Publications by authors named "Xiaofei Zhou"

102 Publications

Effects of preserving the bronchial artery on cough after thoracoscopic lobectomy.

Thorac Cancer 2021 Jun 10. Epub 2021 Jun 10.

Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou, China.

Background: The purpose of this prospective study was to explore the influence of both preoperative three-dimensional (3D) reconstruction and intraoperative preservation of the bronchial artery (BA) on postoperative cough after thoracoscopic lobectomy.

Methods: A total of 60 patients who had received a combination of thoracoscopic lobectomy and systematic lymph node dissection were included in this study. They were divided into two groups, namely the BA preservation group (Group A), and conventional surgical treatment group (Group B). In group A, we used Exoview software for 3D reconstruction of the BA before the operation and the BA was preserved during the operation. 3D reconstruction of the BA was not performed before surgery in group B. The incidence of postoperative cough, the Mandarin Chinese version of the Leicester cough questionnaire (LCQ-MC), physiological, psychological and social dimensions and total score of the two groups were compared and analyzed.

Results: The scores and total scores of LCQ-MC in group B were lower than those in group A one and two months after surgery. There were significant differences between the two groups in physiological and psychological dimensions and total scores (p < 0.05), but there was no significant difference in social dimension between the two groups (p > 0.05). The incidence of postoperative cough in group A (16.7%) was lower than that in group B (30%), while the difference was not statistically significant (p = 0.222).

Conclusions: Preoperative 3D reconstruction and intraoperative preservation of the BA can reduce the severity of postoperative cough.
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http://dx.doi.org/10.1111/1759-7714.14012DOI Listing
June 2021

Enhances Fatty Acid Metabolism of Pea Aphid to Promote Host Development.

Int J Mol Sci 2021 May 31;22(11). Epub 2021 May 31.

State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

Bacterial symbionts associated with insects are often involved in host development and ecological adaptation. , a common facultative endosymbiont harbored in pea aphids, improves host fitness and heat tolerance, but studies concerning the nutritional metabolism and impact on the aphid host associated with carrying are limited. In the current study, we showed that -infected aphids had a shorter nymphal developmental time and higher body weight than -free aphids when fed on detached leaves. Genes connecting to fatty acid biosynthesis and elongation were up-regulated in -infected aphids. Specifically, elevated expression of fatty acid synthase 1 () and diacylglycerol-o-acyltransferase 2 () could result in accumulation of myristic acid, palmitic acid, linoleic acid, and arachidic acid in fat bodies. Impairing fatty acid synthesis in -infected pea aphids either by a pharmacological inhibitor or through silencing and expression prolonged the nymphal growth period and decreased the aphid body weight. Conversely, supplementation of myristic acid (C14:0) to these aphids restored their normal development and weight gain. Our results indicated that promoted development and growth of its aphid host through enhancing fatty acid biosynthesis. Our discovery has shed more light on nutritional effects underlying the symbiosis between aphids and facultative endosymbionts.
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http://dx.doi.org/10.3390/ijms22115951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199403PMC
May 2021

Chlorogenic acid supplementation ameliorates hyperuricemia, relieves renal inflammation, and modulates intestinal homeostasis.

Food Funct 2021 May 21. Epub 2021 May 21.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Food Nutrition and Safety, Ministry of Education of China, Tianjin University of Science and Technology, Tianjin 300457, China. and Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, People's Republic of China.

Hyperuricemia (HUA) is induced by abnormal purine metabolism and elevated serum uric acid (UA) concentrations, and it is often accompanied by inflammatory responses and intestinal disorders. This study aims to assess the protective effects of chlorogenic acid (CGA) on HUA in mice. CGA or allopurinol was given to mice with HUA induced by hypoxanthine and potassium oxonate. CGA lowered the levels of UA, blood urea nitrogen (BUN), creatinine (CR), AST, and ALT; inhibited xanthine oxidase (XOD) activity; and downregulated the mRNA expression of UA secretory proteins in HUA mice. Moreover, CGA significantly reduced serum lipopolysaccharides (LPS) levels and the mRNA expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, NOD-like receptor superfamily pyrin domain containing 3 (NLRP3), and caspase-1, and it inhibited the activation of the toll-like receptor 4/myeloid differentiation factor 88/nuclear factor kappa B (TLR4/MyD88/NF-κB) signaling pathway in the kidney, resulting in inflammation relief in HUA mice. In addition, CGA treatment increased the production of fecal short-chain fatty acids (SCFAs) in HUA mice. Additional investigations showed that CGA significantly lowered the mRNA expression of ileal IL-1β and IL-6, and it increased the mRNA expression of intestinal tight junction proteins (zonula occludens-1 (ZO-1) and occludin). Also, CGA increased the relative abundance of SCFA-producing bacteria, including Bacteroides, Prevotellaceae UGC-001, and Butyricimonas, and it reversed the purine metabolism and glutamate metabolism functions of gut microbiota. In conclusion, CGA may be a potential candidate for relieving the symptoms of HUA and regulating its associated inflammatory responses and intestinal homeostasis.
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http://dx.doi.org/10.1039/d0fo03199bDOI Listing
May 2021

Impact of race on care, readmissions, and survival for patients with glioblastoma: an analysis of the National Cancer Database.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab040. Epub 2021 Mar 6.

Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

Background: The objective of this study was to explore racial/ethnic factors that may be associated with survival in patients with glioblastoma by querying the National Cancer Database (NCDB).

Methods: The NCDB was queried for patients diagnosed with glioblastoma between 2004 and 2014. Patient demographic variables included age at diagnosis, sex, race, ethnicity, Charlson-Deyo score, insurance status, and rural/urban/metropolitan location of zip code. Treatment variables included surgical treatment, extent of resection, chemotherapy, radiation therapy, type of radiation, and treatment facility type. Outcomes included 30-day readmission, 30- and 90-day mortality, and overall survival. Multivariable Cox regression analyses were performed to evaluate variables associated with race and overall survival.

Results: A total of 103 652 glioblastoma patients were identified. There was a difference in the proportion of patients for whom surgery was performed, as well as the proportion receiving radiation, when stratified by race ( < .001). Black non-Hispanics had the highest rates of unplanned readmission (7.6%) within 30 days (odds ratio [OR]: 1.39 compared to White non-Hispanics, < .001). Asian non-Hispanics had the lowest 30- (3.2%) and 90-day mortality (9.8%) when compared to other races (OR: 0.52 compared to White non-Hispanics, = .031). Compared to White non-Hispanics, we found Black non-Hispanics (hazard ratio [HR]: 0.88, < .001), Asian non-Hispanics (HR: 0.72, < .001), and Hispanics (HR: 0.69, < .001) had longer overall survival.

Conclusions: Differences in treatment and outcomes exist between races. Further studies are needed to elucidate the etiology of these race-related disparities and to improve outcomes for all patients.
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http://dx.doi.org/10.1093/noajnl/vdab040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086235PMC
March 2021

Bacillus licheniformis Zhengchangsheng® Inhibits Obesity by Regulating the AMP-Activated Protein Kinase Signaling Pathway.

Probiotics Antimicrob Proteins 2021 May 5. Epub 2021 May 5.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, 130062, People's Republic of China.

As a metabolic syndrome, obesity has become a global public health problem. Bacillus licheniformis has been shown to inhibit obesity by regulating the gut microbiota, but the underlying mechanism of its therapeutic effect is still unknown. In this study, the anti-obesity mechanism of Bacillus licheniformis Zhengchangsheng® was investigated by examining a high-fat diet-induced obesity mouse model. Our results showed that Bacillus licheniformis Zhengchangsheng® significantly decreased body weight gain and fat accumulation, serum lipid profiles, and proinflammatory cytokine levels and improved glucose and lipid metabolism in obese mice. Furthermore, compared with those of high-fat diet-fed mice, Bacillus licheniformis Zhengchangsheng® treatment also inhibited nuclear factor-κB activation, increased phosphorylated AMP-activated protein kinase activation in the liver, and regulated the expression of genes associated with lipid metabolism. These results indicated that Bacillus licheniformis Zhengchangsheng®-induced obesity inhibition could occur by activating the AMP-activated protein kinase signaling pathway. Thus, our results suggested that Bacillus licheniformis Zhengchangsheng® has the potential to treat obesity and related metabolic diseases in the clinic.
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http://dx.doi.org/10.1007/s12602-021-09792-6DOI Listing
May 2021

Sub-chronic exposure to PhIP induces oxidative damage and DNA damage, and disrupts the amino acid metabolism in the colons of Wistar rats.

Food Chem Toxicol 2021 Jul 1;153:112249. Epub 2021 May 1.

Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin, 300071, China. Electronic address:

Heterocyclic amines (HCAs) are a group of mutagenic compounds produced during thermal processing of protein-rich foods. One of the most abundant HCAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) has potential carcinogenic and mutagenic effects on human organs, especially the colon. This study aimed to explore the toxic effects of PhIP on amino acid metabolism in the colon of Wistar rats using RNA-seq and LC-MS/MS. Exposure to PhIP for 4 weeks induced oxidative damage and DNA damage in the colons, and disrupted the expression of related genes involved in tryptophan metabolism, beta(β)-alanine metabolism, valine, leucine, and isoleucine degradation, and glutathione metabolic pathways. Moreover, the levels of fecal metabolites related to amino acid metabolism were affected by PhIP. Cumulatively, these results indicate that PhIP can induce colonic oxidative injury and disorders related to amino acid metabolism, thereby providing a new theoretical basis for the study of PhIP toxicity.
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http://dx.doi.org/10.1016/j.fct.2021.112249DOI Listing
July 2021

Asia-inclusive global development of pevonedistat: Clinical pharmacology and translational research enabling a phase 3 multiregional clinical trial.

Clin Transl Sci 2021 Jan 27. Epub 2021 Jan 27.

Millennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda Pharmaceutical Company Limited), Cambridge, MA, USA.

The investigational NEDD8-activating enzyme inhibitor pevonedistat is being evaluated in combination with azacitidine versus single-agent azacitidine in patients with higher-risk myelodysplastic syndrome (higher-risk MDS), higher-risk chronic myelomonocytic leukemia (higher-risk CMML), or low-blast acute myeloid leukemia (AML) in a Phase 3 trial PANTHER. To support Asia-inclusive global development, we applied multiregional clinical trial (MRCT) principles of the International Conference on Harmonisation E17 guidelines by evaluating similarity in drug-related and disease-related intrinsic and extrinsic factors. A PubMed literature review (January 2000-November 2019) supported similarity in epidemiology of higher-risk MDS, AML, and CMML in Western and East Asian populations. Furthermore, the treatment of MDS/AML was similar in both East Asian and Western regions, with the same dose of azacitidine being the standard of care. Median overall survival in MDS following azacitidine treatment was generally comparable across regions, and the types and frequencies of molecular alterations in AML and MDS were comparable. Dose-escalation studies established the same maximum tolerated dose of pevonedistat in combination with azacitidine in Western and East Asian populations. Pevonedistat clearance was similar across races. Taken together, conservation of drug-related and disease-related intrinsic and extrinsic factors supported design of an Asia-inclusive Phase 3 trial and a pooled East Asian region. A sample size of ~ 30 East Asian patients (of ~ 450 randomized) was estimated as needed to demonstrate consistency in efficacy relative to the global population. This analysis is presented as an exemplar to illustrate application of clinical pharmacology and translational science principles in designing Asia-inclusive MRCTs.
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http://dx.doi.org/10.1111/cts.12972DOI Listing
January 2021

Targeting ubiquitin signaling for cancer immunotherapy.

Signal Transduct Target Ther 2021 Jan 13;6(1):16. Epub 2021 Jan 13.

Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston, TX, 77030, USA.

Cancer immunotherapy has become an attractive approach of cancer treatment with tremendous success in treating various advanced malignancies. The development and clinical application of immune checkpoint inhibitors represent one of the most extraordinary accomplishments in cancer immunotherapy. In addition, considerable progress is being made in understanding the mechanism of antitumor immunity and characterizing novel targets for developing additional therapeutic approaches. One active area of investigation is protein ubiquitination, a post-translational mechanism of protein modification that regulates the function of diverse immune cells in antitumor immunity. Accumulating studies suggest that E3 ubiquitin ligases and deubiquitinases form a family of potential targets to be exploited for enhancing antitumor immunity in cancer immunotherapy.
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http://dx.doi.org/10.1038/s41392-020-00421-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804490PMC
January 2021

NF-κB-inducing kinase maintains T cell metabolic fitness in antitumor immunity.

Nat Immunol 2021 02 4;22(2):193-204. Epub 2021 Jan 4.

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

Metabolic reprograming toward aerobic glycolysis is a pivotal mechanism shaping immune responses. Here we show that deficiency in NF-κB-inducing kinase (NIK) impairs glycolysis induction, rendering CD8 effector T cells hypofunctional in the tumor microenvironment. Conversely, ectopic expression of NIK promotes CD8 T cell metabolism and effector function, thereby profoundly enhancing antitumor immunity and improving the efficacy of T cell adoptive therapy. NIK regulates T cell metabolism via a NF-κB-independent mechanism that involves stabilization of hexokinase 2 (HK2), a rate-limiting enzyme of the glycolytic pathway. NIK prevents autophagic degradation of HK2 through controlling cellular reactive oxygen species levels, which in turn involves modulation of glucose-6-phosphate dehydrogenase (G6PD), an enzyme that mediates production of the antioxidant NADPH. We show that the G6PD-NADPH redox system is important for HK2 stability and metabolism in activated T cells. These findings establish NIK as a pivotal regulator of T cell metabolism and highlight a post-translational mechanism of metabolic regulation.
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http://dx.doi.org/10.1038/s41590-020-00829-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855506PMC
February 2021

2-Amino-1-methyl-6-phenylimidazo[4,5-]pyridine Induced Colon Injury by Disrupting the Intestinal Bacterial Composition and Lipid Metabolic Pathways in Rats.

J Agric Food Chem 2021 Jan 29;69(1):437-446. Epub 2020 Dec 29.

Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, People's Republic of China.

2-Amino-1-methyl-6-phenylimidazo[4,5-]pyridine (PhIP), one of the most abundant heterocyclic amines, is a common carcinogen produced in thermally processed protein-rich foods. Studies have demonstrated that PhIP could induce colon tumors in rodents, leaving mechanisms uncovered. This study aims to investigate the mechanism of PhIP-induced colon injury in a rat model. The results of 16S rRNA gene sequencing and metabolomics showed that PhIP disrupted intestinal bacterial composition and affected the glycerophospholipid metabolism and linoleic acid metabolism. Simultaneously, the lipid metabolism function in the intestinal flora was inhibited by PhIP. Notably, transcriptomics revealed that PhIP remarkably inhibited the expression of gene sets associated with steroid hormone biosynthesis, fatty acid elongation, fatty acid degradation, and glycerolipid metabolism pathways in the colon. The results provide new perspectives to study the mechanism of PhIP-induced colon injury and theoretical bases for further understanding the toxicity of PhIP.
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http://dx.doi.org/10.1021/acs.jafc.0c06588DOI Listing
January 2021

Use of Telemedicine to Improve Interfacility Communication and Aid in Triage of Patients with Intracerebral Hemorrhage: A Pilot Study.

World Neurosurg 2021 Mar 10;147:e189-e199. Epub 2020 Dec 10.

Department of Neurological Surgery, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.

Introduction: Over the past several years there has been a dramatic increase in the implementation of telemedicine technology to aid in the delivery of care across community, inpatient, and emergency settings. This technology has proved valuable for acute life-threatening clinical scenarios. We aimed to pilot a novel neurosurgical telemedicine program within an academic tertiary care center to assist in consultation of patients with high-grade intracranial hemorrhage (ICH) (ICH score 4, 5).

Methods: A quality improvement conceptual framework was developed. Subsequently, a process map and improvement interventions were created. Patients in community hospitals with high-grade ICH or pre-existing Do Not Resuscitate/Do Not Intubate orders with an admitting diagnosis of ICH triggered a TeleNeurosurgery consultation. Patients who met the inclusion criteria, with consent of their decision makers, were enrolled in the study. Post-encounter physician surveys were used to evaluate overall satisfaction with the implementation.

Results: This 18-month pilot study proved feasible, with an enrollment of 63.6% (n = 14 of 22) of patients who met criteria. All patients who were enrolled in the study and participated in TeleNeurosurgery consultation remained at the presenting facility for end-of-life care and palliative medicine consultation. Both community emergency physicians and subspecialists who performed the consultations reported satisfaction with the TeleNeurosurgery consultation process and a perceived benefit both to patients, families, and emergency medicine physicians.

Conclusions: The program proved feasible and several areas in need of improvement within the health system were identified. Emergency physicians reported comfort with the process, program effectiveness, and improved access to care by implementation of this program.
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http://dx.doi.org/10.1016/j.wneu.2020.12.010DOI Listing
March 2021

Application of Machine Learning for Tumor Growth Inhibition - Overall Survival Modeling Platform.

CPT Pharmacometrics Syst Pharmacol 2021 Jan 13;10(1):59-66. Epub 2020 Dec 13.

Clinical Pharmacology, Roche/Genentech, South San Francisco, California, USA.

Machine learning (ML) was used to leverage tumor growth inhibition (TGI) metrics to characterize the relationship with overall survival (OS) as a novel approach and to compare with traditional TGI-OS modeling methods. Historical dataset from a phase III non-small cell lung cancer study (OAK, atezolizumab vs. docetaxel, N = 668) was used. ML methods support the validity of TGI metrics in predicting OS. With lasso, the best model with TGI metrics outperforms the best model without TGI metrics. Boosting was the best linear ML method for this dataset with reduced estimation bias and lowest Brier score, suggesting better prediction accuracy. Random forest did not outperform linear ML methods despite hyperparameter optimization. Kernel machine was marginally the best nonlinear ML method for this dataset and uncovered nonlinear and interaction effects. Nonlinear ML may improve prediction by capturing nonlinear effects and covariate interactions, but its predictive performance and value need further evaluation with larger datasets.
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http://dx.doi.org/10.1002/psp4.12576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825187PMC
January 2021

The E3 ubiquitin ligase Peli1 regulates the metabolic actions of mTORC1 to suppress antitumor T cell responses.

EMBO J 2021 01 20;40(2):e104532. Epub 2020 Nov 20.

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

Metabolic fitness of T cells is crucial for immune responses against infections and tumorigenesis. Both the T cell receptor (TCR) signal and environmental cues contribute to the induction of T cell metabolic reprogramming, but the underlying mechanism is incompletely understood. Here, we identified the E3 ubiquitin ligase Peli1 as an important regulator of T cell metabolism and antitumor immunity. Peli1 ablation profoundly promotes tumor rejection, associated with increased tumor-infiltrating CD4 and CD8 T cells. The Peli1-deficient T cells display markedly stronger metabolic activities, particularly glycolysis, than wild-type T cells. Peli1 controls the activation of a metabolic kinase, mTORC1, stimulated by both the TCR signal and growth factors, and this function of Peli1 is mediated through regulation of the mTORC1-inhibitory proteins, TSC1 and TSC2. Peli1 mediates non-degradative ubiquitination of TSC1, thereby promoting TSC1-TSC2 dimerization and TSC2 stabilization. These results establish Peli1 as a novel regulator of mTORC1 and downstream mTORC1-mediated actions on T cell metabolism and antitumor immunity.
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http://dx.doi.org/10.15252/embj.2020104532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809702PMC
January 2021

TRAF2 regulates T cell immunity by maintaining a Tpl2-ERK survival signaling axis in effector and memory CD8 T cells.

Cell Mol Immunol 2020 Nov 17. Epub 2020 Nov 17.

Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston, TX, 77030, USA.

Generation and maintenance of antigen-specific effector and memory T cells are central events in immune responses against infections. We show that TNF receptor-associated factor 2 (TRAF2) maintains a survival signaling axis in effector and memory CD8 T cells required for immune responses against infections. This signaling axis involves activation of Tpl2 and its downstream kinase ERK by NF-κB-inducing kinase (NIK) and degradation of the proapoptotic factor Bim. NIK mediates Tpl2 activation by stimulating the phosphorylation and degradation of the Tpl2 inhibitor p105. Interestingly, while NIK is required for Tpl2-ERK signaling under normal conditions, uncontrolled NIK activation due to loss of its negative regulator, TRAF2, causes constitutive degradation of p105 and Tpl2, leading to severe defects in ERK activation and effector/memory CD8 T cell survival. Thus, TRAF2 controls a previously unappreciated signaling axis mediating effector/memory CD8 T cell survival and protective immunity.
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http://dx.doi.org/10.1038/s41423-020-00583-7DOI Listing
November 2020

Generation of plane spiral orbital angular momentum using circular double-slot Vivaldi antenna array.

Sci Rep 2020 Oct 27;10(1):18328. Epub 2020 Oct 27.

College of Information Engineering, Engineering University of PAP, Xi'an, 710086, Shaanxi, China.

A novel and feasible solution to generate plane spiral orbital angular momentum (PSOAM) vortex beam is proposed in this paper. The general principle of generating PSOAM in circular antenna array (CAA) is deduced, and verified by the simulation of the dipole CAA. Four double-slot Vivaldi antenna elements connect sequentially and are inserted into a CAA, which makes the proposed antenna easily fabricated and fully miniaturized. Both simulated and measured results show that it can generate PSOAM with l = 3 (l is the mode number of vortex wave) at 5 GHz. The vortex phase of l = 3 is observed, the measured peak gain is 5.7 dB. The VSWR remains below 2 from 4 to 6 GHz, which shows the impedance bandwidth of S < -10 dB is more than 40%.
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http://dx.doi.org/10.1038/s41598-020-75202-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591494PMC
October 2020

Phase I study assessing the mass balance, pharmacokinetics, and excretion of [C]-pevonedistat, a NEDD8-activating enzyme inhibitor in patients with advanced solid tumors.

Invest New Drugs 2021 Apr 22;39(2):488-498. Epub 2020 Oct 22.

Medical Center Hungarian Defense Forces, Budapest, Hungary.

Pevonedistat (TAK-924/MLN4924) is an investigational small-molecule inhibitor of the NEDD8-activating enzyme that has demonstrated preclinical and clinical activity across solid tumors and hematological malignancies. Here we report the results of a phase I trial characterizing the mass balance, pharmacokinetics, and clearance pathways of [C]-pevonedistat in patients with advanced solid tumors (NCT03057366). In part A (n = 8), patients received a single 1-h intravenous infusion of [C]-pevonedistat 25 mg/m. In part B (n = 7), patients received pevonedistat 25 or 20 mg/m on days 1, 3, and 5 in combination with, respectively, docetaxel 75 mg/m or carboplatin AUC5 plus paclitaxel 175 mg/m on day 1 every 3 weeks. Following the single dose of [C]-pevonedistat 25 mg/m in part A, there was a parallel log-linear decline in plasma and whole blood pevonedistat concentration, with systemic exposure of unchanged pevonedistat representing 41% of drug-related material (i.e., unchanged pevonedistat and its metabolites). The mean terminal half-life of pevonedistat and drug-related material in plasma was 8.4 and 15.6 h, respectively. Pevonedistat distributed preferentially in whole blood with a mean whole-blood-to-plasma ratio for pevonedistat AUC of 40.8. By 1 week post dose, the mean recovery of administered radioactivity was 94% (41% in urine and 53% in feces). The pevonedistat safety profile during both study parts was consistent with previous clinical experience, with no new safety signals observed. In part B, pevonedistat in combination with docetaxel or carboplatin plus paclitaxel was generally well tolerated. ClinicalTrials.gov identifier: NCT03057366 .
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http://dx.doi.org/10.1007/s10637-020-01017-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960626PMC
April 2021

A Novel Therapeutic siRNA Nanoparticle Designed for Dual-Targeting CD44 and Gli1 of Gastric Cancer Stem Cells.

Int J Nanomedicine 2020 23;15:7013-7034. Epub 2020 Sep 23.

Key Laboratory of Antibiotic Bioengineering of National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology (IMB), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing 100050, People's Republic of China.

Purpose: Gastric cancer stem cells (CSCs) are important for the initiation, growth, recurrence, and metastasis of gastric cancer, due to their chemo-resistance and indefinite proliferation. Herein, to eliminate gastric CSCs, we developed novel CSC-targeting glioma-associated oncogene homolog 1 () small interfering RNA (siRNA) nanoparticles that are specifically guided by a di-stearoyl-phosphatidyl-ethanolamine- hyaluronic-acid (DSPE-HA) single-point conjugate, as an intrinsic ligand of the CD44 receptor. We refer to these as targeting Gli1 siRNA nanoparticles.

Methods: We used the reductive amination reaction method for attaching amine groups of DSPE to aldehydic group of hyaluronic acid (HA) at the reducing end, to synthesize the DSPE-HA single-point conjugate. Next, targeting Gli1 siRNA nanoparticles were prepared using the layer-by-layer assembly method. We characterized the stem cellular features of targeting Gli1 siRNA nanoparticles, including their targeting efficiency, self-renewal capacity, the migration and invasion capacity of gastric CSCs, and the penetration ability of 3D tumor spheroids. Next, we evaluated the therapeutic efficacy of the targeting Gli1 siRNA nanoparticles by using in vivo relapsed tumor models of gastric CSCs.

Results: Compared with the multipoint conjugates, DSPE-HA single-point conjugates on the surface of nanoparticles showed significantly higher binding affinities with CD44. The targeting Gli1 siRNA nanoparticles significantly decreased Gli1 protein expression, inhibited CSC tumor spheroid and colony formation, and suppressed cell migration and invasion. Furthermore, in vivo imaging demonstrated that targeting Gli1 siRNA nanoparticles accumulated in tumor tissues, showing significant antitumor recurrence efficacy in vivo.

Conclusion: In summary, our targeting Gli1 siRNA nanoparticles significantly inhibited CSC malignancy features by specifically blocking Hedgehog (Hh) signaling both in vitro and in vivo, suggesting that this novel siRNA delivery system that specifically eliminates gastric CSCs provides a promising targeted therapeutic strategy for gastric cancer treatment.
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http://dx.doi.org/10.2147/IJN.S260163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522319PMC
December 2020

Cognitive Behavioral Therapy-Based Short-Term Abstinence Intervention for Problematic Social Media Use: Improved Well-Being and Underlying Mechanisms.

Psychiatr Q 2021 Jun 28;92(2):761-779. Epub 2020 Sep 28.

Department of Industrial Engineering, Tsinghua University, Beijing, China.

Problematic social media use is detrimental to users' subjective well-being. Based on cognitive behavioral therapy (CBT), we proposed a short-term abstinence intervention to treat this problem. A mixed method study with 65 participants was conducted to examine the effectiveness of this intervention and to reveal the underlying mechanisms of how the intervention influences participants. While the experimental group (N = 33) took eight 2.5-h breaks from social media over two weeks and had daily dairies, the control group (N = 32) used social media as usual and had daily diaries. The results demonstrated that the intervention has a positive effect on life satisfaction. The effect varied with the time users conducted abstinence (work hours vs. off hours) and the level of social media addiction (heavy users vs. normal users). Qualitative findings from dairies and interviews unveiled associations among users' behaviors, feelings, and cognitions during and after abstinence. These results extend the understanding of the CBT-based short-term abstinence intervention and suggest opportunities to alleviate problematic social media use.
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http://dx.doi.org/10.1007/s11126-020-09852-0DOI Listing
June 2021

The establishment of humanized IL-4/IL-4RA mouse model by gene editing and efficacy evaluation.

Immunobiology 2020 09 3;225(5):151998. Epub 2020 Aug 3.

College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China; Qinhuangdao BohaiBiological Research Institute of BUCT, No.41 of Shugu Avenue, Qinghuangdao, Hebei, 066000, PR China. Electronic address:

Asthma is a common respiratory immune disease in children and adults, and interleukin-4 (IL-4) is one of the key factors for the onset of asthma. Therefore, targeting human IL-4 and IL-4 receptor alpha (IL-4RA) has become one of the strategies for targeted therapy of cytokines. Herein, we established an animal model of asthmatic airway inflammation using double humanized IL-4/IL-4RA (hIL-4/hIL-4RA) mice, where human IL-4 and IL-4RA replaced their murine counterparts, respectively. We successfully identified the phenotype by Southern blotting, ELISA, and flow cytometry. The hIL-4/hIL-4RA mice induced by ovalbumin (OVA) exhibited several important features of asthma, such as inflammatory cell infiltration, IgE release, goblet cell hyperplasia, and Th2 cytokine secretion. Furthermore, treatment of these humanized mice with anti-human IL-4RA antibodies significantly inhibited level of these pathological indicators. Thus, hIL-4/hIL-4RA mice provide a validated preclinical mouse model to interrogate new therapeutic agents targeting this specific cytokine pathway in asthma.
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http://dx.doi.org/10.1016/j.imbio.2020.151998DOI Listing
September 2020

Differential expression and inhibitory effects of aquaporins on the development of adenomyosis.

Mol Med Rep 2020 Nov 2;22(5):3840-3850. Epub 2020 Sep 2.

Department of Gynecology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570311, P.R. China.

Aquaporin 2 (AQP2), AQP5 and AQP8 participate in adenomyosis (AM). Ηowever, the roles of these three molecules in AM have not been fully elucidated. In the present study, Institute of Cancer Research female mice were used to establish a model of AM. Subsequently, the endometrial tissues of the mice were observed by hematoxylin‑eosin staining, and AM severity, uterus diameter, uterus index, ovary index and numbers of nodules on the uterine surface were evaluated and counted. In addition, eutopic and ectopic endometrial stromal cells (ESCs) were isolated from eutopic and ectopic endometrial samples derived from patients with AM and were then identified by immunofluorescence. The viability, and migratory and invasive ability of ESCs transfected with small interfering RNA targeting AQP5 (siAQP5) were determined by Cell Counting Κit‑8, scratch wound‑healing and Transwell assays, respectively. Reverse transcription‑quantitative polymerase chain reaction was performed to determine the mRNA expression levels of AQP5, epithelial‑mesenchymal transition (EMT)‑related genes (E‑and N‑cadherin), matrix metalloproteinase (MMP)‑2 and ‑9. Protein expression levels of AQP2, AQP5, AQP8, E‑, N‑cadherin, MMP‑2 and ‑9 were detected by western blotting. AM severity and uterus index were higher, and there were a greater number of nodules on the uterine surface in the AM group compared with the sham group. AQP2, AQP5 and AQP8 proteins were highly expressed in eutopic and ectopic endometrium of the AM group, and AQP5 was more highly expressed than AQP2 or AQP8. In addition, the data showed that Vimentin was positively expressed in ESCs, and that siAQP5 suppressed the mRNA expression levels of AQP5, cell viability, migration, invasion, EMT and MMP‑2 and ‑9 expression in ESCs. In conclusion, AQP2, AQP5 and AQP8 were highly expressed in eutopic and ectopic endometrium. Notably, AQP5 silencing may suppress AM by inhibiting viability, migration, invasion, EMT, and MMP‑2 and ‑9 expression in ESCs.
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http://dx.doi.org/10.3892/mmr.2020.11479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533498PMC
November 2020

Intestinal Epithelial TBK1 Prevents Differentiation of T-helper 17 Cells and Tumorigenesis in Mice.

Gastroenterology 2020 11 31;159(5):1793-1806. Epub 2020 Jul 31.

Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas; MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, Texas. Electronic address:

Background & Aims: Intestinal epithelial cells (IECs) regulate intestinal immune cells, particularly development of T-helper 17 (Th17) cells. Deregulation of this process leads to intestinal inflammation and tumorigenesis, via unknown mechanisms. TANK-binding kinase 1 (TBK1) is expressed by IECs and cells in the innate immune system. We studied the functions of TBK1 in the intestinal immune response and tumorigenesis in mice.

Methods: We performed studies of wild-type mice, mice with conditional disruption of Tbk1 (Tbk1), Tbk1 mice crossed with Apc mice, and Mt mice crossed with Apc mice. Some mice were given intraperitoneal injections of a neutralizing antibody against interleukin 17 (IL17) or IL1β. Intestine tissues were collected from mice and analyzed by histology, for numbers of adenomas and Th17 cells, and expression of inflammatory cytokines by real-time PCR. IECs were isolated from wild-type and Tbk1 mice, stimulated with lipopolysaccharide, co-cultured for with bone marrow-derived macrophages, and analyzed by RNA sequencing and biochemical analyses.

Results: Compared to ApcTbk1 mice, ApcTbk1 mice had significant increases in number and size of intestinal polyps, and significantly more Th17 cells in lamina propria. Administration of an antibody against IL17 reduced the number of intestinal polyps in ApcTbk1 mice to that observed in ApcTbk1 mice. In culture, TBK1-deficient IECs promoted expression of IL1β by macrophages, which induced differentiation of naïve CD4 T cells into Th17 cells. RNA sequencing analysis revealed that the TBK1-deficient IECs had increased expression of metallothionein 1 (MT1), an immune regulator that promotes intestinal inflammation. Intestine tissues from ApcMt mice had significant fewer Th17 cells than ApcMt mice, and a significantly lower number of polyps. Analyses of colorectal tumors in the Cancer Genome Atlas found colorectal tumors with high levels of MT1 and IL17 mRNAs to be associated with reduced survival times of patients.

Conclusions: Expression of TBK1 by IECs suppresses expression of MT1 and prevents expression of IL1β by macrophages and differentiation of Th17 cells, to prevent inflammation and tumorigenesis. Strategies to block this pathway might be developed for colorectal tumorigenesis.
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http://dx.doi.org/10.1053/j.gastro.2020.07.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680348PMC
November 2020

Comparative epidemiology of gliosarcoma and glioblastoma and the impact of Race on overall survival: A systematic literature review.

Clin Neurol Neurosurg 2020 08 29;195:106054. Epub 2020 Jun 29.

Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, USA; Department of Neurological Surgery, University Hospitals Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH, USA.

Objective: Gliosarcoma (GSM) is a rare subtype of glioblastoma (GBM) that accounts for approximately four percent of high-grade gliomas. There is scarce epidemiological data on patients with GSM as a distinct subgroup of GBM.

Methods: A systematic literature review was performed of peer-reviewed databases using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate the impact of race and ethnicity on survival in patients with GSM compared to patients with GBM.

Results: Following initial abstract screening, a total of 138 articles pertaining to GSM and 275 pertaining to GBM met criteria for full-text review, with 5 and 27 articles included in the final analysis for GSM and GBM, respectively. The majority of patients in both cohorts were non-Hispanic Whites, representing 85.6 % of total GSM patients and 87.7 % of GBM patients analyzed. Two GSM studies stratified survival by race, with one reporting the longest median survival for the Hispanic population of 10.6 months and the shortest median survival for the Asian population of 9 months. Among the GBM studies analyzed, the majority of studies reported shorter survival and higher risk of mortality among White Non-Hispanics compared to non-White patients; and of the 15 studies which reported data for the Asian population, 12 studies reported this race category to have the longest survival compared to all other races studied. Younger age, female sex, MGMT promoter methylation status, and adjuvant chemoradiation therapy were associated with improved survival in both GSM and GBM cohorts, although these were not further stratified by race.

Conclusion: GSM portends a similarly poor prognosis to other GBM subtypes; however, few studies exist which have examined factors associated with differences in survival between these histologic variants. This review of the literature suggests there is a possible association between race and survival for patients with GBM, however data supporting this conclusion for patients with GSM is lacking. These findings suggest that GSM is a distinct disease from other GBM subtypes, with epidemiologic differences that should be further explored.
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http://dx.doi.org/10.1016/j.clineuro.2020.106054DOI Listing
August 2020

Peli1 signaling blockade attenuates congenital zika syndrome.

PLoS Pathog 2020 06 16;16(6):e1008538. Epub 2020 Jun 16.

Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, United States of America.

Zika virus (ZIKV) infects pregnant women and causes devastating congenital zika syndrome (CZS). How the virus is vertically transmitted to the fetus and induces neuronal loss remains unclear. We previously reported that Pellino (Peli)1, an E3 ubiquitin ligase, promotes p38MAPK activation in microglia and induction of lethal encephalitis by facilitating the replication of West Nile virus (WNV), a closely related flavivirus. Here, we found that Peli1 expression was induced on ZIKV-infected human monocytic cells, peripheral blood mononuclear cells, human first-trimester placental trophoblasts, and neural stem cell (hNSC)s. Peli1 mediates ZIKV cell attachment, entry and viral translation and its expression is confined to the endoplasmic reticulum. Moreover, Peli1 mediated inflammatory cytokine and chemokine responses and induced cell death in placental trophoblasts and hNSCs. ZIKV-infected pregnant mice lacking Peli1 signaling had reduced placental inflammation and tissue damage, which resulted in attenuated congenital abnormalities. Smaducin-6, a membrane-tethered Smad6-derived peptide, blocked Peli1-mediated NF-κB activation but did not have direct effects on ZIKV infection. Smaducin-6 reduced inflammatory responses and cell death in placental trophoblasts and hNSCs, and diminished placental inflammation and damage, leading to attenuated congenital malformations in mice. Collectively, our results reveal a novel role of Peli1 in flavivirus pathogenesis and suggest that Peli1 promotes ZIKV vertical transmission and neuronal loss by mediating inflammatory cytokine responses and induction of cell death. Our results also identify Smaducin-6 as a potential therapeutic candidate for treatment of CZS.
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http://dx.doi.org/10.1371/journal.ppat.1008538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297310PMC
June 2020

Detecting rare haplotypes associated with complex diseases using both population and family data: Combined logistic Bayesian Lasso.

Stat Methods Med Res 2020 11 4;29(11):3340-3350. Epub 2020 Jun 4.

Department of Statistics, 2647The Ohio State University, Columbus, OH, USA.

Haplotype-based association methods have been developed to understand the genetic architecture of complex diseases. Compared to single-variant-based methods, haplotype methods are thought to be more biologically relevant, since there are typically multiple non-independent genetic variants involved in complex diseases, and the use of haplotypes implicitly accounts for non-independence caused by linkage disequilibrium. In recent years, with the focus moving from common to rare variants, haplotype-based methods have also evolved accordingly to uncover the roles of rare haplotypes. One particular approach is regularization-based, with the use of Bayesian least absolute shrinkage and selection operator (Lasso) as an example. This type of methods has been developed for either case-control population data (the logistic Bayesian Lasso (LBL)) or family data (family-triad-based logistic Bayesian Lasso (famLBL)). In some situations, both family data and case-control data are available; therefore, it would be a waste of resources if only one of them could be analyzed. To make full usage of available data to increase power, we propose a unified approach that can combine both case-control and family data (combined logistic Bayesian Lasso (cLBL)). Through simulations, we characterized the performance of cLBL and showed the advantage of cLBL over existing methods. We further applied cLBL to the Framingham Heart Study data to demonstrate its utility in real data applications.
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http://dx.doi.org/10.1177/0962280220927728DOI Listing
November 2020

The Association of ARMC5 with the Renin-Angiotensin-Aldosterone System, Blood Pressure, and Glycemia in African Americans.

J Clin Endocrinol Metab 2020 08;105(8)

The Ohio State University, Columbus, Ohio.

Context: Armadillo repeat containing 5 (ARMC5) on chromosome 16 is an adrenal gland tumor suppressor gene associated with primary aldosteronism, especially among African Americans (AAs). We examined the association of ARMC5 variants with aldosterone, plasma renin activity (PRA), blood pressure, glucose, and glycosylated hemoglobin A1c (HbA1c) in community-dwelling AAs.

Methods: The Jackson Heart Study is a prospective cardiovascular cohort study in AAs with baseline data collection from 2000 to 2004. Kernel machine method was used to perform a single joint test to analyze for an overall association between the phenotypes of interest (aldosterone, PRA, systolic and diastolic blood pressure [SBP, DBP], glucose, and HbA1c) and the ARMC5 single nucleotide variants (SNVs) adjusted for age, sex, BMI, and medications; followed by Baysian Lasso methodology to identify sets of SNVs in terms of associated haplotypes with specific phenotypes.

Results: Among 3223 participants (62% female; mean age 55.6 (SD ± 12.8) years), the average SBP and DBP were 127 and 76 mmHg, respectively. The average fasting plasma glucose and HbA1c were 101 mg/dL and 6.0%, respectively. ARMC5 variants were associated with all 6 phenotypes. Haplotype TCGCC (ch16:31476015-31476093) was negatively associated, whereas haplotype CCCCTTGCG (ch16:31477195-31477460) was positively associated with SBP, DBP, and glucose. Haplotypes GGACG (ch16:31477790-31478013) and ACGCG (ch16:31477834-31478113) were negatively associated with aldosterone and positively associated with HbA1c and glucose, respectively. Haplotype GCGCGAGC (ch16:31471193-ch16:31473597(rs114871627) was positively associated with PRA and negatively associated with HbA1c.

Conclusions: ARMC5 variants are associated with aldosterone, PRA, blood pressure, fasting glucose, and HbA1c in community-dwelling AAs, suggesting that germline mutations in ARMC5 may underlie cardiometabolic disease in AAs.
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http://dx.doi.org/10.1210/clinem/dgaa290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308077PMC
August 2020

Two-Dimensional Transition Metal Dichalcogenides: Synthesis, Biomedical Applications and Biosafety Evaluation.

Front Bioeng Biotechnol 2020 7;8:236. Epub 2020 Apr 7.

School of Public Health, Shandong University, Jinan, China.

Recently, two-dimensional transition metal dichalcogenides (2D TMDCs) have drawn certain attentions in many fields. The unique and diversified electronic structure and ultrathin sheet structure of 2D TMDCs offer opportunities for moving ahead of other 2D nanomaterials such as graphene and expanding the wide application of inorganic 2D nanomaterials in many fields. For a better understanding of 2D TMDCs, one needs to know methods for their synthesis and modification, as well as their potential applications and possible biological toxicity. Herein, we summarized the recent research progress of 2D TMDCs with particular focus on their biomedical applications and potential health risks. Firstly, two kinds of synthesis methods of 2D TMDCs, top-down and bottom-up, and methods for their surface functionalization are reviewed. Secondly, the applications of 2D TMDCs in the field of biomedicine, including drug loading, photothermal therapy, biological imaging and biosensor were summarized. After that, we presented the existing researches on biosafety evaluation of 2D TMDCs. At last, we discussed major research gap in current researches and challenges and coping strategies in future studies.
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http://dx.doi.org/10.3389/fbioe.2020.00236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154136PMC
April 2020

Association of Race with Survival in Intracranial World Health Organization Grade II and III Meningioma in the United States: Systematic Literature Review.

World Neurosurg 2020 06 3;138:e361-e369. Epub 2020 Mar 3.

Department of Neurological Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA; Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

Background: Recent literature has shown significant differences in meningioma incidence among different races, but minimal conclusive data exist on the role of race and ethnicity in overall survival for patients with high-grade intracranial meningioma. We conducted a systematic review to investigate the impact of race and ethnicity on survival in patients with high-grade intracranial meningioma.

Methods: A systematic literature review was conducted for studies using Ovid, PubMed, Cochrane, Embase, and Scopus databases. Databases were queried for the following: Meningioma AND [Ethnic OR Demography, OR African American OR Arab OR Hispanic OR Asian, OR White OR race OR racial] AND [survival OR survival analysis OR survival rate OR treatment outcome OR Survivor OR Outcome].

Results: A literature search yielded a total of 412 abstracts, which were screened according to criteria that were determined a priori, and a total of 129 full-text articles were reviewed. Four articles were included in the final analysis, reporting on a total of 13,424 patients. Three studies saw an overall survival benefit in White non-Hispanics compared with Black non-Hispanics, and 1 reported a survival benefit in White non-Hispanics and Black non-Hispanics among patients who received gross total resection. One study additionally reported an increased likelihood of White patients receiving gross total resection when compared with non-White patients.

Conclusions: The limited data available suggest that White patients have improved measures of survival compared with nonw-White patients, for reasons that are likely complex and multifactorial. Further studies are needed to explore these survival differences seen.
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http://dx.doi.org/10.1016/j.wneu.2020.02.120DOI Listing
June 2020

Four generations of EGFR TKIs associated with different pathogenic mutations in non-small cell lung carcinoma.

J Drug Target 2020 11 12;28(9):861-872. Epub 2020 Mar 12.

Key Laboratory of Antibiotic Bioengineering of National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology (IMB), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P. R. China.

Non-small cell lung carcinoma (NSCLC) is a malignant tumour with poor prognosis and high mortality. Platinum-based dual-agent chemotherapy is the main therapeutic regimen for this disease. In recent years, because of the introduction of molecular targeted therapy, various targeted therapeutic agents against epidermal growth factor receptor (EGFR) have been rapidly developed, which has become a research hotspot for NSCLC treatment. Here, we review the latest studies describing the features and types of EGFR pathogenic mutations, currently established EGFR-tyrosine kinase inhibitors from the first to fourth generation, including their action mechanisms, acquired resistance, and clinical applications, and potential challenges and perspectives that current researchers should address.
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http://dx.doi.org/10.1080/1061186X.2020.1737934DOI Listing
November 2020

Cerebral vessel anatomy as a predictor of first-pass effect in mechanical thrombectomy for emergent large-vessel occlusion.

J Neurosurg 2020 Jan 24:1-9. Epub 2020 Jan 24.

2Department of Neurological Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio.

Objective: Mechanical thrombectomy is effective in acute ischemic stroke secondary to emergent large-vessel occlusion, but optimal efficacy is contingent on fast and complete recanalization. First-pass recanalization does not occur in the majority of patients. The authors undertook this study to determine if anatomical parameters of the intracranial vessels impact the likelihood of first-pass complete recanalization.

Methods: The authors retrospectively evaluated data obtained in 230 patients who underwent mechanical thrombectomy for acute ischemic stroke secondary to large-vessel occlusion at their institution from 2016 to 2018. Eighty-six patients were identified as having pure M1 occlusions, and 76 were included in the final analysis. The authors recorded and measured clinical and anatomical parameters and evaluated their relationships to the first-pass effect.

Results: The first-pass effect was achieved in 46% of the patients. When a single device was employed, aspiration thrombectomy was more effective than stent retriever thrombectomy. A larger M1 diameter (p = 0.001), decreased vessel diameter tapering between the petrous segment of the internal carotid artery (ICA) and M1 (p < 0.001), and distal collateral grading (p = 0.044) were associated with first-pass recanalization. LASSO (least absolute shrinkage and selection operator) was used to generate a predictive model for recanalization using anatomical variables.

Conclusions: The authors demonstrated that a larger M1 vessel diameter, low rate of vessel diameter tapering along the course of the intracranial ICA, and distal collateral status are associated with first-pass recanalization for patients with M1 occlusions.
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http://dx.doi.org/10.3171/2019.11.JNS192673DOI Listing
January 2020