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1. Association Between Sleep Apnea Syndrome and Osteoarthritis: Insights from Bidirectional Mendelian Randomization and Bioinformatics Analysis

Author

Weng L, Luo X, Luo Y, Zhang Q, Yao K, Tan J, and Yin Y

Subjects
sleep apnea syndrome osteoarthritis mendelian randomization bioinformatics, Psychiatry, RC435-571, Neurophysiology and neuropsychology, QP351-495
Abstract

Lian Weng,1– 3,* Xiongjunjie Luo,1– 3,* Yuxi Luo,1– 3 Qian Zhang,1– 3 Kaitao Yao,1– 3 Junjie Tan,1– 3 Yiran Yin1– 3 1Department of orthopedics, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China; 2Sichuan Provincial Laboratory of Orthopedic Engineering, Luzhou, Sichuan Province, 646000, People’s Republic of China; 3Department of Clinical Medicine, Southwest Medical University, Luzhou, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiran Yin, Department of Orthopaedics, The Affiliated Hospital of Southwest Medical University, No. 25 Tai Ping Street, Jiang Yang District, Luzhou, Sichuan Province, 646000, People’s Republic of China, Tel +13982457750, Email yiranyin@swmu.edu.cnBackground: Sleep apnea syndrome(SAS) and osteoarthritis (OA) are two prevalent diseases that often coexist, but the causal relationship between them remains unclear. In light of this, our team utilizes Mendelian Randomization and bioinformatics analysis methods to investigate the potential association between the two diseases.Methods: In this study, we utilized GWAS data pertaining to SAS and OA to assess the causal relationship between the two diseases through Mendelian randomization (MR) analysis. We then employed transcriptomic data to perform differential gene identification, WGCNA, shared gene determination, functional enrichment analysis, and colocalization analysis, all designed to further elucidate the mechanisms underlying the association between the two diseases. In the end, we utilized Mendelian randomization (MR) analysis again to delve deeper into the relationship between the two diseases and immune cells.Results: Our research findings indicate that SAS is a risk factor for OA (p = 0.000004), knee OA (p = 0.0000001) and hip OA(p = 0.001). Furthermore, OA (p = 0.000195), knee OA (p = 0.001) are significant risk factors for SAS. However, there is no clear evidence that hip OA (p = 0.892) is a risk factor for SAS. Interestingly, the genes shared between OA and SAS are significantly enriched in leukocyte migration, leukocyte chemotaxis. Moreover, colocalization analysis suggests that the genes JUNB, COL8A1, FOSB, and IER2 may be key genes associated with both diseases. Furthermore, 57 immune cell phenotypes are associated with SAS, 95 with OA, and 6 shared between both diseases.Conclusion: This research confirmed the bidirectional causal relationship between SAS and OA. Notably, the 4 genes (JUNB, COL8A1, FOSB, IER2) and 6 immune phenotypes are crucial for both diseases, these provide hopeful targets for future interventions against these two diseases.Keywords: sleep apnea syndrome, osteoarthritis, Mendelian randomization, bioinformatics

Published
2024

2. Validation of an ICD-Based Algorithm to Identify Sepsis: A Retrospective Study

Author

Diao ST, Dong R, Peng JM, Chen Y, Li S, He SH, Wang YF, Du B, and Weng L

Subjects
sepsis, validation, international classification of diseases, administrative health data, identification, Public aspects of medicine, RA1-1270
Abstract

Shi-Tong Diao, Run Dong, Jin-Min Peng, Yan Chen, Shan Li, Shu-Hua He, Yi-Fan Wang, Bin Du, Li Weng On behalf of the China Critical Care Clinical Trials Group (CCCCTG)Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Li Weng, Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, 1 Shuai Fu Yuan, Beijing, 100730, People’s Republic of China, Email wengli@gmail.comBackground: Sepsis surveillance was important for resources allocation, prevention, and development of health policy.Objective: The aim of the study was to validate a modified International Classification of Diseases (ICD)-10 based algorithm for identifying hospitalized patients with sepsis.Methods: We retrospectively analyzed a prospective, single-center cohort of adult patients who were consecutively admitted to one medical ICU ward and ten non-ICU wards with suspected or confirmed infections during a 6-month period. A modified ICD-10 based algorithm was validated against a reference standard of Sequential Organ Failure Assessment (SOFA) score based on Sepsis-3. Sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and areas under the receiver operating characteristic curves (AUROCs) were calculated for modified ICD-10 criteria, eSOFA criteria, Martin’s criteria, and Angus’s criteria.Results: Of the 547 patients in the cohort, 332 (61%) patients met Sepsis-3 criteria and 274 (50%) met modified ICD-10 criteria. In the ICU setting, modified ICD-10 criteria had SE (84.47%), SP (88.57%), PPV (95.60), and NPV (65.96). In non-ICU settings, modified ICD-10 had SE (64.19%), SP (80.00%), PPV (80.33), and NPV (63.72). In the whole cohort, the AUROCs of modified ICD-10 criteria, eSOFA, Angus’s criteria, and Martin’s criteria were 0.76, 0.75, 0.62, and 0.62, respectively.Conclusion: This study demonstrated that modified ICD-10 criteria had higher validity compared with Angus’s criteria and Martin’s criteria. Validity of the modified ICD-10 criteria was similar to eSOFA criteria. Modified ICD-10 algorithm can be used to provide an accurate estimate of population-based sepsis burden of China.Keywords: sepsis, validation, International Classification of Diseases, administrative health data, identification

Published
2023

3. Flexible Hollow Human Serum Albumin-Catalase Nanocapsules with High Accumulation and Uptake Ability for Enhanced Photodynamic Therapy

Author

Shi Y, Zhao Y, Kang W, Lu W, Chen D, Tao J, Li J, Yu R, Zhao J, Tang R, Teng Z, and Weng L

Subjects
flexible nanoplatform, human serum albumin, sufficient tumor accumulation, high cellular uptake, photodynamic therapy, Medicine (General), R5-920
Abstract

Yuyuan Shi,1,* Ying Zhao,2,* Wen Kang,2 Wei Lu,3 Dong Chen,3 Jun Tao,3 Jing Li,3 Ruifa Yu,3 Jiajia Zhao,3 Rui Tang,3 Zhaogang Teng,3 Lixing Weng1 1College of Geography and Biological Information, Nanjing University of Posts and Telecommunications, Nanjing, People’s Republic of China; 2Department of Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 3Key Laboratory for Organic Electronics & Information Displays and Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials, Jiangsu National Synergetic Innovation Centre for Advanced Materials, Nanjing University of Posts and Telecommunications, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhaogang Teng; Lixing Weng, Email iamzgteng@njupt.edu.cn; lxweng@njupt.edu.cnIntroduction: Photodynamic therapy (PDT) has attracted increasing attention for tumor treatment because of its minimal invasiveness and specific spatiotemporal selectivity. However, insufficient tumor accumulation and low cellular uptake of photosensitizers limit its therapeutic efficacy.Methods: In this study, flexible hollow human serum albumin/catalase nanocapsules (HSA/CATs) were created using a core-assisted protein-coating method and combined with the photosensitizer chlorin e6 (HSA/CAT@Ce6) for PDT.Results and Discussion: Transmission electron microscopy (TEM) images demonstrate that HSA/CAT nanocapsules are flexible, with a uniform diameter (310 nm) and a well-defined hollow structure. Thanks to their flexibility, HSA/CAT@Ce6 nanocapsules show a higher cellular uptake than rigid nanoparticles. The nanocapsules effectively generate reactive oxygen species (ROS) in 4T1 cells because of their high cellular uptake and catalytic capacity, remarkably enhancing their in vitro PDT efficacy. In addition, the in vivo tumor accumulation of HSA/CAT@Ce6 nanocapsules is significantly larger than that of rigid nanoparticles and Ce6, meaning they are highly effective in tumor cell ablation. This demonstrates that our flexible nanoplatform holds great promise for enhancing PDT of tumor.Keywords: flexible nanoplatform, human serum albumin, sufficient tumor accumulation, high cellular uptake, photodynamic therapy

Published
2023

4. Nanostructured magnesium has fewer detrimental effects on osteoblast function

Author

Weng L and Webster TJ

Subjects
Medicine (General), R5-920
Abstract

Lucy Weng, Thomas J Webster School of Engineering and Department of Orthopedics, Brown University, Providence, RI, USA Abstract: Efforts have been made recently to implement nanoscale surface features on magnesium, a biodegradable metal, to increase bone formation. Compared with normal magnesium, nanostructured magnesium has unique characteristics, including increased grain boundary properties, surface to volume ratio, surface roughness, and surface energy, which may influence the initial adsorption of proteins known to promote the function of osteoblasts (bone-forming cells). Previous studies have shown that one way to increase nanosurface roughness on magnesium is to soak the metal in NaOH. However, it has not been determined if degradation of magnesium is altered by creating nanoscale features on its surface to influence osteoblast density. The aim of the present in vitro study was to determine the influence of degradation of nanostructured magnesium, created by soaking in NaOH, on osteoblast density. Our results showed a less detrimental effect of magnesium degradation on osteoblast density when magnesium was treated with NaOH to create nanoscale surface features. The detrimental degradation products of magnesium are of significant concern when considering use of magnesium as an orthopedic implant material, and this study identified a surface treatment, ie, soaking in NaOH to create nanoscale features for magnesium that can improve its use in numerous orthopedic applications. Keywords: nanostructured magnesium, degradation, detrimental effects, osteoblasts

Published
2013

8. Three-dimensional solid-state qubit arrays with long-lived spin coherence

Author

Stephen, C. J., Green, B. L., Lekhai, Y. N. D., Weng, L., Hill, P., Johnson, S., Frangeskou, A. C., Diggle, P. L., Strain, M. J., Gu, E., Newton, M. E., Smith, J. M., Salter, P. S., and Morley, G. W.

Subjects
Quantum Physics, Condensed Matter - Materials Science, Physics - Optics
Abstract

Three-dimensional arrays of silicon transistors increase the density of bits. Solid-state qubits are much larger so could benefit even more from using the third dimension given that useful fault-tolerant quantum computing will require at least 100,000 physical qubits and perhaps one billion. Here we use laser writing to create 3D arrays of nitrogen-vacancy centre (NVC) qubits in diamond. This would allow 5 million qubits inside a commercially available 4.5x4.5x0.5 mm diamond based on five nuclear qubits per NVC and allowing $(10 \mu m)^3$ per NVC to leave room for our laser-written electrical control. The spin coherence times we measure are an order of magnitude longer than previous laser-written qubits and at least as long as non-laser-written NVC. As well as NVC quantum computing, quantum communication and nanoscale sensing could benefit from the same platform. Our approach could also be extended to other qubits in diamond and silicon carbide., Comment: 8 pages, 4 figures

Published
2018
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9. Microcavity enhanced single photon emission from two-dimensional WSe2

Author

Flatten, L. C., Weng, L., Branny, A., Johnson, S., Dolan, P. R., Trichet, A. A. P., Gerardot, B. D., and Smith, J. M.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics, Physics - Optics
Abstract

Atomically flat semiconducting materials such as monolayer WSe$_2$ hold great promise for novel optoelectronic devices. Recently, quantum light emission has been observed from bound excitons in exfoliated WSe$_2$. As part of developing optoelectronic devices, the control of the radiative properties of such emitters is an important step. Here we report the coupling of a bound exciton in WSe$_2$ to open microcavities. We use a range of radii of curvature in the plano-concave cavity geometry with mode volumes in the $\lambda^3$ regime, giving Purcell factors of up to 8 while increasing the photon flux five-fold. Additionally we determine the quantum efficiency of the single photon emitter to be $\eta = 0.46 \pm 0.03$. Our findings pave the way to cavity-enhanced monolayer based single photon sources for a wide range of applications in nanophotonics and quantum information technologies., Comment: 17 pages, 6 figures

Published
2018
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10. Arithmetic Cohomology Groups

Author

Sugahara, K. and Weng, L.

Subjects
Mathematics - Algebraic Geometry
Abstract

We first introduce global arithmetic cohomology groups for quasi-coherent sheaves on arithmetic varieties, adopting an adelic approach. Then, we establish fundamental properties, such as topological duality and inductive long exact sequences, for these cohomology groups on arithmetic surfaces. Finally, we expose basic structures for ind-pro topologies on adelic spaces of arithmetic surfaces. In particular, we show that these adelic spaces are topologically self-dual., Comment: 42 pages

Published
2015

11. Tunable cavity coupling of the zero phonon line of a nitrogen-vacancy defect in diamond

Author

Johnson, S., Dolan, P. R., Grange, T., Trichet, A. A. P., Hornecker, G., Chen, Y. C., Weng, L., Hughes, G. M., Auffèves, A., and Smith, J. M.

Subjects
Quantum Physics
Abstract

We demonstrate the tunable enhancement of the zero phonon line of a single nitrogen-vacancy color center in diamond at cryogenic temperature. An open cavity fabricated using focused ion beam milling provides mode volumes as small as 1.24 $\mu$m$^3$. In-situ tuning of the cavity resonance is achieved with piezoelectric actuators. At optimal coupling of the full open cavity the signal from individual zero phonon line transitions is enhanced by about a factor of 10 and the overall emission rate of the NV$^-$ center is increased by 40% compared with that measured from the same center in the absence of cavity field confinement. This result is important for the realization of efficient spin-photon interfaces and scalable quantum computing using optically addressable solid state spin qubits., Comment: 11 pages Main Article + 4 pages Supplementary Info Typos fixed from v1

Published
2015
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13. Pharmacometabolomic Assessments of Atenolol and Hydrochlorothiazide Treatment Reveal Novel Drug Response Phenotypes

Author

Rotroff, DM, Shahin, MH, Gurley, SB, Zhu, H, Motsinger‐Reif, A, Meisner, M, Beitelshees, AL, Fiehn, O, Johnson, JA, Elbadawi‐Sidhu, M, Frye, RF, Gong, Y, Weng, L, Cooper‐DeHoff, RM, and Kaddurah‐Daouk, R

Subjects
Medical Biochemistry and Metabolomics, Biomedical and Clinical Sciences, Hypertension, Metabolic and endocrine, Pharmacology and Pharmaceutical Sciences, Medical Physiology, Medical physiology, Pharmacology and pharmaceutical sciences
Abstract

Achieving hypertension (HTN) control and mitigating the adverse health effects associated with HTN continues to be a global challenge. Some individuals respond poorly to current HTN therapies, and mechanisms for response variation remain poorly understood. We used a nontargeted metabolomics approach (gas chromatography time-of-flight/mass spectrometry gas chromatography time-of-flight/mass spectrometry) measuring 489 metabolites to characterize metabolite signatures associated with treatment response to anti-HTN drugs, atenolol (ATEN), and hydrochlorothiazide (HCTZ), in white and black participants with uncomplicated HTN enrolled in the Pharmacogenomic Evaluation of Antihypertensive Responses study. Metabolite profiles were significantly different between races, and metabolite responses associated with home diastolic blood pressure (HDBP) response were identified. Metabolite pathway analyses identified gluconeogenesis, plasmalogen synthesis, and tryptophan metabolism increases in white participants treated with HCTZ (P

Published
2015

15. Targeted sequencing to identify novel genetic risk factors for deep vein thrombosis: a study of 734 genes

Author

de Haan, H.G., van Hylckama Vlieg, A., Lotta, L.A., Gorski, M.M., Bucciarelli, P., Martinelli, I., Baglin, T.P., Peyvandi, F., Rosendaal, F.R., Amouyel, P., de Andrade, M., Basu, S., Berr, C., Brody, J.A., Chasman, D. I, Dartigues, J.‐F., Folsom, A.R., Germain, M., Heit, J., Houwing‐Duitermaat, J., Kabrhel, C., Kraft, P., Le Gal, G., Lindström, S., Monajemi, R., Morange, P.‐E., Psaty, B.M., Reitsma, P.H., Ridker, P.M., Rose, L.M., Saut, N., Slagboom, E., Smadja, D., Smith, N.L., Suchon, P., Tang, W., Taylor, K.D., Trégouët, D.‐A., Tzourio, C., de Visser, M.C.H., Weng, L.‐C., and Wiggins, K.L.

Published
2018
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16. Rearrangement of a Large Novel Pseudomonas aeruginosa Gene Island in Strains Isolated from a Patient Developing Ventilator-Associated Pneumonia

Author

Singh, G, Srinivasan, R, Cheng, J, Peng, Z, Fujimura, K, Baek, MS, Panzer, AR, Tringe, SG, Chen, F, Sorek, R, Weng, L, Bristow, J, Wiener-Kronish, JP, and Lynch, SV

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Lung, Human Genome, Biotechnology, Infectious Diseases, Pneumonia & Influenza, Pneumonia, Genetics, Infection, Anti-Bacterial Agents, Clindamycin, DNA, Bacterial, Electrophoresis, Gel, Pulsed-Field, Gene Rearrangement, Genetic Variation, Genome, Bacterial, Genomic Islands, Humans, Longitudinal Studies, Molecular Typing, Penicillanic Acid, Piperacillin, Piperacillin, Tazobactam Drug Combination, Pneumonia, Ventilator-Associated, Pseudomonas Infections, Pseudomonas aeruginosa, Sequence Analysis, DNA, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Microbiology, Clinical sciences, Medical microbiology
Abstract

Bacterial gene islands add to the genetic repertoire of opportunistic pathogens. Here, we perform comparative analyses of three Pseudomonas aeruginosa strains isolated sequentially over a 3-week period from a patient with ventilator-associated pneumonia (VAP) who received clindamycin and piperacillin-tazobactam as part of their treatment regime. While all three strains appeared to be clonal by standard pulsed-field gel electrophoresis, whole-genome sequencing revealed subtle alterations in the chromosomal organization of the last two strains; specifically, an inversion event within a novel 124-kb gene island (PAGI 12) composed of 137 open reading frames [ORFs]. Predicted ORFs in the island included metabolism and virulence genes. Overexpression of a gene island-borne putative β-lactamase gene was observed following piperacillin-tazobactam exposure and only in those strains that had undergone the inversion event, indicating altered gene regulation following genomic remodeling. Examination of a separate cohort of 76 patients with VAP for integration at this tRNA(lys) recombination site demonstrated that patients exhibiting evidence of integration at this site had significantly higher 28-day mortality. These findings provide evidence that P. aeruginosa can integrate, rapidly remodel, and express exogenous genes, which likely contributes to its fitness in a clinical setting.

Published
2014

19. Thermal Dynamics in Symmetric Magnetic Nanopillars Driven by Spin Transfer

Author

Lim, Weng L., Anthony, Nicholas, Higgins, Andrew, and Urazhdin, Sergei

Subjects
Condensed Matter - Materials Science
Abstract

We study the effects of spin transfer on thermally activated dynamics of magnetic nanopillars with identical thicknesses of the magnetic layers. The symmetric nanopillars exhibit anomalous dependencies of switching statistics on magnetic field and current. We interpret our data in terms of simultaneous current-induced excitation of both layers. We also find evidence for coupling between the fluctuations of the layers due to the spin transfer., Comment: 3 pages, 3 figures

Published
2008
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23. Identification, validation and biological characterisation of novel glioblastoma tumour microenvironment subtypes: implications for precision immunotherapy

Author

White, K., primary, Connor, K., additional, Meylan, M., additional, Bougoüin, A., additional, Salvucci, M., additional, Bielle, F., additional, O’Farrell, A.C., additional, Sweeney, K., additional, Weng, L., additional, Bergers, G., additional, Dicker, P., additional, Ashley, D.M., additional, Lipp, E.S., additional, Low, J.T., additional, Zhao, J., additional, Wen, P., additional, Prins, R., additional, Verreault, M., additional, Idbaih, A., additional, Biswas, A., additional, Prehn, J.H.M., additional, Lambrechts, D., additional, Arijs, I., additional, Lodi, F., additional, Dilcan, G., additional, Lamfers, M., additional, Leenstra, S., additional, Fabro, F., additional, Ntafoulis, I., additional, Kros, J.M., additional, Cryan, J., additional, Brett, F., additional, Quissac, E., additional, Beausang, A., additional, MacNally, S., additional, O’Halloran, P., additional, Clerkin, J., additional, Bacon, O., additional, Kremer, A., additional, Chi Yen, R.T., additional, Varn, F.S., additional, Verhaak, R.G.W., additional, Sautès-Fridman, C., additional, Fridman, W.H., additional, and Byrne, A.T., additional

Published
2023
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24. Bioremediation of PAEs-contaminated saline soil: The application of a marine bacterial strain isolated from mangrove sediment.

Author

Ren, L, Weng, L, Chen, D, Hu, H, Jia, Y, Zhou, JL, Ren, L, Weng, L, Chen, D, Hu, H, Jia, Y, and Zhou, JL

Abstract

Phthalic acid esters (PAEs) are known as the most widely used plasticizer as well as one of the ubiquitously distributed emerging pollutants. Biodegradation and bioremediation via application of PAEs-degrading microbes is promising. In this study, a novel marine microbe, Gordonia hongkongensis RL-LY01, was isolated from mangrove sediment showing high di-(2-ethylhexyl) phthalate (DEHP) degradation capacity. Strain RL-LY01 could degrade a wide range of PAEs and the degradation kinetics of DEHP followed the first-order decay model. Meanwhile, good environmental adaptability, preference to alkaline conditions and good tolerance to salinity and metal ions was shown. Further, metabolic pathway of DEHP in strain RL-LY01 was proposed, with di-ethyl phthalate, phthalic acid, benzoic acid and catechol as intermediates. Additionally, one known mono-alkyl phthalate hydrolase gene (mehpH) was identified. Finally, the excellent performance during bioremediation of artificial DEHP-contaminated saline soil and sediment indicated strain RL-LY01 employs great application potential for the bioremediation of PAE-contaminated environments.

Published
2023

25. Identification, validation and biological characterisation of novel glioblastoma tumour microenvironment subtypes:implications for precision immunotherapy

Author

White, K., Connor, K., Meylan, M., Bougoüin, A., Salvucci, M., Bielle, F., O'Farrell, A. C., Sweeney, K., Weng, L., Bergers, G., Dicker, P., Ashley, D. M., Lipp, E. S., Low, J. T., Zhao, J., Wen, P., Prins, R., Verreault, M., Idbaih, A., Biswas, A., Prehn, J. H.M., Lambrechts, D., Arijs, I., Lodi, F., Dilcan, G., Lamfers, M., Leenstra, S., Fabro, F., Ntafoulis, I., Kros, J. M., Cryan, J., Brett, F., Quissac, E., Beausang, A., MacNally, S., O'Halloran, P., Clerkin, J., Bacon, O., Kremer, A., Chi Yen, R. T., Varn, F. S., Verhaak, R. G.W., Sautès-Fridman, C., Fridman, W. H., Byrne, A. T., White, K., Connor, K., Meylan, M., Bougoüin, A., Salvucci, M., Bielle, F., O'Farrell, A. C., Sweeney, K., Weng, L., Bergers, G., Dicker, P., Ashley, D. M., Lipp, E. S., Low, J. T., Zhao, J., Wen, P., Prins, R., Verreault, M., Idbaih, A., Biswas, A., Prehn, J. H.M., Lambrechts, D., Arijs, I., Lodi, F., Dilcan, G., Lamfers, M., Leenstra, S., Fabro, F., Ntafoulis, I., Kros, J. M., Cryan, J., Brett, F., Quissac, E., Beausang, A., MacNally, S., O'Halloran, P., Clerkin, J., Bacon, O., Kremer, A., Chi Yen, R. T., Varn, F. S., Verhaak, R. G.W., Sautès-Fridman, C., Fridman, W. H., and Byrne, A. T.

Abstract

Background: New precision medicine therapies are urgently required for glioblastoma (GBM). However, to date, efforts to subtype patients based on molecular profiles have failed to direct treatment strategies. We hypothesised that interrogation of the GBM tumour microenvironment (TME) and identification of novel TME-specific subtypes could inform new precision immunotherapy treatment strategies. Materials and methods: A refined and validated microenvironment cell population (MCP) counter method was applied to >800 GBM patient tumours (GBM-MCP-counter). Specifically, partition around medoids (PAM) clustering of GBM-MCP-counter scores in the GLIOTRAIN discovery cohort identified three novel patient clusters, uniquely characterised by TME composition, functional orientation markers and immune checkpoint proteins. Validation was carried out in three independent GBM-RNA-seq datasets. Neoantigen, mutational and gene ontology analysis identified mutations and uniquely altered pathways across subtypes. The longitudinal Glioma Longitudinal AnalySiS (GLASS) cohort and three immunotherapy clinical trial cohorts [treatment with neoadjuvant/adjuvant anti-programmed cell death protein 1 (PD-1) or PSVRIPO] were further interrogated to assess subtype alterations between primary and recurrent tumours and to assess the utility of TME classifiers as immunotherapy biomarkers. Results: TMEHigh tumours (30%) displayed elevated lymphocyte, myeloid cell immune checkpoint, programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 transcripts. TMEHigh/mesenchymal+ patients featured tertiary lymphoid structures. TMEMed (46%) tumours were enriched for endothelial cell gene expression profiles and displayed heterogeneous immune populations. TMELow (24%) tumours were manifest as an ‘immune-desert’ group. TME subtype transitions upon recurrence were identified in the longitudinal GLASS cohort. Assessment of GBM immunoth

Published
2023

29. Natural Disaster

Author

China Critical Care Clinical Trial Group (CCCCTG), Du, B., Xi, X., Kang, Y., Weng, L., Gullo, Antonino, editor, Lumb, Philip D., editor, Besso, José, editor, and Williams, Ged F., editor

Published
2009
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31. Soil Functions in Earth's Critical Zone

Author

Banwart, S.A., primary, Bernasconi, S.M., additional, Blum, W.E.H., additional, de Souza, D.M., additional, Chabaux, F., additional, Duffy, C., additional, Kercheva, M., additional, Krám, P., additional, Lair, G.J., additional, Lundin, L., additional, Menon, M., additional, Nikolaidis, N.P., additional, Novak, M., additional, Panagos, P., additional, Ragnarsdottir, K.V., additional, Robinson, D.A., additional, Rousseva, S., additional, de Ruiter, P., additional, van Gaans, P., additional, Weng, L., additional, White, T., additional, and Zhang, B., additional

Published
2017
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32. Microbiome-metabolome analysis directed isolation of rhizobacteria capable of enhancing salt tolerance of Sea Rice 86

Author

Wang, G, Weng, L, Huang, Y, Ling, Y, Zhen, Z, Lin, Z, Hu, H, Li, C, Guo, J, Zhou, JL, Chen, S, Jia, Y, and Ren, L

Subjects
Soil, Microbiota, Rhizosphere, Metabolome, Oryza, Salt Tolerance, Environmental Sciences, Soil Microbiology, Alphaproteobacteria
Abstract

Soil salinization has been recognized as one of the main factors causing the decrease of cultivated land area and global plant productivity. Application of salt tolerant plants and improvement of plant salt tolerance are recognized as the major routes for saline soil restoration and utilization. Sea rice 86 (SR86) is known as a rice cultivar capable of growing in saline soil. Genome sequencing and transcriptome analysis of SR86 have been conducted to explore its salt tolerance mechanisms while the contribution of rhizobacteria is underexplored. In the present study, we examined the rhizosphere bacterial diversity and soil metabolome of SR86 seedlings under different salinity to understand their contribution to plant salt tolerance. We found that salt stress could significantly change rhizobacterial diversity and rhizosphere metabolites. Keystone taxa were identified via co-occurrence analysis and the correlation analysis between keystone taxa and rhizosphere metabolites indicated lipids and their derivatives might play an important role in plant salt tolerance. Further, four plant growth promoting rhizobacteria (PGPR), capable of promoting the salt tolerance of SR86, were isolated and characterized. These findings might provide novel insights into the mechanisms of plant salt tolerance mediated by plant-microbe interaction, and promote the isolation and application of PGPR in the restoration and utilization of saline soil.

Published
2022

36. Towards an efficient spin-photon interface based on cavity-coupled NV centres in diamond membranes

Author

Weng, L and Smith, J

Subjects
Quantum optics, Solid state physics, Quantum computing, Materials science
Abstract

Quantum computation and information processing is an exciting multi-disciplinary field, whose objective is to harness the power of superposition and entanglement of quantum states to establish a new regime of computation for Mankind. This work demonstrates our efforts, in both materials and device engineering, towards building an efficient spin-photon interface for a promising solid-state spin qubit, namely the nitrogen-vacancy (NV) centre in diamond. Improvement in optical coherence of NV centre is realised via the novel laser-writing fabrication technique and quantified using high-resolution spectroscopy. A new metric concerning the charge-state stability of the NV centre is introduced to better translate the measured NV quality to entanglement generation efficiency. To address the low branching ratio of NV emission into the zero-phonon line (ZPL) transition, a hybrid open-cavity device incorporating low-dimensional micro-structured NV-containing diamond membrane is fabricated and characterised. In addition to the more commonly quoted emission enhancement factor, the collection efficiency of the cavity device is also quantified via numerical simulations. Combining all observed improvements in key metrics under the framework of double-heralding entanglement schemes, a two order of magnitude increase in entanglement generate rate can be expected. The established simulation methodology is widely applicable in the design and analysis of similar devices with an emitter-in-cavity setup.

Published
2021

42. Esketamine combined with remimazolam in painless gastroscopy in obese patients

Author

WENG Liyang*, YANG Yuchun, MAO Gu, ZHANG Yong, XIE Li

Subjects
painless gastroscopy， obesity，remimazolam，esketamine，propofol，remifentanil， mean arterial pressure，nausea， vomiting, Medicine
Abstract

Objective To evaluate the effects and safety of esketamine combined with remimazolam in painless gastroscopy in obese patients. Methods A total of 138 obese patients who received elective painless gastroscopy at the Fourth Affiliated Hospital of Nanjing Medical University and Nanjing First Hospital from January to December 2022 were selected and randomly divided into group S (esketamine+remimazolam, n=69) and group C (propofol+remifentanil, n=69) by random number table method. The incidence of intraoperative hypoxemia, anesthesia induction time, test time, post-anesthesia care unit (PACU) monitoring time, and physician satisfaction were compared between two groups. The mean arterial pressure (MAP) and heart rate (HR) of two groups of patients before anesthesia (T0), at endoscopy insertion (T1), and at endoscopy retraction (T2) were recorded, and the incidence of adverse events were recorded. Results The incidence of hypoxemia in group S was significantly lower than that in group C ［34.78%(24/69) vs 56.52%(39/69)， χ2=6.571， P=0.010］. The induction time for anesthesia in group S was shorter than that in group C［(23.17±2.57) s vs (24.71±2.12) s， t=3.840， P＜0.01］. Compared with group C, the PACU monitoring time of group S was significantly shorter［(14.74±1.46) s vs (17.06±1.87) s, t=8.123， P＜0.01］, and the satisfaction ofgastroenterologists［89.86%(62/69) vs 75.36%(52/69), χ2=5.044， P=0.025］ and satisfaction of anesthesiologists［92.75%(64/69) vs 71.01%(49/69), χ2=10.991， P=0.001］ was significantly higher. At T1, MAP in Group C decreased compared to group S, while HR increased compared to group S (P＜0.05). Nausea and vomiting occurred in 9 patients in group C and 5 patients in group S, and no other adverse event occurred. Conclusion Compared with propofol combined with remifentanil, remimazolam combined with eszketamine for painless gastroscopy in obese patients can reduce the incidence of hypoxemia and has higher safety."

Published
2024
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45. Sleep Through Surveyed: Usage and Efficacy of Streamed Soundscapes Created to Help Infants Sleep

Author

Weng, L., Hulbert, A., Gibbs, E., and Emery Schubert

Subjects
education, humanities
Abstract

This paper reports results of a survey that was conducted to assess the use and efficacy of soundscapes composed for an DAB+ radio station and on demand audio App ‘ABC-Kids listen’ provided by the Australian Broadcasting Corporation (ABC). The soundscapes were a series of previously composed pieces titled Sleep Through. 21 people who had listened to one or more of the compositions completed the survey as part of a qualitative study of how music can aid sleep. Results suggested very high overall efficacy, but also revealed applications to situations that did not involve aiding the parents and/or their infants to sleep. These included using Sleep Through for pleasure, and for breast feeding. Open-ended responses to the survey were organized into themes labelled: Relaxation (the most prevalent theme), Associations (often linked to the title and environments portrayed in the soundscape), Distraction (strongly related to Relaxation), and Auditory Masking. The theme labelled Habit (using Sleep Through to develop healthy sleeping habits) was also considered, but exhibited too great an overlap with other themes. The themes were strongly connected with those found in the literature investigating the use of music for sleep by adults, and also supported the approach of the composer. The study was conducted in collaboration with the composer, with his intentions and responses to the study forming an integral part of the research.

Published
2021
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50. Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices

Author

Natarajan, P. (Pradeep), Pampana, A. (Akhil), Graham, S. E. (Sarah E.), Ruotsalainen, S. E. (Sanni E.), Perry, J. A. (James A.), de Vries, P. S. (Paul S.), Broome, J. G. (Jai G.), Pirruccello, J. P. (James P.), Honigbere, M. C. (Michael C.), Aragam, K. (Krishna), Wolford, B. (Brooke), Brody, J. A. (Jennifer A.), Antonacci-Fulton, L. (Lucinda), Arden, M. (Moscati), Aslibekyan, S. (Stella), Assimes, T. L. (Themistocles L.), Ballantyne, C. M. (Christie M.), Bielak, L. F. (Lawrence F.), Bisl, J. C. (Joshua C.), Cade, B. E. (Brian E.), Do, R. (Ron), Doddapaneni, H. (Harsha), Emery, L. S. (Leslie S.), Hung, Y.-J. (Yi-Jen), Irvin, M. R. (Marguerite R.), Khan, A. T. (Alyna T.), Lange, L. (Leslie), Lee, J. (Jiwon), Lemaitre, R. N. (Rozenn N.), Martin, L. W. (Lisa W.), Metcalf, G. (Ginger), Montasser, M. E. (May E.), Moon, J.-Y. (Jee-Young), Muzny, D. (Donna), Connell, J. R. (Jeffrey R. O.), Palmer, N. D. (Nicholette D.), Peralta, J. M. (Juan M.), Peyser, P. A. (Patricia A.), Stilp, A. M. (Adrienne M.), Tsai, M. (Michael), Wang, F. F. (Fei Fei), Weeks, D. E. (Daniel E.), Yanek, L. R. (Lisa R.), Wilson, J. G. (James G.), Abecasis, G. (Goncalo), Arnett, D. K. (Donna K.), Becker, L. C. (Lewis C.), Blangercy, J. (John), Boerwinkle, E. (Eric), Bowden, D. W. (Donald W.), Chang, Y.-C. (Yi-Cheng), Chen, Y. I. (Yii-Der, I), Choi, W. J. (Won Jung), Correa, A. (Adolfo), Curran, J. E. (Joanne E.), Daly, M. J. (Mark J.), DutcherE, S. K. (Susan K.), Ellinor, P. T. (Patrick T.), Fornage, M. (Myriam), Freedman, B. I. (Barry, I), Gabriel, S. (Stacey), Germer, S. (Soren), Gibbs, R. A. (Richard A.), He, J. (Jiang), Hveem, K. (Kristian), Jarvik, G. P. (Gail P.), Kaplan, R. C. (Robert C.), Kardia, S. L. (Sharon L. R.), Kennyn, E. (Eimear), Kim, R. W. (Ryan W.), Kooperberg, C. (Charles), Laurie, C. C. (Cathy C.), Lee, S. (Seonwook), Lloyd-Jones, D. M. (Don M.), Loos, R. J. (Ruth J. F.), Lubitz, S. A. (Steven A.), Mathias, R. A. (Rasika A.), Martinez, K. A. (Karine A. Viaud), McGarvey, S. T. (Stephen T.), Mitche, B. D. (Braxton D.), Nickerson, D. A. (Deborah A.), North, K. E. (Kari E.), Palotie, A. (Aarno), Park, C. J. (Cheol Joo), Psat, B. M. (Bruce M. Y.), Rao, D. C. (D. C.), Redline, S. (Susan), Reiner, A. P. (Alexander P.), Seo, D. (Daekwan), Seo, J.-S. (Jeong-Sun), Smith, A. V. (Albert, V), Tracy, R. P. (Russell P.), Kathiresan, S. (Sekar), Cupples, L. A. (L. Adrienne), Rotten, J. I. (Jerome, I), Morrison, A. C. (Alanna C.), Rich, S. S. (Stephen S.), Ripatti, S. (Samuli), Wilier, C. (Cristen), Peloso, G. M. (Gina M.), Vasan, R. S. (Ramachandran S.), Abe, N. (Namiko), Albert, C. (Christine), Almasy, L. (Laura), Alonso, A. (Alvaro), Ament, S. (Seth), Anderson, P. (Peter), Applebaum-Bowden, D. (Deborah), Arking, D. (Dan), Ashley-Koch, A. (Allison), Auer, P. (Paul), Avramopoulos, D. (Dimitrios), Barnard, J. (John), Barnes, K. (Kathleen), Barr, R. G. (R. Graham), Barron-Casella, E. (Emily), Beaty, T. (Terri), Becker, D. (Diane), Beer, R. (Rebecca), Begum, F. (Ferdouse), Beitelshees, A. (Amber), Benjamin, E. (Emelia), Bezerra, M. (Marcos), Bielak, L. (Larry), Blackwel, T. (Thomas), Bowler, R. (Russell), Broecke, U. (Ulrich), Bunting, K. (Karen), Burchard, E. (Esteban), Buth, E. (Erin), Cardwel, J. (Jonathan), Carty, C. (Cara), Casaburi, R. (Richard), Casella, J. (James), Chaffin, M. (Mark), Chang, C. (Christy), Chasman, D. (Daniel), Chavan, S. (Sameer), Chen, B.-J. (Bo-Juen), Chen, W.-M. (Wei-Min), Chol, M. (Michael), Choi, S. H. (Seung Hoan), Chuang, L.-M. (Lee-Ming), Chung, M. (Mina), Conomos, M. P. (Matthew P.), Cornell, E. (Elaine), Crapo, J. (James), Curtis, J. (Jeffrey), Custer, B. (Brian), Damcott, C. (Coleen), Darbar, D. (Dawood), Das, S. (Sayantan), David, S. (Sean), Davis, C. (Colleen), Daya, M. (Michelle), de Andrade, M. (Mariza), DeBaunuo, M. (Michael), Duan, Q. (Qing), Devine, R. D. (Ranjan Deka Dawn DeMeo Scott), Duggirala, Q. R. (Qing Ravi), Durda, J. P. (Jon Peter), Dutcher, S. (Susan), Eaton, C. (Charles), Ekunwe, L. (Lynette), Farber, C. (Charles), Farnaml, L. (Leanna), Fingerlin, T. (Tasha), Flickinger, M. (Matthew), Franceschini, N. (Nora), Fu, M. (Mao), Fullerton, S. M. (Stephanie M.), Fulton, L. (Lucinda), Gan, W. (Weiniu), Gao, Y. (Yan), Gass, M. (Margery), Ge, B. (Bruce), Geng, X. P. (Xiaoqi Priscilla), Gignoux, C. (Chris), Gladwin, M. (Mark), Glahn, D. (David), Gogarten, S. (Stephanie), Gong, D.-W. (Da-Wei), Goring, H. (Harald), Gu, C. C. (C. Charles), Guan, Y. (Yue), Guo, X. (Xiuqing), Haessler, J. (Jeff), Hall, M. (Michael), Harris, D. (Daniel), Hawle, N. Y. (Nicola Y.), Heavner, B. (Ben), Heckbert, S. (Susan), Hernandez, R. (Ryan), Herrington, D. (David), Hersh, C. (Craig), Hidalgo, B. (Bertha), Hixson, J. (James), Hokanson, J. (John), Hong, E. (Elliott), Hoth, K. (Karin), Hsiung, C. A. (Chao Agnes), Huston, H. (Haley), Hwu, C. M. (Chii Min), Jackson, R. (Rebecca), Jain, D. (Deepti), Jaquish, C. (Cashell), Jhun, M. A. (Min A.), Johnsen, J. (Jill), Johnson, A. (Andrew), Johnson, C. (Craig), Johnston, R. (Rich), Jones, K. (Kimberly), Kang, H. M. (Hyun Min), Kaufman, L. (Laura), Kell, S. Y. (Shannon Y.), Kessler, M. (Michael), Kinney, G. (Greg), Konkle, B. (Barbara), Kramer, H. (Holly), Krauter, S. (Stephanie), Lange, C. (Christoph), Lange, E. (Ethan), Laurie, C. (Cecelia), LeBoff, M. (Meryl), Lee, S. S. (Seunggeun Shawn), Lee, W.-J. (Wen-Jane), LeFaive, J. (Jonathon), Levine, D. (David), Levy, D. (Dan), Lewis, J. (Joshua), Li, Y. (Yun), Lin, H. (Honghuang), Lin, K. H. (Keng Han), Lin, X. (Xihong), Liu, S. (Simin), Liu, Y. (Yongmei), Lunetta, K. (Kathryn), Luo, J. (James), Mahaney, M. (Michael), Make, B. (Barry), Manichaikul, A. (Ani), Mansonl, J. (JoAnn), Margolin, L. (Lauren), Mathai, S. (Susan), McArdle, P. (Patrick), Mcdonald, M.-L. (Merry-Lynn), McFarland, S. (Sean), McHugh, C. (Caitlin), Mei, H. (Hao), Meyers, D. A. (Deborah A.), Mikulla, J. (Julie), Min, N. (Nancy), Minear, M. (Mollie), Minster, R. L. (Ryan L.), Musani, S. (Solomon), Mwasongwe, S. (Stanford), Mychaleckyj, J. C. (Josyf C.), Nadkarni, G. (Girish), Naik, R. (Rakhi), Naseri, T. (Take), Nekhai, S. (Sergei), Nelson, S. C. (Sarah C.), Nickerson, D. (Deborah), Connell, J. O. (Jeff O.), Connor, T. O. (Tim O.), Ochs-Balcom, H. (Heather), Pankow, J. (James), Papanicolaou, G. (George), Parkerl, M. (Margaret), Parsa, A. (Afshin), Penchey, S. (Sara), Perez, M. (Marco), Peters, U. (Ulrike), Phillips, L. S. (Lawrence S.), Phillips, S. (Sam), Pollin, T. (Toni), Post, W. (Wendy), Becker, J. P. (Julia Powers), Boorgula, M. P. (Meher Preethi), Preuss, M. (Michael), Prokopenko, D. (Dmitry), Qasba, P. (Pankaj), Qiao, D. (Dandi), Rafaels, N. (Nicholas), Raffield, L. (Laura), Rasmussen-Torvik, L. (Laura), Ratan, A. (Aakrosh), Reed, R. (Robert), Reganl, E. (Elizabeth), Reupena, M. S. (Muagututi Sefuiva), Rice, K. (Ken), Roden, D. (Dan), Roselli, C. (Carolina), Ruczinski, I. (Ingo), Russel, P. (Pamela), Ruuska, S. (Sarah), Ryan, K. (Kathleen), Sabino, E. C. (Ester Cerdeira), Sakornsakolpatl, P. (Phuwanat), Salzberg, S. (Steven), Sandow, K. (Kevin), Sankaran, V. G. (Vijay G.), Scheller, C. (Christopher), Schmidt, E. (Ellen), Schwander, K. (Karen), Schwartz, D. (David), Sciurba, F. (Frank), Seidman, C. (Christine), Seidman, J. (Jonathan), Sheehan, V. (Vivien), Shetty, A. (Amol), Shetty, A. (Aniket), Sheu, W. H. (Wayne Hui-Heng), Shoemaker, M. B. (M. Benjamin), Silver, B. (Brian), Silvermanl, E. (Edwin), Smith, J. (Jennifer), Smith, J. (Josh), Smith, N. (Nicholas), Smith, T. (Tanja), Smoller, S. (Sylvia), Snively, B. (Beverly), Soferlm, T. (Tamar), Streeten, E. (Elizabeth), Su, J. L. (Jessica Lasky), Sung, Y. J. (Yun Ju), Sylvia, J. (Jody), Sztalryd, C. (Carole), Taliun, D. (Daniel), Tang, H. (Hua), Taub, M. (Margaret), Taylor, K. D. (Kent D.), Taylor, S. (Simeon), Telen, M. (Marilyn), Thornton, T. A. (Timothy A.), Tinker, L. (Lesley), Tirschwel, D. (David), Tiwari, H. (Hemant), Vaidya, D. (Dhananjay), VandeHaar, P. (Peter), Vrieze, S. (Scott), Walker, T. (Tarik), Wallace, R. (Robert), Waits, A. (Avram), Wan, E. (Emily), Wang, H. (Heming), Watson, K. (Karol), Weir, B. (Bruce), Weiss, S. (Scott), Weng, L.-C. (Lu-Chen), Williams, K. (Kayleen), Williams, L. K. (L. Keoki), Wilson, C. (Carla), Wong, Q. (Quenna), Xu, H. (Huichun), Yang, I. (Ivana), Yang, R. (Rongze), Zaghlou, N. (Norann), Zekavat, M. (Maryam), Zhang, Y. (Yingze), Zhao, S. X. (Snow Xueyan), Zhao, W. (Wei), Zni, D. (Degui), Zhou, X. (Xiang), Zhu, X. (Xiaofeng), Zody, M. (Michael), Zoellner, S. (Sebastian), Daly, M. (Mark), Jacob, H. (Howard), Matakidou, A. (Athena), Runz, H. (Heiko), John, S. (Sally), Plenge, R. (Robert), McCarthy, M. (Mark), Hunkapiller, J. (Julie), Ehm, M. (Meg), Waterworth, D. (Dawn), Fox, C. (Caroline), Malarstig, A. (Anders), Klinger, K. (Kathy), Call, K. (Kathy), Mkel, T. (Tomi), Kaprio, J. (Jaakko), Virolainen, P. (Petri), Pulkki, K. (Kari), Kilpi, T. (Terhi), Perola, M. (Markus), Partanen, J. (Jukka), Pitkranta, A. (Anne), Kaarteenaho, R. (Riitta), Vainio, S. (Seppo), Savinainen, K. (Kimmo), Kosma, V.-M. (Veli-Matti), Kujala, U. (Urho), Tuovila, O. (Outi), Hendolin, M. (Minna), Pakkanen, R. (Raimo), Waring, J. (Jeff), Riley-Gillis, B. (Bridget), Liu, J. (Jimmy), Biswas, S. (Shameek), Diogo, D. (Dorothee), Marshall, C. (Catherine), Hu, X. (Xinli), Gossel, M. (Matthias), Schleutker, J. (Johanna), Arvas, M. (Mikko), Hinttala, R. (Reetta), Kettunen, J. (Johannes), Laaksonen, R. (Reijo), Mannermaa, A. (Arto), Paloneva, J. (Juha), Soininen, H. (Hilkka), Julkunen, V. (Valtteri), Remes, A. (Anne), Klviinen, R. (Reetta), Hiltunen, M. (Mikko), Peltola, J. (Jukka), Tienari, P. (Pentti), Rinne, J. (Juha), Ziemann, A. (Adam), Waring, J. (Jeffrey), Esmaeeli, S. (Sahar), Smaoui, N. (Nizar), Lehtonen, A. (Anne), Eaton, S. (Susan), Landenper, S. (Sanni), Michon, J. (John), Kerchner, G. (Geoff), Bowers, N. (Natalie), Teng, E. (Edmond), Eicher, J. (John), Mehta, V. (Vinay), Gormle, P. Y. (Padhraig Y.), Linden, K. (Kari), Whelan, C. (Christopher), Xu, F. (Fanli), Pulford, D. (David), Frkkil, M. (Martti), Pikkarainen, S. (Sampsa), Jussila, A. (Airi), Blomster, T. (Timo), Kiviniemi, M. (Mikko), Voutilainen, M. (Markku), Georgantas, B. (Bob), Heap, G. (Graham), Rahimov, F. (Fedik), Usiskin, K. (Keith), Maranville, J. (Joseph), Lu, T. (Tim), Oh, D. (Danny), Kalpala, K. (Kirsi), Miller, M. (Melissa), McCarthy, L. (Linda), Eklund, K. (Kari), Palomki, A. (Antti), Isomki, P. (Pia), Piri, L. (Laura), Kaipiainen-Seppnen, O. (Oili), Lertratanaku, A. (Apinya), Bing, D. C. (David Close Marla Hochfeld Nan), Gordillo, J. E. (Jorge Esparza), Mars, N. (Nina), Laitinen, T. (Tarja), Pelkonen, M. (Margit), Kauppi, P. (Paula), Kankaanranta, H. (Hannu), Harju, T. (Terttu), Greenberg, S. (Steven), Chen, H. (Hubert), Betts, J. (Jo), Ghosh, S. (Soumitra), Salomaa, V. (Veikko), Niiranen, T. (Teemu), Juonala, M. (Markus), Metsrinne, K. (Kaj), Khnen, M. (Mika), Junttila, J. (Juhani), Laakso, M. (Markku), Pihlajamki, J. (Jussi), Sinisalo, J. (Juha), Taskinen, M.-R. (Marja-Riitta), Tuomi, T. (Tiinamaija), Laukkanen, J. (Jari), Challis, B. (Ben), Peterson, A. (Andrew), Chu, A. (Audrey), Parkkinen, J. (Jaakko), Muslin, A. (Anthony), Joensuu, H. (Heikki), Meretoja, T. (Tuomo), Aaltonen, L. (Lauri), Auranen, A. (Annika), Karihtala, P. (Peeter), Kauppila, S. (Saila), Auvinen, P. (Pivi), Elenius, K. (Klaus), Popovic, R. (Relja), Schutzman, J. (Jennifer), Loboda, A. (Andrey), Chhibber, A. (Aparna), Lehtonen, H. (Heli), McDonough, S. (Stefan), Crohns, M. (Marika), Kulkarni, D. (Diptee), Kaarniranta, K. (Kai), Turunen, J. (Joni), Ollila, T. (Terhi), Seitsonen, S. (Sanna), Uusitalo, H. (Hannu), Aaltonen, V. (Vesa), Uusitalo-Jrvinen, H. (Hannele), Luodonp, M. (Marja), Hautala, N. (Nina), Strauss, E. (Erich), Chen, H. (Hao), Podgornaia, A. (Anna), Hoffman, J. (Joshua), Tasanen, K. (Kaisa), Huilaja, L. (Laura), Hannula-Jouppi, K. (Katariina), Salmi, T. (Teea), Peltonen, S. (Sirkku), Koulu, L. (Leena), Harvima, I. (Ilkka), Wu, Y. (Ying), Choy, D. (David), Jalanko, A. (Anu), Kajanne, R. (Risto), Lyhs, U. (Ulrike), Kaunisto, M. (Mari), Davis, J. W. (Justin Wade), Quarless, D. (Danjuma), Petrovski, S. (Slav), Chen, C.-Y. (Chia-Yen), Bronson, P. (Paola), Yang, R. (Robert), Chang, D. (Diana), Bhangale, T. (Tushar), Holzinger, E. (Emily), Wang, X. (Xulong), Chen, X. (Xing), Auro, K. (Kirsi), Wang, C. (Clarence), Xu, E. (Ethan), Auge, F. (Franck), Chatelain, C. (Clement), Kurki, M. (Mitja), Karjalainen, J. (Juha), Havulinna, A. (Aki), Palin, K. (Kimmo), Palta, P. (Priit), Parolo, P. D. (Pietro Della Briotta), Zhou, W. (Wei), Lemmel, S. (Susanna), Rivas, M. (Manuel), Harju, J. (Jarmo), Lehisto, A. (Arto), Ganna, A. (Andrea), Llorens, V. (Vincent), Karlsson, A. (Antti), Kristiansson, K. (Kati), Hyvrinen, K. (Kati), Ritari, J. (Jarmo), Wahlfors, T. (Tiina), Koskinen, M. (Miika), Pylkäs, K. (Katri), Kalaoja, M. (Marita), Karjalainen, M. (Minna), Mantere, T. (Tuomo), Kangasniemi, E. (Eeva), Heikkinen, S. (Sami), Laakkonen, E. (Eija), Kononen, J. (Juha), Loukola, A. (Anu), Laiho, P. (Pivi), Sistonen, T. (Tuuli), Kaiharju, E. (Essi), Laukkanen, M. (Markku), Jrvensivu, E. (Elina), Lhteenmki, S. (Sini), Mnnikk, L. (Lotta), Wong, R. (Regis), Mattsson, H. (Hannele), Hiekkalinna, T. (Tero), Jimnez, M. G. (Manuel Gonzlez), Donner, K. (Kati), Prn, K. (KaIle), Nunez-Fontarnau, J. (Javier), Kilpelinen, E. (Elina), Sipi, T. P. (Timo P.), Brein, G. (Georg), Dada, A. (Alexander), Awaisa, G. (Ghazal), Shcherban, A. (Anastasia), Sipil, T. (Tuomas), Laivuori, H. (Hannele), Kiiskinen, T. (Tuomo), Siirtola, H. (Harri), Tabuenca, J. G. (Javier Gracia), Kallio, L. (Lila), Soini, S. (Sirpa), Pitknen, K. (Kimmo), and Kuopio, T. (Teijo)

Subjects
Cardiovascular genetics, Genome-wide association studies
Abstract

Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids.

Published
2021

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