Publications by authors named "Ziqi Wang"

120 Publications

Co-Expression with Membrane CMTM6/4 on Tumor Epithelium Enhances the Prediction Value of PD-L1 on Anti-PD-1/L1 Therapeutic Efficacy in Gastric Adenocarcinoma.

Cancers (Basel) 2021 Oct 15;13(20). Epub 2021 Oct 15.

NHC Key Laboratory of Medical Immunology, Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.

Anti-PD-1/L1 immunotherapy has been intensively used in heavily treated population with advanced gastric adenocarcinoma. However, the immunotherapeutic efficacy is low even in PD-L1 positive patients. We aimed to establish a new strategy based on the co-expression of CMTM6/4 and PD-L1 for patient stratification before immunotherapy. By analyzing the data obtained from TCGA and single-cell RNA sequencing at the mRNA level, and 6-color multiplex immunofluorescence staining of tumor tissues in tissue array and 48-case pre-immunotherapy patients at the protein level, we found that CMTM6/4 and PD-L1 co-expressed in both epithelial and mesenchymal regions of gastric adenocarcinoma. The tumor tissues had higher levels of CMTM6/4 expression than their adjacent ones. A positive correlation was found between the expression of CMTM6/4 and the expression of PD-L1 in tumor epithelium. Epithelial co-expression of CMTM6/4 and PD-L1 in gastric tumor region was associated with shorter overall survival but better short-term response to anti-PD-1/L1 immunotherapy. Thus, we developed a predictive model and three pathological patterns based on the membrane co-expression of CMTM6/4 and PD-L1 in tumor epithelial cells for pre-immunotherapy patient screening in gastric adenocarcinoma.
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http://dx.doi.org/10.3390/cancers13205175DOI Listing
October 2021

Poster Abstract: Protecting User Data Privacy with Adversarial Perturbations.

IPSN 2021 May;2021:386-387

University of California, Los Angeles, Los Angeles, USA.

The increased availability of on-body sensors gives researchers access to rich time-series data, many of which are related to human health conditions. Sharing such data can allow cross-institutional collaborations that create advanced data-driven models to make inferences on human well-being. However, such data are usually considered privacy-sensitive, and publicly sharing this data may incur significant privacy concerns. In this work, we seek to protect clinical time-series data against membership inference attacks, while maximally retaining the data utility. We achieve this by adding an imperceptible noise to the raw data. Known as adversarial perturbations, the noise is specially trained to force a deep learning model to make inference mistakes (in our case, mispredicting user identities). Our preliminary results show that our solution can better protect the data from membership inference attacks than the baselines, while succeeding in all the designed data quality checks.
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http://dx.doi.org/10.1145/3412382.3458776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513393PMC
May 2021

An Injectable Hydrogel for Enhanced FeGA-Based Chemodynamic Therapy by Increasing Intracellular Acidity.

Front Oncol 2021 22;11:750855. Epub 2021 Sep 22.

Department of Molecular Pathology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Hydroxyl radical (•OH)-mediated chemodynamic therapy (CDT) is an emerging antitumor strategy, however, acid deficiency in the tumor microenvironment (TME) hampers its efficacy. In this study, a new injectable hydrogel was developed as an acid-enhanced CDT system (AES) for improving tumor therapy. The AES contains iron-gallic acid nanoparticles (FeGA) and α-cyano-4-hydroxycinnamic acid (α-CHCA). FeGA converts near-infrared laser into heat, which results in agarose degradation and consequent α-CHCA release. Then, as a monocarboxylic acid transporter inhibitor, α-CHCA can raise the acidity in TME, thus contributing to an increase in ·OH-production in FeGA-based CDT. This approach was found effective for killing tumor cells both and , demonstrating good therapeutic efficacy. investigations also revealed that AES had outstanding biocompatibility and stability. This is the first study to improve FeGA-based CDT by increasing intracellular acidity. The AES system developed here opens new opportunities for effective tumor treatment.
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http://dx.doi.org/10.3389/fonc.2021.750855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492932PMC
September 2021

A Novel HO Generator for Tumor Chemotherapy-Enhanced CO Gas Therapy.

Front Oncol 2021 21;11:738567. Epub 2021 Sep 21.

Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Carbon monoxide (CO) gas therapy is a promising cancer treatment. However, gas delivery to the tumor site remains problematic. Proper tunable control of CO release in tumors is crucial to increasing the efficiency of CO treatment and reducing the risk of CO poisoning. To overcome such challenges, we designed ZCM, a novel stable nanotechnology delivery system comprising manganese carbonyl (MnCO) combined with anticancer drug camptothecin (CPT) loaded onto a zeolitic imidazole framework-8 (ZIF-8). After intravenous injection, ZCM gradually accumulates in cancerous tissues, decomposing in the acidic tumor microenvironment, releasing CPT and MnCO. CPT acts as a chemotherapy agent destroying tumors and producing copious HO. MnCO can react with the HO to generate CO, powerfully damaging the tumor. Both and experiments indicate that the ZCM system is both safe and has excellent tumor inhibition properties. ZCM is a novel system for CO controlled release, with significant potential to improve future cancer therapy.
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http://dx.doi.org/10.3389/fonc.2021.738567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496405PMC
September 2021

Comparative Analysis of Unsupervised Protein Similarity Prediction Based on Graph Embedding.

Front Genet 2021 22;12:744334. Epub 2021 Sep 22.

School of Information Science and Engineering, Qufu Normal University, Rizhao, China.

The study of protein-protein interaction and the determination of protein functions are important parts of proteomics. Computational methods are used to study the similarity between proteins based on Gene Ontology (GO) to explore their functions and possible interactions. GO is a series of standardized terms that describe gene products from molecular functions, biological processes, and cell components. Previous studies on assessing the similarity of GO terms were primarily based on Information Content (IC) between GO terms to measure the similarity of proteins. However, these methods tend to ignore the structural information between GO terms. Therefore, considering the structural information of GO terms, we systematically analyze the performance of the GO graph and GO Annotation (GOA) graph in calculating the similarity of proteins using different graph embedding methods. When applied to the actual Human and Yeast datasets, the feature vectors of GO terms and proteins are learned based on different graph embedding methods. To measure the similarity of the proteins annotated by different GO numbers, we used Dynamic Time Warping (DTW) and cosine to calculate protein similarity in GO graph and GOA graph, respectively. Link prediction experiments were then performed to evaluate the reliability of protein similarity networks constructed by different methods. It is shown that graph embedding methods have obvious advantages over the traditional IC-based methods. We found that random walk graph embedding methods, in particular, showed excellent performance in calculating the similarity of proteins. By comparing link prediction experiment results from GO(DTW) and GOA(cosine) methods, it is shown that GO(DTW) features provide highly effective information for analyzing the similarity among proteins.
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http://dx.doi.org/10.3389/fgene.2021.744334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493040PMC
September 2021

Sigma-1 receptor activation alleviates blood-brain barrier disruption post cerebral ischemia stroke by stimulating the GDNF-GFRα1-RET pathway.

Exp Neurol 2021 Sep 25:113867. Epub 2021 Sep 25.

Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.. Electronic address:

Blood-brain barrier (BBB) disruption is one of the most important pathological manifestations of ischemic stroke. Reducing BBB collapse is effective in alleviating brain parenchymal injury and cognitive dysfunction. Our previous study reported that Sigma-1 receptor (Sig-1R) activation in cerebral microvascular endothelial cells (CMECs) ameliorated BBB impairment, but the detailed mechanism remains unclear. In this study, we investigated Sig-1R activation as a BBB integrity promoter via many post ischemic stroke pathways. Sig-1R activation in BBB-associated astrocytes can increase glia-derived neurotrophic factor (GDNF) secretion in bilateral common carotid artery occlusion (BCCAO) mice. Upregulated GDNF activates its receptors in CMECs to promote BBB integrity, and activated Sig-1R in CMECs facilitates this process. In vitro experiments have found that Sig-1R activation in CMECs promotes the interaction between the GDNF α1 receptor and transduction rearrangement gene, increasing PI3K-AKT-junction protein signaling pathway expression. Sig-1R activation could be an effective therapeutic method for preventing BBB damage in ischemic stroke and other neurological conditions.
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http://dx.doi.org/10.1016/j.expneurol.2021.113867DOI Listing
September 2021

The transcriptional characteristics of mast cells derived from skin tissue in type 2 diabetes patients at the single-cell level.

Acta Histochem 2021 Oct 22;123(7):151789. Epub 2021 Sep 22.

Wound Treatment Department, TCM-Integrated Hospital of Southern Medical University, Guangzhou, Guangdong Province, China. Electronic address:

Objectives: The mechanisms underlying the role of mast cells in wound healing have not been thoroughly studied, and even fewer data are available on studies related to mast cells in the skin of patients with type 2 diabetes mellitus (T2DM). Therefore, this study aims to explore the transcriptional characteristics of mast cells at the single-cell level in patients with T2DM and provide experimental data for studying mast cell behaviors under abnormal glucose metabolism.

Methods: Two patients with T2DM and one trauma patient without diabetes were enrolled. Samples were derived from skin tissue resected at the time of surgery and were isolated by single cell capture technology on BD platform to prepare single cell cDNA library. Seurat was used to process raw reads and analyze data downstream of single-cell RNA sequencing, including removal of low-quality cells, identification of cell clusters at the single-cell level, and screening for differential genes with fold change > 1.5 and p < 0.05 by two-sided t-test. We performed single-cell RNA sequencing on skin tissues of T2DM patients and non-diabetics and identified the cell cluster of skin, single-cell subsets, and transcriptional characteristics of mast cells at a single-cell level. Meanwhile, gene set enrichment(GSEA) analysis was performed on the differentially expressed genes.

Results: A total of 8888 cells were obtained from skin tissue. Clustering analysis revealed eight-cell clusters, identified as smooth muscle cells, dendritic cells, mast cells, and T cells, respectively. Cluster 6 was identified as mast cells with the marker genes TPSAB1, CPA3, TPSB2, MS4A2,KIT, etc., which accounting for 2.7% of the total cell number.Compared with the control group, the genes highly expressed in MCs from T2DM patients, include ADH1C, PAXIP1, HAS1, ARG1, etc., and the low expression genes include PHACTR2, GGA1, RASSF2, etc. GSEA analysis suggested that the signal pathways of MCS in T2DM patients included VEGF signaling pathway, Fc gamma R-mediated phagocytosis, the B cell receptor signaling pathway, natural killer cell-mediated cytotoxicity.

Conclusions: The characteristic genes of MCs in the skin tissues of T2DM patients were described at the single-cell level. These genes and enriched signaling pathways provide a theoretical basis and data support for further researches on dermatopathy in patients with diabetes mellitus.
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http://dx.doi.org/10.1016/j.acthis.2021.151789DOI Listing
October 2021

Identification of SRSF3 target mRNAs using inducible TRIBE.

Biochem Biophys Res Commun 2021 Nov 10;578:21-27. Epub 2021 Sep 10.

Department of Orthopedic, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310029, China; Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, Haining, 314400, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou, 310029, China. Electronic address:

Serine and arginine-rich splicing factor 3 (SRSF3), the smallest member of the Ser/Arg-rich (SR) RNA-binding protein family, regulates multiple aspects of post-transcriptional gene expression program. Although SRSF3 is essential for early embryo development, reprogramming, and pluripotency maintenance, the RNA targets and specificity of RNA recognition of SRSF3 are not well understood in human pluripotent stem cells. In this study, we used inducible TRIBE (targets of RNA binding sites by editing) to identify RNA targets and binding motifs of SRSF3 in human embryonic stem cells (hESCs). We identified 3888 confident binding sites of SRSF3, corresponding to 1222 gene targets. Our results showed that nearly half of the binding sites were distributed in exons, reflecting the alternative splicing function of SRSF3. Motif analysis demonstrated that two of the SRSF3 recognition sequences were the same as the motifs identified in mouse embryonic stem cells, suggesting the recognition sequences of SRSF3 may be conserved in mammals. Overall, our analyses revealed the RNA targets of SRSF3 and uncovered its RNA recognition specificity, providing a valuable resource for understanding the function of SRSF3 in human embryonic stem cells.
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http://dx.doi.org/10.1016/j.bbrc.2021.09.019DOI Listing
November 2021

Distribution and diversity of myxomycetes in Tiantangzhai National Forest Park, China.

PeerJ 2021 25;9:e12059. Epub 2021 Aug 25.

College of Life Sciences, Nanjing Normal University, Nanjing, China.

Although myxomycetes are ubiquitous in terrestrial ecosystems, studies on their distribution and diversity in subtropical humid forests are still lacking. Field collections and moist chamber cultures were conducted from May to October within a two-year period in the Tiantangzhai National Forest Park of China. A total of 1,492 records representing 73 species belonging to 26 genera were obtained, of which 243 records/37 species were from field collections, and 1,249 records/52 species were from moist chamber cultures. Among the specimens obtained by culturing, 896 records/38 species and 353 records/37 species were obtained from living bark and ground litter, respectively. ANOVA showed that the sampling months had significant impacts on collection of myxomycetes from field and those that inhabit litter. An LEfSe analysis indicated that was significantly abundant in August, while and were more abundant in July when collected from field. An RDA analysis showed that temperature was the main factor that affected the litter-inhabiting myxomycetes. The ANOVA indicated that forest type was the significant factor for bark-inhabiting myxomycetes. was primarily obtained from mixed forests, while and were more common in coniferous forests. The RDA analysis indicated that the vegetation, pH, water retention, and elevation were the primary factors that affected the bark-inhabiting myxomycetes.
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http://dx.doi.org/10.7717/peerj.12059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401731PMC
August 2021

Gelatin methacrylate hydrogel scaffold carrying resveratrol-loaded solid lipid nanoparticles for enhancement of osteogenic differentiation of BMSCs and effective bone regeneration.

Regen Biomater 2021 Oct 30;8(5):rbab044. Epub 2021 Jul 30.

Department of Orthopedics, First Affiliated Hospital, Bengbu Medical College, Bengbu 233004, China.

Critical-sized bone defects caused by traumatic fractures, tumour resection and congenital malformation are unlikely to heal spontaneously. Bone tissue engineering is a promising strategy aimed at developing replacements for bone transplantation and overcoming the limitations of natural bone grafts. In this study, we developed an innovative bone engineering scaffold based on gelatin methacrylate (GelMA) hydrogel, obtained via a two-step procedure: first, solid lipid nanoparticles (SLNs) were loaded with resveratrol (Res), a drug that can promote osteogenic differentiation and bone formation; these particles were then encapsulated at different concentrations (0.01%, 0.02%, 0.04% and 0.08%) in GelMA to obtain the final Res-SLNs/GelMA scaffolds. The effects of these scaffolds on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and bone regeneration in rat cranial defects were evaluated using various characterization assays. Our and investigations demonstrated that the different Res-SLNs/GelMA scaffolds improved the osteogenic differentiation of BMSCs, with the ideally slow and steady release of Res; the optimal scaffold was 0.02 Res-SLNs/GelMA. Therefore, the 0.02 Res-SLNs/GelMA hydrogel is an appropriate release system for Res with good biocompatibility, osteoconduction and osteoinduction, thereby showing potential for application in bone tissue engineering.
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http://dx.doi.org/10.1093/rb/rbab044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358478PMC
October 2021

An intratumoral injectable nanozyme hydrogel for hypoxia-resistant thermoradiotherapy.

Colloids Surf B Biointerfaces 2021 Nov 6;207:112026. Epub 2021 Aug 6.

Key Laboratory of Artificial Micro and Nano-structures of Ministry of Education, Center for Theoretical Physics, School of Physics and Technology, Wuhan University, Wuhan, 430072, China. Electronic address:

Hypoxia in local tumors leads to the failure or resistance of radiotherapy (RT) and high-dose RT will cause systemic reactions and local radiation damage. As a non-chemotherapeutic intervention, photothermal therapy (PTT) can remove tumor tissues through thermal ablation as well as effectively improve the microenvironment of hypoxic cells. Therefore, the combined use of PTT and RT (thermoradiotherapy) has urgently become an efficient treatment. In this work, by encapsulating prussian blue (PB) nanoparticles in agarose hydrogel, we developed an injectable hybrid light-controlled hydrogel system as a PB reservoir and release controller (PRC) which can realize single injection and multiple treatments in vivo. Under the irradiation of 808 nm near-infrared (NIR) laser, PB nanoparticles convert laser energy into heat energy, causing degradation of agarose hydrogel and the release of PB nanoparticles. Due to the excellent photothermal properties of PB, photothermal treatment in the NIR Biological Windows can greatly enhance the sensitivity of tumor cells to RT. Meanwhile, PB nanoparticles can also be a nanozyme to drive the decomposition of endogenous hydrogen peroxide (HO), and then generate oxygen (O) to improve the tumor hypoxic microenvironment, achieving the further enhancement of the radiation sensitivity. Notably, this study is the first design to utilize hydrogel for thermoradiotherapy. Both in vitro and in vivo experiments, the PRC demonstrated excellent effects of PTT-RT, good stability and biocompatibility, indicating our nanoplatform promote the development of anti-cancer combination thermoradiotherapy with greater clinical significance.
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http://dx.doi.org/10.1016/j.colsurfb.2021.112026DOI Listing
November 2021

Insights into stress degradation behavior of gibberellic acid by UHPLC Q-Exactive Orbitrap mass spectrometry.

Food Chem 2022 Jan 21;367:130662. Epub 2021 Jul 21.

Tea Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou 310008, China; Key Laboratory of Tea Quality and Safety & Risk Assessment, Ministry of Agriculture, Hangzhou 310008, China. Electronic address:

Gibberellic acid (GA) is widely applied in agriculture and food worldwide. Profiling the degradation products and their formation pattern under stress are helpful for deeply understanding GA regulating plant physiology and GA safety in agricultural crops. This study firstly investigated the degradation behavior of GA. Different stress factors such as light, pH and temperatures were investigated through photolysis and hydrolysis experiments. Five degradation products were identified using ultra high-performance liquid chromatography Q-Exactive Orbitrap mass spectrometry (UHPLC Q-Exactive Orbitrap MS). Three degradation products were produced under ultraviolet photolysis conditions. Two isomers (iso-GA and gibberellenic acid) were formed under alkaline conditions. In order to characterize each degradation product, complete mass fragmentation pathways of all analytes were initially established. These results could provide a practical reference for the safety of agricultural products and the guidance for scientific application of GA and proposed storage conditions of GA.
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http://dx.doi.org/10.1016/j.foodchem.2021.130662DOI Listing
January 2022

Retinal Vascular Changes during the Menstrual Cycle Detected with Optical Coherence Tomography Angiography.

J Ophthalmol 2021 12;2021:5514575. Epub 2021 Jul 12.

Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Purpose: To evaluate the effects of the menstrual cycle on the retinal vascular status of healthy women by optical coherence tomography angiography (OCTA).

Materials And Methods: Healthy women with regular natural menstrual cycles of 28 to 30 days were recruited for this prospective study. The women's retinal vascular status was measured by OCTA at 3 time points: the early follicular, ovulatory, and midluteal phases of the menstrual cycle. The main outcome measures were foveal avascular zone (FAZ) parameters, perfusion density (PD) percentage in the superficial retinal capillary plexus (SCP), and PD percentage in the deep retinal capillary plexus (DCP). The mean arterial pressure (MAP), spherical equivalent (SE), best-corrected visual acuity (BCVA), intraocular pressure (IOP), and axial (AL) were also measured in a same menstrual cycle.

Results: In total, 62 right eyes of 62 women were included in the study. The mean age was 27.0 ± 1.73 (range, 24 to 31) years, and the mean menstrual cycle was 28.90 ± 0.84 (range, 28 to 30) days. The mean values of the DCP-PD parameters were significantly decreased in the nasal and inferior ETDRS subfields during the ovulatory phase. The mean DCP-PD in the nasal ETDRS subfield in the early follicular, ovulatory, and luteal phases was 54.11 ± 2.85, 56.39 ± 3.03, and 55.70 ± 3.27, respectively. The mean DCP-PD in the inferior ETDRS subfield in the early follicular, ovulatory, and midluteal phases was 52.90 ± 3.30, 54.86 ± 2.51, and 55.21 ± 2.64, respectively. No significant differences were found in MAP, SE, AL, IOP, FAZ area, or other quadrants of PD parameters, and no significant correlation was found between parameters by OCTA and age, MAP,SE, axial length, or IOP.

Conclusions: The DCP-PD decreased in the nasal and inferior ETDRS subfields during the ovulatory phase in our study. This may indicate the need to consider the menstrual phase when interpreting DCP-PD parameters by OCTA in healthy women.
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http://dx.doi.org/10.1155/2021/5514575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292083PMC
July 2021

Review on the Application of Metalearning in Artificial Intelligence.

Comput Intell Neurosci 2021 5;2021:1560972. Epub 2021 Jul 5.

College of Science, North China University of Science and Technology, Tangshan 063210, China.

In recent years, artificial intelligence supported by big data has gradually become more dependent on deep reinforcement learning. However, the application of deep reinforcement learning in artificial intelligence is limited by prior knowledge and model selection, which further affects the efficiency and accuracy of prediction, and also fails to realize the learning ability of autonomous learning and prediction. Metalearning came into being because of this. Through learning the information metaknowledge, the ability to autonomously judge and select the appropriate model can be formed, and the parameters can be adjusted independently to achieve further optimization. It is a novel method to solve big data problems in the current neural network model, and it adapts to the development trend of artificial intelligence. This article first briefly introduces the research process and basic theory of metalearning and discusses the differences between metalearning and machine learning and the research direction of metalearning in big data. Then, four typical applications of metalearning in the field of artificial intelligence are summarized: few-shot learning, robot learning, unsupervised learning, and intelligent medicine. Then, the challenges and solutions of metalearning are analyzed. Finally, a systematic summary of the full text is made, and the future development prospect of this field is assessed.
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http://dx.doi.org/10.1155/2021/1560972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277507PMC
August 2021

Assessment of Parkinson's Disease Severity from Videos using Deep Architecture.

IEEE J Biomed Health Inform 2021 Jul 26;PP. Epub 2021 Jul 26.

Parkinson's disease (PD) diagnosis is based on clinical criteria, i.e., bradykinesia, rest tremor, rigidity, etc. Assessment of the severity of PD symptoms with clinical rating scales, however, is subject to inter-rater variability. In this paper, we propose a deep learning based automatic PD diagnosis method using videos to assist the diagnosis in clinical practices. We deploy a 3D Convolutional Neural Network (CNN) as the baseline approach for the PD severity classification and show the effectiveness. Due to the lack of data in clinical field, we explore the possibility of transfer learning from non-medical dataset and show that PD severity classification can benefit from it. To bridge the domain discrepancy between medical and non-medical datasets, we let the network focus more on the subtle temporal visual cues, i.e., the frequency of tremors, by designing a Temporal Self-Attention (TSA) mechanism. Seven tasks from the Movement Disorders Society - Unified PD rating scale (MDS-UPDRS) part III are investigated, which reveal the symptoms of bradykinesia and postural tremors. Furthermore, we propose a multi-domain learning method to predict the patient-level PD severity through task-assembling. We show the effectiveness of TSA and task-assembling method on our PD video dataset empirically. We achieve the best MCC of 0.55 on binary task-level and 0.39 on three-class patient-level classification.
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http://dx.doi.org/10.1109/JBHI.2021.3099816DOI Listing
July 2021

Single-Ion Conducting Double-Network Hydrogel Electrolytes for Long Cycling Zinc-Ion Batteries.

ACS Appl Mater Interfaces 2021 Jul 24;13(26):30594-30602. Epub 2021 Jun 24.

Nano Center, Institute of Textiles & Clothing, Hong Kong Polytechnic University, Hong Kong, China.

As one of the promising alternatives of lithium-ion batteries, zinc-ion batteries (ZIBs) have received growing interest from researchers due to their good safety, eco-friendliness, and low cost. Nevertheless, aqueous ZIBs are still a step away from practical applications due to the nonuniform deposition of Zn and parasitic side reactions, which cause capacity fading and even short circuit. To tackle these problems, here we introduce a single-Zn-ion conducting hydrogel electrolyte (SIHE), P(ICZn-AAm), synthesized with iota carrageenan (IC) and acrylamide (AAm). The SIHE manifests single Zn conductivity via the abundant sulfates fixed on the IC polymer backbone, delivering a high Zn transference number of 0.93. It also exhibits outstanding ionic conductivity of 2.15 × 10 S cm at room temperature. The enhanced compatibility at the electrode-electrolyte interface was verified by the stable Zn striping/plating performance along with a homogenous and smooth Zn deposition layer. It is also found that the passivation of the Zn anode can be effectively prohibited due to the lack of free anions in the electrolyte. The practical performance of the SIHE is further investigated with Zn-VO batteries, which showed a stable capacity of 271.6 mA h g over 150 cycles at 2 C and 127.5 mA h g over 500 cycles at 5 C.
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http://dx.doi.org/10.1021/acsami.1c05941DOI Listing
July 2021

A longitudinal follow-up of COVID-19 patients in the convalescent phase showed recovery in radiological results, the dynamics of lymphocytes, and a decrease in the level of IgG antibody: a single-centre, observational study.

J Thorac Dis 2021 May;13(5):2986-3000

Department of Respiratory and Critical Care Medicine, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, China.

Background: Given the high prevalence of coronavirus disease 2019 (COVID-19) globally, and the increased number of patients being discharged, it is necessary to understand the health consequences of COVID-19 to formulate and manage public policy concerning convalescent patients.

Methods: A longitudinal follow-up investigation of 25 patients from a tertiary hospital in Henan provincial was conducted 8 weeks after discharge. Of these patients, 15 attended a second follow-up appointment 8 weeks after that. A throat swab reverse transcription-polymerase chain reaction (RT-PCR) analysis for SARS-CoV-2 and chest computerized tomography (CT) scans were implemented at the first follow-up appointment, and a total of 40 blood samples (25 from the first and 15 from the second follow-up appointment) were collected. Patients' levels of Immunoglobulin G (IgG) antibody against S-Receptor binding domain (S-RBD) and Nucleocapsid Protein (NP) of SARS-CoV-2 and the subpopulation of lymphocytes were evaluated using an enzyme-linked immunoassay (ELISA) test and flow cytometry, respectively.

Results: At the first follow-up appointment, 10 of the 25 patients (40.0%) showed complete radiological resolution. Of these patients, 80.0% were classified as moderate, and 80.0% were younger (those whose age was ≤ the median age of all the patients). The predominant patterns of abnormalities included an irregular line (12/25, 48.0%), ground-glass opacity (GGO) (44.0%), and multiple GGOs (28.0%). At the first follow-up appointment, 40.0% (10/25) of patients still had lymphopenia. Of the 15 patients who were followed-up with twice, the ratio of lymphopenia was 80% (12/15), 60.0% (9/15), and 46.7% (7/15) at 0, 8, and 16 weeks after discharge, respectively. This was mainly due to a decrease in the cluster of differentiation (CD) 4+ T lymphocyte, which was observed in 60% (9/15), 60% (9/15), and 46.7% (7/15) of total patients at 0, 8, and 16 weeks after discharge, respectively. All of the patients were S-RBD and NP IgG antibody positive at the first follow-up appointment. 40.0% (6/15) and 66.7% (10/15) of patients showed a decrease over 50.0% in the level of NP and S-RBD IgG antibodies, respectively, at the second follow-up appointment. The NP and S-RBD IgG antibodies' levels declined to 44.6% (P=0.044) and 28.1% (P=0.18), respectively. 0 and 26.7% (4/15) of patients turned from NP and S-RBD IgG antibody positive to negative, respectively.

Conclusions: About half of the patients still showed at least 1 abnormality in chest CT scans 8 weeks after discharge and lymphopenia 16 weeks after discharge. The level of the IgG antibody had declined by the follow-up appointment. Notably, the S-RBD IgG antibody declined more dramatically than that of NP. These results may have implications in the making of policies related to disease prevention, the long-term management of discharged patients, and vaccines' development.
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http://dx.doi.org/10.21037/jtd-20-3011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182512PMC
May 2021

Towards High-Energy and Anti-Self-Discharge Zn-Ion Hybrid Supercapacitors with New Understanding of the Electrochemistry.

Nanomicro Lett 2021 Mar 18;13(1):95. Epub 2021 Mar 18.

College of Chemistry and Materials Science, Jinan University, Guangzhou, 511443, People's Republic of China.

Aqueous Zn-ion hybrid supercapacitors (ZHSs) are increasingly being studied as a novel electrochemical energy storage system with prominent electrochemical performance, high safety and low cost. Herein, high-energy and anti-self-discharge ZHSs are realized based on the fibrous carbon cathodes with hierarchically porous surface and O/N heteroatom functional groups. Hierarchically porous surface of the fabricated free-standing fibrous carbon cathodes not only provides abundant active sites for divalent ion storage, but also optimizes ion transport kinetics. Consequently, the cathodes show a high gravimetric capacity of 156 mAh g, superior rate capability (79 mAh g with a very short charge/discharge time of 14 s) and exceptional cycling stability. Meanwhile, hierarchical pore structure and suitable surface functional groups of the cathodes endow ZHSs with a high energy density of 127 Wh kg, a high power density of 15.3 kW kg and good anti-self-discharge performance. Mechanism investigation reveals that ZHS electrochemistry involves cation adsorption/desorption and ZnSO(OH)·5HO formation/dissolution at low voltage and anion adsorption/desorption at high voltage on carbon cathodes. The roles of these reactions in energy storage of ZHSs are elucidated. This work not only paves a way for high-performance cathode materials of ZHSs, but also provides a deeper understanding of ZHS electrochemistry.
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http://dx.doi.org/10.1007/s40820-021-00625-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006207PMC
March 2021

Simultaneously Regulating Uniform Zn Flux and Electron Conduction by MOF/rGO Interlayers for High-Performance Zn Anodes.

Nanomicro Lett 2021 Feb 15;13(1):73. Epub 2021 Feb 15.

School of Advanced Materials, Peking University Shenzhen Graduate School, Shenzhen, 518055, People's Republic of China.

Owing to the merits of low cost, high safety and environmental benignity, rechargeable aqueous Zn-based batteries (ZBs) have gained tremendous attention in recent years. Nevertheless, the poor reversibility of Zn anodes that originates from dendrite growth, surface passivation and corrosion, severely hinders the further development of ZBs. To tackle these issues, here we report a Janus separator based on a Zn-ion conductive metal-organic framework (MOF) and reduced graphene oxide (rGO), which is able to regulate uniform Zn flux and electron conduction simultaneously during battery operation. Facilitated by the MOF/rGO bifunctional interlayers, the Zn anodes demonstrate stable plating/stripping behavior (over 500 h at 1 mA cm), high Coulombic efficiency (99.2% at 2 mA cm after 100 cycles) and reduced redox barrier. Moreover, it is also found that the Zn corrosion can be effectively retarded through diminishing the potential discrepancy on Zn surface. Such a separator engineering also saliently promotes the overall performance of Zn|MnO full cells, which deliver nearly 100% capacity retention after 2000 cycles at 4 A g and high power density over 10 kW kg. This work provides a feasible route to the high-performance Zn anodes for ZBs.
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http://dx.doi.org/10.1007/s40820-021-00594-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187534PMC
February 2021

Multiomics analysis provides insights into alkali stress tolerance of sunflower (Helianthus annuus L.).

Plant Physiol Biochem 2021 Sep 29;166:66-77. Epub 2021 May 29.

Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, 130024, China. Electronic address:

Alkali stress is an extreme complex stress type, which exerts negative effects on plants via chemical destruction, osmotic stress, ion injury, nutrient deficiency, and oxygen deficiency. Soil alkalization has produced severe problems in some area, while plant alkali tolerance is poorly understood. Sunflower (Helianthus annuus L.) is an important oilseed crop with strong alkali tolerance. Here we exposed sunflower plants to alkali stress (NaHCO/NaCO = 9:1; pH 8.7) for whole life cycle. We applied transcriptomics, metabolomics, lipidomics and phytohormone analysis to elucidate the alkali tolerance mechanism of sunflower plant. Lipidomic analysis showed that alkali stress enhanced accumulation of saccharolipids and glycerolipids and lowered the accumulation of glycerophospholipids in sunflower seeds, indicating that alkali stress can change the lipid components of sunflower seeds, and that cultivating sunflower plants on alkalized farmlands will change the quality of sunflower seed oils. In addition, alkali stress downregulated expression of two rate-controlling genes of glycolysis in the leaves of sunflower but upregulated their expression in the roots. Enhanced glycolysis process provided more carbon sources and energy for alkali stress response of sunflower roots. Under alkali stress, accumulation of many fatty acids, amino acids, carbohydrates, and organic acids was greatly stimulated in sunflower roots. Alkali stress enhanced ACC, GA1, and ABA concentrations in the leaves but not in the roots, however, alkali stress elevated accumulation of BR (typhasterol) and CTK (Isopentenyladenosine) in the roots. We propose that multiple phytohormones and bioactive molecules interact to mediate alkali tolerance of sunflower.
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http://dx.doi.org/10.1016/j.plaphy.2021.05.032DOI Listing
September 2021

Synergistic population coding of natural communication stimuli by hindbrain electrosensory neurons.

Sci Rep 2021 05 25;11(1):10840. Epub 2021 May 25.

Department of Physiology, McGill University, Montreal, Canada.

Understanding how neural populations encode natural stimuli with complex spatiotemporal structure to give rise to perception remains a central problem in neuroscience. Here we investigated population coding of natural communication stimuli by hindbrain neurons within the electrosensory system of weakly electric fish Apteronotus leptorhynchus. Overall, we found that simultaneously recorded neural activities were correlated: signal but not noise correlations were variable depending on the stimulus waveform as well as the distance between neurons. Combining the neural activities using an equal-weight sum gave rise to discrimination performance between different stimulus waveforms that was limited by redundancy introduced by noise correlations. However, using an evolutionary algorithm to assign different weights to individual neurons before combining their activities (i.e., a weighted sum) gave rise to increased discrimination performance by revealing synergistic interactions between neural activities. Our results thus demonstrate that correlations between the neural activities of hindbrain electrosensory neurons can enhance information about the structure of natural communication stimuli that allow for reliable discrimination between different waveforms by downstream brain areas.
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http://dx.doi.org/10.1038/s41598-021-90413-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149419PMC
May 2021

Uncommon presentation and complications of herpes zoster infection involving the cervical, vagus and accessory nerves which caused a delay in diagnosis and treatment.

BMJ Case Rep 2021 May 7;14(5). Epub 2021 May 7.

Department of Community Health and Family Medicine, University of Florida Physicians Family Practice Medical Group, Gainesville, Florida, USA

A 70-year-old man with a history of invasive anal squamous cell carcinoma treated with excision and chemoradiation presented to the emergency department with right-sided neck pain and submandibular lymphadenopathy. CT imaging of the head and neck was unrevealing. The patient eventually developed cranial nerves X and XI dysfunction, manifesting as severe vocal cord paralysis (dysphonia), dysphagia, asymmetric palate elevation/deviation and trapezius muscle atrophy, in addition to scalene muscle atrophy. After an extensive workup, the patient's symptoms were determined to be due to sequelae of varicella zoster infection, which was confirmed with antibody titers. The patient's dysphagia and dysphonia eventually improved with vocal cord medialisation injection and Botox injection. However, despite delayed treatment with acyclovir and valacyclovir, the patient continued to have neuropathic pain and exhibit signs of CN X and CN XI paresis, in addition to scalene muscle atrophy.
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http://dx.doi.org/10.1136/bcr-2021-241881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108672PMC
May 2021

Effects of Morning Blue-Green 500 nm Light Therapy on Cognition and Biomarkers in Middle-Aged and Older Adults with Subjective Cognitive Decline and Mild Cognitive Impairment: Study Protocol for a Randomized Controlled Trial.

J Alzheimers Dis 2021 ;83(4):1521-1536

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.

Background: Given that there is no specific drug to treat Alzheimer's disease, non-pharmacologic interventions in people with subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are one of the most important treatment strategies.

Objective: To clarify the efficacy of blue-green (500 nm) light therapy on sleep, mood, and physiological parameters in patients with SCD and aMCI is an interesting avenue to explore.

Methods: This is a monocentric, randomized, and controlled trial that will last for 4 weeks. We will recruit 150 individuals aged 45 years or older from memory clinics and divide them into 5 groups: SCD treatment (n = 30), SCD control (n = 30), aMCI treatment (n = 30), aMCI control (n = 30), and a group of healthy adult subjects (n = 30) as a normal control (NC).

Results: The primary outcome is the change in subjective and objective cognitive performance between baseline and postintervention visits (4 weeks after baseline). Secondary outcomes include changes in performance assessing from baseline, postintervention to follow-up (3 months after the intervention), as well as sleep, mood, and physiological parameters (including blood, urine, electrophysiology, and neuroimaging biomarkers).

Conclusion: This study aims to provide evidence of the impact of light therapy on subjective and objective cognitive performance in middle-aged and older adults with SCD or aMCI. In addition, we will identify possible neurophysiological mechanisms of action underlying light therapy. Overall, this trial will contribute to the establishment of light therapy in the prevention of Alzheimer's disease.
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http://dx.doi.org/10.3233/JAD-201560DOI Listing
January 2021

Clinical and functional significance of a novel ferroptosis-related prognosis signature in lung adenocarcinoma.

Clin Transl Med 2021 03;11(3):e364

Department of Respiratory and Critical Care Medicine, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan, China.

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http://dx.doi.org/10.1002/ctm2.364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968124PMC
March 2021

De Novo Development of a Universal Biosensing Platform by Rapid Direct Native Protein Modification.

Anal Chem 2021 03 18;93(12):5291-5300. Epub 2021 Mar 18.

Key Laboratory of Theoretical Organic Chemistry and Function Molecule, Ministry of Education, Hunan University of Science and Technology, Xiangtan 411201, China.

An innovative biosensing assay was developed for simplified, cost-effective, and sensitive detection. By rapid, direct treatment of target proteins with iron porphyrin (TPPFe) , a carboxyl group of amino acid conjugates with an Fe atom of the TPPFe molecule, forming a stable protein complex. We have shown that this complex not only maintains the integrity and functions of original proteins but also acquires peroxidase activity that can turn TMB to a comparably visible signal like that in ELISA. This study is unique since such conversion is difficult to achieve with standard chemical modification or molecular biology methods. In addition, the proposed immunoassay is superior to traditional ELISA as it eliminates an expensive and complicated cross-linking process of an enzyme-labeled antibody. From a practical point of view, we extended this assay to rapid detection of clinically relevant proteins and glucose in blood samples. The results show that this simple immunoassay provides clinical diagnosis, food safety, and environmental monitoring in an easy-to-implement manner.
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http://dx.doi.org/10.1021/acs.analchem.1c00341DOI Listing
March 2021

How the growth of ice depends on the fluid dynamics underneath.

Proc Natl Acad Sci U S A 2021 Mar;118(10)

Department of Applied Physics, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands.

Convective flows coupled with solidification or melting in water bodies play a major role in shaping geophysical landscapes. Particularly in relation to the global climate warming scenario, it is essential to be able to accurately quantify how water-body environments dynamically interplay with ice formation or melting process. Previous studies have revealed the complex nature of the icing process, but have often ignored one of the most remarkable particularities of water, its density anomaly, and the induced stratification layers interacting and coupling in a complex way in the presence of turbulence. By combining experiments, numerical simulations, and theoretical modeling, we investigate solidification of freshwater, properly considering phase transition, water density anomaly, and real physical properties of ice and water phases, which we show to be essential for correctly predicting the different qualitative and quantitative behaviors. We identify, with increasing thermal driving, four distinct flow-dynamics regimes, where different levels of coupling among ice front and stably and unstably stratified water layers occur. Despite the complex interaction between the ice front and fluid motions, remarkably, the average ice thickness and growth rate can be well captured with the theoretical model. It is revealed that the thermal driving has major effects on the temporal evolution of the global icing process, which can vary from a few days to a few hours in the current parameter regime. Our model can be applied to general situations where the icing dynamics occur under different thermal and geometrical conditions.
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http://dx.doi.org/10.1073/pnas.2012870118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958393PMC
March 2021

Paenibacillus glycinis sp. nov., an Endophytic Bacterium Isolated from the Nodules of Soybean (Glycine max (L.) Merr).

Curr Microbiol 2021 Apr 5;78(4):1678-1685. Epub 2021 Mar 5.

Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, 11340, Cd. México, México.

A Gram-negative-staining, endospore-forming, rod-shaped bacterium, designated T1, was isolated from root nodules of soybean (Glycine max (L.) Merr) in Heilongjiang Province of China. The isolate was identified as a member of the genus Paenibacillus based on phenotypic and phylogenetic characteristics. The 16S rRNA sequence was closely related to that of Paenibacillus sacheonensis SY01 with a similarity of 98.4%. Average nucleotide identity and in silico DNA-DNA hybridization values between strain T1 and P. sacheonensis DSM 23054 were 81.4% and 25.4%, respectively. The DNA G + C content of strain T1 was 58.2 mol%. meso-Diaminopimelic acid was detected in the cell-wall peptidoglycan. The major cellular fatty acids were anteiso-C, iso-C and iso-C. The predominant respiratory quinone was MK-7. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, five unidentified phospholipids, four unidentified aminophospholipids, an unidentified glycolipid and an unidentified lipid. Based on these results, T1 is considered to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus glycinis sp. nov. is proposed. The type strain is T1 (= CGMCC 1.18563 = KCTC43227).
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http://dx.doi.org/10.1007/s00284-021-02403-1DOI Listing
April 2021

Ultrasound-Induced Microbubble Cavitation Combined with miR-34a-Loaded Nanoparticles for the Treatment of Castration-Resistant Prostate Cancer.

J Biomed Nanotechnol 2021 Jan;17(1):78-89

Currently chemotherapy drugs are usually used as first-line treatments for castration-resistant prostate cancer (CRPC), but they are ineffective and accompanied by serious side effects. MicroRNA-34a (miR-34a) simultaneously targets multiple genes related to the cell apoptosis in CRPC cells without obvious side effects. It has shown great potential in the treatment of CRPC. Previous studies focused on miR-34a increasing the sensitivity of chemotherapy drugs to chemoresistant prostate cancer cells. There are few researches on miR-34a alone in the treatment of CRPC. But the macromolecular miR-34a is difficult to enter the cell and is easily degraded by nuclease. Therefore, we constructed methoxy polyethylene glycol-polylacticco-glycolic acid-polylysine (mPEG-PLGA-PLL) nanoparticles to encapsulate miR-34a (miR-34a/NP). The results showed that miR-34a/NP protects miR-34a from degradation by nucleases and can be phagocytized by PC-3 CRPC cells. Ultrasound induces microbubble cavitation (UIMC) improves cell membrane permeability and capillary gaps, and further promotes miR-34a/NP to enter cells PC-3 and prostate cancer xenografts. The miR-34a/NP that enters the cell and tumor tissue releases miR-34a, which suppressed CRPC cells PC-3 proliferation, promoted its apoptosis, and inhibited the growth of CRPC xenografts. Our research verified that miR-34a/NP, especially combined with UIMC, has a significant anti-tumor effect on CRPC.
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http://dx.doi.org/10.1166/jbn.2021.3020DOI Listing
January 2021

Clinical features and prognostic factors of patients with COVID-19 in Henan Province, China.

Hum Cell 2021 Mar 13;34(2):419-435. Epub 2021 Feb 13.

Department of Respiratory and Critical Care Medicine, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, No. 7 Weiwu Road, Zhengzhou, 450003, Henan, China.

Since December 2019, the novel coronavirus SARS-CoV-2 pandemic (COVID-19) outbroke in Wuhan and spread in China. Here we aimed to investigate the clinical and radiological characteristics of COVID-19 cases. We collected and analyzed the clinical data of 172 hospitalized cases of COVID-19 who were diagnosed via qRT-PCR of nasopharyngeal swabs during January 2020 and February 2020. The chest images were reviewed by radiologists and respirologists. The older patients with COVID-19 in Henan Province had more severe disease and worse prognosis. The male sex, smoking history and Wuhan exposure of patients are not related to the severity or prognosis of COVID-19. Family gatherings were showed among 26.7% of patients. A greater proportion of patients in the severe group suffer from combined chronic diseases. CT results showed that most patients had bilateral lung lesions and multiple lung lobes. The lungs of severe patients are more damaged. Both the infection range and inflammatory factor levels are related to the poor prognosis. Antiviral drugs, immunoglobulin and traditional Chinese medicine are mainly used for the treatment of COVID-19 patients. The discharge rate of COVID-19 patients was 93.0%, and the mortality rate was 2.3%. Case type, lymphocyte ratio grade, and respiratory failure at admission are risk factors for poor prognosis, except for the number of infiltrating lung lobes. The results showed that severe disease process, lymphopenia and respiratory failure are risk factors for the COVID-19.
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http://dx.doi.org/10.1007/s13577-021-00499-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882230PMC
March 2021

Psychometric properties of the critical thinking disposition assessment test amongst medical students in China: a cross-sectional study.

BMC Med Educ 2021 Jan 6;21(1):10. Epub 2021 Jan 6.

Institute for International Health Professions Education and Research, China Medical University, Shenyang, 110122, China.

Background: Critical thinking disposition helps medical students and professionals overcome the effects of personal values and beliefs when exercising clinical judgment. The lack of effective instruments to measure critical thinking disposition in medical students has become an obstacle for training and evaluating students in undergraduate programs in China. The aim of this study was to evaluate the psychometric properties of the CTDA test.

Methods: A total of 278 students participated in this study and responded to the CTDA test. Cronbach's α coefficient, internal consistency, test-retest reliability, floor effects and ceiling effects were measured to assess the reliability of the questionnaire. Construct validity of the pre-specified three-domain structure of the CTDA was evaluated by explanatory factor analysis (EFA) and confirmatory factor analysis (CFA). The convergent validity and discriminant validity were also analyzed.

Results: Cronbach's alpha coefficient for the entire questionnaire was calculated to be 0.92, all of the domains showed acceptable internal consistency (0.81-0.86), and the test-retest reliability indicated acceptable intra-class correlation coefficients (ICCs) (0.93, p < 0.01). The EFA and the CFA demonstrated that the three-domain model fitted the data adequately. The test showed satisfactory convergent and discriminant validity.

Conclusions: The CTDA is a reliable and valid questionnaire to evaluate the disposition of medical students towards critical thinking in China and can reasonably be applied in critical thinking programs and medical education research.
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http://dx.doi.org/10.1186/s12909-020-02437-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786903PMC
January 2021
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