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Positive health:An integrated quantitative approach in patients with chronic gastrointestinal and hepato-pancreatico-biliary disorders

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World Journal of Gastroenterology 2024年第28期30卷 3418-3427页

作者： Anja H W M Lemlijn-Slenter Karolina AP Wijnands Gijs van der Hamsvoort Luuk P van Iperen Nico Wolter Angelique E de Rijk Ad am Masclee department of Social Medicine Faculty of HealthMedicine and Life sciencesCare and Public Health Research Institute Maastricht UniversityMaastricht 6200 MDLimburgNetherlands Division of Gastroenterology and Hepatology Department of Internal MedicineSchool of Nutrition and Translational Research in MetabolismMaastricht 6200 MDLimburgNetherlands Social Medical Affairs Employee Insurance Agency(UWV)Heerlen 6400 ACLimburgNetherlands department of Research Academic Knowledge Center Work and Health South-East Netherlands(AKAG-ZON)Heerlen 6400 ACLimburgNetherlands

BACKGROUND The concept of positive health(PH)supports an integrated approach for patients by taking into account six dimensions of *** approach is especially relevant for patients with chronic *** gastrointestinal and hepatopancreatico-biliary(GI-HPB)disorders are among the top-6 of the most prevalent chronically affected organ *** impact of chronic GI-HPB disorders on individuals may be disproportionally high because:(1)The affected organ system frequently contributes to a malnourished state;and(2)persons with chronic GIHPB disorders are often younger than persons with chronic diseases in other organ *** To describe and quantify the dimensions of PH in patients with chronic GI-HPB *** Prospective,observational questionnaire study performed between 2019 and 2021 in 235 patients with a chronic GIHPB disorder attending the Outpatient department of the Maastricht University Medical *** questionnaires and data from patient files were used to quantify the six dimensions of *** consistency was tested with McDonald’s ***-order Pearson correlations and t-tests were used to assess associations and differences.A P valuedered *** The GI-HPB patients scored significantly worse in all dimensions of PH compared to control data or norm scores from the general *** quality of life,participation and daily functioning,GI-HPB patients scored in the same range as patients with chronic disorders in other organ systems,but depressive symptoms(in 35%)and malnutrition(in 45%)were more frequent in patients with chronic GI-HPB *** scores between the six dimensions were only very weak to weak,forcing us to quantify each domain *** All six dimensions of PH are impaired in the GI-HPB *** and depressive symptoms are more prevalent compared to patients with chronic disorders in other organ systems.

关键词： Positive health Chronic gut disorders Gastrointestinal disorders Hepato-pancreatico-biliary disorders Integrated care

A Golden Touch in the design of Multifunctional Porphyrin Metallacages:Host-Guest Chemistry for Drug-Target Interactions

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CCS Chemistry 2024年第7期6卷 1662-1671页

作者： Tamara Rodríguez-Prieto Darren Wragg Nicole Heiduk Mihyun Park Nicole Strittmatter Roland A.Fischer Angela Casini Guillermo Moreno-alcántar Chair of Medicinal and Bioinorganic Chemistry Department of ChemistrySchool of Natural SciencesTechnical University of Munich85748 Garching b.München Professorship for Analytical Chemistry Department of ChemistrySchool of Natural SciencesTechnical University of Munich85748 Garching b.München Chair of Inorganic and MetalOrganic Chemistry Department of ChemistrySchool of Natural SciencesTechnical University of Munich85748 Garching b.München Munich Data Science Institute(MDSI) Technical University of Munich85748 Garching b.München

The use of three-dimensional self-assembled metallacages(MCgs)as multimodal drug platforms holds great ***,the synthesis of MCgs with increased complexity and functionality is a great challenge since understanding of the interaction of MCgs with biological targets is still *** this context,this work reports on the integration of a gold(III)porphyrin scaffold into a prismatic MCg structure and explores its application for multimodal therapy of cancer in vitro,namely enabling both photodynamic therapy and *** experimental approaches with a state-of-the-art metadynamics theoretical study,we discovered that the gold cage shows unprecedented host-guest interaction-driven selective stabilization of guanine-quadruplex(G4)structures-validated anticancer drug targets-disclosing a new mechanism to pursue in the design of supramolecular drugs.

关键词： gold metallacages porphyrins G4stabili-zation host-guestchemistry anticanceragents

development of a Ready-to-Use PSMA-11 Kit Formulation and Biological Evaluation of Binding Affinity

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Advances in Molecular Imaging 2024年第2期13卷 7-22页

作者： Maria Renata Valente Brandão Freire Natália Marchesan Bexiga Marco Antonio Stephano João Ezequiel Oliveira Carlos Roberto Jorge Soares Ana Cláudia Camargo Miranda Anna Carolina de alcântara Barbosa Marycel Figols de Barboza Laura Fernanda Garcia Luiz Felipe S. Teixeira Maria Helena Marumo Bellini Natanael Gomes da Silva Luiza Mascarenhas Balieiro Joel Mendes Elaine Bortoleti de Araújo Centro de Radiofarmcia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil departamento de Tecnologia Farmacutica Faculdade de Cincias Farmacuticas (USP) Cidade Universitria So Paulo Brasil Centro de Biotecnologia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil departamento de Medicina Nuclear do Hospital Israelita Albert Einstein So Paulo/SP Brasil

Introduction: 68Ga-PSMA-11 is considered the gold standard in detection of micro and oligometastases in advanced prostate cancer, being used for therapeutic planning, as well as, potentially, for evaluating response to treatment. The development of ready-to-use lyophilized kit of PSMA-11 adds quality and safety to the routine use of this radiopharmaceutical and represents a pharmacotechnical challenge as it must preserve the integrity and specificity of the ligand. Methods: PSMA-11 kit formulation was proposed, considering radiolabeling parameters and the preservation of the peptide during the lyophilization process, using mannitol as an excipient. Critical temperature characterization studies were carried out using DSC equipment and the freeze-drying process was developed. The direct radiolabeling conditions were evaluated and standardized using 68Ge/68Ga generator eluate from two different manufacturers (ITG and Eckert & Ziegler). The radiochemical purity was evaluated by TLC and HPLC. Biological evaluation was carried out with lyophilized PSMA-11 to demonstrate the integrity of the peptide and preservation of biological activity after the lyophilization process. Results: Based on critical temperature characterization studies, the freeze-drying cycle was designed to reach a freezing temperature of around −40˚C and primary drying at 2˚C. Using 20 mg of mannitol, an intact and elegant lyophilized cake was obtained. PSMA-11 lyophilized kit was directly labeled with 68Ga eluate from 68Ge/68Ga GMP generators (ITG and Eckert & Ziegler) resulting in % RP > 95% at pH 4.0 to 4.5. The results obtained from in vitro and in vivo biological competition studies confirmed the preservation of PSMA-11 affinity for the receptor after lyophilization. Conclusion: A lyophilized formulation (Kit) of PSMA-11 was successfully obtained, which preserved the integrity and biological activity of the peptide and guaranteed radiolabeling efficiency.

关键词： 68Ga-PSMA-11 Prostate-Specific Membrane Antigen (PSMA) Ready-to-Use Kit GMP-Grade Generators Metastatic Prostate Cancer PET Imaging

Interplay of RNA-binding proteins controls germ cell development in zebrafish

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Journal of Genetics and Genomics 2024年第9期51卷 889-899页

作者： de-Li Shi Laboratory of developmental Biology CNRS-UMR7622Institut de Biologie Paris-Seine(IBPS)Sorbonne University75005 ParisFrance

The specification of germ cells in zebrafish mostly relies on an inherited mechanism by which localized maternal determinants,called germ plasm,confer germline fate in the early *** studies have partially allowed the identification of key regulators governing germ plasm formation and subsequent germ cell ***-binding proteins,acting in concert with other germ plasm components,play essential roles in the organization of the germ plasm and the specification,migration,maintenance,and differentiation of primordial germ *** loss of their functions impairs germ cell formation and causes sterility or sexual *** is emerging that they instruct germline development through differential regulation of mRNA fates in somatic and germ ***,the challenge remains to decipher the complex interplay of maternal germ plasm components in germ plasm compartmentalization and germ cell *** failure to control the developmental outcome of germ cells disrupts the formation of gametes,it is important to gain a complete picture of regulatory mechanisms operating in the germ cell *** review sheds light on the contributions of RNA-binding proteins to germ cell development in zebrafish and highlights intriguing questions that remain open for future investigation.

关键词： Germplasm Primordialgerm cell Germlinestem cell Gametogenesis Zebrafish RNA-binding protein Posttranscriptional gene expression Translational activation and repression

Early Warning Systems: Lost in Translation or Late by definition? A FORIN Approach

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International Journal of Disaster Risk Science 2019年第3期10卷 317-331页

作者： Irasema alcántara-Ayala Anthony Oliver-Smith Institute of Geography National Autonomous University of Mexico(UNAM)04510 Mexico CityMexico University of Florida GainesvilleFL 32611USA

Early warning systems(EWSs) are widely considered to be one of the most important mechanisms to prevent disasters around the globe. But as disasters continue to affect countries where EWSs have already been implemented, the striking disaster consequences have led us to reflect on the focus, architecture, and function of the warning systems. Since the 2004 Indian Ocean tsunami there has been a rapid rise in the promotion and use of EWSs to minimize disaster losses and damage. However,few researchers have addressed the question of their acceptability as an adaptive measure to the existing exposure conditions. EWSs are far more linked to emergency response and humanitarian crises and accepted technological interventions as solutions than they are to explicitly advance integrated analysis, disaster risk reduction, and policy making. A major flaw of EWSs is that the term‘‘early’’ has been essentially used in reference to the speed of hazard onset, founded on a physicalist perspective that has encouraged a considerable dependence on *** this article we address the need for a clear understanding of the root causes and risk drivers of disaster risk creation,as advanced in the FORIN(forensic investigation of disasters) approach, as a prerequisite for the development of more articulated EWSs that could contribute to disaster risk reduction through policy making and practice, based on integrated and transdisciplinary management, in the interest of sustainable development, and human welfare and well-being.

关键词： Disaster risk drivers Disaster root causes Early warning systems Forensic disaster investigations FORIN

Landslide risk perception and communication for disaster risk management in mountain areas of developing countries：a Mexican foretaste

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Journal of Mountain Science 2016年第12期13卷 2079-2093页

作者： Irasema alcántara-AYALA Ana Rosa MORENO Institute of Geography National Autonomous University of Mexico(UNAM)Ciudad UniversitariaCoyoaedn04510Mexico CityMexico Faculty of Medicine Department of Public HealthNational Autonormous University of Mexico(UNAM)Ciudad UniversitariaCoyoacan04510Mexico CityMexico

The increasing impact of disasters at local,national,regional and global scales in recent decades has provided enough evidence to urgently direct attention towards the necessity of disaster risk reduction and management,and this requires *** without communication is barren,and to communicate the risk of disaster it is necessary to understand the perception of the people at *** particular,this paper deals with the necessity to delineate strategies of risk communication in pursuance of risk knowledge as a core of disaster risk reduction and management,especially in mountain areas of developing *** portray this issue,an analysis of landslide risk perception in terms of experience,landslide risk awareness,exposure,preparedness,and risk communication and trust was undertaken in the municipality of Teziutlán,Puebla,Mexico,an area that has been affected for several decades by episodes of mass *** of the responses to a risk perception questionnaire has offered valuable insights in terms of the information and knowledge most required by the people living in the area of interest,in order to devise a realistic and functional strategy to communicate the risk of a landslide *** includes better understanding of controlling factorsand drivers of this risk,and the establishment of potential trusted sources of risk *** considering practical matters of risk assessment and management,risk perception and communication can increase the resilience of vulnerable people,and can enhance capacity building for present and future generations.

关键词： Risk perception Risk communication Landslides Disaster risk Mountain areas

Routine utilization of machine perfusion in liver transplantation:Ready for prime time?

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World Journal of Gastroenterology 2024年第11期30卷 1488-1493页

作者： Alessandro Parente Keyue Sun Philipp Dutkowski am James Shapiro Andrea Schlegel department of Surgery Division of TransplantationUniversity of Alberta HospitalEdmonton T6G 2B7Canada Immunity and Inflammation Lerner Research InstituteClevelandOH 44195United States Swiss Hepato-Pancreato-Biliary Center Department of Visceral and Transplantation SurgeryUniversity Hospital ZurichZurich 8091Switzerland Immunity and Inflammation Digestive Disease and Surgery InstituteClevelandOH 44195United States

The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver *** evidence from numerous randomized controlled trials has been pooled by meta-analyses,providing the highest available evidence on the protective effect of machine perfusion(MP)over static cold storage in liver transplantation(LT).Based on a protective effect with less complications and improved graft survival,the field has seen a paradigm shift in organ *** editorial focuses on the role of MP in LT and how it could become the new“gold standard”.Strong collaborative efforts are needed to explore its effects on long-term outcomes.

关键词： Liver transplantation Machine perfusion Viability assessment Hypothermic oxygenated perfusion Normothermic machine perfusion

Stereotactic body radiotherapy in pancreatic adenocarcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 14-19页

作者： Carolina de la Pinta Radiation Oncology department Ramón y Cajal University HospitalIRYCISAlcaláUniversity28034 MadridSpain

Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding *** review aimed at the SBRT application in the treatment of pancreatic *** sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to december *** used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were *** articles were assessed for validity and relevant ***:Optimal doses and fractionation have not yet been ***,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to ***,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic ***:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease *** opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.

关键词： Chemoradiotherapy Pancreatic adenocarcinoma Radiotherapy Stereotactic body radiotherapy Stereotactic ablative radiotherapy

The use of UAVs for landslide disaster risk research and disaster risk management: a literature review

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Journal of Mountain Science 2021年第2期18卷 482-498页

作者： Ricardo J.GARNICA-PEÑA Irasema alcÁntara-AYALA Institute of Geography National Autonomous University of Mexico(UNAM)Mexico City 04510Mexico

On a global scale,from 2005 to 2019,there were 275 high-magnitude,low-frequency disasters that involved 14,172 fatalities and four million affected *** patterns have taken place during longer periods of time in recent *** paper aims to analyse the contribution of the international landslide research community to disaster risk reduction and disaster risk management in reference to the use of Unmanned Aerial Vehicles(UAVs)in a literature *** first section notes the relevance of disaster risk research contributions for the implementation of initiatives and strategies concerning disaster risk *** second section highlights background information and current applications of drones in the field of hazards and *** methodology,which included a systematic peer review of journals in the ISI Web of Science and SCOPUS,was presented in the third section,where the results include analyses of the considered *** study concludes that most current scholarly efforts remain rooted in hazards and post-disaster evaluation and *** landslide disaster risk research should be transdisciplinary in order to strengthen participation of the various relevant stakeholders in contributing to integrated disaster risk management at local,subnational,national,regional and global levels.

关键词： UAVs Landslides Disaster risk Landslide research Vulnerability Exposure Disaster risk management