PMC
October 2021

X-band TE101 rectangular aperture cavity for in vivo EPR tooth dosimetry after radiation emergency.

Appl Radiat Isot 2021 Sep 21;178:109958. Epub 2021 Sep 21.

Beijing Institute of Radiation Medicine, No.27 Tai-Ping Road, Beijing, 100850, China; Beijing Key Laboratory of Radiation Biology No. BZ0325, No.27 Tai-Ping Road, Beijing, 100850, China. Electronic address:

The TE101 mode rectangle EPR cavity was newly developed to achieve X-band in vivo EPR tooth dosimetry for the rescue of nuclear emergency. An aperture for sample detection was opened on the cavity's surface. Its characteristics were evaluated by measuring DPPH and intact human incisor samples. Remarkable radiation induced signal from EPR spectrum of 1Gy-8Gy irradiated teeth was observed. In vivo measurements of rat was performed to verify its application for in vivo tooth dosimetry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.apradiso.2021.109958DOI Listing
September 2021

Predictors of outcomes in adults with acute myeloid leukemia and KMT2A rearrangements.

Blood Cancer J 2021 Sep 29;11(9):162. Epub 2021 Sep 29.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, TX, Houston, USA.

Acute myeloid leukemia (AML) with rearrangement of the lysine methyltransferase 2a gene (KMT2Ar) has adverse outcomes. However, reports on the prognostic impact of various translocations causing KMT2Ar are conflicting. Less is known about associated mutations and their prognostic impact. In a retrospective analysis, we identified 172 adult patients with KMT2Ar AML and compared them to 522 age-matched patients with diploid AML. KMT2Ar AML had fewer mutations, most commonly affecting RAS and FLT3 without significant impact on prognosis, except for patients with ≥2 mutations with lower overall survival (OS). KMT2Ar AML had worse outcomes compared with diploid AML when newly diagnosed and at relapse, especially following second salvage (median OS of 2.4 vs 4.8 months, P < 0.0001). Therapy-related KMT2Ar AML (t-AML) had worse outcomes compared with de novo KMT2Ar AML (median OS of 0.7 years vs 1.4 years, P < 0.0001). Allogeneic hematopoietic stem cell transplant (allo-HSCT) in first remission was associated with improved OS (5-year, 52 vs 14% for no allo-HSCT, P < 0.0001). In a multivariate analysis, translocation subtypes causing KMT2Ar did not predict survival, unlike age and allo-HSCT. In conclusion, KMT2Ar was associated with adverse outcomes regardless of translocation subtype. Therefore, AML risk stratification guidelines should include all KMT2Ar as adverse.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41408-021-00557-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481264PMC
September 2021

Feasibility of in vivo Imaging of Fibroblast Activation Protein in Human Arterial Walls.

J Nucl Med 2021 Sep 16. Epub 2021 Sep 16.

Medical University of Vienna, Austria.

Increased expression of fibroblast activating protein (FAP) in fibrous caps may contribute to progression of atherosclerotic plaques. Forty-one patients who underwent gallium-68-conjugated quinoline-based FAP inhibitor (Ga-FAPI-04) PET/CT for non-cardiovascular indications were retrospectively analyzed. Correlations were assessed between the uptake of Ga-FAPI-04 in large arterial walls (SUV and target-to-background ratio, TBR) and degree of calcification and cardiovascular risk factors. Focal arterial uptake of Ga-FAPI-04 or calcification was detected in 1,177 arterial segments in all 41 patients. TBR was negatively correlated with the degree of calcification (HU) (r = -0.27, < 0.01). Mean TBR in higher-risk patients was greater than lower-risk patients (2.2 ± 0.3 vs. 1.8 ± 0.3, < 0.01). Immunohistochemical labeling of carotid plaques exhibited prominent FAP expression in a thin fibrous cap and moderate FAP expression in a thick cap. Ga-FAPI-04 PET/CT might have potential for imaging fibroblastic activation in the arterial wall.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2967/jnumed.121.262863DOI Listing
September 2021

Evaluation of the efficacy and adverse reactions of hysteroscopy in the treatment of endometrial polyps.

Minerva Surg 2021 Sep 15. Epub 2021 Sep 15.

Department of Obstetrics and Gynecology, Hainan Hospital of PLA General Hospital, Sanya, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S2724-5691.21.09072-9DOI Listing
September 2021

Potential role of anti-inflammatory HDL subclasses in metabolic unhealth/obesity.

Artif Cells Nanomed Biotechnol 2021 Dec;49(1):565-575

Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.

High-density lipoprotein (HDL) particles comprising heterogeneous subclasses of different functions exert anti-inflammatory effects by interacting with immune-response cells. However, the relationship of HDL subclasses with immune-response cells in metabolic unhealth/obesity has not been defined clearly. The purpose of this study was to delineate the relational changes of HDL subclasses with immune cells and inflammatory markers in metabolic unhealth/obesity to understand the role of anti-inflammatory HDL subclasses. A total of 316 participants were classified by metabolic health. HDL subclasses were detected by microfluidic chip electrophoresis. White blood cell (WBC) counts and lymphocytes were assessed using automatic haematology analyser. Levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) were measured. In our study, not only the distribution of HDL subclasses, but also HDL-related structural proteins changed with the deterioration of metabolic disease. Moreover, lymphocytes and inflammation factors significantly gradually increased. The level of HDL2b was negatively associated with WBC, lymphocytes and hs-CRP in multivariable linear regression analysis. In multinomial logistic regression analysis, high levels of HDL3 and low levels of HDL2b increased the probability of having an unfavourable metabolic unhealth/obesity status. We supposed that HDL2b particles may play anti-inflammation by negatively regulating lymphocytes activation. HDL2b may be a therapeutic target for future metabolic disease due to the anti-inflammatory effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21691401.2021.1961798DOI Listing
December 2021

A NIR fluorescent probe for fatty acid amide hydrolase bioimaging and its application in development of inhibitors.

J Mater Chem B 2021 Aug 7;9(32):6460-6465. Epub 2021 Aug 7.

The Second Affiliated Hospital, College of Pharmacy, Dalian Medical University, Dalian, China.

Fatty acid amide hydrolase (FAAH) is primarily responsible for the inactivation of fatty acid ethanolamide (FAE) and is involved in a variety of biological functions related to diseases of the nervous system. Herein, we developed a highly selective and sensitive FAAH-activated near-infrared fluorescent probe named DAND and achieved the real-time detection and imaging of FAAH activity in complex biosystems. Moreover, a visual high-throughput screening method was established using DAND, piperine was identified as a novel inhibitor of FAAH. Based on the interaction of piperine with FAAH, a more potent FAAH inhibitor (11f) was designed and synthesized which possessed an IC value of 0.65 μM. Furthermore, 11f could attenuate the liposaccharide (LPS)-induced activation of BV2 cells, exhibiting an excellent anti-inflammatory activity. These results indicated that DAND could be used as a promising molecular tool for exploring FAAH activity and for rapidly screening potential FAAH inhibitors. In addition, piperine and its derivatives could serve as potential candidate drugs for the treatment of neurodegenerative diseases in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1tb01054aDOI Listing
August 2021

International Investment and Indigenous Peoples' Environment: A Survey of ISDS Cases from 2000 to 2020.

Int J Environ Res Public Health 2021 07 22;18(15). Epub 2021 Jul 22.

Guanghua Law School, Zhejiang University, Hangzhou 310008, China.

Indigenous peoples' environments can be easily disrupted by foreign investments, and disputes have occasionally occurred over the past few years. The objective of this research article is to examine if current international investment law, especially its investor-state dispute settlement (ISDS) mechanism, could provide necessary protection to Indigenous rights. We searched all publicly available ISDS cases from 2000 to 2020, and selected 10 typical ones for comprehensive case study by using various research methods such as doctrinal legal research and comparative analysis. Our research revealed that Indigenous peoples' participation in the ISDS proceedings is legally restrained, time-consuming, and rarely favorably decided by the arbitral tribunals. Responsibility for such undesirable outcomes rests with all stakeholders involved in the process, while the consequences of post-arbitration tend to be "triple losing". These findings highlight the quest for a more sustainable international investment regime that promotes Indigenous peoples' wellbeing and environment protection. We argue that future reform could be promoted not only over ISDS procedural matters, but also by upgrading substantive rules in international investment agreements (IIAs), emphasizing free, prior, and informed consent (FPIC), and strengthening foreign investors' corporate social responsibilities (CSR).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph18157798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345368PMC
July 2021

Ten-day decitabine with venetoclax versus intensive chemotherapy in relapsed or refractory acute myeloid leukemia: A propensity score-matched analysis.

Cancer 2021 Aug 3. Epub 2021 Aug 3.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Relapsed/refractory (R/R) acute myeloid leukemia (AML) has poor outcomes. Although lower-intensity venetoclax-containing regimens are standard for older/unfit patients with newly diagnosed AML, it is unknown how such regimens compare with intensive chemotherapy (IC) for R/R AML.

Methods: Outcomes of R/R AML treated with 10-day decitabine and venetoclax (DEC10-VEN) were compared with IC-based regimens including idarubicin with cytarabine, with or without cladribine, clofarabine, or fludarabine, with or without additional agents. Propensity scores derived from patient baseline characteristics were used to match DEC10-VEN and IC patients to minimize bias.

Results: Sixty-five patients in the DEC10-VEN cohort were matched to 130 IC recipients. The median ages for the DEC10-VEN and IC groups were 64 and 58 years, respectively, and baseline characteristics were balanced between the 2 cohorts. DEC10-VEN conferred significantly higher responses compared with IC including higher overall response rate (60% vs 36%; odds ratio [OR], 3.28; P < .001), complete remission with incomplete hematologic recovery (CRi, 19% vs 6%; OR, 3.56; P = .012), minimal residual disease negativity by flow cytometry (28% vs 13%; OR, 2.48; P = .017), and lower rates of refractory disease. DEC10-VEN led to significantly longer median event-free survival compared with IC (5.7 vs 1.5 months; hazard ratio [HR], 0.46; 95% CI, 0.30-0.70; P < .001), as well as median overall survival (OS; 6.8 vs 4.7 months; HR, 0.56; 95% CI, 0.37-0.86; P = .008). DEC10-VEN was independently associated with improved OS compared with IC in multivariate analysis. Exploratory analysis for OS in 27 subgroups showed that DEC10-VEN was comparable with IC as salvage therapy for R/R AML.

Conclusion: DEC10-VEN represents an appropriate salvage therapy and may offer better responses and survival compared with IC in adults with R/R AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.33814DOI Listing
August 2021

Carbon- and metal-based mediators modulate anaerobic methanogenesis and phenol removal: Focusing on stimulatory and inhibitory mechanism.

J Hazard Mater 2021 10 10;420:126615. Epub 2021 Jul 10.

School of Environment and Nature Resources, Renmin University of China, Beijing 100872, China; Key Laboratory of Energy Resource Utilization from Agriculture Residue, Ministry of Agriculture and Rural Affairs, China. Electronic address:

In this study, anaerobic batch experiments were conducted to investigate the effect of carbon-based (biochar) and metal-based (nanoscale zero-valent iron, NZVI and zero valent iron, ZVI) mediators on the AD process treating phenolic wastewater. Fresh apricot shell- and wood-derived biochar (BiocharA, BiocharB) could remove the phenol efficiently (77.1% and 86.2%), suggesting that biodegradation cooperated with adsorption had advantage in phenol removal. BiocharB, NZVI and ZVI enhanced the methane production by 17.6%, 23.7% and 23.2%, respectively. Apart from serving as carrier for microbial growth, BiocharB might promote the direct interspecies electron transfer (DIET) since the Anaerolineaceae/Clostridium sensu stricto, which have potential for DIET, were enriched. NZVI and ZVI added systems mainly enhanced the abundance of Clostridium sensu stricto (24.5%, 37.6%) and Methanosaeta. Interestingly, BiocharA inhibited the methanogenesis completely. An inhibitory mechanism was proposed: the exposure of absorbed microbes on the BiocharA to the highly concentrated phenol in biochar' pores resulted in the inhibition of methanogens, especially for Methanosarcina. In conclusion, this study showed that suitable biochar (BiocharB) could serve as an alternative redox mediator for realizing simultaneously the efficient phenol removal and methane production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2021.126615DOI Listing
October 2021

Tungsten-Modulated Molybdenum Selenide/Graphene Heterostructure as an Advanced Electrode for All-Solid-State Supercapacitors.

Nanomaterials (Basel) 2021 Jun 2;11(6). Epub 2021 Jun 2.

The State Key Discipline Laboratory of Wide Band Gap Semiconductor Technology, Xidian University, Xi'an 710071, China.

Transition metal dichalcogenides (TMDs) have attracted widespread attention due to their excellent electrochemical and catalytic properties. In this work, a tungsten (W)-modulated molybdenum selenide (MoSe)/graphene heterostructure was investigated for application in electrochemistry. MoSe/graphene heterojunctions with low-doped W compositions were synthesized by a one-step hydrothermal catalysis approach. Based on the conducted density functional theory (DFT) calculations, it was determined that inserting a small amount of W (≈5%) into the MoSe/graphene heterostructure resulted in the modification of its lattice structure. Additionally, an increase in the distance between layers (≈8%) and a decrease in the adsorption energy of the potassium ions (K) (≈-1.08 eV) were observed following W doping. Overall, the electrochemical performance of the MoSe/graphene hybrid was enhanced by the presence of W. An all-solid-state supercapacitor device prepared using electrodes based on the W-doped MoSe/graphene composite achieved excellent capacitance of 444.4 mF cm at 1 mV s. The results obtained herein revealed that the MoSe/graphene hybrid exhibiting low W composition could be valuable in the field of energy storage and isoelectronic doping of TMDs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nano11061477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228879PMC
June 2021

Addressing patient heterogeneity in disease predictive model development.

Biometrics 2021 Jun 28. Epub 2021 Jun 28.

Department of Biostatistics, Columbia University, New York, New York, USA.

This paper addresses patient heterogeneity associated with prediction problems in biomedical applications. We propose a systematic hypothesis testing approach to determine the existence of patient subgroup structure and the number of subgroups in patient population if subgroups exist. A mixture of generalized linear models is considered to model the relationship between the disease outcome and patient characteristics and clinical factors, including targeted biomarker profiles. We construct a test statistic based on expectation maximization (EM) algorithm and derive its asymptotic distribution under the null hypothesis. An important computational advantage of the test is that the involved parameter estimates under the complex alternative hypothesis can be obtained through a small number of EM iterations, rather than optimizing the objective function. We demonstrate the finite sample performance of the proposed test in terms of type-I error rate and power, using extensive simulation studies. The applicability of the proposed method is illustrated through an application to a multicenter prostate cancer study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/biom.13514DOI Listing
June 2021

High-Quality Transferred GaN-Based Light-Emitting Diodes through Oxygen-Assisted Plasma Patterning of Graphene.

ACS Appl Mater Interfaces 2021 Jul 28;13(27):32442-32449. Epub 2021 Jun 28.

The State Key Discipline Laboratory of Wide Band Gap Semiconductor Technology, Xidian University, 710071 Shaanxi, PR China.

Two-dimensional (2D) release layers are commonly used to realize flexible nitride films. Here, high-quality, large-area, and transferable nitride films can be precisely controlled grown on O-plasma-assisted patterned graphene. The first-principles calculation indicates that the patterned graphene introduced by O plasma changes the original wettability of sapphire and the growth behavior of Al atoms is related with layer number of graphene, which is consistent with experimental results. The as-fabricated violet GaN-based light-emitting diodes (LEDs) show high stability and high light output power (LOP). This work provides a general rule for the growth of high-quality and transferable III-nitride films on graphene from the atomic scale and provide actual demonstration in LED. The advantages of the proposed new growth method can supply new ways for electronic and optoelectronic flexible devices of group III nitride semiconductors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c04659DOI Listing
July 2021

On the time-varying predictive performance of longitudinal biomarkers: Measure and estimation.

Stat Med 2021 10 22;40(23):5065-5077. Epub 2021 Jun 22.

Department of Biostatistics and Data Science, The University of Texas Health Science Center at Houston, Houston, Texas, USA.

In many biomedical studies, participants are monitored at periodic visits until the occurrence of the failure event. Biomarkers are often measured repeatedly during these visits, and such measurements can facilitate updated disease prediction. In this work, we propose a two-dimensional incident dynamic area under curve (AUC), to capture the variability due to both the biomarker assessment time and the prediction time to comprehensively quantify the predictive performance of a longitudinal biomarker. We propose a pseudo partial-likelihood to achieve consistent estimation of the AUC under two realistic scenarios of visit schedules. Variance estimation methods are designed to facilitate inferential procedures. We examine the finite-sample performance of our method through extensive simulations. The methods are applied to a study of chronic myeloid leukemia to evaluate the predictive performance of longitudinally collected gene expression levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/sim.9111DOI Listing
October 2021

Superior Pseudocapacitive Storage of a Novel NiSi/NiOOH/Graphene Nanostructure for an All-Solid-State Supercapacitor.

Nanomicro Lett 2020 Oct 27;13(1). Epub 2020 Oct 27.

The State Key Discipline Laboratory of Wide Band Gap Semiconductor Technology, Xidian University, Xi'an, 710071, People's Republic of China.

Recent developments in the synthesis of graphene-based structures focus on continuous improvement of porous nanostructures, doping of thin films, and mechanisms for the construction of three-dimensional architectures. Herein, we synthesize creeper-like NiSi/NiOOH/graphene nanostructures via low-pressure all-solid melting-reconstruction chemical vapor deposition. In a carbon-rich atmosphere, high-energy atoms bombard the Ni and Si surface, and reduce the free energy in the thermodynamic equilibrium of solid Ni-Si particles, considerably catalyzing the growth of Ni-Si nanocrystals. By controlling the carbon source content, a NiSi single crystal with high crystallinity and good homogeneity is stably synthesized. Electrochemical measurements indicate that the nanostructures exhibit an ultrahigh specific capacity of 835.3 C g (1193.28 F g) at 1 A g; when integrated as an all-solid-state supercapacitor, it provides a remarkable energy density as high as 25.9 Wh kg at 750 W kg, which can be attributed to the free-standing NiSi/graphene skeleton providing a large specific area and NiOOH inhibits insulation on the electrode surface in an alkaline solution, thereby accelerating the electron exchange rate. The growth of the high-performance composite nanostructure is simple and controllable, enabling the large-scale production and application of microenergy storage devices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40820-020-00527-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187555PMC
October 2020

GPC3 affects the prognosis of lung adenocarcinoma and lung squamous cell carcinoma.

BMC Pulm Med 2021 Jun 10;21(1):199. Epub 2021 Jun 10.

Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Nanjingbei Street, Heping District, Shenyang, 110001, Liaoning Province, China.

Background: Glypican 3 (GPC3) is a heparin sulphate proteoglycan whose expression is associated with several malignancies. However, its expression in non-small-cell lung carcinoma (NSCLC) is limited and ambiguous. This study aimed to comprehensively evaluate the expression of GPC3 in NSCLC and develop a risk-score model for predicting the prognosis of NSCLC.

Methods: The gene expression profiles of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were downloaded from the UCSC Xena database. Using the limma package, the differentially expressed genes (DEGs) between different comparison groups were analysed and the differential expression of GPC3 was calculated. A functional enrichment analysis was conducted for GPC3-associated genes using the DAVID tool. For the GPC3-associated genes shared by the four comparison groups, a protein-protein interaction network was built using the Cytoscape software. After conducting a survival analysis and a Cox regression analysis, the genes found to be significantly correlated with prognosis were selected to construct a risk-score model. Besides, the gene and protein levels of GPC3 were examined by quantitative reverse transcriptase-PCR (qRT-PCR) and immunohistochemistry (IHC) in LUSC tissues and paracancer tissues.

Results: The differential expression of GPC3 was significant (adjusted P < 0.05) in the NSCLC vs. normal, LUAD vs. normal, LUSC versus normal, and LUAD versus. LUSC comparison groups. GPC3 directly interacted with SERPINA1, MFI2, and FOXM1. Moreover, GPC3 expression was significantly correlated with pathologic N, pathologic T, gender, and tumour stage in LUAD samples. Finally, the risk-score model (involving MFI2, FOXM1, and GPC3) for LUAD and that (involving SERPINA1 and FOXM1) for LUSC were established separately. The qRT-PCR result showed that GPC3 expression was much higher in the LUSC tissues than that in the normal group. The IHC results further showed that GPC3 is highly expressed in LUSC tissues, but low in paracancer tissues.

Conclusion: The three-gene risk-score model for LUAD and the two-gene risk-score model for LUSC might be valuable in improving the prognosis of these carcinomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12890-021-01549-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194200PMC
June 2021

A Bayesian hierarchical monitoring design for phase II cancer clinical trials: Incorporating information on response duration into monitoring rules.

Stat Med 2021 09 7;40(21):4629-4639. Epub 2021 Jun 7.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.

We propose a Bayesian hierarchical monitoring design for single-arm phase II clinical trials of cancer treatments that incorporates the information on the duration of response (DOR) into the monitoring rules. To screen a new treatment by evaluating its preliminary therapeutic effect, futility monitoring rules are commonly used in phase II clinical trials to make "go/no-go" decisions timely and efficiently. These futility monitoring rules are usually focused on a single outcome (eg, response rate), although a single outcome may not adequately determine the efficacy of the experimental treatment. For example, targeted agents with a long response duration but a similar response rate may be worth further evaluation in cancer research. To address this issue, we propose Bayesian hierarchical futility monitoring rules to consider both the response rate and duration. The first level of monitoring evaluates whether the response rate provides evidence that the experimental treatment is worthy of further evaluation. If the evidence from the response rate does not support continuing the trial, the second level monitoring rule, which is based on the DOR, will be triggered. If both stopping rules are satisfied, the trial will be stopped for futility. We conducted simulation studies to evaluate the operating characteristics of the proposed monitoring rules and compared them to those of standard method. We illustrated the proposed design with a single-arm phase II cancer clinical trial to assess the safety and efficacy of combined treatment of nivolumab and azacitidine in patients with relapsed/refractory acute myeloid leukemia. The proposed design avoids an aggressive early termination for futility when the experimental treatment substantially prolongs the DOR but fails to improve the response rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/sim.9084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376777PMC
September 2021

A Signature Enrichment Design with Bayesian Adaptive Randomization.

J Appl Stat 2021 27;48(6):1091-1110. Epub 2020 Apr 27.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center.

Clinical trials in the era of precision cancer medicine aim to identify and validate biomarker signatures which can guide the assignment of individually optimal treatments to patients. In this article, we propose a group sequential randomized phase II design, which updates the biomarker signature as the trial goes on, utilizes enrichment strategies for patient selection, and uses Bayesian response-adaptive randomization for treatment assignment. To evaluate the performance of the new design, in addition to the commonly considered criteria of type I error and power, we propose four new criteria measuring the benefits and losses for individuals both inside and outside of the clinical trial. Compared with designs with equal randomization, the proposed design gives trial participants a better chance to receive their personalized optimal treatments and thus results in a higher response rate on the trial. This design increases the chance to discover a successful new drug by an adaptive enrichment strategy, i.e., identification and selective enrollment of a subset of patients who are sensitive to the experimental therapies. Simulation studies demonstrate these advantages of the proposed design. It is illustrated by an example based on an actual clinical trial in non-small-cell lung cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02664763.2020.1757048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132854PMC
April 2020

HMGB1 enhances chemotherapy resistance in multiple myeloma cells by activating the nuclear factor-κB pathway.

Exp Ther Med 2021 Jul 2;22(1):705. Epub 2021 May 2.

Department of Hematology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.

Chemotherapy resistance is a main obstacle in the clinical chemotherapeutic treatment of multiple myeloma (MM). High-mobility group box 1 (HMGB1) has been revealed to be associated with the sensitivity of MM cells to chemotherapy, but how HMGB1 regulates chemotherapy resistance in MM has yet to be fully elucidated. In the present study, the exact molecular mechanism underlying HMGB1-mediated drug resistance in MM was explored using three chemotherapy-resistant MM cells (RPMI8226/ADR, RPMI8226/BOR and RPMI8226/DEX) that were successfully established. Reverse transcription-quantitative polymerase chain reaction revealed that the three chemotherapy-resistant MM cells exhibited a higher release of HMGB1 compared with the parental RPMI8226 cells. Interference with endogenous HMGB1 increased the sensitivity of drug-resistant MM cells to chemotherapy, which was supported by the low IC value and the enlargement of cell apoptosis. Furthermore, short hairpin (sh)RNA-transfected MM cells showed an obvious elevation in phosphorylated (p)-IKKα/β, p-IκBα and p-p65 in whole cell lysate and/or nucleus, and treatment of nuclear factor (NF)-κB activator reversed the effect of shHMGB1-mediated cell viability and apoptosis in MM cells. In conclusion, HMGB1 regulates drug resistance in MM cells by regulating NF-κB signaling pathway, suggesting that HMGB1 has the potential to serve as a target for MM treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2021.10137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120504PMC
July 2021

Inotuzumab ozogamicin with bosutinib for relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia or lymphoid blast phase of chronic myeloid leukemia.

Am J Hematol 2021 08 28;96(8):1000-1007. Epub 2021 May 28.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Relapsed/refractory (R/R) Philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL) and lymphoid blast phase of chronic myeloid leukemia (LBP-CML) have poor outcomes. We designed a phase 1/2 study combining inotuzumab ozogamicin with bosutinib for this patient population. Patients with T315I mutation were excluded. Bosutinib was administered daily at three dose levels (300 mg/d, 400 mg/d, 500 mg/d) in a 3 + 3 design. Inotuzumab ozogamicin was dosed weekly during cycle one, and once every 4 weeks subsequently for a total of six cycles. The primary objective was to determine the safety and the maximum tolerated dose (MTD) of bosutinib in combination with inotuzumab ozogamicin. Eighteen patients were enrolled (Ph-positive ALL, n = 16; LBP-CML, n = 2). The median age was 62 years (range, 19-74) and the median number of prior therapies was one (range, 1-5). Dose limiting toxicities included grade 3 skin rash and bosutinib 400 mg daily was determined as the MTD. The most frequent grade 3/4 treatment-emergent adverse events were thrombocytopenia (60%) and neutropenia (38%). A complete response (CR) / CR with incomplete count recovery (CRi) was achieved in 15/18 (83%) patients; 11/18 (61%) patients achieved negative measurable residual disease by flow cytometry. Complete molecular response was noted in 10/18 (56%) patients. The 30-day mortality was 0%. After a median follow-up of 44 months, the median duration of response and overall survival were 7.7 months and 13.5 months, respectively. Six patients had a subsequent allogeneic stem cell transplant. No patient developed veno-occlusive disease. Inotuzumab ozogamicin with bosutinib was well tolerated in R/R Ph-positive ALL and LBP-CML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajh.26238DOI Listing
August 2021

Tumor Mutation Burden and Differentially Mutated Genes Among Immune Phenotypes in Patients with Lung Adenocarcinoma.

Onco Targets Ther 2021 4;14:2953-2965. Epub 2021 May 4.

Department of Medical Oncology, Shanghai Pulmonary Hospital, Shanghai, 200433, People's Republic of China.

Introduction: Nowadays, immune checkpoint blockades (ICBs) have been extensively applied in non-small cell lung cancer (NSCLC) treatment. However, the outcome of anti-program death-1/program death ligand-1 (anti-PD-1/PD-L1) therapy is not satisfying in -mutant lung adenocarcinoma (LUAD) patients and its exact mechanisms have not been fully understood. Since tumor mutation burden (TMB) and tumor immune phenotype had been thought as potential predictors for efficacy of ICBs, we further studied the TMB and immune phenotype in LUAD patients to explore potential mechanisms for poor efficacy of ICBs in positive mutated patients and to find possible factors that could impact the tumor immune phenotype which might uncover some new therapeutic strategies or combination therapies.

Methods: We enrolled 223 LUAD patients who underwent surgery in our hospital. We evaluated TMB through targeted panel sequencing. The tumor immune phenotype, which could be divided into non-inflamed, intermediate and inflamed, was determined through immunohistochemistry using formalin-fixed paraffin-embedded samples. Enumeration data were analyzed by Chi-square test or Fisher exact test and shown as number (proportion). Logistic regression model was employed for univariate and multivariate analysis of the association between TMB levels and clinical characteristics.

Results: The median TMB level was 4.0445 mutations/Mb. Multivariate analysis showed the TMB level was significantly associated with age (=0.026), gender (=0.041) and mutation status (=0.015), and in -mutant patients we found a lower proportion of patients with mutated and . Furthermore, we found patients with or without metastatic lesions would have different immune phenotype (=0.007). And the mutational frequencies of and were significantly different among three immune phenotypes.

Conclusion: Low TMB level could be the reason for the poor efficacy of ICBs in patients having mutation. And mutational frequencies of and were lower in -mutant patients. Furthermore, and might involve in the formation of immune phenotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S294993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106479PMC
May 2021

Prophylactic cranial irradiation reduces the incidence of brain metastasis in a mouse model of metastatic, HER2-positive breast cancer.

Genes Cancer 2021 13;12:28-38. Epub 2021 Mar 13.

Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Prophylactic cranial irradiation (PCI) can reduce the incidence of brain metastasis and improve overall survival in some patients with acute lymphoblastic leukemia or small-cell lung cancer. We examined the potential effects of PCI in a mouse model of breast cancer brain metastasis. The HER2+ inflammatory breast cancer cell line MDA-IBC3 was labeled with green fluorescent protein and injected via tail-vein into female SCID/Beige mice. Mice were then given 0 Gy or 4 Gy of whole-brain irradiation 2 days before tumor-cell injection or 5 days, 3 weeks, or 6 weeks after tumor-cell injection. Mice were sacrificed 4-weeks or 8-weeks after injection and brain tissues were examined for metastasis by fluorescent stereomicroscopy. In the unirradiated control group, brain metastases were present in 77% of mice at 4 weeks and in 90% of mice at 8 weeks; by comparison, rates for the group given PCI at 5 days after tumor-cell injection were 20% at 4 weeks (=0.01) and 30% at 8 weeks (=0.02). The PCI group also had fewer brain metastases per mouse at 4 weeks (=0.03) and 8 weeks (=0.006) versus the unirradiated control as well as a lower metastatic burden (=0.01). Irradiation given either before tumor-cell injection or 3-6 weeks afterward had no significant effect on brain metastases compared to the unirradiated control. These results underscore the importance of timing for irradiating subclinical disease. Clinical whole brain strategies to target subclinical brain disease as safely as possible may warrant further study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/genesandcancer.212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045965PMC
March 2021

Duration of cytopenias with concomitant venetoclax and azole antifungals in acute myeloid leukemia.

Cancer 2021 Jul 1;127(14):2489-2499. Epub 2021 Apr 1.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Venetoclax (VEN) combined with the hypomethylating agent (HMA) azacitidine improves survival in patients aged ≥75 years with newly diagnosed acute myeloid leukemia (AML). VEN and HMA treatment can result in prolonged and often profound neutropenia, and this warrants antifungal prophylaxis. Azole antifungals inhibit cytochrome P450 3A4, the primary enzyme responsible for VEN metabolism; this results in VEN dose reductions for each concomitant antifungal. Limited clinical data exist on outcomes for patients treated with VEN, an HMA, and various azoles.

Methods: The time to neutrophil recovery (absolute neutrophil count [ANC] > 1000 cells/mm ) and platelet (PLT) recovery (PLT count > 100,000 cells/mm ) in 64 patients with newly diagnosed AML who achieved a response after course 1 of VEN plus an HMA were evaluated. HMA therapy included azacitidine (75 mg/m intravenously/subcutaneously for 7 days) or decitabine (20 mg/m intravenously for 5 or 10 days).

Results: Forty-seven patients (73%) received an azole: posaconazole (n = 17; 27%), voriconazole (n = 9; 14%), isavuconazole (n = 20; 31%), or fluconazole (n = 1; 2%). The median time to ANC recovery were similar for patients who did receive an azole (37 days; 95% confidence interval [CI], 34-38 days) and patients who did not receive an azole (39 days; 95% CI, 30 days to not estimable; P = .8). The median time to PLT recovery was significantly longer for patients receiving azoles (28 vs 22 days; P = .01). The median times to ANC recovery (35 vs 38 days) and PLT recovery (26 vs 32 days) were similar with posaconazole and voriconazole.

Conclusions: VEN plus an HMA resulted in neutropenia and thrombocytopenia, with the latter prolonged in patients receiving concomitant azoles. Concomitant posaconazole or voriconazole and VEN (100 mg) resulted in similar ANC and PLT recovery times, suggesting the safety of these dosage combinations during course 1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.33508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249340PMC
July 2021

Prognostic value of measurable residual disease after venetoclax and decitabine in acute myeloid leukemia.

Blood Adv 2021 04;5(7):1876-1883

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX.

Assessment of measurable residual disease (MRD) provides prognostic information in acute myeloid leukemia (AML). However, the utility of MRD with venetoclax-based lower intensity regimens is unknown. We analyzed the prognostic value of achieving a negative MRD in older/"unfit" patients with AML receiving first-line therapy with 10-day decitabine and venetoclax. MRD was evaluated in bone marrow specimens using multicolor flow cytometry (sensitivity 0.1%). Ninety-seven patients achieving either a complete remission (CR) or CR with incomplete hematologic recovery (CRi) or morphologic leukemia-free state were included. Median age was 72 years (interquartile range, 68-78 years), and 64% had adverse-risk AML. Eighty-three patients achieved CR/CRi, and 52 (54%) became MRD negative. Median time to becoming MRD negative was 2.0 months (interquartile range, 0.9-3.1 months). Patients becoming MRD negative by 2 months had longer relapse-free survival (RFS) compared with those remaining MRD positive (median RFS, not reached vs 5.2 months; hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.12-0.78; P = .004), longer event-free survival (EFS) (median EFS, not reached vs 5.8 months; HR, 0.25; 95% CI, 0.12-0.55; P < .001), as well as longer overall survival (OS) (median OS, 25.1 vs 7.1 months; HR, 0.23; 95% CI, 0.11-0.51; P < .001). Patients achieving an MRD-negative CR had longer OS compared with those with an inferior response (median OS, 25.1 vs 11.6 months; HR, 0.33; 95% CI, 0.19-0.58; P < .0005). Patients becoming MRD negative within 1 month had an improved OS compared with MRD-positive patients (median OS, 25.1 vs 3.4 months; HR, 0.15; 95% CI, 0.03-0.64; P < .0001). Differential impact of MRD status on survival outcomes persisted at a later 4-month time point of evaluation. In conclusion, MRD-negative status at 1, 2, and 4 months after starting therapy confers significantly better survival in older/unfit patients with AML receiving first-line therapy with 10-day decitabine and venetoclax. This trial was registered at www.clinicaltrials.gov as #NCT03404193.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2020003717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045494PMC
April 2021

Amentoflavone from Selaginella tamariscina as a potent inhibitor of gut bacterial β-glucuronidase: Inhibition kinetics and molecular dynamics stimulation.

Chem Biol Interact 2021 May 27;340:109453. Epub 2021 Mar 27.

Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention, College of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian, China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. Electronic address:

Gut bacterial β-glucuronidase (GUS) plays a pivotal role in the metabolism and reactivation of a vast of glucuronide conjugates of both endogenous and xenobiotic compounds in the gastrointestinal tract of human, which has been implicated in certain drug-induced gastrointestinal tract (GI) toxicity in clinic. Inhibitors of gut microbial GUS exhibited great potentials in relieving the drug-induced GI toxicity. In this study, Selaginella tamariscina and its major biflavonoid amentoflavone (AMF) were evaluated for their inhibitory activity against Escherichia coli GUS. Two selective probe substrates for GUS (a specific fluorescent probe substrate for GUS, DDAOG and a classical drug substrate for GUS, SN38G) were used in parallel for charactering the inhibition behaviors. Both the extract of S. tamariscina and its major biflavonoid AMF displayed evident inhibitory effects on GUS, and the IC values of AMF against GUS mediated DDAOG and SN-38G hydrolysis were 0.62 and 0.49 μM, respectively. Inhibition kinetics studies indicated that AMF showed mixed type inhibition for GUS-mediated DDAOG hydrolysis, while displayed competitive type inhibition against GUS-mediated SN-38G hydrolysis, with the K values of 0.24 and 1.25 μM, respectively. Molecular docking studies and molecular dynamics stimulation results clarified the role of amino acid residues Leu361, Ile363, and Glu413 in the inhibition of AMF on GUS. These results provided some foundations for the potential clinical utility of S. tamariscina and its major biflavonoid AMF for treating drug-induced enteropathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cbi.2021.109453DOI Listing
May 2021
-->