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Optimizing artificial intelligence in sepsis management: Opportunities in the present and looking closely to the future

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Journal of Intensive Medicine 2024年第1期4卷 34-45页

作者： Darragh O’Reilly Jennifer McGrath Ignacio Martin-Loeches department of Intensive Care Medicine Multidisciplinary Intensive Care Research Organization(MICRO)St James’HospitalDublinIreland department of Respiratory Intensive care Hospital ClinicUniversitat de BarcelonaIDIBAPSCIBERESBarcelonaSpain

Sepsis remains a major challenge internationally for healthcare systems.Its incidence is rising due to poor public awareness and delays in its recognition and subsequent management.In sepsis,mortality increases with every hour left untreated.Artificial intelligence(AI)is transforming worldwide healthcare delivery at present.This review has outlined how AI can augment strategies to address this global disease burden.AI and machine learning(ML)algorithms can analyze vast quantities of increasingly complex clinical datasets from electronic medical records to assist clinicians in diagnosing and treating sepsis earlier than traditional methods.Our review highlights how these models can predict the risk of sepsis and organ failure even before it occurs.This gives providers additional time to plan and execute treatment plans,thereby avoiding increasing complications associated with delayed diagnosis of sepsis.The potential for cost savings with AI implementation is also discussed,including improving workflow efficiencies,reducing administrative costs,and improving healthcare outcomes.Despite these advantages,clinicians have been slow to adopt AI into clinical practice.Some of the limitations posed by AI solutions include the lack of diverse data sets for model building so that they are widely applicable for routine clinical use.Furthermore,the subsequent algorithms are often based on complex mathematics leading to clinician hesitancy to embrace such technologies.Finally,we highlight the need for robust political and regulatory frameworks in this area to achieve the trust and approval of clinicians and patients to implement this transformational technology。

关键词： Artificial intelligence Data science Machine learning Intensive care unit(ICU) Critical care Sepsis

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SWI1 Is Required for Meiotic Chromosome Remodeling Events

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Molecular Plant 2008年第4期1卷 620-633页

作者： Kingsley A. Boateng Xiaohui Yang Fuqui Dong Heather A. Owen Christopher A. Makaroff department of Chemistry and Biochemistry Miami University Oxford OH 45056 USA present address: department of Biological Sciences University of Wisconsin-Milwaukee Milwaukee Wl 53211 USA

The Arabidopsis dsy10 mutant was previously identified as being defective in the synapsis of meiotic chromosomes resulting in male and female sterility. We report here the molecular analysis of the mutation and show that it represents a T-DNA insertion in the third exon of the SWll gene. Four mutations have now been identified in SWI1, several of which exhibit different phenotypes. For example, the swil- 1 and dyad mutations only affect meiosis in megasporocytes, while the swil-2 and dsy10 mutations block both male and female meiosis. Furthermore, as part of a detailed cytological characterization of dsy10 meiocytes, we identified several differences during male meiosis between the swil-2 and dys10 mutants, including variations in the formation of axial elements, the distribution of cohesin proteins and the timing of the premature loss of sister chromatid cohesion. We demonstrate that dsy10 represents a complete loss-of-function mutation, while a truncated form of SWll is expressed during meiosis in swil-2 plants. We further show that dys10 meiocytes exhibit alterations in modified histone patterns, including acetylated histone H3 and dimethylated histone H3-Lysine 4.

关键词： Arabidopsis meiosis sister chromatid cohesion chromatin remodeling histone.

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Blocking the Metabolism of Starch Breakdown Products in Arabidopsis Leaves Triggers Chloroplast Degradation

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Molecular Plant 2009年第6期2卷 1233-1246页

作者： Michaela Stettler Simona Eicke Tabea Mettler Gaelle Messerli Stefan Hortensteiner Samuel C. Zeeman department of Biology ETH Zurich CH-8092 Zurich Switzerland Institute of Plant Biology University of Zurich CH-8008 Zurich Switzerland present address: Max Planck Institute for Molecular Plant Physiology Potsdam-Golm 14476 Germany present address: Johnson & Johnson Medical CH-8957 Spreitenbach Switzerland

In most plants, a large fraction of photo-assimilated carbon is stored in the chloroplasts during the day as starch and remobilized during the subsequent night to support metabolism. Mutations blocking either starch synthesis or starch breakdown in Arabidopsis thaliana reduce plant growth. Maltose is the major product of starch breakdown exported from the chloroplast at night. The maltose excess 1 mutant （mex1）, which lacks the chloroplast envelope maltose transporter, accumulates high levels of maltose and starch in chloroplasts and develops a distinctive but previously unexplained chlorotic phenotype as leaves mature. The introduction of additional mutations that prevent starch synthesis, or that block maltose production from starch, also prevent chlorosis of mex1. In contrast, introduction of mutations in disproportionating enzyme （DPE1） results in the accumulation of maltotriose in addition to maltose, and greatly increases chlorosis. These data suggest a link between maltose accumulation and chloroplast homeostasis. Microscopic analyses show that the mesophyll cells in chlorotic mex1 leaves have fewer than half the number of chloroplasts than wild-type cells. Transmission electron microscopy reveals autophagy-like chloroplast degradation in both mex1 and the dpe1/mex1 double mutant. Microarray analyses reveal substantial reprogramming of metabolic and cellular processes, suggesting that organellar protein turnover is increased in mex1, though leaf senescence and senescence-related chlorophyll catabolism are not induced. We propose that the accumulation of maltose and malto-oligosaccharides causes chloroplast dysfunction, which may by signaled via a form of retrograde signaling and trigger chloroplast degradation.

关键词： Carbohydrate metabolism photosynthesis senescence chloroplast biology Arabidopsis autophagy.

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The boys are back in town: Rethinking the function of ribosomal DNA repeats in the genomic era

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Molecular Plant 2023年第3期16卷 514-516页

作者： Francesca B.Lopez Peter C.McKeown Antoine Fort Galina Brychkova Charles Spillane Genetics and Biotechnology Laboratory Plant&AgriBiosciences Research Centre(PABC)Ryan InstituteUniversity of GalwayH91 REW4 GalwayIreland present address:department of Plant Biology and Genome Center University of CaliforniaDavisUC Davis Genome CenterDavisCA 95616USA

Next-generation sequencing technological advances,affording high-throughput,scalable,and fast assemblies,have enabled genome editing techniques that allow us to remove,insert,and modify genes for rapid and precise fun... 详细信息

关键词： remove precise function

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Highly Luminescent Positively Charged Quantum Dots Interacting with Proteins and Cells

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Chinese Journal of Chemistry 2022年第22期40卷 2685-2693页

作者： Haixia Wang Karin Nienhaus Li Shang Gerd Ulrich Nienhaus Institute of Applied Physics Karlsruhe Institute of Technology(KIT)76131 KarlsruheGermany Institute of Nanotechnology Karlsruhe Institute of Technology(KIT)76344 Eggenstein-LeopoldshafenGermany InstituteofBiologicaland Chemical Systems Karlsruhe Institute of Technology(KIT)76344 Eggenstein-LeopoldshafenGermany department of Physics University of llinois at Urbana-ChampaignUrbanaIL61801USA present address:Laboratory of Biomaterials and Translational Medicine Center for NanomedicineThe Third Affiliated HospitalSun Yat-sen UniversityGuangzhou510630China present address:School of Materials Science and Engineering Northwestern PolytechnicalUniversityXi'an 710072China

We have studied interactions between positively charged MUTAB-stabilized quantum dots(QDs)and model proteins,serum and live cells using fluorescence correlation spectroscopy(FCS),dynamic light scattering(DLS),time-resolved photoluminescence(PL)and live-cell fluorescence imaging.Using human serum albumin(HSA)as a model protein,we measured the growth of a protein adsorption layer(“protein corona”)via time-resolved FCS.Corona formation was characterized by an apparent equilibrium dissociation coefficient,KD≈10μM.HSA adlayer growth was surprisingly slow(timescale ca.30 min),in stark contrast to many similar measurements with HSA and other proteins and different NPs.Time-resolved PL data revealed a characteristic quenching behavior depending on the QD surface coverage with HSA.Taken together,we found that MUTAB-QDs initially bind HSA molecules weakly(KD≈700μM);however,the affinity is enhanced over time,presumably due to proton injection into the MUTAB layer by HSA triggering ligand dissociation.This process was also observed with human blood serum,showing equal kinetics for comparable HSA concentration.Moreover,imaging experiments with cultured human cells(HeLa)revealed that MUTAB-QDs bind to the cell membrane and perforate it.This process is reduced upon pre-adsorption of proteins on the MUTAB-QD.

关键词： Quantum dots Nanoparticles Agglomeration Protein adsorption Quantitative fluorescence microscopy

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Albumosomes formed by cytoplasmic pre-folding albumin maintain mitochondrial homeostasis and inhibit nonalcoholic fatty liver disease

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Signal Transduction and Targeted Therapy 2023年第7期8卷 3466-3485页

作者： Boyuan Ma Anji Ju Shaosen Zhang Qi An Siran Xu Jie Liu Li Yu Yan Fu Yongzhang Luo School of Life Sciences Tsinghua University100084 BeijingChina The National Engineering Research Center for Protein Technology Tsinghua University100084 BeijingChina Beijing Key Laboratory for Protein Therapeutics Tsinghua University100084 BeijingChina State Key Laboratory of Membrane Biology Tsinghua University-Peking University Joint Centre for Life SciencesBeijing Frontier Research Center for Biological StructureSchool of Life SciencesTsinghua University100084 BeijingChina present address:department of Etiology and Carcinogenesis National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College100021 BeijingChina present address:Immunogenetics Laboratory Shenzhen Blood Center518025 ShenzhenGuangdongChina

Hepatic mitochondrial dysfunction contributes to the progression of nonalcoholic fatty liver disease(NAFLD).However,the factors that maintain mitochondrial homeostasis,especially in hepatocytes,are largely unknown.Hepatocytes synthesize various high-level plasma proteins,among which albumin is most abundant.In this study,we found that pre-folding albumin in the cytoplasm is completely different from folded albumin in the serum.

关键词： homeostasis maintain folding

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The differential requirement of mushroom body α/β subdivisions in long-term memory retrieval in Drosophila

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Protein & Cell 2013年第7期4卷 512-519页

作者： Cheng Huang Pengzhi Wang Zhiyong Xie Lianzhang Wang Yi Zhong School of Life Sciences Tsinghua UniversityBeijing 100084China Cold Spring Harbor Laboratory Cold Spring HarborNY 11724USA present address:department of Biological Sciences Stanford UniversityStanfordCA 94305USA present address:department of Bioengineering University of CaliforniaSan DiegoLa JollaCA 92093USA

The mushroom body(MB),a bilateral brain structure pos-sessing about 2000-2500 neurons per hemisphere,plays a central role in olfactory learning and memory in Dros-ophila melanogaster.Extensive studies have demonstrat-ed that three major types of MB neurons(α/β,α’/β’andγ)exhibit distinct functions in memory processing,including the critical role of approximately 1000 MBα/βneurons in retrieving long-term memory.Inspired by recent fi ndings that MBα/βneurons can be further divided into three subdivisions(surface,posterior and core)and wherein theα/βcore neurons play an permissive role in long-term memory consolidation,we examined the functional differ-ences of all the three morphological subdivisions of MBα/βby temporally precise manipulation of their synaptic outputs during long-term memory retrieval.We found the normal neurotransmission from a combination of MBα/βsurface and posterior neurons is necessary for retrieving both aversive and appetitive long-term memory,whereas output from MBα/βposterior or core subdivision alone is dispensable.These results imply a specifi c requirement of about 500 MBα/βneurons in supporting long-term memory retrieval and a further functional partitioning for memory processing within the MBα/βregion.

关键词： memory retrieval neural circuits aversive olfactory conditioning appetitive olfactory conditioning mush-room body

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Identification of Early Nuclear Target Genes of Plastidial Redox Signals that Trigger the Long- Term Response of Arabidopsis to Light Quality Sh∽ts

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Molecular Plant 2015年第8期8卷 1237-1252页

作者： Lars Dietzel Christine Glaeer Monique Liebers Stefan Hiekel Florence Courtois Olaf Czarneckit Hagen Schlicke Yan Zubo Thomas Borner Klaus Mayer Bernhard Grimm Thomas Pfannschmidt department of Plant Physiology Institute of General Botany and Plant Physiology Friedrich-Schiller-University of Jena Domburger Strasse 159 07743 JenaGermany MIPS/IBI Helmholtz Zentrum MGnchen German Research Center for Environmental Health (GmbH) Ingolst~dter Landstrasse 1 85764 Neuherberg Germany Institute of Biology/Plant Physiology Humboldt-University Berlin Philippstrasse 13 Building 12 10115 Berlin Germany Institute of Biology Genetics Humboldt-University Berlin Chausseestrasse 117 10115 Berlin Germany present address: Institut fer Molekulare Biowissenschaften Pflanzliche Zellphysiologie Max-von-Laue-Strasse 9 Biozentrum Goethe-Universit~t Frankfurt 60438Frankfurt am Main Germany present address: Zentrum fur Molekulare Biologie an der Universitat zu Heidelberg (ZMBH) Im Neuenheimer Feld 282 69120 Heidelberg Germany present address: Universite Grenoble-Alpes F-38000 Grenoble France present address: CNRS UMR5168 F-38054 Grenoble France present address: CEA iRTSV Laboratoire de Physiologie Cellulaire & Vgetale F-38054 Grenoble France present address: INRA USC1359 F-38054 Grenoble France present address: Plant Reproductive Biology Group Department of Physiology and Ceil-Biology Leibniz Institute of Rant Genetics and Crop Plant Research (IPK)OT Gatersleben Corrensstrasse 3 D-06466 Stadt Seeland Germany present address: KWS Saat AG Grimsehlstrasse 31 37555 Einbeck Germany present address: Dartmouth College Department of Biological Sciences Ufe Sciences Center 78 College Street Hanover NH 03755 USA

Natural illumination conditions are highly variable and because of their sessile life style, plants are forced to acclimate to them at the cellular and molecular level. Changes in light intensity or quality induce changes in the reduction/oxidation （redox） state of the photosynthetic electron chain that acts as a trigger for compen- satory acclimation responses comprising functional and structural adjustments of photosynthesis and metabolism. Such responses include redox-controlled changes in plant gene expression in the nucleus and organelles. Here we describe a strategy for the identification of early redox-regulated genes （ERGs） in the nucleus of the model organism Arabidopsis thaliana that respond significantly 30 or 60 min after the generation of a reduction signal in the photosynthetic electron transport chain. By comparing the response of wild-type plants with that of the acclimation mutant stn7, we could specifically identify ERGs. The results reveal a significant impact of chloroplast redox signals on distinct nuclear gene groups including genes for the mitochondrial electron transport chain, tetrapyrrole biosynthesis, carbohydrate metabolism, and signaling lipid synthesis. These expression profiles are clearly different from those observed in response to the reduction of photosynthetic electron transport by high light treatments. Thus, the ERGs identified are unique to redox imbalances in photosynthetic electron transport and were then used for analyzing potential redox-responsive cis-elements, trans-factors, and chromosomal regulatory hot spots. The data identify a novel redox-responsive element and indicate extensive redox control at transcriptional and chromosomal levels that point to an unprecedented impact of redox signals on epigenetic processes.

关键词： plastidial redox signaling,early redox-regulated gene Arabidopsis thaliana Molecular Plant

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Inhibition of tumor suppressor p73 by nerve growth factor receptor via chaperone-mediated autophagy

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Journal of Molecular Cell Biology 2020年第9期12卷 700-712页

作者： Daniel Nguyen Kun Yang Lucia Chiao Yun Deng Xiang Zhou Zhen Zhang Shelya X.Zeng Hua Lu department of Biochemistry and Molecular Biology Tulane Cancer CenterTulane University School of MedicineNew OrleansLA 70112USA department of Radiation Oncology Shanghai Cancer CenterDepartment of OncologyShanghai Medical SchoolFudan UniversityShanghai 200032China present address:Verna and Marrs McLean department of Biochemistry and Molecular Biology Baylor College of MedicineHoustonTX 77030USA present address:department of Radiation Oncology Shanghai Cancer CenterFudan UniversityShanghai 200032China present address:Institute of Biomedical Sciences Shanghai Cancer CenterFudan UniversityShanghai 200032China

The tumor suppressr p73 is a homolog of p53 and is capable of inducing cell cycle arrest and apoptosis.Here,we identify nerve growth factor receptor(NGFR,p75NTR,or CD271)as a novel negative p73 regulator.p73 activates NGFR transcription,which,in turn,promotes p73 degradation in a negative feedback loop.NGFR directly binds to p73 central DNA-binding domain and suppresses p73 transcriptional activity as well as p73-mediated apoptosis in cancer cells.Surprisingly,we uncover a previously unknown mechanism of NGFR-facilitated p73 degradation through the chaperone-mediated autophagy(CMA)pathway.Collectively,our studies demonstrate a new oncogenic function for NGFR in inactivating p73 activity by promoting its degradation through the CMA.

关键词： p73 NGFR chaperone-mediated autophagy Lamp2a HSPA8

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SINGLE CRYSTAL HARDENING——MECHANISMS AND DESCRIPTION

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Acta Mechanica Sinica 1995年第2期11卷 162-167页

作者：孙守光黄克智 present address: department of Mechanical Engineering Northern Jiaotong UniversityBeijing China 100044 department of Engineering Mechanics Tsinghua University Beijing China 100084

Various work hardening mechanisms, on the basis of their characteristics, are classified into two categories: the pile-up hardening and the tangle hardening. Together with a discussion about the experimental investigations of work hardening, the descriptions for those two basic hardening mechanisms are suggested, respectively. Combining these descriptions, a new single crystal hardening law is proposed, which can be used to describe work hardening, particularly the cyclic hardening of a crystal grain in a polycrystalline material. Furthermore, some relevant discussion on the new single crystal hardening law is also made in this paper.

关键词： CRYSTAL PLASTICITY SINGLE CRYSTAL HARDENING CYCLIC HARDENING

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