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基于大语言模型的糖尿病管理:潜力与展望

Science Bulletin 2024年第5期69卷 583-588页

作者：盛斌管洲榆 Lee-Ling Lim 江泽铧 Nestoras Mathioudakis 李佳佳刘茹涵包玉倩 Yong Mong Bee 王亚星郑颖丰 Gavin Siew Wei Tan 纪宏伟 Josip Car 王海波 david C.Klonoff 李华婷覃宇宗黄天荫贾伟平 Shanghai International Joint Laboratory of Intelligent Prevention and Treatment for Metabolic Diseases Department of Computer Science and EngineeringSchool of ElectronicInformationand Electrical EngineeringShanghai Jiao Tong UniversityDepartment of Endocrinology and MetabolismShanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Diabetes InstituteShanghai Clinical Center for DiabetesShanghai 200240China MOE Key Laboratory of Artificial Intelligence Artificial Intelligence InstituteShanghai Jiao Tong UniversityShanghai 200240China Department of Medicine Faculty of MedicineUniversity of MalayaKuala Lumpur 50603Malaysia Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina Asia Diabetes Foundation Hong KongChina Tsinghua Medicine of Tsinghua University Beijing 100084China School of Clinical Medicine Beijing Tsinghua Changgung HospitalBeijing 102218China Division of Endocrinology Diabetes&MetabolismJohns Hopkins University School of MedicineBaltimoreMD 21211USA Department of Endocrinology Singapore General HospitalSingapore 169608Singapore Beijing Institute of Ophthalmology Beijing Tongren HospitalCapital University of Medical ScienceBeijing Ophthalmology and Visual Sciences Key LaboratoryBeijing 100730China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou 510060China Singapore Eye Research Institute Singapore National Eye CentreSingapore 168751Singapore Department of Cardiology the Affiliated Hospital of Qingdao UniversityQingdao 266011China Centre for Population Health Sciences Lee Kong Chian School of MedicineNanyang Technological University SingaporeSingapore 639798Singapore Department of Primary Care and Public Health School of Public HealthImperial College LondonLondon SW72BUUK Clinical Trial Unit Research Centre of Big Data and Artificial Intelligence in Medicine

The increasing prevalence of diabetes has become a global public health concern in the 21st *** 2021,it was estimated that 537 million people had diabetes,and this number is projected to reach 643 million by 2030,and 783 million by 2045[1].Such a huge burden of diabetes brings great challenges in its prevention and management,including early diagnosis,timely interventions,and regular monitoring of risk factor control and complications *** self-care support and patient empowerment can enhance clinical and psychobehavioural outcomes[2],although these require additional resources including manpower,infrastructure(hard and technology),and *** emergence of digital health technologies(DHTs),especially artificial intelligence(AI),may help address these obstacles and alleviate the burden of diabetes[3].Large language models(LLMs),a generative AI that can accept image and text inputs and produce text outputs,have shown promise in various aspects of medical care.

关键词： prevention diagnosis finance

Estimating the subsolar magnetopause position from soft X-ray images using a low-pass image filter

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Earth and Planetary Physics 2024年第1期8卷 173-183页

作者： Hyangpyo Kim Hyunju K.Connor Jaewoong Jung Brian M.Walsh david Sibeck Kip D.Kuntz Frederick S.Porter Catriana K.Paw U Rousseau A.Nutter Ramiz Qudsi Rumi Nakamura Michael Collier Space Research Institute Austrian Academy of Sciences8042 GrazAustria Geophysical Institute University of Alaska FairbanksFairbanksAlaska 99775USA National Aeronautics and Space Administration(NASA)Goddard Space Flight Center GreenbeltMaryland 20771USA Astronomy Department University of Maryland College ParkCollege ParkMaryland 20742USA Center for Space Physics Boston UniversityBostonMassachusetts 02215USA Department of Physics and Astronomy Johns Hopkins UniversityBaltimoreMaryland 21218USA Howard University WashingtonDC 20059USA

The Lunar Environment heliospheric X-ray Imager(LEXI)and Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)missions will image the Earth’s dayside magneto pause and cusps in soft X-rays after their respective launches in the near future,to specify glo bal magnetic reconnection modes for varying solar wind *** suppo rt the success of these scientific missions,it is critical to develop techniques that extract the magnetopause locations from the observed soft X-ray *** this research,we introduce a new geometric equation that calculates the subsolar magnetopause position(RS)from a satellite position,the look direction of the instrument,and the angle at which the X-ray emission is *** assumptions are used in this method:(1)The look direction where soft X-ray emissions are maximized lies tangent to the magnetopause,and(2)the magnetopause surface near the subsolar point is almost spherical and thus RSis nea rly equal to the radius of the magneto pause *** create synthetic soft X-ray images by using the Open Geospace General Circulation Model(OpenGGCM)global magnetohydrodynamic model,the galactic background,the instrument point spread function,and Poisson *** then apply the fast Fourier transform and Gaussian low-pass filte rs to the synthetic images to re move noise and obtain accurate look angles for the soft X-ray pea *** the filte red images,we calculate RS and its accuracy for different LEXI locations,look directions,and solar wind densities by using the OpenGGCM subsolar magnetopause location as ground *** method estimates RS with an accuracy of10 *** accuracy improves for greater solar wind densities and during southward interplanetary magnetic *** method ca ptures the magnetopause motion during southwa rd interplaneta ry magnetic field ***,the technique will enable quantitative analysis of the magnetopause motion and help reveal the daysi

关键词： soft X-ray magnetopause reconnection low-pass filter LEXI SMILE

The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

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Bone Research 2024年第2期12卷 289-301页

作者： Heeseog Kang Amy L.Strong Yuxiao Sun Lei Guo Conan Juan Alec C.Bancroft Ji Hae Choi Chase A.Pagani Aysel A.Fernandes Michael Woodard Juhoon Lee Sowmya Ramesh Aaron W.James david Hudson Kevin N.Dalby Lin Xu Robert J.Tower Benjamin Levi Center for Organogenesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Plastic Surgery Department of SurgeryUniversity of MichiganAnn ArborMI 48109USA Quantitative Biomedical Research Center Peter O’Donnell Jr.School of Public HealthUniversity of Texas SouthwesternDallasTX 75390USA Department of Orthopedics and Sports Medicine University of WashingtonSeattleWA 98195USA Division of Chemical Biology and Medicinal Chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Pathology Johns Hopkins UniversityBaltimoreMD 21218USA

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be ***(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal *** andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote ***,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to ***,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell ***-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in *** mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in ***-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of ***,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α*** a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic *** suggests that the HIF-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPC *** results suggest that the HIF-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.

关键词： metabolism skeletal aberrant

Microarray, SAGE and their applications to cardiovascular diseases

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Cell Research 2002年第2期12卷 105-115页

作者： SHUI QING YE, TERA LAVOIE, david C USHER, LI Q. ZHANG1 Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, School of Medicine, baltimore, MD 21224, USA2Department of Biological Science, University of Delaware, Newark, DE 19716, USA 1Division of Pulmonary and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore MD 21224 USA 1Division of Pulmonary and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore MD 21224 USA 2Department of Biological Science University of Delaware Newark DE 19716 USA 3Department of Surgery University of Maryland Baltimore MD 21201 USA

The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on elucidating the role of genes in human diseases. One powerful method to reveal insight into gene functions is the systematic analysis of gene expression. Two popular high-throughput gene expression technologies, microarray and Serial Analysis of Gene Expression (SAGE) are capable of producing large amounts of gene expression data with the potential of providing novel insights into fundamental disease processes, especially complex syndromes such as cardiovascular disease, whose etiologies are due to multiple genetic factors and their interplay with the environment. Microarray and SAGE have already been used to examine gene expression patterns of cell-culture, animal and human tissues models of cardiovascular diseases. In this review, we will first give a brief introduction of microarray and SAGE

关键词： Microarray SAGE cardiovascular diseases RNA gene expression profiling.

Current endoscopic approach to indeterminate biliary strictures

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World Journal of Gastroenterology 2012年第43期18卷 6197-6205页

作者： david W Victor Stuart Sherman Tarkan Karakan Mouen A Khashab Department of Medicine Johns Hopkins Hospital Baltimore MD 21287 United States Department of Medicine Indiana University School of Medicine Indianapolis IN 46202 United States Department of Medicine Gazi University 06710 Ankara Turkey

Biliary strictures are considered indeterminate when basic work-up, including transabdominal imaging and endoscopic retrograde cholangiopancreatography with routine cytologic brushing, are non-diagnostic. Indeterminate biliary strictures can easily be mischaracterized which may dramatically affect patient's outcome. Early and accurate diagnosis of malignancy impacts not only a patient's candidacy for surgery, but also potential timely targeted chemotherapies. A significant portion of patients with indeterminate biliary strictures have benign disease and accurate diagnosis is, thus, paramount to avoid unnecessary surgery. Current sampling strategies have suboptimal accuracy for the diagnosis of malignancy. Emerging data on other diagnostic modalities, such as ancillary cytology techniques, single operator cholangioscopy, and endoscopic ultrasonography-guided fine needle aspiration, revealed promising results with much improved sensitivity.

关键词： Indeterminate stricture Bile duct Single operator cholangioscope Cholangioscopy Endoscopic ultrasound Endoscopic retrograde cholangiopancrea-tography Bile duct stricture Indeterminate biliary stricture Confocal microscopy Transpapillary biopsy Cholangiocarcinoma Primary sclerosing cholangitis Spyglass

Stress enhances expression of calcium-binding proteins and NMDAR subunit genes in the rat hippocampus

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Neuroprotection 2024年第2期2卷 167-178页

作者： Aravind Parthasarathy Ramesha Hanumanthappa Sarojini R.Bulbule Kiran P.C. Hemalatha Nanjaiah Gopinath G. Siddaiah B.M. david Muniswamy Devaraju Kuramkote Shivanna Neurochemistry Lab Department of BiochemistryKarnatak UniversityDharwadIndia Department of Microbiology and Immunology University of Maryland School of MedicineBaltimoreMarylandUSA Department of Zoology Karnatak UniversityDharwadIndia

Backgrounds:Oxidative stress impairs the function of calcium-binding proteins and deregulates calcium signaling in living *** have previously explored the overexpression of calcium-binding protein genes in a reactive oxygen and nitrogen species-induced in vitro cell model of stress that leads to ***,in in vivo models,low levels of stress leads to depressive-like ***,we aimed to analyze gene expression of major calcium-binding proteins(calcineurin,calmodulin,calsyntenin,synaptotagmin,and calreticulin)and N-methyl-D-aspartic acid(NMDA)receptor subunits(glutamate receptor ionotropic[GluN]GluN1,GluN2A,and GluN2B)in the hippocampus of stress-induced ***:Six-week-old male Wistar rats were assigned to two stress induction groups and a control group without stress(n=6).Stress was induced by using H_(2)O_(2)(3%in water)or by immobilization(using a sticky mat)over a period of 30 *** of calcium-binding protein genes in the hippocampus,antioxidant assays,structural alterations in hippocampal neurons,and depressive-like behavior were ***:Expression of genes encoding calcium-binding proteins calcineurin,calsyntenin,synaptotagmin and NMDA receptor subunit GluN1 was enhanced in both chemical and physical stress-induced rats compared with control rats(4.25±0.05 vs.1.03±0.02,p<0.05,2.05±0.08vs.1.03±0.02,p<0.005;2.2±0.4 vs.1.02±0.03,p<0.05,1.98±0.07 vs.1.02±0.03,p<0.005;1.4±0.6 vs.1.15±0.09,p<0.05,1.39±0.05 vs.1.15±0.09,p<0.005),*** stress-induced rats,neurons in the CA2 region of the hippocampus were fewer and appeared disorganized compared with control ***,stressinduced rats showed decreased mobility and lower sucrose preference in behavioral studies compared with control ***:Lower levels of reactive oxygen and nitrogen species(RONS)can also lead to stress in rats by affecting their calcium signaling,buffering capacity in the neurons leading to depressive symptoms.

关键词： calcineurin H_(2)O_(2) hippocampus immobilization NMDA receptors

Depletion and dysfunction of Vy,2Vo2 T cells in HIV disease： mechanisms, impacts and therapeutic implications

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Cellular & Molecular Immunology 2013年第1期10卷 42-49页

作者： Haishan Li Suchita Chaudry Bhawna Poonia Yiming Shao C david Pauza Institute of Human Virology and Department of Medicine University of Maryland School of Medicine Baltimore MD USA and State Key Laboratory for Infectious Disease Controland Prevention National Center for AIDS/STD Control and Prevention Chinese Center for Disease Control and Prevention Beijing 102206 China

Infection with human immunodeficiency virus （HIV） disrupts the balance among yT cell subsets, with increasing Vo1＋ cells and substantial depletion of circulating Vo2＋ cells. Depletion is an indirect effect of HIV in CD4-negative Vo2 cells, but is specific for phosphoantigen-responsive subpopulations identified by the Vy2-Jy1.2 （also called Vy9-JyP） T cell receptor rearrangement. The extent of cell loss and recovery is related closely to clinical status, with highest levels of functional V cells present in virus controllers （undetectable viremia in the absence of antiretroviral therapy）. We review the mechanisms and clinical consequences for V cell depletion in HIV disease. We address the question of whether HIV-mediated V cell depletion, despite being an indirect effect of infection, is an important part of the immune evasion strategy for this virus. The important roles for V cells, as effectors and immune regulators, identify key mechanisms affected by HIV and show the strong relationships between V62 cell loss and immunodeficiency disease. This field is moving toward immune therapies based on targeting V cells and we now have clear goals and expectations to Ruide interventional clinical trials.

关键词： HIV disease ST cells mechanisms impacts therapeutic implications

The ALMaQUEST Survey ⅩⅤ:The dependence of the molecular-to-atomic gas ratios on resolved optical diagnostics

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Science China(Physics,Mechanics & Astronomy) 2024年第9期67卷 174-196页

作者： Niankun Yu Zheng Zheng Chao-Wei Tsai Pei Zuo Sara L.Ellison david V.Stark Di Li Jingwen Wu Karen L.Masters Ting Xiao Yinghui Zheng Zongnan Li Kai Zhang Hongying Chen Shu Liu Sihan Jiao Fanyi Meng National Astronomical Observatories Chinese Academy of SciencesBeijing 100101China Key Laboratory of Radio Astronomy and Technology Chinese Academy of SciencesBeijing 100101China Institute for Frontiers in Astronomy and Astrophysics Beijing Normal UniversityBeijing 102206China School of Astronomy and Space Science University of Chinese Academy of SciencesBeijing 100049China Department of Physics&Astronomy University of VictoriaVictoriaV8P 1A1Canada Departments of Physics and Astronomy Haverford CollegeHaverford19041USA Space Telescope Science Institute San Martin Dr.Baltimore 21218USA Zhejiang Laboratory Hangzhou 311121China New Cornerstone Science Laboratory Shenzhen 518054China School of Physics Zhejiang UniversityHangzhou 310058China

The atomic-to-molecular gas conversion is a critical step in the baryon cycle of galaxies,which sets the initial conditions for subsequent star formation and influences the multi-phase interstellar *** compiled a sample of 94 nearby galaxies with observations of multi-phase gas contents by utilizing public H_(Ⅰ),CO,and optical IFU data from the Ma NGA survey together with new FAST H_(Ⅰ)*** agreement with previous results,our sample shows that the global molecular-to-atomic gas ratio(R_(mol)≡log M_(H2)/M_(H_(Ⅰ)))is correlated with the global stellar mass surface densityμ_*with a Kendall'sτcoefficient of 0.25 and p<10^(-3),less tightly but still correlated with stellar mass and NUV-r color,and not related to the specific star formation rate(sSFR).The cold gas distribution and kinematics inferred from the H_(Ⅰ)and CO global profile asymmetry and shape do not significantly rely on R_(mol).Thanks to the availability of kpc-scale observations of MaNGA,we decompose galaxies into H_(Ⅱ),composite,and AGN-dominated regions by using the BPT *** increasing R_(mol),the fraction of H_(Ⅱ)regions within 1.5 effective radius decreases slightly;the density distribution in the spatially resolved BPT diagram also changes significantly,suggesting changes in metallicity and ionization *** with high R_(mol)tend to have high oxygen abundance,both at one effective radius with a Kendall'sτcoefficient of 0.37(p<10^(-3))and their central *** all parameters investigated here,the oxygen abundance at one effective radius has the strongest relation with global R_(mol).The dependence of gas conversion on gas distribution and galaxy ionization states is *** contrast,the observed positive relation between oxygen abundance(μ_(*))and R_(mol)indicates that the gas conversion is efficient in regions of high metallicity(density).

关键词： Galaxies baryon cycle radio lines H_(Ⅰ)21 cm atomic-to-molecular gas conversion

Phage lytic enzymes: a history

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Virologica Sinica 2015年第1期30卷 26-32页

作者： david Trudil New Horizons Diagnostic Corporation Baltimore MD 21227 USA

There are many recent studies regarding the efficacy of bacteriophage-related lytic enzymes: the enzymes of ‘bacteria-eaters' or viruses that infect bacteria. By degrading the cell wall of the targeted bacteria, these lytic enzymes have been shown to efficiently lyse Gram-positive bacteria without affecting normal flora and non-related bacteria. Recent studies have suggested approaches for lysing Gram-negative bacteria as well(Briersa Y, et al., 2014). These enzymes include: phage-lysozyme, endolysin, lysozyme, lysin, phage lysin, phage lytic enzymes, phageassociated enzymes, enzybiotics, muralysin, muramidase, virolysin and designations such as Ply, PAE and others. Bacteriophages are viruses that kill bacteria, do not contribute to antimicrobial resistance, are easy to develop, inexpensive to manufacture and safe for humans, animals and the environment. The current focus on lytic enzymes has been on their use as anti-infectives in humans and more recently in agricultural research models. The initial translational application of lytic enzymes, however, was not associated with treating or preventing a specifi c disease but rather as an extraction method to be incorporated in a rapid bacterial detection assay(Bernstein D, 1997).The current review traces the translational history of phage lytic enzymes–from their initial discovery in 1986 for the rapid detection of group A streptococcus in clinical specimens to evolving applications in the detection and prevention of disease in humans and in agriculture.

关键词： bacteriophage phage lytic enzymes translational application lysin