Publications by authors named "Yichen Zhang"

61 Publications

Understanding the patient journey to diagnosis of lung cancer.

BMC Cancer 2021 Apr 14;21(1):402. Epub 2021 Apr 14.

Department of Health Policy and Management, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal Street, Suite 1900, New Orleans, LA, 70112, USA.

Objective: This research describes the clinical pathway and characteristics of two cohorts of patients. The first cohort consists of patients with a confirmed diagnosis of lung cancer while the second consists of patients with a solitary pulmonary nodule (SPN) and no evidence of lung cancer. Linked data from an electronic medical record and the Louisiana Tumor Registry were used in this investigation.

Materials And Methods: REACHnet is one of 9 clinical research networks (CRNs) in PCORnet®, the National Patient-Centered Clinical Research Network and includes electronic health records for over 8 million patients from multiple partner health systems. Data from Ochsner Health System and Tulane Medical Center were linked to Louisiana Tumor Registry (LTR), a statewide population-based cancer registry, for analysis of patient's clinical pathways between July 2013 and 2017. Patient characteristics and health services utilization rates by cancer stage were reported as frequency distributions. The Kaplan-Meier product limit method was used to estimate the time from index date to diagnosis by stage in lung cancer cohort.

Results: A total of 30,559 potentially eligible patients were identified and 2929 (9.58%) had primary lung cancer. Of these, 1496 (51.1%) were documented in LTR and their clinical pathway to diagnosis was further studied. Time to diagnosis varied significantly by cancer stage. A total of 24,140 patients with an SPN were identified in REACHnet and 15,978 (66.6%) had documented follow up care for 1 year. 1612 (10%) had no evidence of any work up for their SPN. The remaining 14,366 had some evidence of follow up, primarily office visits and additional chest imaging.

Conclusion: In both cohorts multiple biopsies were evident in the clinical pathway. Despite clinical workup, 70% of patients in the lung cancer cohort had stage III or IV disease. In the SPN cohort, only 66% were identified as receiving a diagnostic work-up.
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http://dx.doi.org/10.1186/s12885-021-08067-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045203PMC
April 2021

3D printed silk-gelatin hydrogel scaffold with different porous structure and cell seeding strategy for cartilage regeneration.

Bioact Mater 2021 Oct 19;6(10):3396-3410. Epub 2021 Mar 19.

National Engineering Research Center for Tissue Restoration and Reconstruction (NERC-TRR), South China University of Technology, Guangzhou, GuangDong, 510641, China.

Hydrogel scaffolds are attractive for tissue defect repair and reorganization because of their human tissue-like characteristics. However, most hydrogels offer limited cell growth and tissue formation ability due to their submicron- or nano-sized gel networks, which restrict the supply of oxygen, nutrients and inhibit the proliferation and differentiation of encapsulated cells. In recent years, 3D printed hydrogels have shown great potential to overcome this problem by introducing macro-pores within scaffolds. In this study, we fabricated a macroporous hydrogel scaffold through horseradish peroxidase (HRP)-mediated crosslinking of silk fibroin (SF) and tyramine-substituted gelatin (GT) by extrusion-based low-temperature 3D printing. Through physicochemical characterization, we found that this hydrogel has excellent structural stability, suitable mechanical properties, and an adjustable degradation rate, thus satisfying the requirements for cartilage reconstruction. Cell suspension and aggregate seeding methods were developed to assess the inoculation efficiency of the hydrogel. Moreover, the chondrogenic differentiation of stem cells was explored. Stem cells in the hydrogel differentiated into hyaline cartilage when the cell aggregate seeding method was used and into fibrocartilage when the cell suspension was used. Finally, the effect of the hydrogel and stem cells were investigated in a rabbit cartilage defect model. After implantation for 12 and 16 weeks, histological evaluation of the sections was performed. We found that the enzymatic cross-linked and methanol treatment SFGT hydrogel combined with cell aggregates promoted articular cartilage regeneration. In summary, this 3D printed macroporous SF-GT hydrogel combined with stem cell aggregates possesses excellent potential for application in cartilage tissue repair and regeneration.
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http://dx.doi.org/10.1016/j.bioactmat.2021.03.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010633PMC
October 2021

Unidimensional Two-Way Continuous-Variable Quantum Key Distribution Using Coherent States.

Entropy (Basel) 2021 Feb 27;23(3). Epub 2021 Feb 27.

State Key Laboratory of Information Photonics and Optical Communications, School of Electronic Engineering, Beijing University of Posts and Telecommunications, Beijing 100876, China.

We propose a unidimensional two-way continuous-variable quantum key distribution protocol with coherent states, where the sender modulates a single quadrature of the coherent states rather than both quadratures to simplify the structure of a two-way system. Security analysis is performed with a general attack strategy, known as two-mode attack, which helps to reduce limitations in the analysis. The performance of the protocol under all accessible two-mode attacks at fixed distance is illustrated. Further, two typical two-mode attack strategies are obtained from it, which are one-mode attack strategy and optimal two-mode attack strategy. Between them, the one-mode attack is the simplest form of the two-mode attack, while the optimal two-mode attack is the most complicated one. Simulations show that though the system is simplified, the performance of the two-way protocol with unidimensional modulation is still comparable to that of the counterpart with Gaussian modulation even against the optimal two-mode attack when Eve's ability is maximized. Thus, the proposed protocol simplifies the two-way system while guaranteeing its performance to a certain extent. Especially in a practical system with short transmission distance and high excess noise, the protocol has a good application prospect.
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http://dx.doi.org/10.3390/e23030294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997235PMC
February 2021

Biopsy frequency and complications among lung cancer patients in the United States.

Lung Cancer Manag 2020 Aug 17;9(4):LMT40. Epub 2020 Aug 17.

Intuitive, 1020 Kifer Road, Sunnyvale, CA 94086, USA.

Objective: This study aimed to describe the frequency and distribution of biopsy procedures for patients diagnosed and treated for primary lung cancer.

Study Design: Retrospective cohort study within an administrative database.

Materials & Methods: This observational study used data from the IBM MarketScan Databases between 2013 and 2015.

Results: The total number of lung biopsies performed among eligible subjects was 32,814; an average of 1.7 biopsies per patient. Bronchoscopy and percutaneous approaches accounted for 95% of all procedures. Complication rates by procedure are remarkably similar irrespective of biopsy frequency.

Conclusion: Nearly half (46%) of patients in this population experienced multiple biopsies prior to diagnosis. Further, biopsy choice or sequence in patients receiving multiple procedures was unpredictable.
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http://dx.doi.org/10.2217/lmt-2020-0022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729592PMC
August 2020

A Gaussian-Distributed Quantum Random Number Generator Using Vacuum Shot Noise.

Entropy (Basel) 2020 Jun 2;22(6). Epub 2020 Jun 2.

Department of Electronics, and Center for Quantum Information Technology, State Key Laboratory of Advanced Optical Communication Systems and Networks, Peking University, Beijing 100871, China.

Among all the methods of extracting randomness, quantum random number generators are promising for their genuine randomness. However, existing quantum random number generator schemes aim at generating sequences with a uniform distribution, which may not meet the requirements of specific applications such as a continuous-variable quantum key distribution system. In this paper, we demonstrate a practical quantum random number generation scheme directly generating Gaussian distributed random sequences based on measuring vacuum shot noise. Particularly, the impact of the sampling device in the practical system is analyzed. Furthermore, a related post-processing method, which maintains the fine distribution and autocorrelation properties of raw data, is exploited to extend the precision of generated Gaussian distributed random numbers to over 20 bits, making the sequences possible to be utilized by the following system with requiring high precision numbers. Finally, the results of normality and randomness tests prove that the generated sequences satisfy Gaussian distribution and can pass the randomness testing well.
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http://dx.doi.org/10.3390/e22060618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517154PMC
June 2020

Sending-or-Not-Sending Twin-Field Quantum Key Distribution with Light Source Monitoring.

Entropy (Basel) 2019 Dec 26;22(1). Epub 2019 Dec 26.

State Key Laboratory of Advanced Optical Communication, Systems and Networks, Department of Electronics, and Center for Quantum Information Technology, Peking University, Beijing 100871, China.

Twin-field quantum key distribution (TF-QKD) is proposed to achieve a remote key distribution with a maximum secure transmission distance up to over 500 km. Although the security of TF-QKD in its detection part is guaranteed, there are some remaining problems in the source part. The sending-or-not-sending (SNS) protocol is proposed to solve the security problem in the phase post-selection process; however, the light source is still assumed to be an ideal coherent state. This assumption is not satisfied in real-life QKD systems, leading to practical secure issues. In this paper, we discuss the condition that the photon number distribution (PND) of the source is unknown for the SNS protocol, demonstrate that the security analysis is still valid under a source with unknown PND, and show that with light source monitoring, the performance of the SNS protocol can remain almost unchanged.
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http://dx.doi.org/10.3390/e22010036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516458PMC
December 2019

Tough thermoplastic hydrogels with re-processability and recyclability for strain sensors.

J Mater Chem B 2021 01 25;9(1):176-186. Epub 2020 Nov 25.

School of Materials Science and Engineering, South China University of Technology, Guangzhou 510006, P. R. China.

Tough hydrogels with the ability to be repeatedly processed into various shapes as thermoplastics are highly desired in advanced medical devices and tissue engineering. Here, we have developed a kind of versatile supramolecular hydrogel with a network cross-linked by double hydrogen bonds from poly(N-acryloyl glycinamide) (PNAGA). The resulting PNAGA-30 hydrogels (30 wt% solid content) are tough, re-processable, and recyclable similar to thermoplastics. The hydrogels in the form of fragments can be easily re-processed into various shapes including sheet, filament, cylinder and other complex shapes by using simple stamping and injection methods. The mechanical properties of the re-programed hydrogels are comparable to the properties of the original hydrogels. The re-processability and robust mechanical properties of the PNAGA hydrogels are promising for practical applications in soft materials, tissue engineering and wearable devices. Furthermore, the PNAGA-30&LiCl ionic hydrogels can be fabricated by simply compositing LiCl into thermoplastic hydrogels. The PNAGA-30&LiCl hydrogels can function as multifunctional strain sensors to monitor large human movements and tiny vibrations, thereby showing great application potential in robotics, biomedical prosthetics, personal healthcare monitoring and so on.
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http://dx.doi.org/10.1039/d0tb02049dDOI Listing
January 2021

Specific white matter connectomic changes in schizophrenia compared with psychotic bipolar disorder.

Asian J Psychiatr 2021 Jan 2;55:102468. Epub 2020 Nov 2.

Department of Psychiatry, the Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong Province, 510630, China. Electronic address:

Background: Schizophrenia (SZ) and bipolar disorder with psychosis (BDP) can be clinically confusing. The specific connectomic changes in SZ compared with BDP may lead to a deeper comprehension of the pathophysiological core of SZ. Therefore, this study explored the common and distinct white matter (WM) structural connectomic alterations between these two diseases.

Method: Diffusion tensor imaging data were collected from 19 drug-naïve patients with first episode SZ, 19 drug-naïve patients with BDP, and 19 healthy controls (HC). A graph theoretical approach was used to assess the brain WM network properties.

Results: Except for the clustering coefficients, no significant differences in the global parameters was found between SZ and BDP. Five brain regions, the right precentral, right post-cingulum, right insula, left superior occipital, and left inferior temporal gyri, showed specific differences in the nodal parameters in SZ compared with BDP and HC. Nine brain regions, the left rectus, left lingual, right inferior parietal, left superior temporal, right precentral, right postcentral, bilateral middle frontal, and right post-cingulum gyri, showed specific differences in the nodal parameters in BDP. Significant correlations between clinical symptoms and connectomic changes were detected in the right insula and left superior occipital gyrus in patients with SZ but in the left lingual gyrus in patients with BDP.

Conclusions: Identifying shared and distinct WM structural networks between SZ and BDP may improve the understanding of the neuroanatomy of mental diseases. Specifically, the insula, the inferior temporal, superior temporal, and the lingual gyri may help to distinguish between SZ and BDP.
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http://dx.doi.org/10.1016/j.ajp.2020.102468DOI Listing
January 2021

High-speed Gaussian-modulated continuous-variable quantum key distribution with a local local oscillator based on pilot-tone-assisted phase compensation.

Opt Express 2020 Oct;28(22):32882-32893

A high-speed Gaussian-modulated continuous-variable quantum key distribution (CVQKD) with a local local oscillator (LLO) is experimentally demonstrated based on pilot-tone-assisted phase compensation. In the proposed scheme, the frequency-multiplexing and polarization-multiplexing techniques are used for the separate transmission and heterodyne detection between quantum signal and pilot tone, guaranteeing no crosstalk from strong pilot tone to weak quantum signal and different detection requirements of low-noise for quantum signal and high-saturation limitation for pilot tone. Moreover, compared with the conventional CVQKD based on homodyne detection, the proposed LLO-CVQKD scheme can measure X and P quadrature simultaneously using heterodyne detection without need of extra random basis selection. Besides, the phase noise, which contains the fast-drift phase noise due to the relative phase of two independent lasers and the slow-drift phase noise introduced by quantum channel disturbance, has been compensated experimentally in real time, so that a low level of excess noise with a 25 km optical fiber channel (with 5 dB loss) is obtained for the achievable secure key rate of 7.04 Mbps in the asymptotic regime and 1.85 Mbps under the finite-size block of 10.
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http://dx.doi.org/10.1364/OE.404611DOI Listing
October 2020

Bias-free source-independent quantum random number generator.

Opt Express 2020 Jul;28(15):22388-22398

A bias-free source-independent quantum random number generator scheme based on the measurement of vacuum fluctuation is proposed to realize the effective elimination of system bias and common mode noise introduced by the local oscillator. Optimal parameter settings are derived to avoid the system recording two canonically conjugate quadratures simultaneously in each measurement. In particular, it provides a new approach to investigate the performance difference between measuring two quadratures of equal and unequal intensity. It is experimentally demonstrated that the system supports 4.2 Gbps bias-free source-independent random number generation, where its common mode rejection ratio reaches 61.17 dB. Furthermore, the scheme offers an all-optical method facilitating the integration of source-independent quantum random number generators into compact chips.
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http://dx.doi.org/10.1364/OE.396461DOI Listing
July 2020

Long-Distance Continuous-Variable Quantum Key Distribution over 202.81 km of Fiber.

Phys Rev Lett 2020 Jul;125(1):010502

State Key Laboratory of Advanced Optical Communication Systems and Networks, Department of Electronics, and Center for Quantum Information Technology, Peking University, Beijing 100871, China.

Quantum key distribution provides secure keys resistant to code-breaking quantum computers. The continuous-variable version of quantum key distribution offers the advantages of higher secret key rates in metropolitan areas, as well as the use of standard telecom components that can operate at room temperature. However, the transmission distance of these systems (compared with discrete-variable systems) are currently limited and considered unsuitable for long-distance distribution. Herein, we report the experimental results of long distance continuous-variable quantum key distribution over 202.81 km of ultralow-loss optical fiber by suitably controlling the excess noise and employing highly efficient reconciliation procedures. This record-breaking implementation of the continuous-variable quantum key distribution doubles the previous distance record and shows the road for long-distance and large-scale secure quantum key distribution using room-temperature standard telecom components.
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http://dx.doi.org/10.1103/PhysRevLett.125.010502DOI Listing
July 2020

Oxygen reduction reaction electrocatalysis inducing Fenton-like processes with enhanced electrocatalytic performance based on mesoporous ZnO/CuO cathodes: Treatment of organic wastewater and catalytic principle.

Chemosphere 2020 Nov 20;259:127463. Epub 2020 Jun 20.

School of Chemistry and Chemical Engineering, Xi'an University of Architecture and Technology, Xi'an, 710055, China.

To treat typical organic wastewater efficiently, a novel Fenton-like processes based on ZnO/CuO composite cathode induced by oxygen reduction reaction (ORR) electrocatalysis with enhanced electrocatalytic performance was established successfully. Electrochemical testing investigation indicated that the ZnO/CuO cathode possessed conspicuous redox peak and better conductivity than uncompounded electrodes. Additionally, the removal efficiency of methylene blue and its chemical oxygen demand (COD) reached 96.4% and 70.8% after 120 min, respectively. Next, the feasibility of the material in practical application was also discussed. Subsequently, electrocatalytic principle based on valence state changes of metal elements on the electrode surface were also studied by x-ray photoelectron spectroscopy (XPS). Redox reactions between the active species HO and the species Cu promoting Fenton-like processes were deduced. Namely, the conversion of Cu(I) and Cu(II) on the electrode surface was accompanied by OH generation. The combination of ZnO and CuO improved the surface morphology, increasing the active site of ORR and the yield of HO, thus greatly enhanced the Fenton-like activity. Finally, the main intermediates were identified by Gas chromatography-mass spectrometer (GC-MS), and possible pathways for dye degradation were proposed. In short, the research of ZnO/CuO cathode provided great significance for heterogeneous Fenton-like degradation and also showed its application potential in water treatment and remediation.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127463DOI Listing
November 2020

Femoral bone mineral density distribution is dominantly regulated by strain energy density in remodeling.

Biomed Mater Eng 2020 ;31(3):179-190

Department of Mechanical Engineering, University of Manitoba, Winnipeg, Canada.

Background: It is well known that there is a relationship between bone strength and the forces that are daily applied to the bone. However, bone is a highly heterogeneous material and it is still not clear how mechanical variables regulate the distribution of bone mass in a femur.

Methods: We studied the role of four mechanical variables, i.e. principal tensile/compressive stress, von Mises stress, and strain energy density (SED), in the regulation of bone mineral density (BMD) distribution in the human femur. The actual BMD in a femur was extracted from quantitative computed tomography (QCT) and used as a reference for comparison. A finite element model of the femur was constructed from the same set of QCT scans and then used in iterative simulations of femur remodeling under stance and walking loading. The finite element model was initially assigned a homogeneous BMD distribution. During the remodeling, femur BMD was locally modified according to one of the four mechanical variables. The simulations were stopped when BMD change in two consecutive iterations was adequately small. The four simulated BMD patterns were then compared with the actual BMD.

Results: It was found that the BMD pattern regulated by SED had the best similarity with the actual BMD. The medullary canal was successfully reproduced by simulated remodeling, indicating that in addition to its biological functions, the medullary canal has important biomechanical functions.

Conclusions: Both the actual and simulated BMD distributions showed that the proximal femur has much lower BMD than the femur shaft, which may explain why hip fractures most often occur at the proximal femur.
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http://dx.doi.org/10.3233/BME-206000DOI Listing
January 2020

Continuous-variable source-device-independent quantum key distribution against general attacks.

Sci Rep 2020 Apr 21;10(1):6673. Epub 2020 Apr 21.

State Key Laboratory of Advanced Optical Communication Systems and Networks, Department of Electronics, and Center for Quantum Information Technology, Peking University, Beijing, 100871, China.

The continuous-variable quantum key distribution with entanglement in the middle, a semi-device-independent protocol, places the source at the untrusted third party between Alice and Bob, and thus has the advantage of high levels of security with the purpose of eliminating the assumptions about the source device. However, previous works considered the collective-attack analysis, which inevitably assumes that the states of the source has an identical and independently distributed (i.i.d) structure, and limits the application of the protocol. To solve this problem, we modify the original protocol by exploiting an energy test to monitor the potential high energy attacks an adversary may use. Our analysis removes the assumptions of the light source and the modified protocol can therefore be called source-device-independent protocol. Moreover, we analyze the security of the continuous-variable source-device-independent quantum key distribution protocol with a homodyne-homodyne structure against general coherent attacks by adapting a state-independent entropic uncertainty relation. The simulation results indicate that, in the universal composable security framework, the protocol can still achieve high key rates against coherent attacks under the condition of achievable block lengths.
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http://dx.doi.org/10.1038/s41598-020-63024-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174339PMC
April 2020

Entecavir prophylaxis for hepatitis B virus reactivation in patients with CAR T-cell therapy.

Blood 2020 07;136(4):516-519

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei China.

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http://dx.doi.org/10.1182/blood.2020004907DOI Listing
July 2020

Revealing Fine Structures of the Retinal Receptive Field by Deep-Learning Networks.

IEEE Trans Cybern 2020 Mar 10. Epub 2020 Mar 10.

Deep convolutional neural networks (CNNs) have demonstrated impressive performance on many visual tasks. Recently, they became useful models for the visual system in neuroscience. However, it is still not clear what is learned by CNNs in terms of neuronal circuits. When a deep CNN with many layers is used for the visual system, it is not easy to compare the structure components of CNNs with possible neuroscience underpinnings due to highly complex circuits from the retina to the higher visual cortex. Here, we address this issue by focusing on single retinal ganglion cells with biophysical models and recording data from animals. By training CNNs with white noise images to predict neuronal responses, we found that fine structures of the retinal receptive field can be revealed. Specifically, convolutional filters learned are resembling biological components of the retinal circuit. This suggests that a CNN learning from one single retinal cell reveals a minimal neural network carried out in this cell. Furthermore, when CNNs learned from different cells are transferred between cells, there is a diversity of transfer learning performance, which indicates that CNNs are cell specific. Moreover, when CNNs are transferred between different types of input images, here white noise versus natural images, transfer learning shows a good performance, which implies that CNNs indeed capture the full computational ability of a single retinal cell for different inputs. Taken together, these results suggest that CNNs could be used to reveal structure components of neuronal circuits, and provide a powerful model for neural system identification.
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http://dx.doi.org/10.1109/TCYB.2020.2972983DOI Listing
March 2020

EQ-5D-3L Decrements by Diabetes Complications and Comorbidities in China.

Diabetes Ther 2020 Apr 9;11(4):939-950. Epub 2020 Mar 9.

Department of Health Policy and Management, Tulane University, New Orleans, LA, 70112, USA.

Introduction: Patients with type 2 diabetes have lower quality of life, which is further impaired by diabetes complications and comorbidities. This study aims to evaluate the impact of diabetes complications and comorbidities on EuroQol Five-Dimension Three-Level (EQ-5D-3L) scores among patients with type 2 diabetes with ongoing oral drug treatments in China.

Methods: This retrospective cross-sectional analysis included 9570 patients with type 2 diabetes on oral drug treatments, who were enrolled from 75 hospitals in nine cities in China. Patient characteristics, including demographic data, health conditions, oral treatment history, and health insurance coverage, were collected through self-reported questionnaires. Health utility was measured by the EQ-5D-3L scale in the questionnaire and a Chinese version of the EQ-5D-3L scoring weights was applied in the analysis. The associations between complications and health utility were assessed using linear regression.

Results: A total of 7081 patients with complete survey data were included in the analytic sample; 3479 (49.13%) patients were female. The mean age was 59.6 years old, with a standard deviation (SD) of 12.64. The average duration with type 2 diabetes was 7.91 (SD = 6.22) years. A total of 5189 (73.28%) patients reported complications. Hypertension (51.25%) and hyperlipidemia (28.90%) were the most common complications. Other complications reported by patients included cardiovascular disease, stroke, retinopathy, nephropathy, diabetic foot, and hypoglycemia. On average, each patient had 1.54 complications. All complications and comorbidities decreased the EQ-5D-3L score. Among patients with complications, the worst effect on EQ-5D-3L score was caused by diabetic foot, decreasing by 0.118 (p < 0.001), followed by stroke (decreasing by 0.101, p < 0.001) and nephropathy (decreasing by 0.058, p < 0.001).

Conclusion: The diabetes complications and comorbidities among patients with type 2 diabetes were associated with poor health utility scores, especially for those with diabetic foot, stroke, and nephropathy.
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http://dx.doi.org/10.1007/s13300-020-00788-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136375PMC
April 2020

Reconstruction of natural visual scenes from neural spikes with deep neural networks.

Neural Netw 2020 May 8;125:19-30. Epub 2020 Feb 8.

Centre for Systems Neuroscience, Department of Neuroscience, Psychology and Behavior, University of Leicester, Leicester, UK. Electronic address:

Neural coding is one of the central questions in systems neuroscience for understanding how the brain processes stimulus from the environment, moreover, it is also a cornerstone for designing algorithms of brain-machine interface, where decoding incoming stimulus is highly demanded for better performance of physical devices. Traditionally researchers have focused on functional magnetic resonance imaging (fMRI) data as the neural signals of interest for decoding visual scenes. However, our visual perception operates in a fast time scale of millisecond in terms of an event termed neural spike. There are few studies of decoding by using spikes. Here we fulfill this aim by developing a novel decoding framework based on deep neural networks, named spike-image decoder (SID), for reconstructing natural visual scenes, including static images and dynamic videos, from experimentally recorded spikes of a population of retinal ganglion cells. The SID is an end-to-end decoder with one end as neural spikes and the other end as images, which can be trained directly such that visual scenes are reconstructed from spikes in a highly accurate fashion. Our SID also outperforms on the reconstruction of visual stimulus compared to existing fMRI decoding models. In addition, with the aid of a spike encoder, we show that SID can be generalized to arbitrary visual scenes by using the image datasets of MNIST, CIFAR10, and CIFAR100. Furthermore, with a pre-trained SID, one can decode any dynamic videos to achieve real-time encoding and decoding of visual scenes by spikes. Altogether, our results shed new light on neuromorphic computing for artificial visual systems, such as event-based visual cameras and visual neuroprostheses.
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http://dx.doi.org/10.1016/j.neunet.2020.01.033DOI Listing
May 2020

Differences in reimbursement listing of anticancer therapies in China: an observational study.

BMJ Open 2020 01 6;10(1):e031203. Epub 2020 Jan 6.

Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA.

Objective: Access to highly priced anticancer medications usually requires insurance coverage. A first step towards coverage of such medications is their inclusion in reimbursement lists. We assessed listing for reimbursement in China between 2009 and 2018 of anticancer medications on the WHO's Essential Medicines List.

Setting And Study Design: Using publicly available data, we assessed which anticancer medications listed in the 20th WHO Model List of Essential Medicines (EML) were included in China's National Reimbursement Drug List (NRDL). For five targeted anticancer medications on the WHO EML, we also assessed inclusion in the 31 Chinese Provincial Reimbursement Drug Lists (PRDLs). Logistic regression was used to test whether inclusion of targeted anticancer medications was associated with provincial economic levels.

Primary Outcome Measures: Inclusion of five targeted anticancer medications in the NRDL and PRDLs before and after 2017.

Results: The 2017 NRDL included all anticancer medications on the WHO EML (except for one not approved in China at the time), and by 2018, all 31 PRDLs listed the targeted anticancer medications except for nilotinib; four provinces had covered all five targeted medications before the 2017 NRDL coverage mandate. Provincial economic level and regional incidence of specific cancers seemed unrelated to the inclusion of five targeted anticancer medications in PRDLs.

Conclusion: Our findings suggest that by including medications in the national and provincial reimbursement lists, China has taken an important first step in promoting access to targeted anticancer medications. Further research is needed to determine whether inclusion in PRDLs improved the availability, appropriate use and affordability of highly priced targeted anticancer medications in China.
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http://dx.doi.org/10.1136/bmjopen-2019-031203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955534PMC
January 2020

In Situ Proteolysis Condition-Induced Crystallization of the XcpVWX Complex in Different Lattices.

Int J Mol Sci 2020 Jan 2;21(1). Epub 2020 Jan 2.

Department of Biomedical and Molecular Sciences, Queen's University, 18 Stuart Street, Kingston, ON K7L 3N6, Canada.

Although prevalent in the determination of protein structures; crystallography always has the bottleneck of obtaining high-quality protein crystals for characterizing a wide range of proteins; especially large protein complexes. Stable fragments or domains of proteins are more readily to crystallize; which prompts the use of in situ proteolysis to remove flexible or unstable structures for improving crystallization and crystal quality. In this work; we investigated the effects of in situ proteolysis by chymotrypsin on the crystallization of the XcpVWX complex from the Type II secretion system of . Different proteolysis conditions were found to result in two distinct lattices in the same crystallization solution. With a shorter chymotrypsin digestion at a lower concentration; the crystals exhibited a P3 hexagonal lattice that accommodates three complex molecules in one asymmetric unit. By contrast; a longer digestion with chymotrypsin of a 10-fold higher concentration facilitated the formation of a compact P222 orthorhombic lattice with only one complex molecule in each asymmetric unit. The molecules in the hexagonal lattice have shown high atomic displacement parameter values compared with the ones in the orthorhombic lattice. Taken together; our results clearly demonstrate that different proteolysis conditions can result in the generation of distinct lattices in the same crystallization solution; which can be exploited in order to obtain different crystal forms of a better quality.
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http://dx.doi.org/10.3390/ijms21010308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981927PMC
January 2020

Removing tetracycline and Hg(II) with ball-milled magnetic nanobiochar and its potential on polluted irrigation water reclamation.

J Hazard Mater 2020 02 24;384:121095. Epub 2019 Aug 24.

Key Laboratory of Plant Nutrition and the Agri-environment in Northwest China, Ministry of Agriculture, College of Natural Resources & Environment, Northwest A&F University, Yangling, Shaanxi 712100, China.

The feasibility of ball-milled magnetic nanobiochars (BMBCs) derived from wheat straw for adsorptive removal of tetracycline (TC) and Hg(II) from aqueous solution was assessed against that of pristine magnetic biochars (PMBCs). Ball milling conversion of PMBCs into BMBCs greatly improved TC and Hg(II) removal, and ≥ 99% TC and Hg(II) were adsorbed by BMBC prepared at 700 °C (BMBC700) within 12 h. The maximum adsorptive removal capacities of BMBC700 for TC and Hg(II) were 268.3 and 127.4 mg/g, respectively. The amounts of TC and Hg(II) removed by BMBC700 decreased gradually as the ionic strength of the solution increased, but increased as the solution temperature increased from 25 to 45 °C. The further FTIR and XPS analysis confirmed removal of TC was predominately regulated by the combination of electrostatic interactions, hydrogen bonds, and Cπ-Cπ interaction, while, the adsorption of Hg(II) was mainly governed by several mechanisms, including electrostatic attractions, Hg-Cπ bond formation, and surface complexation. Overall, BMBC700 presented great potential for TC and Hg(II) removal from polluted irrigation water and exhibited acceptable recyclability performance as well as magnetic separation advantage in use.
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http://dx.doi.org/10.1016/j.jhazmat.2019.121095DOI Listing
February 2020

Structure-Dependent Modulation of Substrate Binding and Biodegradation Activity of Pirin Proteins toward Plant Flavonols.

ACS Chem Biol 2019 12 23;14(12):2629-2640. Epub 2019 Oct 23.

Department of Biomedical and Molecular Sciences , Queen's University , Kingston , Ontario K7L 3N6 , Canada.

Pirin is a nonheme metalloprotein that occurs widely in human tissues and is highly conserved across all taxa. Pirin proteins typically function as nuclear transcription regulators, but two Pirin orthologs, YhhW (from ) and hPirin (from humans) were revealed to possess enzymatic activity of degrading quercetin. The exact role of Pirin homologues and their catalytic specificity remain poorly understood. In this work, by screening against a panel of plant flavonoids, we found that both Pirins catalyze the oxidative degradation of a wide spectrum of flavonol analogues and release carbon monoxide (CO) in the process. This shows that Pirin acts on a broad range of substrates and could represent a novel dietary source of CO . Although the kinetic profiles differ substantially between two Pirins, the identified substrate structures all share a 2,3-double bond and 3-hydroxyl and 4-oxo groups on their "flavonol backbone," which contribute to the specific enzyme-substrate interaction. While hPirin is iron-dependent, YhhW is identified as a novel nickel-containing dioxygenase member of the bicupin family. Besides the expanded Pirin activity, we present the crystal structures of the native Ni-YhhW and tag-free Fe-hPirin, revealing the distinctive differences occurring at the metal-binding site. In addition, YhhW features a flexible Ω-loop near the catalytic cavity, which may help stabilize the reaction intermediates via a Ni-flavonol complex. The structure-dependent modulation of substrate binding to the catalytic cavity adds to understanding the differential dispositions of natural flavonols by human and bacterial Pirins.
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http://dx.doi.org/10.1021/acschembio.9b00575DOI Listing
December 2019

Risk Assessment of An Earthquake-Collapse-Landslide Disaster Chain by Bayesian Network and Newmark Models.

Int J Environ Res Public Health 2019 09 10;16(18). Epub 2019 Sep 10.

School of Environment, Northeast Normal University, Changchun 130024, China.

Severe natural disasters and related secondary disasters are a huge menace to society. Currently, it is difficult to identify risk formation mechanisms and quantitatively evaluate the risks associated with disaster chains; thus, there is a need to further develop relevant risk assessment methods. In this research, we propose an earthquake disaster chain risk evaluation method that couples Bayesian network and Newmark models that are based on natural hazard risk formation theory with the aim of identifying the influence of earthquake disaster chains. This new method effectively considers two risk elements: hazard and vulnerability, and hazard analysis, which includes chain probability analysis and hazard intensity analysis. The chain probability of adjacent disasters was obtained from the Bayesian network model, and the permanent displacement that was applied to represent the potential hazard intensity was calculated by the Newmark model. To validate the method, the Changbai Mountain volcano earthquake-collapse-landslide disaster chain was selected as a case study. The risk assessment results showed that the high-and medium-risk zones were predominantly located within a 10 km radius of Tianchi, and that other regions within the study area were mainly associated with very low-to low-risk values. The verified results of the reported method showed that the area of the receiver operating characteristic (ROC) curve was 0.817, which indicates that the method is very effective for earthquake disaster chain risk recognition and assessment.
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http://dx.doi.org/10.3390/ijerph16183330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765995PMC
September 2019

A Method for Improving Controlling Factors Based on Information Fusion for Debris Flow Susceptibility Mapping: A Case Study in Jilin Province, China.

Entropy (Basel) 2019 Jul 15;21(7). Epub 2019 Jul 15.

College of Construction Engineering, Jilin University, Changchun 130026, China.

Debris flow is one of the most frequently occurring geological disasters in Jilin province, China, and such disasters often result in the loss of human life and property. The objective of this study is to propose and verify an information fusion (IF) method in order to improve the factors controlling debris flow as well as the accuracy of the debris flow susceptibility map. Nine layers of factors controlling debris flow (i.e., topography, elevation, annual precipitation, distance to water system, slope angle, slope aspect, population density, lithology and vegetation coverage) were taken as the predictors. The controlling factors were improved by using the IF method. Based on the original controlling factors and the improved controlling factors, debris flow susceptibility maps were developed while using the statistical index (SI) model, the analytic hierarchy process (AHP) model, the random forest (RF) model, and their four integrated models. The results were compared using receiver operating characteristic (ROC) curve, and the spatial consistency of the debris flow susceptibility maps was analyzed while using Spearman's rank correlation coefficients. The results show that the IF method that was used to improve the controlling factors can effectively enhance the performance of the debris flow susceptibility maps, with the IF-SI-RF model exhibiting the best performance in terms of debris flow susceptibility mapping.
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http://dx.doi.org/10.3390/e21070695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515198PMC
July 2019

Improving Parameter Estimation of Entropic Uncertainty Relation in Continuous-Variable Quantum Key Distribution.

Entropy (Basel) 2019 Jul 2;21(7). Epub 2019 Jul 2.

State Key Laboratory of Advanced Optical Communication, Systems and Networks, Department of Electronics, and Center for Quantum Information Technology, Peking University, Beijing 100871, China.

The entropic uncertainty relation (EUR) is of significant importance in the security proof of continuous-variable quantum key distribution under coherent attacks. The parameter estimation in the EUR method contains the estimation of the covariance matrix (CM), as well as the max-entropy. The discussions in previous works have not involved the effect of finite-size on estimating the CM, which will further affect the estimation of leakage information. In this work, we address this issue by adapting the parameter estimation technique to the EUR analysis method under composable security frameworks. We also use the double-data modulation method to improve the parameter estimation step, where all the states can be exploited for both parameter estimation and key generation; thus, the statistical fluctuation of estimating the max-entropy disappears. The result shows that the adapted method can effectively estimate parameters in EUR analysis. Moreover, the double-data modulation method can, to a large extent, save the key consumption, which further improves the performance in practical implementations of the EUR.
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http://dx.doi.org/10.3390/e21070652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515145PMC
July 2019

Environmental Risk Assessment of Metals in the Volcanic Soil of Changbai Mountain.

Int J Environ Res Public Health 2019 06 10;16(11). Epub 2019 Jun 10.

Institute of Natural Disaster Research, Department of Environment, Northeast Normal University, Changchun 130024, China.

Tianchi volcano is a dormant active volcano with a risk of re-eruption. Volcanic soil and volcanic ash samples were collected around the volcano and the concentrations of 21 metals (major and trace elements) were determined. The spatial distribution of the metals was obtained by inverse distance weight (IDW) interpolation. The metals' sources were identified and their pollution levels were assessed to determine their potential ecological and human health risks. The metal concentrations were higher around Tianchi and at the north to the west of the study area. According to the geo-accumulation index (), enrichment factor (EF) and contamination factor (CF) calculations, Zn pollution was high in the study area. Pearson's correlation analysis and principal component analysis showed that with the exception of Fe, Mn and As, the metals that were investigated (Al, K, Ca, Na, Mg, Ti, Cu, Pb, Zn, Cr, Ni, Ba, Ga, Li, Co, Cd, Sn, Sr) were mostly naturally derived. A small proportion of Li, Pb and Zn may have come from vehicle traffic. There is no potential ecological risk and non-carcinogenic risk because of the low concentrations of the metals; however, it is necessary to pay attention to the carcinogenic risk of Cr and As in children.
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http://dx.doi.org/10.3390/ijerph16112047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604000PMC
June 2019

A novel complement C3 like gene (Lv-C3L) from Litopenaeus vannamei with bacteriolytic and hemolytic activities and its role in antiviral immune response.

Fish Shellfish Immunol 2019 Aug 21;91:376-387. Epub 2019 May 21.

Tianjin Key Laboratory of Animal and Plant Resistance/College of Life Sciences, Tianjin Normal University, Tianjin, 300387, China. Electronic address:

As a core component of the complement system, complement component 3 (C3) plays a central role in the opsonization of pathogens, immune defense and immune regulation in the mammalian for its activation is required to trigger classical as well as alternative complement pathways. However, the molecular mechanism underlying C3 activation in invertebrates remains unknown. Several C3 genes have been characterized in invertebrates but very few in crustacean. To understand the molecular characterization and immunological functions of shrimp C3, we characterized a novel complement C3 like gene (designated Lv-C3L) with full-length cDNA sequence identified from pacific white shrimp Litopenaeus vannamei in the present study. The full length cDNA of Lv-C3L sequence was 4769 bp (GenBank accession number: MH638255) containing a 4077 bp open reading frame (ORF), which encodes 1358 amino acids contained a putative signal peptide of 17 amino acids. Six model motifs of C3 were found in Lv-C3L including typical A2M domain, a highly conserved thioester region (GCGEQ) and proteolytic cleavage site of ANATO. In addition to typical conservative domains, Lv-C3L also contains a particular GLN-rich region which might be involved in the protein interaction and transcriptional activation. The transcripts of Lv-C3L were mainly detected in hemocytes and gill which might be involved in defense response. At 36 h post V.parahaemolyticus and B.thuringensis infection, the expression level of Lv-C3L gene in hemocytes were significantly upregulated. At 48 h and 72 h post WSSV infection, the expression level of Lv-C3L gene in hemocytes and gill were significantly upregulated. These results indicated that Lv-C3L gene play a pivotal role in innate immune responses to the WSSV and G/G bacterial infection. The obvious immune function of Lv-C3L was described as an effective membrane rupture in bacteriolytic and hemolytic activities on V.parahaemolyticus, V.anguillarum and rabbit erythrocytes. Combining with WSSV copy number, WSSV-VP28 gene expression profile and shrimp cumulative mortality analysis, RNAi knockdown of Lv-C3L gene could obviously promote the in vivo propagation of WSSV in shrimp. This is the first report in crustaceans that Lv-C3L, as a key complement like components, is involved in shrimp antiviral immune response. It is speculated that complicated complement response cascade may exist in shrimp. These results collectively indicated that the complement pathway in shrimp might play an important protective role against pathogenic infection and activation of complement pathway including C3 could restrict the propagation of WSSV.
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http://dx.doi.org/10.1016/j.fsi.2019.05.045DOI Listing
August 2019

6 Gbps real-time optical quantum random number generator based on vacuum fluctuation.

Rev Sci Instrum 2019 Apr;90(4):043105

State Key Laboratory of Advanced Optical Communication Systems and Networks, School of Electronics Engineering and Computer Science and Center for Quantum Information Technology, Peking University, Beijing 100871, China.

We demonstrate a 6 Gbps real-time optical quantum random number generator by measuring vacuum fluctuation. To address the common problem that speed gap exists between fast randomness generation and slow randomness extraction in most high-speed real-time quantum random number generator systems, we present an optimized extraction algorithm based on parallel implementation of Toeplitz hashing to reduce the influence of classical noise due to the imperfection of devices. Notably, the real-time rate of randomness extraction we have achieved reaches the highest speed of 12 Gbps by occupying less computing resources, and the algorithm has the ability to support hundreds of Gbps randomness extraction. By assuming that the eavesdropper with complete knowledge of the classical noise, our generator has a randomness generation speed of 6.83 Gbps and this supports the generation of 6 Gbps information-theoretically provable quantum random numbers, which are output in real-time through peripheral component interconnect express interface.
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http://dx.doi.org/10.1063/1.5078547DOI Listing
April 2019

Design of peptide nucleic acid probes on plasmonic gold nanorods for detection of circulating tumor DNA point mutations.

Biosens Bioelectron 2019 Apr 29;130:236-244. Epub 2019 Jan 29.

Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755, USA; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, NH 03766, USA. Electronic address:

Here we present a gold nanorod-based platform for the sequence-specific detection of circulating tumor DNA (ctDNA) point mutations without the need for amplification or fluorescence labeling. Peptide nucleic acid probes complimentary to the G12V mutation in the KRAS gene were conjugated to gold nanorods, and the localized surface plasmon resonance absorbance through the sample was measured after exposure to synthetic ctDNA at various concentrations. Each step of the reaction was thoroughly controlled, starting from reagent concentrations and including conjugation, sonication, and incubation time. The platform was evaluated in both buffer and spiked healthy patient serum, demonstrating a linear working range below 125 nanograms of ctDNA per milliliter solution, and an effective limit of detection of 2 nanograms of ctDNA per milliliter. A clear distinction between mutant and wild type synthetic ctDNA was also found using this platform. In order to improve upon the selectivity of the sensor, a DNA hybridization simulation was performed to understand how the addition of mutations to the peptide nucleic acid probe could enhance the selectivity for capture of mutant over wild type sequences. The top candidate from the simulations, which had an additional mutation two base pairs away from the mutation of interest, had a significant impact on the selectivity between mutant and wild type capture. This paper provides a framework for sequence-specific capture of ctDNA, and a method of improving selectivity for desired point mutations through careful probe design.
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http://dx.doi.org/10.1016/j.bios.2019.01.045DOI Listing
April 2019