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Drug-and Herb-Induced Liver Injury in Clinical and Translational Hepatology:Causality Assessment Methods, Quo Vadis?

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Journal of Clinical and Translational Hepatology 2013年第1期1卷 59-74页

作者： Rolf Teschke Axel Eickhoff johannes Schulze Department of Internal Medicine Ⅱ Division of Gastroenterology and Hepatology Klinikum Hanau Academic Teaching Hospital of the Medical Faculty Goethe University Frankfurt/Main Germany Institute of Industrial Environmental and Social Medicine Medical Faculty Goethe University Frankfurt/Main Germany

Drug-induced liver injury (DILI) and herb-induced liver injury (HILI) are typical diseases of clinical and translational hepatology. Their diagnosis is complex and requires an experienced clinician to translate basic science into clinical judgment and identify a valid causality algorithm. To pro-spectively assess causality starting on the day DILI or HILI is suspected, the best approach for physicians is to use the Council for International Organizations of Medical Sciences (CIOMS) scale in its original or preferably its updated version. The CIOMS scale is validated, liver-specific, structured, and quantitative, providing final causality grades based on scores of specific items for individual patients. These items include latency period, decline in liver values after treatment cessa-tion, risk factors, co-medication, alternative diagnoses, hepatotoxicity track record of the suspected product, and unintentional re-exposure. Provided causality is established as probable or highly probable, data of the CIOMS scale with all individual items, a short clinical report, and complete raw data should be transmitted to the regulatory agencies, manufacturers, expert panels, and possibly to the scientific community for further refinement of the causality evaluation in a setting of retrospective expert opinion. Good-quality case data combined with thorough CIOMS-based assessment as a standardized approach should avert subsequent necessity for other complex causality assessment methods that may have inter-rater problems because of poor-quality data. In the future, the CIOMS scale will continue to be the preferred tool to assess causality of DILI and HILI cases and should be used consistently, both prospectively by physicians, and retrospectively for subsequent expert opinion if needed. For comparability and international harmonization, all parties assessing causality in DILI and HILI cases should attempt this standardized approach using the updated CIOMS scale.

关键词： Drug-induced liver injury Drug hepatotoxicity Herb-induced liver injury Herbal hepatotoxicity Causality assessment

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Performance of two complementary machine-learned potentials in modelling chemically complex systems

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npj Computational Materials 2023年第1期9卷 1008-1022页

作者： Konstantin Gubaev Viktor Zaverkin Prashanth Srinivasan Andrew Ian Duff johannes Kästner Blazej Grabowski Institute for Materials Science University of StuttgartPfaffenwaldring 5570569 StuttgartGermany Institute for Theoretical Chemistry University of StuttgartPfaffenwaldring 5570569 StuttgartGermany Scientific Computing Department STFC Daresbury LaboratoryWarrington WA44ADUK Present address:NEC Laboratories Europe GmbH Kurfürsten-Anlage 3669115 HeidelbergGermany

Chemically complex multicomponent alloys possess exceptional properties derived from an inexhaustible compositional *** complexity however makes interatomic potential development *** explore two complementary machine-learned potentials—the moment tensor potential(MTP)and the Gaussian moment neural network(GM-NN)—in simultaneously describing configurational and vibrational degrees of freedom in the Ta-V-Cr-W alloy *** models are equally accurate with excellent performance evaluated against *** achieve root-mean-square-errors(RMSEs)in energies of less than a few meV/atom across 0 K ordered and high-temperature disordered configurations included in the *** for compositions not in training,relative energy RMSEs at high temperatures are within a few meV/***-temperature molecular dynamics forces have similarly small RMSEs of about 0.15 eV/Åfor the disordered quaternary included in,and ternaries not part of *** achieve faster convergence with training size;GM-NNs are faster in *** learning is partially beneficial and should be complemented with conventional human-based training set generation.

关键词： alloy faster complex

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Structure-Function Analysis of Arabidopsis thaliana Histidine Kinase AHK5 Bound to Its Cognate Phosphotransfer Protein AHP1

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Molecular Plant 2013年第3期6卷 959-970页

作者： johannes Bauer Kerstin Reiss Manikandan Veerabagu Michael Heunemann Klaus Harter Thilo Stehle Interfaculty Institute of Biochemistry University of Tubingen D-72076 Tubingen Germany Center for Plant Molecular Biology University of TObingen D-72076 T0bingen Germany Department of Pediatrics Vanderbilt University School of Medicine Nashville TN 37232 USA

The multi-step phosphorelay （MSP） system defines a key signal transduction pathway in plants and many eukaryotes. In this system, external stimuli first lead to the activation of a histidine kinase, followed by transfer of a phosphoryl group from the receiver domain of the kinase （HKRD） to downstream, cytosolic phosphotransfer proteins （HPs）. In order to establish the determinants of specificity for this signaling relay system, we have solved the first crystal structure of a plant HKRD, AHK5RD, in complex with one of its cognate HPs, AHP1. AHP1 binds AHK5RD via a prominent hydrogen bond docking ridge and a hydrophobic patch. These features are conserved among all AHP proteins, but differ significantly from other structurally characterized prokaryotic and eukaryotic HPs. Surface plasmon resonance experiments show that AHK5RD binds to AHP1-3 with similar, micromolar affinity, consistent with the transient nature of this signaling complex. Our correlation of structural and functional data provide the first insight, at the atomic level as well as with quantitative affinity data, into the molecular recognition events governing the MSP in plants.

关键词： multi-step phosphorelay phosphotransfer protein plant signaling sensor histidine kinase two-component system.

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Cut it out or wait it out? Case series of middle fossa arachnoid cysts presenting with psychiatric symptoms and a discussion of the ethics of neurosurgical management

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General Psychiatry 2021年第6期34卷 1-4,I0001页

作者： Petrus johannes Steyn Leigh Luella Van den Heuvel Psychiatry Stellenbosch University Faculty of Medicine and Health SciencesCape TownSouth Africa

Arachnoid cysts have been linked to neuropsychiatric *** describe two patients presenting with dissociative and manic symptoms believed to be associated with middle fossa arachnoid *** were managed medically and remitted eventually,but symptoms were *** briefly review the literature to discuss mechanisms by which cysts could cause symptoms and consider whether neurosurgical management would be *** neurosurgery can be considered,its role is currently limited by practical and ethical considerations.

关键词： symptoms psychiatric eventually

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Hirudotherapy attenuates arthritic pain in patients with various chronic pain syndromes: A retrospective analysis

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Journal of Integrative Medicine 2020年第5期18卷 425-433页

作者： johannes Loeser Brigitte Layer Christopher Plata Klaus-Maria Perrar Tim Hucho Rebecca Kulbida Department of Anaesthesiology and Intensive Care Medicine University Clinic of CologneKoeln 50937Germany Department of Palliative Care University Clinic of CologneKoeln 50937Germany

Objective: Osteoarthritis is a degenerative disease that affects synovial joints. Micro-injuries of articular structures initiate inflammatory processes, leading to persistent pain. Due to various risk factors,osteoarthritis is often diagnosed in multimorbid patients. This makes pain management one of the key challenges, with a consistent need for new therapeutic strategies. Hence, complementary and integrative methods such as hirudotherapy have become increasingly important, even though their mechanisms of action are not entirely ***: We retrospectively analyzed the longitudinal effect of a single leech application on osteoarthritic joints in a heterogenic cohort of 24 cases with various chronic pain syndromes. We assessed articular pain intensity ratings and movability of the treated joint after one-time leeching for up to 12 *** further investigated the effect of hirudotherapy on the systemic pain status and multimodal treatment strategies of the ***: There was a significant reduction in pain intensity ratings at the joint of leech application for up to 12 months after treatment. The improvements in pain intensities were independent of the form of osteoarthritis treated. In addition, we saw a considerable enhancement in local movability of the treated joint. Hirudotherapy did not seem to influence the systemic pain status as well as the previously established individualized multimodal treatment model of the ***: Leeching as an adjuvant therapy has a great potential especially in terms of safety and longterm outcome.

关键词： Hirudotherapy Medicinal leeching Chronic pain syndromes Pain management Osteoarthritis

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Developing a TRL-oriented roadmap for the adoption of biocomposite materials in the construction industry

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Frontiers of Engineering Management 2023年第2期10卷 223-236页

作者： Tudor-Cristian PETRESCU johannes T.VOORDIJK Petru MIHAI Department of Structural Mechanics Faculty of Civil Engineering and Building ServicesGheorghe Asachi Technical University of Iasi700050 IasiRomania Department of Civil Engineering Faculty of Engineering TechnologyUniversity of Twente7552 LW Enschedethe Netherlands Department of Concrete MaterialsTechnology and ManagementFaculty of Civil Engineering and Building ServicesGheorghe Asachi Technical University of Iasi700050 IasiRomania

The construction industry is a major contributor to environmental *** effect of the construction industry on the environment may be mitigated using eco-friendly construction materials,such as *** developed,biocomposites may offer a viable alternative to the current materials in ***,biocomposites are lagging in terms of adoption and eventual use in the construction *** article provides insights into the steps for biocomposites to become a product that is ready to use by the construction industry in a structural *** development and the adoption of such a material is tackled with the use of two concepts,i.e.,technology readiness level and roadmapping,and explored in a case study on the“liquid wood”.Furthermore,interviews in the construction industry are carried out to identify the industry’s take on biocomposites.A customized roadmap,which underlines a mostly nontechnical perspective concerning this material,has ***,the adoption and diffusion issues that the“liquid wood”may encounter are outlined and complemented with further recommendations.

关键词： biocomposite technology readiness level roadmap interview “liquid wood”

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Laser additive manufacturing of Zn porous scaffolds: Shielding gas flow, surface quality and densification

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Journal of Materials Science & Technology 2019年第2期35卷 368-376页

作者： Peng Wen Yu Qin Yanzhe Chen Maximilian Voshage Lucas Jauer Reinhart Poprawe johannes Henrich Schleifenbaum The State Key Laboratory of Tribology Tsinghua University Key Laboratory for Advanced Materials Processing Technology MOE Tsinghua University Department of Mechanical Engineering Tsinghua University Digital Additive Production (DAP) RWTH Aachen University Fraunhofer Institute for Laser Technology (ILT)

Zn based metals have exhibited promising prospects as a structural material for biodegradable applications. Pure Zn porous scaffolds were produced by laser powder bed fusion(LPBF) based on data files of designing and CT scanning. Massive Zn evaporation during laser melting largely influenced the formation quality during LPBF of Zn metal. The metal vapor in processing chamber was blown off and suctioned out efficiently by an optimized gas circulation system. Numerical analysis was used to design and testify the performance of gas flow. The surface of scaffolds was covered with numerous particles in different sizes. Processing pores occurred near the outline contour of struts. The average grain size in width was8.5m, and the hardness was 43.8 HV. Chemical plus electrochemical polishing obtained uniform and smooth surface without processing pores, but the diameter of struts reduced to 250 αm from the design value 300 m. The poor surface quality and processing pores were resulted by the splashing particles included spatters and powders due to the recoil force of evaporation, and the horizontal movement of liquid metal due to overheating and wetting. The insufficient melting at the outline contour combined with good wetting of Zn liquid metal further increased the surface roughness and processing pores.

关键词： Additive manufacturing Powder bed fusion Laser Porous scaffold Zn

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Nanoscale imaging of electric pathways in epitaxial graphene nanoribbons

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Nano Research 2019年第7期12卷 1697-1702页

作者： johannes Aprojanz Pantelis Bampoulis Alexei A. Zakharov Harold J. W. Zandvliet Christoph Tegenkamp Institut fur Physik Technische Universitat ChemnitzChemnitz 09126Germany Institutfur Festkoperphysik Leibniz Universitat HannoverHannover 30167Germany Physics of Interfaces and Nanomaterials MESA+ Institute for NanotechnologyUniversity of TwenteEnschede 7522 NHThe Netherlands MAX TV Laboratory and Lund University Lund 22100Sweden

Graphene nanoribbons (GNRs) are considered as major building blocks in future carbon-based *** electronic performance of graphene nanostructures is essentially influenced and determined by their edge termination and their supporting *** particular,semi-conducting,as well as metallic GNRs,can be fabricated by choosing the proper template which is favorable for device architecture *** study highlights the impact of microscopic details of the environment of the GNRs on the charge transport in *** means of lateral force,conductive atomic force and nanoprobe measurements,we explore the charge propagation in both zig-zag and armchair GNRs epitaxially grown on SiC *** directly image transport channels on the nanoscale and identify SiC substrate steps and nano-instabilities of SiC facets as dominant charge scattering centers.

关键词： sidewall graphene nanoribbons nanoprobe conductive-AFM nanoscale transport

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Biophotonic sensors with integrated Si_(3)N_(4)-organic hybrid (SiNOH) lasers for point-of-care diagnostics

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Light(Science & Applications) 2021年第4期10卷 648-659页

作者： Daria Kohler Gregor Schindler Lothar Hahn johannes Milvich Andreas Hofmann Kerstin Lange Wolfgang Freude Christian Koos Institute of Photonics and Quantum Elearo nics(IPQ) Karlsruhe Institute of Technology(KIT)Engesserstrasse 576131 KarlsruheGermany lnstitute of Microstructure Technology(IMT) Karlsruhe Institute of Technology(KIT)Hermann-von-Helmholtz-Platz 176344 Eggenstein-LeopoldshafenGermany Robert Bosch GmbH Robert-Bosch-Campus 171272 RenningenGermany lnstitute for Autom ation and Applied Informatics(IAI) Karlsruhe Institute of Technology(KIT)Hermann-von-Helmholtz-Platz 176344 Eggenstein-LeopoldshafenGermany

Early and efficient disease diagnosis with low-cost point-of-care devices is gaining importance for personalized medicine and public health *** this context,waveguide-(WG)-based optical biosensors on the siliconnitride(Si_(3)N_(4))platform represent a particularly promising option,offering highly sensitive detection of indicative biomarkers in multiplexed sensor arrays operated by light in the visible-wavelength ***,while passive Si_(3)N_(4)-based photonic circuits lend themselves to highly scalable mass production,the integration of low-cost light sources remains a *** this paper,we demonstrate optical biosensors that combine Si_(3)N_(4)sensor circuits with hybrid on-chip organic *** Si_(3)N_(4)-organic hybrid(SiNOH)lasers rely on a dye-doped cladding material that are deposited on top of a passive WG and that are optically pumped by an external light *** of the devices is simple:The underlying Si_(3)N_(4)WGs are structured in a single lithography step,and the organic gain medium is subsequently applied by dispensing,spin-coating,or ink-jet printing processes.A highly parallel read-out of the optical sensor signals is accomplished with a simple *** our proof-of-concept experiment,we demonstrate the viability of the approach by detecting different concentrations of fibrinogen in phosphate-buffered saline solutions with a sensor-length(L-)-related sensitivity of S/L=0.16 rad nM^(-1)mm^(-1).To our knowledge,this is the first demonstration of an integrated optical circuit driven by a co-integrated low-cost organic light *** expect that the versatility of the device concept,the simple operation principle,and the compatibility with cost-efficient mass production will make the concept a highly attractive option for applications in biophotonics and point-of-care diagnostics.

关键词： passive waveguide pumped

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三氧化钨催化糖分子选择裂解新机理及其对生物质利用的重要意义

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Chinese Journal of Catalysis 2023年第3期46卷 1-3页

作者： johannes A.Lercher 德国慕尼黑工业大学德国加兴美国西北太平洋国家实验室美国里奇兰

糖类化合物催化转化合成燃料和化学品为现有化石路线提供了可行的替代方案.碳化钨、氧化钨和钨酸等钨基催化剂具有催化糖分子碳-碳键选择性断裂生成乙二醇、丙二醇等C_(2,3)产物的独特性能.然而,对该催化反应的机理还一直缺乏明确的认识... 详细信息

糖类化合物催化转化合成燃料和化学品为现有化石路线提供了可行的替代方案.碳化钨、氧化钨和钨酸等钨基催化剂具有催化糖分子碳-碳键选择性断裂生成乙二醇、丙二醇等C_(2,3)产物的独特性能.然而,对该催化反应的机理还一直缺乏明确的认识.最近北京大学刘海超团队报道,糖分子的羰基、α-和β-羟基与三氧化钨(WO_(3))表面的两个邻近钨原子(W-O-W结构)配位,形成一种双钨三齿螯合物;该螯合物作为反应的关键中间体,引发羰基β-位的碳-碳键断裂,从而实现糖分子的选择裂解.该新反应机理不仅为糖化学提供了新的认识,而且为糖基生物质提供了一个经乙醇醛、甘油醛等C_(2,3)中间体转化为化学品的有效策略.固体核磁表征结果表明,吸附到WO_(3)表面的^(13)Cc标记葡萄糖的C1、C2和C3三个碳原子与表面钨原子形成了C-O-W键,从而在去屏蔽作用下化学位移向低场移动,说明糖分子需要羰基以及α-和β-羟基三个官能团共同参与才具有反应活性.催化反应结果表明,含有W-O-W结构的钨基化合物均表现出催化糖分子裂解生成C_(2,3)产物的活性,例如:仲钨酸铵、磷钨酸盐和钨青铜等均相、多相催化剂都能有效地将葡萄糖转化为乙二醇.通过理论计算分别模拟L-苏阿糖和2-脱氧-L-苏阿糖在WO_(3)(001)晶面上的反应过程,发现前者形成的L-苏阿糖-三氧化钨三齿螯合物,在后续碳-碳键选择性断裂生成一分子乙醇醛和一分子表面结合的乙烯二醇中间物种过程中,只有-0.01 eV的能量变化以及0.53 eV的能垒;而2-脱氧-L-苏阿糖则不同,由于缺乏α-羟基,后续碳-碳键断裂过程中需要吸收0.20 eV的能量和克服0.62 eV的能垒.计算结果进一步证明了糖-三氧化钨三齿螯合物中间体和糖分子α-羟基在反应中发挥了至关重要的作用.刘海超团队这项开拓性的工作揭示了三氧化钨催化糖分子碳-碳键选择性断裂的新机理,扩展了教科书中对经典逆羟醛缩合反应机理的描述.在该机理指导下,来源多样、纯度不同和结构各异的糖类化合物均能够在钨基催化剂作用下经乙醇醛和甘油醛等C_(2,3)中间体转化为化学品,从而为糖基生物质高效利用提供了具有实用意义的新策略.这正如现代石油化工所普遍采用的方法,首先将石油原料经过催化裂化或水汽裂解转化为乙烯、丙烯等C_(2,3)中间体,然后进一步转化为下游丰富的化学品.因此,该项研究工作对于纤维素、半纤维素等糖基生物质的高效转化利用具有重要意义.

关键词：生物质糖三氧化钨碳–碳键断裂非经典逆羟醛缩合反应机理

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