Publications by authors named "Yang Guo"

655 Publications

YAP inhibits autophagy and promotes progression of colorectal cancer via upregulating Bcl-2 expression.

Cell Death Dis 2021 May 7;12(5):457. Epub 2021 May 7.

Department of Immunology, School of Basic Medical Sciences, Hubei University of Medicine, 442000, Shiyan, Hubei, P. R. China.

Colorectal cancer (CRC) is one of the most aggressive and lethal cancers. The role of autophagy in the pathobiology of CRC is intricate, with opposing functions manifested in different cellular contexts. The Yes-associated protein (YAP), a transcriptional coactivator inactivated by the Hippo tumor-suppressor pathway, functions as an oncoprotein in a variety of cancers. In this study, we found that YAP could negatively regulate autophagy in CRC cells, and consequently, promote tumor progression of CRC in vitro and in vivo. Mechanistically, YAP interacts with TEAD forming a complex to upregulate the transcription of the apoptosis-inhibitory protein Bcl-2, which may subsequently facilitate cell survival by suppressing autophagy-related cell death; silencing Bcl-2 expression could alleviate YAP-induced autophagy inhibition without affecting YAP expression. Collectively, our data provide evidence for YAP/Bcl-2 as a potential therapeutic target for drug exploration against CRC.
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http://dx.doi.org/10.1038/s41419-021-03722-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105309PMC
May 2021

A Vital Signs Telemonitoring Programme Improves the Dynamic Prediction of Readmission Risk in Patients with Heart Failure.

AMIA Annu Symp Proc 2020 25;2020:432-441. Epub 2021 Jan 25.

Institute for Infocomm Research, Agency for Science Technology & Research, Singapore.

Heart failure (HF) is a leading cause of hospital readmissions. There is great interest in approaches to efficiently predict emerging HF-readmissions in the community setting. We investigate the possibility of leveraging streaming telemonitored vital signs data alongside readily accessible patient profile information for predicting evolving 30-day HF-related readmission risk. We acquired data within a non-randomized controlled study that enrolled 150 HF patients over a 1-year post-discharge telemonitoring and telesupport programme. Using the sequential data and associated ground truth readmission outcomes, we developed a recurrent neural network model for dynamic risk prediction. The model detects emerging readmissions with sensitivity > 71%, specificity > 75%, AUROC ~80%. We characterize model performance in relation to telesupport based nurse assessments, and demonstrate strong sensitivity improvements. Our approach enables early stratification of high-risk patients and could enable adaptive targeting of care resources for managing patients with the most urgent needs at any given time.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075426PMC
January 2021

Threshold-Based Hierarchical Clustering for Person Re-Identification.

Entropy (Basel) 2021 Apr 24;23(5). Epub 2021 Apr 24.

College of Computer Science, National University of Defense Technology, Changsha 410073, China.

Unsupervised domain adaptation is a challenging task in person re-identification (re-ID). Recently, cluster-based methods achieve good performance; clustering and training are two important phases in these methods. For clustering, one major issue of existing methods is that they do not fully exploit the information in outliers by either discarding outliers in clusters or simply merging outliers. For training, existing methods only use source features for pretraining and target features for fine-tuning and do not make full use of all valuable information in source datasets and target datasets. To solve these problems, we propose a hreshold-based ierarchical clustering method with ontrastive loss (THC). There are two features of THC: (1) it regards outliers as single-sample clusters to participate in training. It well preserves the information in outliers without setting cluster number and combines advantages of existing clustering methods; (2) it uses contrastive loss to make full use of all valuable information, including source-class centroids, target-cluster centroids and single-sample clusters, thus achieving better performance. We conduct extensive experiments on Market-1501, DukeMTMC-reID and MSMT17. Results show our method achieves state of the art.
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http://dx.doi.org/10.3390/e23050522DOI Listing
April 2021

Electrochemical Activity and Damage of Single Carbon Fiber.

Materials (Basel) 2021 Apr 2;14(7). Epub 2021 Apr 2.

Chemical and Materials Systems Lab, GM Global R&D, 30500 Mound Rd., Warren, MI 48090, USA.

The electrochemical activity of a carbon fiber was characterized at different potentials in 3.5 wt.% NaCl solution, and the fiber cylindrical surface changed by polarization at different potentials was revealed by SEM, AFM, optical microscopy, FTIR spectroscopy, Raman spectroscopy, and XRD. The results showed that the carbon fiber exhibited different electrochemical activities at some polarization potentials; within a 3V potential range the anodic and cathodic polarization current densities stepped up by more than 5 orders of magnitude, and the carbon fiber (CF) surface dramatically changed with time. Strong anodic polarization appeared to facilitate the breakdown of C-C covalent bonds in the carbon fiber and enhance the amorphization of the fiber surface.
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http://dx.doi.org/10.3390/ma14071758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038226PMC
April 2021

Knockout of interleukin-17A diminishes ventricular arrhythmia susceptibility in diabetic mice via inhibiting NF-κB-mediated electrical remodeling.

Acta Pharmacol Sin 2021 Apr 28. Epub 2021 Apr 28.

Department of Pharmacology (State-Province Key Laboratories of Biomedicine Pharmaceutics of China, Key Laboratory of Cardiovascular research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.

Interleukin-17A (IL-17), a potent proinflammatory cytokine, has been shown to participate in cardiac electrical disorders. Diabetes mellitus is an independent risk factor for ventricular arrhythmia. In this study, we investigated the role of IL-17 in ventricular arrhythmia of diabetic mice. Diabetes was induced in both wild-type and IL-17 knockout mice by intraperitoneal injection of streptozotocin (STZ). High-frequency electrical stimuli were delivered into the right ventricle to induce ventricular arrhythmias. We showed that the occurrence rate of ventricular tachycardia was significantly increased in diabetic mice, which was attenuated by IL-17 knockout. We conducted optical mapping on perfused mouse hearts and found that cardiac conduction velocity (CV) was significantly decreased, and action potential duration (APD) was prolonged in diabetic mice, which were mitigated by IL-17 knockout. We performed whole-cell patch clamp recordings from isolated ventricular myocytes, and found that the densities of I, I and I were reduced, the APDs at 50% and 90% repolarization were increased, and early afterdepolarization (EAD) was markedly increased in diabetic mice. These alterations were alleviated by the knockout of IL-17. Moreover, knockout of IL-17 alleviated the downregulation of Nav1.5 (the pore forming subunit of I), Cav1.2 (the main component subunit of I) and KChIP2 (potassium voltage-gated channel interacting protein 2, the regulatory subunit of I) in the hearts of diabetic mice. The expression of NF-κB was significantly upregulated in the hearts of diabetic mice, which was suppressed by IL-17 knockout. In neonatal mouse ventricular myocytes, knockdown of NF-κB significantly increased the expression of Nav1.5, Cav1.2 and KChIP2. These results imply that IL-17 may represent a potential target for the development of agents against diabetes-related ventricular arrhythmias.
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http://dx.doi.org/10.1038/s41401-021-00659-8DOI Listing
April 2021

CXCL13 promotes intestinal tumorigenesis through the activation of epithelial AKT signaling.

Cancer Lett 2021 Apr 22;511:1-14. Epub 2021 Apr 22.

Laboratory of Inflammation and Molecular Pharmacology, School of Basic Medical Sciences & Biomedical Research Institute, Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan 442000, China. Electronic address:

The excessive release of proinflammatory chemokines promotes cell proliferation and tumor growth in colorectal cancer. However, their regulatory functions and molecular pathogenesis have not been well elucidated. Here, we observed the upregulation of chemokine (C-X-C motif) ligand 13 (CXCL13) in human colorectal cancers and mouse intestinal tumors. Both CXCL13 deficiency and blockade of CXCL13 signaling ameliorated disease progression. CXCL13 promoted intestinal tumorigenesis through the activation of the AKT signaling pathway in a C-X-C chemokine receptor type 5 (CXCR5)-dependent manner. Intestinal microbiota translocation drove CXCL13 production in dendritic cells through the activation of NF-κB signaling. Inhibition of microbiota translocation decreased CXCL13 production and ameliorated intestinal tumorigenesis. Together, the results of this study identify a role for the CXCL13-CXCR5 axis is involved in the crosstalk between chemokines and cell growth during the development of intestinal tumorigenesis, which also provides a therapeutic strategy for targeting CXCL13/CXCR5 in the future clinical treatment of intestinal tumors.
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http://dx.doi.org/10.1016/j.canlet.2021.04.012DOI Listing
April 2021

Internal structure and textural properties of a milk protein composite gel construct produced by three-dimensional printing.

J Food Sci 2021 Apr 22. Epub 2021 Apr 22.

Laboratory of Food Soft Matter Structure and Advanced Manufacturing, College of Food Science and Engineering, Collaborative Center for Modern Grain Circulation and Safety, Key Laboratory of Grain and Oil Quality Control and Processing, Nanjing University of Finance and Economics, Nanjing, China.

Three-dimensional (3D) printing technology is an emerging technology that can be used to fabricate food products composed of milk protein composite gel with desired structures. In this study, the products were printed by an extrusion-based 3D printer with the variation of perimeters (3, 5, and 7), infill patterns (Hilbert curve, honeycomb, and rectilinear), and infill levels (10%, 40%, and 70%). The textural properties, geometrical accuracy, and internal structure of the products were evaluated by texture analyzer, camera, and scanning electron microscope, respectively. The geometrical accuracies of products were all apparently close to 100%. Gumminess and hardness were bound with the infill level and perimeters. However, the gumminess and hardness were not associated with the infill pattern, which was created to fill the products. In addition, only the infill percentage affected Young's modulus and firmness. Products exhibited uniform internal structures, and the hardness of products with 100% infill level was still lower than that of nonprinted material. Three-dimensional extrusion behavior will modify the textural and structural properties of products by adjusting the infill level and perimeters, offering a new method for improving the biophysics of sensory properties of products that are suitable for people with different chewing abilities. PRACTICAL APPLICATION: Milk protein composite gel, also called "milk cube," is a delicious snack that is widely consumed around the world. This study aimed to explore the effect of internal structure on the texture and geometrical accuracy of printed milk protein composite gel when different perimeters, infill patterns, and levels were used. This study proved that 3D food printing technology can provide a new way to modify the texture of the printed food by regulating and controlling perimeters, infill patterns, and levels to fill the printed products. This kind of printed food can be designed for people with different chewing abilities.
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http://dx.doi.org/10.1111/1750-3841.15727DOI Listing
April 2021

Estrogen profile- and pharmacogenetics-based lamotrigine dosing regimen optimization: Recommendations for pregnant women with epilepsy.

Pharmacol Res 2021 Apr 20;169:105610. Epub 2021 Apr 20.

Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. Electronic address:

During pregnancy, various physiological changes occur that can alter the pharmacokinetics of antiepileptic drugs, such as lamotrigine (LTG). Anticipating the change in LTG dose required to achieve a pre-pregnancy target concentration is challenging. This study aimed to develop a refined population pharmacokinetic (PopPK) model of LTG in pregnant women with epilepsy (WWE) to identify factors explaining the variability in pharmacokinetics and to establish a model-informed individualized dosing regimen. On that basis, a coarsened model containing only clinical variables was also developed to examine its predictive performance compared to the refined model. In total, 322 concentration-time points from 51 pregnant WWE treated with LTG were employed to establish a refined PopPK model that included endogenous estrogen profiles, variants of candidate genes encoding LTG-metabolizing enzymes and -transporter proteins, and other clinical variables and a coarsened model that included only clinical variables, respectively. Data from an additional 11 patients were used for external validation of these two models. A nonlinear mixed-effect modeling approach was used for PopPK analysis of LTG. The standard goodness-of-fit method, bootstrap, normalized prediction distribution errors and external evaluation were adopted to estimate the stability and predictive performance of the candidate models. Akaike information criterion (AIC) was used to compare the goodness of fit between these two models. A lower AIC indicates a better fit of the data and the preferred model. Recommended dosing regimens for pregnant WWE were selected using Monte Carlo simulation based on the established optimal model. In the refined PopPK model, the population mean of apparent LTG clearance (CL/F) in pregnant WWE was estimated to be 2.82 L/h, with an inter-individual variability of 23.6%. PopPK analysis indicated that changes in estrogen profile during pregnancy were the predominant reason for the significant variations in LTG-CL/F. Up to the 3rd trimester, the concentration accumulation effect of E2 increased LTG-CL/F by 5.109 L/h from baseline levels. Contrary to effect of E2, E3 as the main circulating estrogen in pregnancy with a peak value of 34.41 ng/mL is 1000-fold higher than that in non-pregnancy reduced LTG-CL/F by 1.413 L/h. In addition, the UGT2B7 rs4356975 C > T and ABCB1 rs1128503 A > G variants may contribute to a better understanding of the inter-individual variability in LTG-CL/F. LTG-CL/F was 1.66-fold higher in UGT2B7 rs4356975 CT or TT genotype carriers than in CC genotype carriers. In contrast, ABCB1 rs1128503 GG genotype carriers had only 71.9% of the LTG-CL/F of AA or AG genotype carriers. In the coarsened PopPK model, the gestational age was a promising predictor of changes in LTG-CL/F. When comparing these two models, the refined PopPK model was favored over the coarsened PopPK model (AIC = -30.899 vs. -20.017). Monte Carlo simulation based on optimal PopPK model revealed that the LTG dosage administered to carriers of the UGT2B7 rs4356975 CT or TT genotype required a 33-50% increase to reach the pre-pregnancy target concentration, and carriers of the ABCB1 rs1128503 GG genotype required a 33-66% lower dose of LTG than carriers of the ABCB1 rs1128503 AA or AG genotype. Changes in estrogen profile during pregnancy was a better predictor of variations in LTG-CL/F than gestational age. The developed model based on estrogen profile and pharmacogenetics can serve as a foundation for further optimization of dosing regimens of LTG in pregnant WWE.
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http://dx.doi.org/10.1016/j.phrs.2021.105610DOI Listing
April 2021

Prevalence, Subtype Classification, and Outcomes of Treatment of Primary Aldosteronism: A Prospective Study in China.

Endocr Pract 2021 May 14;27(5):478-483. Epub 2020 Dec 14.

Center of Laboratory Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. Electronic address:

Objective: To investigate the prevalence of primary aldosteronism (PA) among participants with hypertension, evaluate the concordance of PA classification between adrenal computed tomography and adrenal venous sampling, and compare the outcomes of surgery and medication for unilateral PA.

Methods: A prospective study was conducted among all inpatients with hypertension (n = 7594) at the National Center for Cardiovascular Diseases, China, from May 2016 to April 2018.

Results: Of the 7594 participants, 8.12% (n = 617) with plasma aldosterone-renin ratio ≥3.7 were possible PA cases. Three hundred sixty-seven cases with plasma aldosterone-renin ratio ≥3.7 and plasma aldosterone concentration ≥10 ng/dL were confirmed using the recumbent saline infusion test (69.20%, 182 of 263) or the captopril challenge test (66.5%, 69 of 104, P > .05). The prevalence of PA was 3.31% (n = 251). Of the 251 patients with PA, all of them had multiple comorbidities, and 49.40% (n = 124) had spontaneous hypokalemia. The concordance of PA classification between adrenal computed tomography and adrenal venous sampling was only 47.11%. The patients' blood pressure declined to normal ranges in the adrenalectomy (85.71%, 30 of 35) and spironolactone (63.04%; 29 of 46) groups (P < .05). Furthermore, hypokalemia was normalized in the adrenalectomy (100.00%; 26 of 26) and spironolactone (94.74%; 18 of 19) groups.

Conclusion: It is necessary to incorporate PA screening into routine practice for those with hypertension in the Chinese population. This will assist in ensuring that the best therapeutic schedule based on PA subtypes is devised. Additionally, as a result, it may contribute to restoring the blood pressure levels and reducing the prevalence of comorbidities in these patients with PA.
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http://dx.doi.org/10.1016/j.eprac.2020.10.007DOI Listing
May 2021

Hypoglycemic effect of root extract and its synergism with extract.

Food Sci Nutr 2021 Apr 26;9(4):2075-2085. Epub 2021 Feb 26.

School of Forestry Northeast Forestry University Harbin China.

(dandelion) and are traditional medicinal and edible plants with high nutritional value. In this study, the synergistic hypoglycemic effect of DRE and extract (RAE) was evaluated. Our results showed that water extract of dandelion (DRE-w), mainly containing polysaccharides (63.92 ± 1.82 mg/g), total flavonoid (2.57 ± 0.06 mg/g), total phenolic compounds (8.93 ± 0.34 mg/g), and saponins (0.54 ± 0.05 mg/g), exhibited significantly inhibitory effect on α-glucosidase and α-amylase. DRE-w and RAE had synergistic hypoglycemic effect; we found that DRE-w and its combination with RAE could relieve the state of insulin resistance in IR-HepG2 cells. The combination could more significantly increase the glucose consumption and intracellular glycogen content, and improve the activity of hexokinase and pyruvate kinase in IR-HepG2 cells. In summary, DRE and its combination with RAE can be developed as the drugs or functional foods for diabetes prevention and treatment.
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http://dx.doi.org/10.1002/fsn3.2176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020951PMC
April 2021

Comprehensive analyses of correlation and survival reveal informative lncRNA prognostic signatures in colon cancer.

World J Surg Oncol 2021 Apr 9;19(1):104. Epub 2021 Apr 9.

School of Computer Science and Engineering, Northwestern Polytechnical University, Xi'an, People's Republic of China.

Background: Colon cancer is a commonly worldwide cancer with high morbidity and mortality. Long non-coding RNAs (lncRNAs) are involved in many biological processes and are closely related to the occurrence of colon cancer. Identification of the prognostic signatures of lncRNAs in colon cancer has great significance for its treatment.

Methods: We first identified the colon cancer-related mRNAs and lncRNAs according to the differential analysis methods using the expression data in TCGA. Then, we performed correlation analysis between the identified mRNAs and lncRNAs by integrating their expression values and secondary structure information to estimate the co-regulatory relationships between the cancer-related mRNAs and lncRNAs. Besides, the competing endogenous RNA regulation network based on co-regulatory relationships was constructed to reveal cancer-related regulatory patterns. Meanwhile, we used traditional regression analysis (univariate Cox analysis, random survival forest analysis, and lasso regression analysis) to screen the cancer-related lncRNAs. Finally, by combining the identified colon cancer-related lncRNAs according to the above analyses, we constructed a risk prognosis model for colon cancer through multivariate Cox analysis and also validated the model in the colon cancer dataset in TCGA cohorts.

Results: Six lncRNAs were found highly correlated with the overall survival of colon cancer patients, and a risk prognosis model based on them was constructed to predict the overall survival of colon cancer patients. In particular, EVX1-AS, ZNF667-AS1, CTC-428G20.6, and CTC-297N7.9 were first reported to be related to colon cancer by using our model, among which EVX1-AS and ZNF667-AS1 have been predicted to be related to colon cancer in LncRNADisease database.

Conclusions: This study identified the potential regulatory relationships between lncRNAs and mRNAs by integrating their expression values and secondary structure information and presented a significant 6-lncRNA risk prognosis model to predict the overall survival of colon cancer patients.
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http://dx.doi.org/10.1186/s12957-021-02196-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035745PMC
April 2021

Evaluation of Adjacent Segment With Pre-Existing Degeneration Using the Cerebrospinal Fluid Occlusion Sign on MRI Before Posterior Lumbar Fusion: A Multi-Center Observational Cohort Study.

Global Spine J 2021 Apr 7:21925682211007116. Epub 2021 Apr 7.

Orthopaedic Department of 105738Beijing Tiantan Hospital, Beijing, China.

Study Design: Prospective cohort study.

Objective: To evaluate whether pre-existing adjacent spinal canal stenosis (SCS) is associated with short-term outcomes after lumbar fusion surgery.

Methods: We included patients with lumbar spinal stenosis treated surgically between July 2015 and December 2017 at 4 centers. All patients had the same pathology, with L4-S1 as the culprit sections. Patients were divided into 2 groups based on the cerebrospinal fluid occlusion sign on MRI at the adjacent L3/4 level. Patients without SCS (grade 0) and with mild SCS (grade 1) were classified into the non-stenosis (NS) and mild stenosis (MS) groups, respectively. All patients underwent PLIF and completed at least 1-year follow-up. The incidence of adjacent segment degeneration (ASDeg) and clinical outcomes were compared between the 2 groups.

Results: A total of 308 patients (NS, 156; MS, 152) met the inclusion criteria. The incidence of ASDeg in the NS group (n = 40, 25.6%) was significantly lower than that in the MS group (n = 74, 48.7%; < .001). The most frequent type of ASDeg in the 2 groups was the SCS-aggravated type. No significant difference was observed in adjacent segment disease incidence between the 2 groups ( = .243). The NS group had better outcomes according to the clinical function scores ( < .05).

Conclusions: The cerebrospinal fluid occlusion sign on MRI is valuable for evaluating the adjacent segment with pre-existing degeneration. Patients with mild SCS in adjacent segments were more likely to have ASDeg, and the most frequent type of ASDeg was the SCS-aggravated type at early follow-up.
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http://dx.doi.org/10.1177/21925682211007116DOI Listing
April 2021

Low-intensity pulsed ultrasound stimulates proliferation of stem/progenitor cells: what we need to know to translate basic science research into clinical applications.

Asian J Androl 2021 Apr 2. Epub 2021 Apr 2.

Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA 94143, USA.

Low-intensity pulsed ultrasound (LIPUS) is a promising therapy that has been increasingly explored in basic research and clinical applications. LIPUS is an appealing therapeutic option as it is a noninvasive treatment that has many advantages, including no risk of infection or tissue damage and no known adverse reactions. LIPUS has been shown to have many benefits including promotion of tissue healing, angiogenesis, and tissue regeneration; inhibition of inflammation and pain relief; and stimulation of cell proliferation and differentiation. The biophysical mechanisms of LIPUS remain unclear and the studies are ongoing. In recent years, more and more research has focused on the relationship between LIPUS and stem/progenitor cells. A comprehensive search of the PubMed and Embase databases to July 2020 was performed. LIPUS has many effects on stem cells. Studies show that LIPUS can stimulate stem cells in vitro; promote stem cell proliferation, differentiation, and migration; maintain stem cell activity; alleviate the problems of insufficient seed cell source, differentiation, and maturation; and circumvent the low efficiency of stem cell transplantation. The mechanisms involved in the effects of LIPUS are not fully understood, but the effects demonstrated in studies thus far have been favorable. Much additional research is needed before LIPUS can progress from basic science research to large-scale clinical dissemination and application.
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http://dx.doi.org/10.4103/aja.aja_25_21DOI Listing
April 2021

Transcriptome Analysis Reveals Genes Involved in Thermogenesis in Two Cold-Exposed Sheep Breeds.

Genes (Basel) 2021 Mar 6;12(3). Epub 2021 Mar 6.

Northwest Institute of Ecological Environment and Resources, Chinese Academy of Sciences, Lanzhou 730070, China.

Thermogenesis plays an important role in the survival of sheep exposed to low temperatures; however, little is known about the genetic mechanisms underlying cold adaptation in sheep. We examined 6 Altay (A) and 6 Hu (H) six-month-old ewe lambs. Altay sheep are raised in northern China and are adapted to dry, cold climates, while Hu sheep are raised in southern China and are adapted to warm, humid climates. Each breed was divided into two groups: chronic cold sheep, exposed to -5 °C for 25 days (3 A; 3 H), and thermo-neutral sheep, maintained at 20 °C (3 A; 3 H). The transcriptome profiles of hypothalamus, tail-fat and perirenal fat tissues from these four groups were determined using paired-end sequencing for RNA expression analysis. There are differences in cold tolerance between Hu and Altay sheep. Under cold exposure of the lambs: (1) UCP1-dependent thermogenesis and calcium- and cAMP-signaling pathways were activated; and (2) different fat tissues were activated in Hu and Altay lambs. Several candidate genes involved in thermogenesis including , , , , and were identified. Molecular mechanisms of thermogenesis in the sheep are discussed and new avenues for research are suggested.
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http://dx.doi.org/10.3390/genes12030375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999592PMC
March 2021

Mononuclear nickel(II) dithiolate complexes with chelating diphosphines: Insight into protonation and electrochemical proton reduction.

J Inorg Biochem 2021 Jun 27;219:111449. Epub 2021 Mar 27.

School of Materials Science and Engineering, North University of China, Taiyuan 030051, PR China. Electronic address:

Inspired by the metal active sites of [FeFe]- and [NiFe]‑hydrogenases, a series of mononuclear Ni(II) ethanedithiolate complexes [{(PhPCH)×}Ni(SCHCHS)] (X = NCHCHN-p (2a), NCHCH (2b), NCHCHMe (2c), and CH (2d)) with chelating diphosphines were readily synthesized through the room-temperature treatments of mononuclear Ni(II) dichlorides [{(PhPCH)×}NiCl] (1a-1d) with ethanedithiol (HSCHCHSH) in the presence of triethylamine (EtN) as acid-binding agent. All the as-prepared complexes 1a-1d and 2a-2d are fully characterized through elemental analysis, nuclear magnetic resonance (NMR) spectrum, and by X-ray crystallography for 1b, 2a-2d. To further explore proton-trapping behaviors of this type of mononuclear Ni(II) complexes for catalytic hydrogen (H) evolution, the protonation and electrochemical proton reduction of 2a-2c with aminodiphosphines (labeled PCNCP = (PhPCH)NR) and reference analogue 2d with nitrogen-free diphosphine (dppp = (PhPCH)CH) are studied and compared under trifluoroacetic acid (TFA) as a proton source. Interestingly, the treatments of 2a-2d with excess TFA resulted in the unexpected formation of dinuclear Ni(II)-Ni(II) dication complexes [{(PhPCH)×}Ni(μ-SCHCHS)](CFCO) (3a-3d) and mononuclear Ni(II) N-protonated complexes [{(PhPCH)N(H)R}Ni(SCHCHS)](CFCO) (4a-4c), which has been well supported by high-resolution electrospray ionization mass spectroscopy (HRESI-MS), NMR (P, H) as well as fourier transform infrared spectroscopy (FT-IR) techniques, and especially by X-ray crystallography for 3d. Additionally, the electrochemical properties of 2a-2d are investigated in the absence and presence of strong acid (TFA) by using cyclic voltammetry (CV), showing that the complete protonation of 2a-2d gave rise to dinuclear NiS species 3a-3d for electrocatalytic proton reduction to H.
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http://dx.doi.org/10.1016/j.jinorgbio.2021.111449DOI Listing
June 2021

Upregulating hsa-miR-128a Increased the Effects of Pembrolizumab on Laryngeal Cancer Cells via the p53 Pathway.

Biomed Res Int 2021 18;2021:2342784. Epub 2021 Mar 18.

Department of Otolaryngology-Head and Neck Surgery, Eye and ENT Hospital of Fudan University, No. 83, Fenyang Road, Xuhui District, 200031 Shanghai, China.

Objectives: Recently, immunotherapy and microRNA have shown much more promises in oncology research, inspiring new hope for a cure for various malignancies. Specifically, the function and mechanisms of action of pembrolizumab have been investigated in many cancers, but not in laryngeal squamous cell carcinoma. The present study thus focused on the effect of hsa-miR-128a on pembrolizumab in laryngeal cancer cells as well as tried to elucidate the mechanisms that may mediate this effect.

Methods: Hep2 and AMC-HN8 cell lines were utilized to create stable cell lines that overexpressing hsa-miR-128a. Using the immunotherapy assay, the contribution of hsa-miR-128a to pembrolizumab sensitivity was evaluated. By performing the dual luciferase assay and quantitative real-time polymerase chain reaction, the possible mechanisms of hsa-miR-128a were identified.

Results: Hsa-miR-128a was overexpressed in laryngeal cancer cell lines successfully. The immunotherapy assay revealed that upregulating hsa-miR-128a augmented the effect of pembrolizumab. Moreover, hsa-miR-128a targeted BMI-1 and might played a role in the p53 pathway.

Conclusion: Hsa-miR-128a boosted the effect of pembrolizumab on laryngeal cancer cells, perhaps via the p53 pathway. Therefore, hsa-miR-128a might be a novel target in laryngeal cancer treatment.
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http://dx.doi.org/10.1155/2021/2342784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997759PMC
March 2021

MLKL inhibits intestinal tumorigenesis by suppressing STAT3 signaling pathway.

Int J Biol Sci 2021 17;17(3):869-881. Epub 2021 Feb 17.

Laboratory of Inflammation and Molecular Pharmacology, Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences & Biomedical Research Institute, Hubei University of Medicine, Shiyan 442000, China.

Mixed lineage kinase domain-like protein (MLKL) plays an important role in necroptosis, but the role and mechanism of MLKL in intestinal tumorigenesis remain unclear. Here, we found that hematopoietic- and nonhematopoietic-derived MLKL affected intestinal inflammation, but nonhematopoietic-derived MLKL primarily inhibited intestinal tumorigenesis. Loss of MLKL enhanced intestinal regeneration and the susceptibility to intestinal tumorigenesis in mice by hyperactivating the Janus kinase 2 (JAK2)/ signal transducer and activator of transcription 3 (STAT3) axis. Furthermore, MLKL deficiency increased interleukin-6 (IL-6) production in dendritic cells. Administration of anti-IL-6R antibody therapy reduced intestinal tumorigenesis in mice. Notably, low MLKL expression in human colorectal tumors, which enhanced STAT3 activation, was associated with decreased overall survival. Together, our results reveal that MLKL exhibits a suppressive effect during intestinal tumorigenesis by suppressing the IL-6/JAK2/STAT3 signals.
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http://dx.doi.org/10.7150/ijbs.56152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975698PMC
February 2021

The clinical characteristics and prognosis of COVID-19 patients with comorbidities: a retrospective analysis of the infection peak in Wuhan.

Ann Transl Med 2021 Feb;9(4):280

Trauma Center, Peking University People's Hospital, Key Laboratory of Trauma and Neural Regeneration (Peking University), Ministry of Education, Beijing, China.

Background: This study aims to determine the clinical characteristics and prognosis of COVID-19 patients with comorbidities and to identify survival factors.

Methods: A retrospective study was conducted in Wuhan, China, between February 8, 2020, and March 9, 2020. Based on underlying diseases, patients were assigned to either the comorbidity group or the non-comorbidity group. The clinical characteristics and outcomes of COVID-19 were analyzed and a Kaplan-Meier survival analysis was used to evaluate the prognosis predictive value of each comorbidity.

Results: During the study period, 278 COVID-19 patients were enrolled, 175 (62.95%) were assigned to the comorbidity group, and 103 (37.05%) to the non-comorbidity group. Of the patients in the comorbidity group, 34.86% were classified as critical. Further, patients in the comorbidity group had lower lymphocyte cell counts, and higher concentrations of D-dimer, high sensitivity C-reactive protein, interleukin 6, and serum ferritin as well as higher critical illness severity scores than patients in the non-comorbidity group (P<0.05). Patients in the comorbidity group also had higher mortality, acute respiratory distress syndrome, and ventilation treatment rates than patients in the non-comorbidity group (P<0.05). The length of hospital stay was longer in the comorbidity group than in the non-comorbidity group (P<0.05). The most common underlying diseases included hypertension (40.65%), diabetes mellitus (20.5%), and cardiovascular disease (19.42%). Patients with comorbidities were more likely to develop cardiovascular sequelae associated with COVID-19, shock, acute kidney injury, and multiple organ dysfunction syndrome (30.86% 12.62%, P=0.001; 18.86% 8.74%, P=0.023; 24.57% 11.65%, P=0.009; 33.71% 14.56%, P=0.000, respectively). In the Kaplan-Meier survival analysis, older patients (¡Ý65 years) (log-rank test: χ=4.202, P=0.040) and patients with chronic obstructive pulmonary disease (COPD) (log-rank test: χ=4.839, P=0.028) or diabetes mellitus (log-rank test: χ=4.377, P=0.036) had shorter survival than those without comorbidities.

Conclusions: Patients with comorbidities were more severely affected and had a higher mortality rate. Age, COPD and diabetes mellitus were the main factors affecting the survival of patients.
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http://dx.doi.org/10.21037/atm-20-4052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944295PMC
February 2021

Next-generation sequencing facilitates differentiating between multiple primary lung cancer and intrapulmonary metastasis: a case series.

Diagn Pathol 2021 Mar 11;16(1):21. Epub 2021 Mar 11.

Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, China.

Background: In lung cancer management, differential diagnosis between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IMP) is a critical point that is of direct therapeutic and clinical importance. However, this process often suffers from absence of a gold standard, resulting in equivocal cases. Herein, we present a series of three cases, in which genomic alteration patterns revealed by next-generation sequencing (NGS) facilitated the differential diagnosis between MPLC and IMP.

Case Presentation: Case 1 was a 57-year-old female with two separate lesions in the upper lobe and the lower lobe of left lung, which were both histopathologically determined as T2aN0M0 adenocarcinomas. NGS identified an EGFR L858R in one lesion and an EGFR 20 exon insertion in the other one, suggestive of double primary malignancies. The patient underwent wedge resections and received an adjuvant treatment of icotinib and chemotherapy. She had a disease-free survival (DFS) of 19 months and counting. Case 2 was a 55-year-old female with multiple small lesions in both lungs. Histopathological examinations of resected lesions from right upper lobe revealed three subtypes: atypical adenomatous hyperplasia of alveolar epithelium, adenocarcinomas in situ and minimally invasive adenocarcinoma. NGS identified two different BRAF driver mutations G466E and V600_K601delinsE in two lesions of adenocarcinoma in situ, and a BRAF K601E in a lesion of minimally invasive adenocarcinoma. Case 3, a 68-year-old male, had the right upper lobe lesion histophathologically classified as a stage T3NxM0 mixed adenoneuroendocrine carcinoma and the left upper lobe lesion as a stage T1aN0M0 adenocarcinoma. NGS performed with different loci of surgical tissues revealed a rare sensitizing EGFR mutation G719A shared by the right upper lobe lesion and lymph node, and two EGFR mutations L861Q and G719S in left upper lobe lesion. The patient received icotinib treatment postoperatively and achieved a stable disease with a progression-free survival of 5 months.

Conclusion: Our cases provide evidence for utility of NGS in facilitating diagnosis and treatment decisions.
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http://dx.doi.org/10.1186/s13000-021-01083-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953741PMC
March 2021

CX3CR1 might be a promising predictor of systemic lupus erythematosus patients with pulmonary fibrosis.

Scand J Immunol 2021 Mar 4:e13038. Epub 2021 Mar 4.

Institute of Basic Medical Science, Hubei University of Medicine, Shiyan, China.

The inflammatory process in systemic lupus erythematosus (SLE) affects many organs including the lungs. Chemokines are suggested to play important roles in the pathogenesis of SLE with pulmonary fibrosis (PF). In the present study, our objective is to evaluate the correlation between chemokines and PF in SLE patients. Transcriptome sequencing analysis was used to find the different expressed genes between SLE patients with PF and without PF. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of chemokines in SLE patients and healthy controls. Expression of CX3CR1 was measured by real-time polymerase chain reaction (PCR) and flow cytometer. Sixteen differentially chemokine genes were found to be associated to SLE with PF. Meanwhile, the upregulation of C-X3-C motif chemokine receptor 1 (CX3CR1) and its ligand, CX3C chemokine ligand 1 (CX3CL1) were observed in SLE patients with PF than that of SLE patients without PF and healthy control. Phenotypic analysis also showed that the surface expression of CX3CR1 increased in PBMCs from SLE patients with PF. Our observations indicated that CX3CL1/CX3CR1 axis is associated with PF in SLE. CX3CR1 might be a promising predictor of SLE with PF and the interactions between CX3CL1 and CX3CR1 might provide potential candidate target for the treatment of SLE with PF.
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http://dx.doi.org/10.1111/sji.13038DOI Listing
March 2021

Symptomatic spinal cord compression: an uncommon symptom in pseudohypoparathyroidism.

Ann N Y Acad Sci 2021 Mar 4. Epub 2021 Mar 4.

Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, PR China.

We describe symptomatic spinal cord compression associated with pseudohypoparathyroidism (PHP) in a young female patient and reviewed similar cases previously reported in the literature. The characteristics of these cases were analyzed from etiology, clinical subtypes, symptoms, treatment, and prognosis. Neurological examination revealed functional upper extremities with bilateral lower extremity paraplegia. Laboratory tests showed hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone; high-throughput sequencing showed a heterozygous GNAS mutation in exon 12, specifically c.1006C > T (p.R336W). Imaging findings showed multilevel spinal stenosis with significant spinal cord compression at the T2-T3 level. Seventeen cases with similar characteristics were reviewed. We found that the primary clinical manifestation of these patients was bilateral lower extremity spastic paraplegia. Multilevel spinal cord compression was commonly observed, especially at the lower cervical and upper thoracic spinal cord. Most of the patients had poor surgical treatment outcome and prognosis. Clinicians should be aware of paraplegia due to spinal cord compression as a rare neurological complication in patients with PHP. Early diagnosis and treatment of PHP is one basis for preventing severe spinal cord-related complications.
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http://dx.doi.org/10.1111/nyas.14584DOI Listing
March 2021

Changes of the mice intestinal microbes by the oligosaccharides-enriched fermented milk in a gender-dependent pattern.

Food Res Int 2021 Feb 24;140:110047. Epub 2020 Dec 24.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Animal Protein Deep Processing Technology of Zhejiang, School of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315211, Zhejiang, PR China. Electronic address:

Oligosaccharides are prebiotics that can be used to regulate microbes in the host intestine. In this study, we investigated the effects of different oligosaccharides on the changes of the intestinal microbial communities and co-related functional genes in the intestinal microbes. Fructo-oligosaccharide (FOS), galacto-oligosaccharide (GOS) and oligomannose (MOS) were enriched in milk and fermented by Lactobacillus plantarum and tested in ICR mice model in vivo. Then the changes of the fecal microbial communities were examined by 16S rDNA gene sequencing approach. We found that the relative abundance of several taxa was markedly different between genders at the level of phylum and genera, additionally to the changes in the microbial community. Meanwhile, compared with male mice, the intestinal microbes of the female mice group had significant changes. Furthermore, the intestinal microbial diversity was enhanced in the female mice when treated with the FOS enriched fermented milk. Therefore, this data suggests that oligosaccharides have the potential to improve the host microbial diversity in the intestinal tract, and FOS has potential applications in the fermented dairy industry. It revealed a gender-dependent changes of different oligosaccharides-enriched fermented milk on the intestinal microbes of mice, providing a reference for regulating the intestinal microbes by oligosaccharides.
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http://dx.doi.org/10.1016/j.foodres.2020.110047DOI Listing
February 2021

Evaluation of the concentration and contribution of superoxide radical for micropollutant abatement during ozonation.

Water Res 2021 Apr 13;194:116927. Epub 2021 Feb 13.

School of Environment, Beijing Key Laboratory for Emerging Organic Contaminants Control, State Key Joint Laboratory of Environmental Simulation and Pollution Control, Tsinghua University, Beijing 100084 China. Electronic address:

Due to the fast reaction of superoxide radical (O) with ozone (O), it has been suggested that O is present at very low concentrations during ozonation. Therefore, while O has been considered a critical chain carrier for promoting O decomposition to hydroxyl radicals (•OH), the direct reactions of O with micropollutants have been assumed to be insignificant during ozonation. In this study, we monitored the exposures of O, •OH, and O by following the depletion of O, p-chlorobenzoic acid (pCBA, as •OH probe), and tetrachloromethane (CCl, as O probe) during ozonation of various water matrices (surface water, groundwater, and secondary wastewater effluent). For a given water matrix, the ratio between •OH and O exposures (R), O and O exposures (R), as well as O and •OH exposures (R) remained almost constant over the entire reaction time. This suggests that during ozonation, the ratios between the transient concentrations of •OH and O, O and O, and O and •OH were also constant and equaled to the R, R, and R, respectively. Based on the O, •OH, and O exposures observed during ozonation, a chemical kinetic model was proposed to simulate the abatement of ten ozone-resistant micropollutants in the three water matrices by ozonation. The results indicate that due to the higher concentrations of O than •OH (R = ~5-8), the reactions with O played a non-negligible or even dominant role in the abatement of some micropollutants that have similar or higher O reactivity than •OH reactivity (e.g., tetrachloroethylene, chloroform, and PFOA). Compared with the previous model that neglected the contribution of O to micropollutant abatement, the proposed model more accurately simulated the abatement efficiencies of the test micropollutants during ozonation. These results indicate that the proposed model can provide a useful tool for the generalized prediction of micropollutant abatement by ozonation.
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http://dx.doi.org/10.1016/j.watres.2021.116927DOI Listing
April 2021

Co and Pt Dual-Single-Atoms with Oxygen-Coordinated Co-O-Pt Dimer Sites for Ultrahigh Photocatalytic Hydrogen Evolution Efficiency.

Adv Mater 2021 Apr 22;33(13):e2003327. Epub 2021 Feb 22.

Beijing Key Lab of Microstructure and Properties of Advanced Materials, Beijing University of Technology, Beijing, 100124, P. R. China.

The platinum single-atom-catalyst is verified as a very successful route to approach the size limit of Pt catalysts, while how to further improve the catalytic efficiency of Pt is a fundamental scientific question and is challenging because the size issue of Pt is approached at the ultimate ceiling as single atoms. Here, a new route for further improving Pt catalytic efficiency by cobalt (Co) and Pt dual-single-atoms on titanium dioxide (TiO ) surfaces, which contains a fraction of nonbonding oxygen-coordinated Co-O-Pt dimers, is reported. These Co-Pt dimer sites originate from loading high-density Pt single-atoms and Co single-atoms, with them anchoring randomly on the TiO substrate. This dual-single-atom catalyst yields 13.4% dimer sites and exhibits an ultrahigh and stable photocatalytic activity with a rate of 43.467 mmol g h and external quantum efficiency of ≈83.4% at 365 nm. This activity far exceeds those of equal amounts of Pt single-atom and typical Pt clustered catalysts by 1.92 and 1.64 times, respectively. The enhancement mechanism relies on the oxygen-coordinated Co-O-Pt dimer coupling, which can mutually optimize the electronic states of both Pt and Co sites to weaken H* binding. Namely, the "mute" Co single-atom is activated by Pt single-atom and the activity of the Pt atom is further enhanced through the dimer interaction. This strategy of nonbonding interactive dimer sites and the oxygen-mediated catalytic mechanisms provide emerging rich opportunities for greatly improving the catalytic efficiency and developing novel catalysts with creating new electronic states.
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http://dx.doi.org/10.1002/adma.202003327DOI Listing
April 2021

Icariin promotes the repair of PC12 cells by inhibiting endoplasmic reticulum stress.

BMC Complement Med Ther 2021 Feb 19;21(1):69. Epub 2021 Feb 19.

Department of Traumatology and Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People's Republic of China.

Background: Endoplasmic reticulum stress (ERS) is one of the main mechanisms of spinal cord injury (SCI) pathology and can affect the physiological state of neurons. Icariin (ICA), the main pharmacological component of Epimedium, can relieve the symptoms of patients with SCI and has obvious protective effects on neurons through ERS.

Methods: PC12 cells were induced to differentiate into neurons by nerve growth factor and identified by flow cytometry. Cell proliferation was detected by CCK8 method, cell viability was detected by SRB assay, apoptosis was detected by flow cytometry and microstructure of ER was observed by transmission electron microscope. Western blot was used to detect the protein expression of CHOP and Grp78, and qPCR was used to detect the mRNA expression of CHOP and Grp78.

Results: The results of CCK8, SRB and flow cytometry showed that ICA could relieve ERS and reduce apoptosis of PC12 cells. The results of transmission microscope showed that ICA could reduce apoptosis of PC12 cells caused by ERS. The results of Western blot and q-PCR showed that ICA could inhibit ERS by down-regulating the expression of CHOP and Grp78.

Conclusions: ICA can inhibit ERS and promote the repair of PC12 cells by down-regulating the expression of CHOP and Grp78. ICA has the potential to promote the recovery of spinal cord injury.
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http://dx.doi.org/10.1186/s12906-021-03233-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896365PMC
February 2021

Machine learning for early prediction of in-hospital cardiac arrest in patients with acute coronary syndromes.

Clin Cardiol 2021 Mar 14;44(3):349-356. Epub 2021 Feb 14.

Department of Cardiovascular Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fujian, China.

Background: Previous studies have used machine leaning to predict clinical deterioration to improve outcome prediction. However, no study has used machine learning to predict cardiac arrest in patients with acute coronary syndrome (ACS). Algorithms are required to generate high-performance models for predicting cardiac arrest in ACS patients with multivariate features.

Hypothesis: Machine learning algorithms will significantly improve outcome prediction of cardiac arrest in ACS patients.

Methods: This retrospective cohort study reviewed 166 ACS patients who had in-hospital cardiac arrest. Eight machine learning algorithms were trained using multivariate clinical features obtained 24 h prior to the onset of cardiac arrest. All machine learning models were compared to each other and to existing risk prediction scores (Global Registry of Acute Coronary Events, National Early Warning Score, and Modified Early Warning Score) using the area under the receiver operating characteristic curve (AUROC).

Results: The XGBoost model provided the best performance with regard to AUC (0.958 [95%CI: 0.938-0.978]), accuracy (88.9%), sensitivity (73%), negative predictive value (89%), and F1 score (80%) compared with other machine learning models. The K-nearest neighbor model generated the best specificity (99.3%) and positive predictive value (93.8%) metrics, but had low and unacceptable values for sensitivity and AUC. Most, but not all, machine learning models outperformed the existing risk prediction scores.

Conclusions: The XGBoost model, which was generated based on a machine learning algorithm, has high potential to be used to predict cardiac arrest in ACS patients. This proposed model significantly improves outcome prediction compared to existing risk prediction scores.
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http://dx.doi.org/10.1002/clc.23541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943901PMC
March 2021

Low-Density Granulocytes Affect T-SPOT.TB Assay by Inhibiting the Production of Interferon-γ in T Cells via PD-L1/PD-1 Pathway.

Front Microbiol 2020 28;11:622389. Epub 2021 Jan 28.

Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Background: T-SPOT TB (T-SPOT) assay is widely used for detection of infection that is based on the detection of -specific interferon-γ-secreting T cells (ISCs) in peripheral blood mononuclear cells (PBMCs). Recently, high frequencies of low-density granulocytes (LDGs) were found in the PBMCs of tuberculosis patients. Whether these LDGs affect the detection of T-SPOT has not been investigated. The impact of LDGs on T-SPOT assay and related mechanism were investigated in this study.

Methods: The correlations between the frequencies of LDGs and the results of T-SPOT were analyzed. T-SPOT with LDG-removed PBMCs and PBMCs with exogenous addition of LDGs were performed. The possible mechanism was explored by detecting the levels of negative immune regulatory molecules on LDGs. The impact of programmed death ligand 1 (PD-L1) on T-SPOT was evaluated and confirmed by function blocking with neutralizing antibody.

Results: The positive rates of T-SPOT and ISCs in tuberculosis patients with low LDGs frequency ( = 22) were significantly higher than those with high LDGs frequency ( = 39). Removal or exogenous addition of LDGs significantly increased or decreased the ISCs and the positive rate of T-SPOT. The frequencies of interferon-γ-producing T cells were negatively correlated with the frequencies of LDGs. The expression of PD-L1 was significantly elevated on LDGs. Pretreatment of LDGs with anti-PD-L1 antibody significantly counteracted the impact of LDGs on T-SPOT. Treatment of PBMCs with anti-PD-L1 antibody resulted in comparable ISCs with that of LDG removal.

Conclusion: LDGs can inhibit the production of interferon-γ in T cells and decrease the positive rated of T-SPOT assay via highly expressed PD-L1.
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http://dx.doi.org/10.3389/fmicb.2020.622389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876290PMC
January 2021

Measuring and Controlling Bias for Some Bayesian Inferences and the Relation to Frequentist Criteria.

Entropy (Basel) 2021 Feb 4;23(2). Epub 2021 Feb 4.

Department of Statistical Sciences, University of Toronto, Toronto, ON M5G 1Z5, Canada.

A common concern with Bayesian methodology in scientific contexts is that inferences can be heavily influenced by subjective biases. As presented here, there are two types of bias for some quantity of interest: bias against and bias in favor. Based upon the principle of evidence, it is shown how to measure and control these biases for both hypothesis assessment and estimation problems. Optimality results are established for the principle of evidence as the basis of the approach to these problems. A close relationship is established between measuring bias in Bayesian inferences and frequentist properties that hold for any proper prior. This leads to a possible resolution to an apparent conflict between these approaches to statistical reasoning. Frequentism is seen as establishing figures of merit for a statistical study, while Bayes determines the inferences based upon statistical evidence.
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http://dx.doi.org/10.3390/e23020190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914689PMC
February 2021

Prevalence and Risk Factors for Spasticity After Stroke: A Systematic Review and Meta-Analysis.

Front Neurol 2020 20;11:616097. Epub 2021 Jan 20.

Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Spasticity is a common sequela of stroke. The incidence of poststroke spasticity (PSS) has not been systematically reviewed in recent years, and some risk factors remain debated. This systematic review and meta-analysis was conducted to determine the prevalence and risk factors for PSS. We searched electronic databases (PubMed, Embase, Cochrane Library, CNKI, WANFANG and CBM) inception to May 12, 2020. Observational studies summarizing the incidence or risk factors for PSS were included. Only cohort studies were enrolled in meta-analysis. For risk factors examined in at least three different studies, we combined effects into odds ratios (OR) and 95% confidence intervals (CI). One thousand four hundred sixty-seven studies were retrieved and 23 were involved in meta-analysis. The pooled prevalence of spasticity after stroke was 25.3% and that after the first-ever stroke was 26.7%. The incidence of spasticity after the first-ever stroke with paresis was 39.5%. The prevalence of disabling or severe spasticity (MAS ≥ 3) in stroke patients with paresis was 9.4% (95% CI 0.056-0.133), and severe spasticity was 10.3% (95% CI 0.058-0.149). Moderate to severe paresis (OR = 6.573, 95% CI 2.579-16.755, = 0.0%), hemorrhagic stroke (OR = 1.879, 95% CI 1.418-2.490, = 27.3%) and sensory disorder were risk factors for PSS. The incidence of PSS was significantly higher in stroke patients with paresis. Patients with moderate to severe paresis and sensory disorder should be closely followed up. The role of hemorrhagic stroke in predicting PSS remains to be further explored.
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http://dx.doi.org/10.3389/fneur.2020.616097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855612PMC
January 2021