Publications by authors named "Jun Shen"

911 Publications

Single-cell transcriptome of early hematopoiesis guides arterial endothelial-enhanced functional T cell generation from human PSCs.

Sci Adv 2021 Sep 3;7(36):eabi9787. Epub 2021 Sep 3.

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.

[Figure: see text].
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http://dx.doi.org/10.1126/sciadv.abi9787DOI Listing
September 2021

Rational design for high-yield monolayer WSfilms in confined space under fast thermal processing.

Nanotechnology 2021 Sep 21;32(50). Epub 2021 Sep 21.

Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, People's Republic of China.

Tungsten Disulfide (WS) films, as one of the most attractive members in the family of transition metal dichalcogenides, were synthesized typically on SiO/Si substrate by confine-spaced chemical vapor deposition method. The whole process could be controlled efficiently by precursor concentration and fast thermal process. To be priority, the effect of fast heating-up to cooling-down process and source ratio-dependent rule for WSstructure have been systematically studied, leading to high-yield and fine structure of monolayer WSfilms with standard triangular morphology and average edge length of 92.4m. The growth time of the samples was regulated within 3 min, and the optimal source ratio of sulfur to tungsten oxide is about 200:3. The whole experimental duration was about 50 min, which is only about quarter in comparison to relevant reports. We assume one type of 'multi-nucleation dynamic process' to provide a potential way for fast synthesis of the samples. Finally, the good performance of as-fabricated field-effect transistor on WSfilm was achieved, which exhibits high electron mobility of 4.62 cmVs, fast response rate of 42 ms, and remarkable photoresponsivity of 3.7 × 10A W. Our work will provide a promising robust way for rapid synthesis of high-quality monolayer TMDs films and pave the way for the potential applications of TMDCs.
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http://dx.doi.org/10.1088/1361-6528/ac23f8DOI Listing
September 2021

A 28-Day Challenge to Help Quit Smoking Using Telephone Follow-Ups Combined With the WeChat App: The Impact of the Humanistic Approach on Smoking Cessation.

J Addict Nurs 2021 Jul-Sep 01;32(3):211-215

Abstract: The study aims to assess the effectiveness of telephone follow-ups combined with a smartphone app (e.g., WeChat [Tencent], which is one of the most widely used communication apps in China), as a smoking cessation intervention. Social volunteers were recruited on March 1, 2017, and randomized to supervision groups with five participants in each group. Every day, the specialists shared some information related to smoking cessation including the videos, songs, and scientific knowledge in WeChat groups and conducted telephone follow-ups on the third, fifth, seventh, ninth, 12th, 17th, 22nd, 27th, and 30th day in March and on April 1. Ultimately, a comparison was made of the self-reported smoking abstinence and self-reported average number of cigarettes smoked between the participants. One hundred ten volunteers participated in the study, with 105 who completed follow-up. Self-reported smoking abstinence in the past 7 days occurred in 65.7% of the participants (n = 69) compared with 34.3% (n = 36) in whom smoking abstinence did not occur. The mean age of those who failed was 40.15 years (range: 22-70 years), and 55.5% (n = 20) attributed their failure to personal reasons. However, the self-reported average number of cigarettes smoked every day was less than that before the study (on average, 10.34 ± 8.17 per day), and this difference was statistically significant (95% CI [8.312, 12.364], p < .01). It was effective to deliver a telephone follow-up combined with a smartphone app follow-up as an intervention for smoking cessation.
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http://dx.doi.org/10.1097/JAN.0000000000000420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410085PMC
September 2021

Selectivity Profile of the Tyrosine Kinase 2 Inhibitor Deucravacitinib Compared with Janus Kinase 1/2/3 Inhibitors.

Dermatol Ther (Heidelb) 2021 Aug 30. Epub 2021 Aug 30.

Bristol Myers Squibb, Princeton, NJ, USA.

Introduction: Deucravacitinib, a novel, oral, selective inhibitor of tyrosine kinase 2 (TYK2) signaling, acts via an allosteric mechanism by binding to the enzyme's regulatory domain instead of the catalytic domain. This unique binding provides high functional selectivity for TYK2 versus the closely related Janus kinases (JAKs) 1/2/3. Deucravacitinib was efficacious in phase 2 and 3 psoriasis trials, without clinical or laboratory parameters indicative of JAK 1/2/3 inhibition being observed. This analysis compared the kinase specificities of deucravacitinib versus JAK 1/2/3 inhibitors at therapeutic exposures.

Methods: Signaling via JAK 1/3, JAK 2/2, and TYK2/JAK 2 dimers was measured in in vitro whole blood assays. Concentrations providing half-maximal inhibition (IC) in these assays were determined for deucravacitinib and the JAK 1/2/3 inhibitors tofacitinib, upadacitinib, and baricitinib. Newly derived whole blood IC values were plotted against available pharmacokinetic profiles using doses evaluated in phase 2/3 trials. Simulated average daily inhibition and durations over which concentrations exceeded IC were evaluated.

Results: At clinically relevant exposures, projected steady-state deucravacitinib plasma concentrations were higher than TYK2 IC for approximately 9-18 h. Maximal plasma concentrations (C) of deucravacitinib were 8- to 17-fold lower than JAK 1/3 IC and > 48- to > 102-fold lower than JAK 2/2 IC. Simulated daily average TYK2 inhibition by deucravacitinib ranged from 50% to 69%. Simulations indicated that tofacitinib, upadacitinib, and baricitinib at steady state exhibited varying degrees of JAK 1/3 (daily average inhibition, 70-94%) and JAK 2/2 (23%-67%) inhibition at therapeutic concentrations, with C values 17- to 33-fold lower than their TYK2 IC levels.

Conclusion: At clinically relevant doses and exposures, deucravacitinib demonstrates highly selective inhibition of TYK2 and not JAK 1/2/3. Tofacitinib, upadacitinib, and baricitinib variably inhibit JAK 1/2/3 but not TYK2. These results indicate that deucravacitinib is a distinct class of kinase inhibitor compared with JAK 1/2/3 inhibitors.
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http://dx.doi.org/10.1007/s13555-021-00596-8DOI Listing
August 2021

Transcriptomes of (Asteraceae) Provide Insights into High-Altitude Adaptation.

Plants (Basel) 2021 Aug 20;10(8). Epub 2021 Aug 20.

CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, China.

Understanding how species adapt to extreme environments is an extension of the main goals of evolutionary biology. While alpine plants are an ideal system for investigating the genetic basis of high-altitude adaptation, genomic resources in these species are still limited. In the present study, we generated reference-level transcriptomic data of five species through high-throughput sequencing and assembly. Three of them are located in the highland of the Qinghai-Tibet Plateau (QTP), and the other two are close relatives distributed in the lowland. A series of comparative and evolutionary genomics analyses were conducted to explore the genetic signatures of adaptive evolution to high-altitude environments. Estimation of divergence time using single-copy orthologs revealed that species diversified during the Miocene, a period with extensive tectonic movement and climatic fluctuation on the QTP. We characterized gene families specific to the alpine species, including genes involved in oxidoreductase activity, pectin catabolic process, lipid transport, and polysaccharide metabolic process, which may play important roles in defense of hypoxia and freezing temperatures of the QTP. Furthermore, in a phylogenetic context with the branch model, we identified hundreds of genes with signatures of positive selection. These genes are involved in DNA repair, membrane transport, response to UV-B and hypoxia, and reproductive processes, as well as some metabolic processes associated with nutrient intake, potentially responsible for adaptation to the harsh environments of high altitude. Overall, our study provides valuable genomic resources for alpine species and gained helpful insights into the genomic basis of plants adapting to extreme environments.
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http://dx.doi.org/10.3390/plants10081715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402177PMC
August 2021

Alumina-Doped Silica Aerogels for High-Temperature Thermal Insulation.

Gels 2021 Aug 14;7(3). Epub 2021 Aug 14.

Shanghai Key Laboratory of Special Artificial Microstructure Materials and Technology, School of Physics Science and Engineering, Tongji University, Shanghai 200092, China.

In this study, we used two methods to prepare alumina-doped silica aerogels with the aim of increasing the thermal stability of silica aerogels. The first method was physical doping of α-AlO nano powders, and the second method was to create a chemical compound via the co-precursor of TEOS and AlCl·6HO in different proportions. The shrinkage, chemical composition, and specific surface area (SSA) of samples after heating at different temperatures were analyzed. Our results show that the silicon hydroxyl groups of samples derived from AlCl·6HO gradually decreased and nearly disappeared after heating at 800 °C, which indicates the complete dehydration of the silicon hydroxyl. Thus, the samples exhibited a large linear shrinkage and decreased SSA after high-temperature heat treatment. By contrast, samples doped with α-AlO powders retained abundant silicon hydroxyl groups, and the 6.1 wt.% α-AlO-doped sample exhibited the lowest linear shrinkage of 11% and the highest SSA of 1056 m/g after heat treatment at 800 °C. The alumina-doped silica aerogels prepared using a simple and low-price synthesized method pave the way for the low-cost and large-scale production of high-temperature thermal insulation.
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http://dx.doi.org/10.3390/gels7030122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395836PMC
August 2021

Bioelectrical impedance analysis-based nomogram construction for predicting secondary loss of response to infliximab in bio-naïve Crohn's disease patients.

Biomed Pharmacother 2021 Oct 24;142:112076. Epub 2021 Aug 24.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, 160# Pu Jian Ave, Shanghai 200127, China; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160# Pu Jian Ave, Shanghai 200127, China; Shanghai Institute of Digestive Disease, 160# Pu Jian Ave, Shanghai 200127, China. Electronic address:

Background: Infliximab is emerging as the first-line therapy for Crohn's disease (CD); however, the rate of secondary loss of response (SLR) can exceed 50%. This study aimed to construct a nomogram based on bioelectrical impedance analysis (BIA) indexes and laboratory markers to predict SLR to infliximab in biologically naïve CD patients.

Methods: Data of 136 biologically naïve CD patients treated between September 2019 and March 2021 were retrospectively retrieved. BIA-based body composition parameters and laboratory markers were obtained before the infliximab therapy. Predictor selection was conducted using the least absolute shrinkage and selection operator (LASSO) and univariate logistic regression. The nomogram was developed using multivariable logistic regression, and internal validation was made by ten-fold cross-validation.

Results: SLR occurred in 51% of the CD patients during 54 weeks. The nomogram predictors included hemoglobin, albumin, serum iron, and BIA scores. The nomogram showed significant discrimination (area under the curve [AUC], 0.920; 95% confidence interval, 0.873-0.967) and calibration (mean error = 0.012). Decision curve analysis (DCA) indicated that the nomogram provided net clinical benefit when the risk probability was between 2% and 83%. Internal validation assessment of the nomogram robustness found an AUC of 0.904 and an accuracy of 0.841.

Conclusions: This BIA-based body composition parameters- and laboratory markers-based novel nomogram could act as a predictive tool to evaluate SLR to infliximab therapy, crucial for optimizing treatment strategies and switching biologics in CD.
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http://dx.doi.org/10.1016/j.biopha.2021.112076DOI Listing
October 2021

STAT5a Confers Doxorubicin Resistance to Breast Cancer by Regulating ABCB1.

Front Oncol 2021 15;11:697950. Epub 2021 Jul 15.

Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.

Chemoresistance is a daunting challenge to the prognosis of patients with breast cancer. Signal transducer and activator of transcription (STAT) 5a plays vital roles in the development of various cancers, but its function in breast cancer is controversial, and its role in chemoresistance in breast cancer remains unexplored. Here we identified STAT5a as a chemoresistance inducer that regulates the expression of ABCB1 in breast cancer and can be targeted by pimozide, an FDA-approved psychotropic drug. First, we found that STAT5a and ABCB1 were expressed at higher levels in doxorubicin-resistant cell lines and chemoresistant patients, and their expression was positively correlated. Then, we confirmed the essential roles of STAT5a and ABCB1 in doxorubicin resistance in breast cancer cells and the regulation of ABCB1 transcription by STAT5a. Subsequently, the efficacy of pimozide in inhibiting STAT5a and sensitizing doxorubicin-resistant breast cancer cells was tested. Finally, we verified the role of STAT5a in doxorubicin resistance in breast cancer and the efficacy of pimozide in reversing this resistance . Our study demonstrated the vital role of STAT5a in doxorubicin resistance in breast cancer. Targeting STAT5a might be a promising strategy for treating doxorubicin-resistant breast cancer. Moreover, repurposing pimozide for doxorubicin resensitization is attractive due to the safety profile of pimozide.
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http://dx.doi.org/10.3389/fonc.2021.697950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320598PMC
July 2021

Artificial Intelligence Enhances Studies on Inflammatory Bowel Disease.

Front Bioeng Biotechnol 2021 8;9:635764. Epub 2021 Jul 8.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is an idiopathic condition related to a dysregulated immune response to commensal intestinal microflora in a genetically susceptible host. As a global disease, the morbidity of IBD reached a rate of 84.3 per 100,000 persons and reflected a continued gradual upward trajectory. The medical cost of IBD is also notably extremely high. For example, in Europe, it has €3,500 in CD and €2,000 in UC per patient per year, respectively. In addition, taking into account the work productivity loss and the reduced quality of life, the indirect costs are incalculable. In modern times, the diagnosis of IBD is still a subjective judgment based on laboratory tests and medical images. Its early diagnosis and intervention is therefore a challenging goal and also the key to control its progression. Artificial intelligence (AI)-assisted diagnosis and prognosis prediction has proven effective in many fields including gastroenterology. In this study, support vector machines were utilized to distinguish the significant features in IBD. As a result, the reliability of IBD diagnosis due to its impressive performance in classifying and addressing region problems was improved. Convolutional neural networks are advanced image processing algorithms that are currently in existence. Digestive endoscopic images can therefore be better understood by automatically detecting and classifying lesions. This study aims to summarize AI application in the area of IBD, objectively evaluate the performance of these methods, and ultimately understand the algorithm-dataset combination in the studies.
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http://dx.doi.org/10.3389/fbioe.2021.635764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297505PMC
July 2021

Growth, Structure, and Properties of a Multifunctional Crystal PrCaBO.

Inorg Chem 2021 Aug 20;60(15):10895-10898. Epub 2021 Jul 20.

Center for Crystal Research and Development, Key Laboratory of Functional Crystals and Laser Technology, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.

A new praseodymium-based borate crystal PrCaBO (PCB) has been grown through the high temperature solution method. PCB crystallizes in monoclinic space group 2 with unit cell parameters of = 10.9475(10) Å, = 6.5343(7) Å, = 9.0336(8) Å, β = 91.652(3)°, and = 2, in which BO groups and PrO and CaO polyhedra constitute the three-dimensional framework. PCB exhibits a similar second harmonic response intensity to that of LaCaBO and an intense orange fluorescence emission with a long fluorescence lifetime at about 610 nm excited by a xenon lamp light of 466 nm. The band gap, partial density of states, and birefringence have been investigated via theoretical calculations.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01885DOI Listing
August 2021

Metabolic Brain Network Analysis With F-FDG PET in a Rat Model of Neuropathic Pain.

Front Neurol 2021 2;12:566119. Epub 2021 Jul 2.

School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Neuropathic pain has been found to be related to profound reorganization in the function and structure of the brain. We previously demonstrated changes in local brain activity and functional/metabolic connectivity among selected brain regions by using neuroimaging methods. The present study further investigated large-scale metabolic brain network changes in 32 Sprague-Dawley rats with right brachial plexus avulsion injury (BPAI). Graph theory was applied in the analysis of 2-deoxy-2-[18F] fluoro-D-glucose (F-FDG) PET images. Inter-subject metabolic networks were constructed by calculating correlation coefficients. Global and nodal network properties were calculated and comparisons between pre- and post-BPAI (7 days) status were conducted. The global network properties (including global efficiency, local efficiency and small-world index) and nodal betweenness centrality did not significantly change for all selected sparsity thresholds following BPAI ( > 0.05). As for nodal network properties, both nodal degree and nodal efficiency measures significantly increased in the left caudate putamen, left medial prefrontal cortex, and right caudate putamen ( < 0.001). The right entorhinal cortex showed a different nodal degree ( < 0.05) but not nodal efficiency. These four regions were selected for seed-based metabolic connectivity analysis. Strengthened connectivity was found among these seeds and distributed brain regions including sensorimotor area, cognitive area, and limbic system, etc. ( < 0.05). Our results indicated that the brain had the resilience to compensate for BPAI-induced neuropathic pain. However, the importance of bilateral caudate putamen, left medial prefrontal cortex, and right entorhinal cortex in the network was strengthened, as well as most of their connections with distributed brain regions.
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http://dx.doi.org/10.3389/fneur.2021.566119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284720PMC
July 2021

High GP73 Expression Correlates with Poor Response to Neoadjuvant Chemotherapy and Survival in Gastric Cancer: A Tissue Microarray Study.

Pathol Oncol Res 2021 30;27:603838. Epub 2021 Mar 30.

Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Golgi protein 73 (GP73) is a type II Golgi transmembrane protein which is overexpressed in several cancers, however, its role in gastric cancer is still unclear. The aim of this study is to investigate if high GP73 expression is associated with pathological tumor response to neoadjuvant chemotherapy and prognosis for patients with gastric cancer. A total of 348 patients with gastric cancer, who had undergone surgery between 1999 and 2011 were retrospectively reviewed, GP73 expression was examined in tumor tissues using tissue microarray and the correlations between its expression and pathological response to neoadjuvant chemotherapy as well as patients prognosis were analyzed. We found that GP73 expression was not associated with clinicopathologic features including tumor size, differentiation and TNM stage. High expression of GP73 was associated with less pathological tumor response to neoadjuvant chemotherapy and poor survival in gastric cancer, multivariate analysis showed GP73 expression was an independent predictive factor for pathological response to neoadjuvant chemotherapy and for prognosis in patients with gastric cancer. Our results suggest that GP73 expression correlates with the effect of neoadjuvant chemotherapy and is a promising biomarker to identify patients with poor prognosis.
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http://dx.doi.org/10.3389/pore.2021.603838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262201PMC
March 2021

Bilateral iris mass as the first manifestation of NK cell lymphoma: A case report.

Eur J Ophthalmol 2021 Jul 13:11206721211029136. Epub 2021 Jul 13.

Department of Ophthalmology, Huashan Hospital of Fudan University, Shanghai, China.

Introduction: Natural killer (NK) cell lymphoma is a progressive non-Hodgkin's lymphoma with rare prevalence. Intraocular involvement of NK cell lymphoma is very rare, with only case reports to date.

Case Presentation: Here, we report a case of intraocular involvement of NK cell lymphoma which was presented with bilateral uveitis, iris mass, and diffuse infiltration into the center nerve system (CNS), skin, and possibly myocardium.

Conclusions: Iris mass and uveitis which is not responsive to steroids may be ocular manifestations of intraocular lymphoma, such as NK cell lymphoma. Ophthalmological and systemic examinations should be required for early diagnosis and treatment.
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http://dx.doi.org/10.1177/11206721211029136DOI Listing
July 2021

Etiology of Severe Pneumonia in Children in Alveolar Lavage Fluid Using a High-Throughput Gene Targeted Amplicon Sequencing Assay.

Front Pediatr 2021 25;9:659164. Epub 2021 Jun 25.

Infectious Disease Department, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.

To evaluate the diagnostic value of a high-throughput gene targeted amplicon sequencing (TAS) assay for detecting pathogenic microorganisms in alveolar lavage fluid (ALF) from children with severe community-acquired pneumonia (SCAP). A retrospective study was performed on 48 frozen ALF samples from 47 severe pneumonia cases admitted to Children's Hospital of Fudan University from January 1, 2019, to March 31, 2019. All samples were tested by a multiplex PCR (Multi-PCR) assay and a TAS assay. The results of the TAS panels were parallel compared with Multi-PCR and Conventional Tests (CT) including culture, direct fluorescent antibody method (DFA), and singleplex polymerase chain reaction (PCR). The proportion of pathogens detection by CT was 81.2% (39/48). The 8 common respiratory viruses including respiratory syncytial virus (RSV), adenovirus (ADV), influenza A virus (FLUA), influenza B virus (FLUB), parainfluenza virus 1-3 (PIV1-3), and human Metapneumovirus (hMPV) were found in 31.2% (15/48) of the 48 samples by DFA. With the criteria of CT results used as "Golden Standard" for determing of TAS results, the proportion of pathogens detection by TAS was 70.8% (34/48). The difference of proportion of pathogens detection between TAS and CT was not statistically significant ( = 0.232). The sensitivity and specificity of TAS for pathogens detection based on CT were 87.1% (95% CI, 71.77-95.18%) and 100.0% (95% CI, 62.88-100%), the positive predictive value (PPV) and negative predictive value (NPV) were 100.0% (95% CI, 87.35-100%) and 64.2% (95% CI, 35.62-86.02%), respectively. While Multi-PCR results were used as "Golden Standard," the total pathogens detection rate of TAS was 83.3% (40/48), which had a significant difference with that of Multi-PCR ( = 0.003). The sensitivity and PPV of TAS compared with Multi-PCR were 83.3% (95% CI, 69.23-92.03%) and 100.0% (95% CI, 89.08-100%), respectively. High rates of co-infection were proved by CT, Multi-PCR, and TAS. Mycoplasma pneumoniae (MP) and ADV were the two most frequently detected pathogens in all three assays. Compared with the CT and Multi-PCR methods, this TAS assay had a good performance in detecting bacteriological and viral pathogens from ALF. More research is needed to establish interpretation criteria based on TAS reads or analysis platforms.
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http://dx.doi.org/10.3389/fped.2021.659164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267249PMC
June 2021

Altered Posterior Cerebellar Lobule Connectivity With Perigenual Anterior Cingulate Cortex in Women With Primary Dysmenorrhea.

Front Neurol 2021 22;12:645616. Epub 2021 Jun 22.

Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

This study aimed to investigate the potential connectivity mechanism between the cerebellum and anterior cingulate cortex (ACC) and the cerebellar structure in primary dysmenorrhea (PDM). We applied the spatially unbiased infratentorial template (SUIT) of the cerebellum to obtain anatomical details of cerebellar lobules, upon which the functional connectivity (FC) between the cerebellar lobules and ACC subregions was analyzed and the gray matter (GM) volume of cerebellar lobules was measured by using voxel-based morphometry (VBM) in 35 PDM females and 38 age-matched healthy females. The potential relationship between the altered FC or GM volume and clinical information was also evaluated in PDM females. PDM females showed higher connectivity between the left perigenual ACC (pACC) and lobule vermis_VI, between the left pACC and left lobule IX, and between right pACC and right cerebellar lobule VIIb than did the healthy controls. Compared with healthy controls, no altered GM volume was found in PDM females. No significant correlation was found between altered cerebellum-ACC FC and the clinical variables in the PDM females. PDM females have abnormal posterior cerebellar connectivity with pACC but no abnormal structural changes. ACC-cerebellar circuit disturbances might be involved in the PDM females.
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http://dx.doi.org/10.3389/fneur.2021.645616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258113PMC
June 2021

Disease-specific ACMG/AMP guidelines improve sequence variant interpretation for hearing loss.

Genet Med 2021 Jul 6. Epub 2021 Jul 6.

Al Genomics Center, Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates.

Purpose: The ClinGen Variant Curation Expert Panels (VCEPs) provide disease-specific rules for accurate variant interpretation. Using the hearing loss-specific American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines, the Hearing Loss VCEP (HL VCEP) illustrates the utility of expert specifications in variant interpretation.

Methods: A total of 157 variants across nine HL genes, previously submitted to ClinVar, were curated by the HL VCEP. The curation process involved collecting published and unpublished data for each variant by biocurators, followed by bimonthly meetings of an expert curation subgroup that reviewed all evidence and applied the HL-specific ACMG/AMP guidelines to reach a final classification.

Results: Before expert curation, 75% (117/157) of variants had single or multiple variants of uncertain significance (VUS) submissions (17/157) or had conflicting interpretations in ClinVar (100/157). After applying the HL-specific ACMG/AMP guidelines, 24% (4/17) of VUS and 69% (69/100) of discordant variants were resolved into benign (B), likely benign (LB), likely pathogenic (LP), or pathogenic (P). Overall, 70% (109/157) variants had unambiguous classifications (B, LB, LP, P). We quantify the contribution of the HL-specified ACMG/AMP codes to variant classification.

Conclusion: Expert specification and application of the HL-specific ACMG/AMP guidelines effectively resolved discordant interpretations in ClinVar. This study highlights the utility of ClinGen VCEPs in supporting more consistent clinical variant interpretation.
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http://dx.doi.org/10.1038/s41436-021-01254-2DOI Listing
July 2021

Efficient continuous-wave eye-safe Nd:YVO self-Raman laser at 1.5  µm.

Opt Lett 2021 Jul;46(13):3183-3186

Due to a high Raman threshold and serious thermal effect, a challenge is to achieve efficient continuous-wave (CW) operation of a crystalline Raman laser at 1.5 µm. Based on effective thermal management and the self-Raman effect, we demonstrate, to our knowledge, the first efficient CW operation of a : Raman laser at 1.5 µm. We achieve 685 mW of CW eye-safe emission at 1524.5 nm by the use of a 20-mm-long composite : and 300-µm pump beam radius, with a diode-to-Stokes conversion efficiency of 4.8%. Lasers operating at ∼1.5µ have found many important applications in various areas such as optical communication, laser radar, laser ranging, remote sensing, and spectral research.
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http://dx.doi.org/10.1364/OL.429982DOI Listing
July 2021

A Novel Radiomics Nomogram for the Prediction of Secondary Loss of Response to Infliximab in Crohn's Disease.

J Inflamm Res 2021 24;14:2731-2740. Epub 2021 Jun 24.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, 200127, People's Republic of China.

Purpose: The prediction of the loss of response (LOR) to infliximab (IFX) is crucial for optimizing treatment strategies and shifting biologics. However, a secondary LOR is difficult to predict by endoscopy due to the intestinal stricture, perforation, and fistulas. This study aimed to develop and validate a radiomic nomogram for the prediction of secondary LOR to IFX in patients with Crohn's disease (CD).

Patients And Methods: A total of 186 biologic-naive patients diagnosed with CD between September 2016 and June 2019 were enrolled. Secondary LOR was determined during week 54. Computed tomography enterography (CTE) texture analysis (TA) features were extracted from lesions and analyzed using LIFEx software. Feature selection was performed by least absolute shrinkage and selection operator (LASSO) and ten-fold cross validation. A nomogram was constructed using multivariable logistic regression, and the internal validation was approached by ten-fold cross validation.

Results: Predictors contained in the radiomics nomogram included three first-order and five second-order signatures. The prediction model presented significant discrimination (AUC, 0.880; 95% CI, 0.816-0.944) and high calibration (mean absolute error of = 0.028). Decision curve analysis (DCA) indicated that the nomogram provided clinical net benefit. Ten-fold cross validation assessed the stability of the nomogram with an AUC of 0.817 and an accuracy of 0.819.

Conclusion: This novel radiomics nomogram provides a predictive tool to assess secondary LOR to IFX in patients with Crohn's disease. This tool will help physicians decide when to switch therapy.
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http://dx.doi.org/10.2147/JIR.S314912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238542PMC
June 2021

Sevoflurane inhibits neuroblastoma cell proliferation and invasion and induces apoptosis by miR-144-3p/YAP1 axis.

Basic Clin Pharmacol Toxicol 2021 Oct 9;129(4):297-307. Epub 2021 Aug 9.

Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, China.

Background: Sevoflurane (SEV) is a typical volatile anaesthetic and has an antitumour activity in various cancer cells. Here, we were curious whether SEV has tumour-suppressive effects in neuroblastoma (NB).

Methods: NB cell lines (K-N-SH and SK-N-AS) were treated with SEV (1%, 2% and 4%). Cell Counting Kit-8 (CCK8) and Transwell assays were conducted to examine cell proliferation and invasion, respectively. The apoptosis was verified by flow cytometry, and the yes-associated protein 1 (YAP1), Bax, Bcl2 and cleaved caspase3 levels were detected by western blotting. Quantitative real-time PCR (qRT-PCR) was conducted to monitor the miR-144-3p level in SEV-treated NB cells. The targeted relationship between miR-144-3p and YAP1 was predicted by bioinformatics and testified by the dual-luciferase reporter assay.

Results: SEV mitigated NB cell proliferation and invasion and strengthened apoptosis dose-dependently. SEV upregulated miR-144-3p. Moreover, the miR-144-3p inhibitor transfection significantly reduced the tumour-suppressive effect of SEV on NB cells. Furthermore, the dual-luciferase reporter assay confirmed that miR-144-3p targeted YAP1 and overexpressing YAP1 partially weakened the inhibitive effects of miR-144-3p on NB cells.

Conclusion: SEV abated NB cell proliferation and invasion and accelerated apoptosis through the miR-144-3p/YAP1 axis.
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http://dx.doi.org/10.1111/bcpt.13629DOI Listing
October 2021

Gene editing in a Myo6 semi-dominant mouse model rescues auditory function.

Mol Ther 2021 Jun 24. Epub 2021 Jun 24.

ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai 200031, China. Electronic address:

Myosin VI(MYO6) is an unconventional myosin that is vital for auditory and vestibular function. Pathogenic variants in the human MYO6 gene cause autosomal-dominant or -recessive forms of hearing loss. Effective treatments for Myo6 mutation causing hearing loss are limited. We studied whether adeno-associated virus (AAV)-PHP.eB vector-mediated in vivo delivery of Staphylococcus aureus Cas9 (SaCas9-KKH)-single-guide RNA (sgRNA) complexes could ameliorate hearing loss in a Myo6 mouse model that recapitulated the phenotypes of human patients. The in vivo editing efficiency of the AAV-SaCas9-KKH-Myo6-g2 system on Myo6 is 4.05% on average in Myo6 mice, which was ∼17-fold greater than editing efficiency of Myo6 alleles. Rescue of auditory function was observed up to 5 months post AAV-SaCas9-KKH-Myo6-g2 injection in Myo6 mice. Meanwhile, shorter latencies of auditory brainstem response (ABR) wave I, lower distortion product otoacoustic emission (DPOAE) thresholds, increased cell survival rates, more regular hair bundle morphology, and recovery of inward calcium levels were also observed in the AAV-SaCas9-KKH-Myo6-g2-treated ears compared to untreated ears. These findings provide further reference for in vivo genome editing as a therapeutic treatment for various semi-dominant forms of hearing loss and other semi-dominant diseases.
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http://dx.doi.org/10.1016/j.ymthe.2021.06.015DOI Listing
June 2021

Is Externally Corrected Coupled Cluster Always Better Than the Underlying Truncated Configuration Interaction?

J Chem Theory Comput 2021 Jul 23;17(7):4006-4027. Epub 2021 Jun 23.

Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States.

The short answer to the question in the title is "no". We identify classes of truncated configuration interaction (CI) wave functions for which the externally corrected coupled-cluster (ec-CC) approach using the three-body () and four-body () components of the cluster operator extracted from CI does not improve the results of the underlying CI calculations. Implications of our analysis, illustrated by numerical examples, for the ec-CC computations using truncated and selected CI methods are discussed. We also introduce a novel ec-CC approach using the and amplitudes obtained with the selected CI scheme abbreviated as CIPSI, correcting the resulting energies for the missing correlations not captured by CIPSI with the help of moment expansions similar to those employed in the completely renormalized CC methods.
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http://dx.doi.org/10.1021/acs.jctc.1c00181DOI Listing
July 2021

Borate-driven ionic rectifiers based on sugar-bearing single nanochannels.

Nanoscale 2021 Jul 21;13(25):11232-11241. Epub 2021 Jun 21.

Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CONICET - CC 16 Suc. 4, 1900 La Plata, Argentina.

Recently, much scientific effort has been centered on the control of the ionic transport properties of solid state nanochannels and the rational design and integration of chemical systems to induce changes in the ionic transport by means of interactions with selected target molecules. Here, we report the fabrication of a novel nanofluidic device based on solid-state nanochannels, which combines silane chemistry with both track-etched and atomic layer deposition (ALD) technologies. Nanodevice construction involves the coating of bullet-shaped single-pore nanochannels with silica (SiO) by ALD and subsequent surface modification by reaction between silanol groups exposed on pore walls and N-(3-triethoxysilylpropyl)-gluconamide, in order to create a gluconamide-decorated nanochannel surface. The formation of a boroester derivative resulting from the selective reaction of borate with the appended saccharides leads to important changes in the surface charge density and, concomitantly, in the iontronic properties of the nanochannel. Furthermore, we propose a binding model to rationalize the specific interaction saccharide-borate in the surface. Besides, this unique nanodevice exhibits a highly selective and reversible response towards borate/fructose exposure. On the basis of the surface charge variation resulting from borate binding, the nanochannel can reversibly switch between "ON" and "OFF" states in the presence of borate and fructose, respectively. In addition, this work describes the first report of the functionalization of PET/SiO nanochannels by the ALD technique. We believe that this work provides a promising framework for the development of new nanochannel-based platforms suitable for multiple applications, such as water quality monitoring or directed molecular transport and separation.
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http://dx.doi.org/10.1039/d0nr07733jDOI Listing
July 2021

Pelvic Pain Alters Functional Connectivity Between Anterior Cingulate Cortex and Hippocampus in Both Humans and a Rat Model.

Front Syst Neurosci 2021 3;15:642349. Epub 2021 Jun 3.

Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, China.

The anterior cingulate cortex (ACC) and hippocampus (HIPP) are two key brain regions associated with pain and pain-related affective processing. However, whether and how pelvic pain alters the neural activity and connectivity of the ACC and HIPP under baseline and during social pain, and the underlying cellular and molecular mechanisms, remain unclear. Using functional magnetic resonance imaging (fMRI) combined with electrophysiology and biochemistry, we show that pelvic pain, particularly, primary dysmenorrhea (PDM), causes an increase in the functional connectivity between ACC and HIPP in resting-state fMRI, and a smaller reduction in connectivity during social exclusion in PDM females with periovulatory phase. Similarly, model rats demonstrate significantly increased ACC-HIPP synchronization in the gamma band, associating with reduced modulation by ACC-theta on HIPP-gamma and increased levels of receptor proteins and excitation. This study brings together human fMRI and animal research and enables improved therapeutic strategies for ameliorating pain and pain-related affective processing.
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http://dx.doi.org/10.3389/fnsys.2021.642349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210850PMC
June 2021

Establishment and Characterization of a HER2-Positive Cell Line Derived From the Pleural Effusion of a Drug-Resistant Breast Cancer Patient.

Front Cell Dev Biol 2021 1;9:680968. Epub 2021 Jun 1.

Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.

Drug resistance is a daunting challenge in the treatment of breast cancer, making it an urgent problem to solve in studies. Cell lines are important tools in basic and preclinical studies; however, few breast cell lines from drug-resistant patients are available. Herein, we established a novel HER2-positive breast cancer cell line from the pleural effusion of a drug-resistant metastatic breast cancer patient. This cell line has potent proliferative capability and tumorigenicity in nude mice but weak invasive and colony-forming capability. The molecular subtype of the cell line and its sensitivity to chemotherapeutics and HER2-targeting agents are different from those of its origin, suggesting that the phenotype changes between the primary and metastatic forms of breast cancer.
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http://dx.doi.org/10.3389/fcell.2021.680968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204809PMC
June 2021

Research on Geriatric Care for Equalizing the Topological Layout of Health Care Infrastructure Networks.

J Healthc Eng 2021 26;2021:8306479. Epub 2021 May 26.

Shanghai University of Medicine & Health Sciences, Shanghai 201318, China.

In this paper, through the study of elderly care, the method of equalizing the topological layout of the health care infrastructure network is used for in-depth analysis. With the evaluation method of senior care facility fairness as the research base theory, the analysis and evaluation of senior care facilities are carried out from two aspects of supply and demand fairness and spatial fairness, and the problems and shortcomings of senior care facilities in terms of facility scale, spatial layout, service level, and policy management are summarized. This paper analyses the contradictory points of the nonequitable layout of urban senior care facilities, to propose planning suggestions and optimization measures for the planning of the senior care service facility system. It discusses the problems in the spatial layout of senior care facilities from the perspective of social equity, focuses on the needs of urban disadvantaged groups, promotes the equalization of public services, and provides the theoretical basis and technical support for the planning policy of urban public service facilities. The study fully combines the theory of urban planning disciplines with geographic information system technology, mathematical and statistical technology, and network data acquisition technology to establish the evaluation of the spatial layout of senior care facilities based on social equity framework, to contribute to the planning of similar urban public service facilities. It comes to make an integrated consideration of the supply content and scope of basic public service facilities and check the gaps, which is conducive to improving the scientific and intensive nature of public resource input according to local conditions and more speed and provides some reference to the method of public service facility allocation.
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http://dx.doi.org/10.1155/2021/8306479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175159PMC
May 2021

Distinguishing nontuberculous mycobacteria from Mycobacterium tuberculosis lung disease from CT images using a deep learning framework.

Eur J Nucl Med Mol Imaging 2021 Jun 16. Epub 2021 Jun 16.

TCM Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, Tianjin Institute of Respiratory Diseases, Haihe Hospital, Tianjin University, Tianjin, People's Republic of China.

Purpose: To develop and evaluate the effectiveness of a deep learning framework (3D-ResNet) based on CT images to distinguish nontuberculous mycobacterium lung disease (NTM-LD) from Mycobacterium tuberculosis lung disease (MTB-LD).

Method: Chest CT images of 301 with NTM-LD and 804 with MTB-LD confirmed by pathogenic microbiological examination were retrospectively collected. The differences between the clinical manifestations of the two diseases were analysed. 3D-ResNet was developed to randomly extract data in an 8:1:1 ratio for training, validating, and testing. We also collected external test data (40 with NTM-LD and 40 with MTB-LD) for external validation of the model. The activated region of interest was evaluated using a class activation map. The model was compared with three radiologists in the test set.

Result: Patients with NTM-LD were older than those with MTB-LD, patients with MTB-LD had more cough, and those with NTM-LD had more dyspnoea, and the results were statistically significant (p < 0.05). The AUCs of our model on training, validating, and testing datasets were 0.90, 0.88, and 0.86, respectively, while the AUC on the external test set was 0.78. Additionally, the performance of the model was higher than that of the radiologist, and without manual labelling, the model automatically identified lung areas with abnormalities on CT > 1000 times more effectively than the radiologists.

Conclusion: This study shows the efficacy of 3D-ResNet as a rapid auxiliary diagnostic tool for NTB-LD and MTB-LD. Its use can help provide timely and accurate treatment strategies to patients with these diseases.
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http://dx.doi.org/10.1007/s00259-021-05432-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205608PMC
June 2021

PLAC8 promotes adriamycin resistance via blocking autophagy in breast cancer.

J Cell Mol Med 2021 Jul 11;25(14):6948-6962. Epub 2021 Jun 11.

Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Adriamycin (ADM) is currently one of the most effective chemotherapeutic agents in breast cancer treatment. However, growing resistance to ADM could lead to treatment failure and poor outcome. PLAC8 was reported as a novel highly conserved protein and functioned as an oncogene or tumour suppressor in various tumours. Here, we found higher PLAC8 expression was correlated with worse outcome and aggressive phenotype in breast cancer. Breast cancer patients with higher PLAC8 expression showed potential ADM resistance. In vitro experiments further confirmed that PLAC8 inhibited by siRNA or enforced overexpression by infecting pcDNA3.1(C)-PLAC8 plasmid correspondingly decreased or increased ADM resistance. Subsequently, we demonstrated that ectopic PLAC8 expression in MCF-7/ADMR cell blocked the accumulation of the autophagy-associated protein LC3 and resulted in cellular accumulation of p62. Rapamycin-triggered autophagy significantly increased cell response to ADM, while the autophagy inhibitor 3-MA enhanced ADM resistance. 3-MA and PLAC8 could synergistically cause ADM resistance via blocking the autophagy process. Additionally, the down-regulation of p62 by siRNA attenuated the activation of autophagy and PLAC8 expression in breast cancer cells. Thus, our findings suggest that PLAC8, through the participation of p62, inhibits autophagy and consequently results in ADM resistance in breast cancer. PLAC8/p62 pathway may act as novel therapeutic targets in breast cancer treatment and has potential clinical application in overcoming ADM resistance.
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http://dx.doi.org/10.1111/jcmm.16706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278087PMC
July 2021

Relating the transcriptome and microbiome by paired terminal ileal Crohn disease.

iScience 2021 Jun 5;24(6):102516. Epub 2021 May 5.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 160# Pu Jian Avenue, Shanghai 200127, China.

Management of terminal ileal Crohn disease (CD) is difficult due to fibrotic prognosis and failure to achieve mucosal healing. A limited number of synchronous analyses have been conducted on the transcriptome and microbiome in unpaired terminal ileum tissues. Therefore, our study focused on the transcriptome and mucosal microbiome in terminal ileal tissues of patients with CD with the aim of determining the role of cross-talk between the microbiome and transcriptome in the pathogenesis of terminal ileal CD. Mucosa-attached microbial communities were significantly associated with segmental inflammation status. Interaction-related transcription factors (TFs) are the panel nodes for cross-talk between the gene patterns and microbiome for terminal ileal CD. The transcriptome and microbiome in terminal ileal CD can be differently related to the local inflammatory status, and specific differentially expressed genes may be targeted for mucosal healing. TFs connect gene patterns with the microbiome by reflecting environmental stimuli and signals from microbiota.
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http://dx.doi.org/10.1016/j.isci.2021.102516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170125PMC
June 2021

Author Correction: A retrospective clinical analysis of pediatric paragonimiasis in a Chinese children's hospital from 2011 to 2019.

Sci Rep 2021 Jun 8;11(1):12450. Epub 2021 Jun 8.

Department of Infectious Disease, Children's Hospital of Fudan University, 399 WanYuan Road, Shanghai, 201102, China.

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http://dx.doi.org/10.1038/s41598-021-90897-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187660PMC
June 2021
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