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Targeted cytokine delivery:cell therapy to remodel the pre-metastatic niche

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2278-2279页

作者： michael a.morgan Lucas Lange Axel Schambach Institute of Experimental Hematology Hannover Medical SchoolHannoverGermany REBIRTH Research Center for Translational Regenerative Medicine Hannover Medical SchoolHannoverGermany Division of Hematology/Oncology Boston Children’s HospitalHarvard Medical SchoolBostonMAUSA

Tumor metastases present an often difficult to treat therapeutic challenge for cancer patients and their *** recent paper by the Kaplan group(Kaczanowska et al.)exploited the natural capacity of monocytes or a subset of monocytes to migrate to tumor sites and pre-metastatic niches to deliver IL-12 in a novel anticancer approach designed to stimulate local immune responses.1 This raises the possibility to simultaneously fight cancer on at least two critical fronts,(1)elimination of the primary tumor and(2)inhibition of newly developing pre-metastatic lesions.

关键词： metastatic cytokine migrate

Prime time for base editing in the mitochondria

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Signal Transduction and Targeted Therapy 2022年第8期7卷 2630-2631页

作者： michael a.morgan Lucas Lange Axel Schambach Institute of Experimental Hematology Hannover Medical SchoolHannover 30625Germany REBIRTH Research Center for Translational Regenerative Medicine Hannover Medical SchoolHannover 30625Germany Division of Hematology/Oncology Boston Children’s HospitalHarvard Medical SchoolBostonMA 02115USA

A recent study published in Cell by the Kim lab represents a great advance towards expanding DNA editing possibilities to mitochondrial DNA(mtDNA)as they show reasonable targeted A-to-G conversions in human mtDNA using base editors to broaden the arsenal of available tools.1 Mutations in mitochondrial DNA(mtDNA)are linked to several diseases(Fig.1),thus,development of gene therapy and editing approaches could lead to curative options for patients suffering from these *** this direction,gene editing tools such as zinc-finger nucleases(mitoZFN),transcription activator-like effector nucleases(mitoTALENs)and meganucleases(mitoARCUS)were shown to eliminate mutant mtDNA and shift heteroplasmy.

关键词： diseases base curative

Automated Machine Learning Algorithm Using Recurrent Neural Network to Perform Long-Term Time Series Forecasting

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Computers, Materials & Continua 2024年第3期78卷 3529-3549页

作者： Ying Su morgan C.Wang Shuai Liu Department of Statistics and Data Science University of Central FloridaOrlandoFL32816-2370USA School of Mathematics and Statistics Beijing Technology and Business UniversityBeijing100048China

Long-term time series forecasting stands as a crucial research domain within the realm of automated machine learning(AutoML).At present,forecasting,whether rooted in machine learning or statistical learning,typically relies on expert input and necessitates substantial manual *** manual effort spans model development,feature engineering,hyper-parameter tuning,and the intricate construction of time series *** complexity of these tasks renders complete automation unfeasible,as they inherently demand human intervention at multiple *** surmount these challenges,this article proposes leveraging Long Short-Term Memory,which is the variant of Recurrent Neural Networks,harnessing memory cells and gating mechanisms to facilitate long-term time series ***,forecasting accuracy by particular neural network and traditional models can degrade significantly,when addressing long-term time-series ***,our research demonstrates that this innovative approach outperforms the traditional Autoregressive Integrated Moving Average(ARIMA)method in forecasting long-term univariate time *** is a high-quality and competitive model in time series prediction,and yet it requires significant preprocessing *** multiple accuracy metrics,we have evaluated both ARIMA and proposed method on the simulated time-series data and real data in both short and long ***,our findings indicate its superiority over alternative network architectures,including Fully Connected Neural Networks,Convolutional Neural Networks,and Nonpooling Convolutional Neural *** AutoML approach enables non-professional to attain highly accurate and effective time series forecasting,and can be widely applied to various domains,particularly in business and finance.

关键词： Automated machine learning autoregressive integrated moving average neural networks time series analysis

Severe acute respiratory syndrome coronavirus-2-related and imputable deaths in children:results from the French pediatric national registry

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World Journal of Pediatrics 2024年第6期20卷 611-620页

作者： Marguerite Lockhart-Bouron Noemie Vanel michael Levy Anais R.Briant Etienne Javouhey Sophie Breinig Julia Dina Marion Caseris Francois Angoulvant Stephane Leteurtre morgan Recher David W.Brossier Univ.Lille CHU LilleULR 2694-METRICS:Evaluation Des Technologies de Sante Et Des Pratiques Medicales59000LilleFrance Pediatric Intensive Care Unit CHU de MarseilleMarseilleFrance Pediatric Intensive Care Unit CHU Robert-DebreAssistance Publique Hopitaux de ParisParisFrance UniversitéParis-Cite ParisFrance Biostatistics and Clinical Research Unit CHU de Caen Normandie14000CaenFrance Pediatric Intensive Care Hospices Civils de LyonLyonFrance Neonatal andPediatric IntensiveCare Unit Children's HospitalToulouseFrance Virology Department INSERM U1311 DynamicureUniv CAEN NormandieCHU de Caen14000 CaenFrance Medical School Universite Caen Normandie14000 CaenFrance Department of Pediatrics CHU Robert-DebréAssistance Publique Hopitaux de ParisParisFrance Department Women-Mother-Child Service of PediatricsLausanne University Hospital(CHUV)LausanneSwitzerland Pediatric Intensive Care Unit Réanimation Et Soins Intensifs PéediatriquesCHU de CAENAvenue de La Cote de Nacre14000 CaenFrance CHU Sainte Justine Research Center MontréalCanada

Background Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)is responsible for an important mortality rate *** aimed to evaluate the actual imputability of SARS-CoV-2 on the mortality rate associated with SARS-CoV-2-related illnesses in the pediatric intensive care unit(PICU).Secondary objectives were to identify risk factors for *** This national multicenter comparative study comprised all patients under 18 years old with positive SARS-CoV-2 polymerase chain reactions(PCRs)[acute corona virus disease 2019(COVID-19)or incidental SARS-CoV-2 infection]and/or pediatric inflammatory multisystem syndrome(PIMS)recorded in the French PICU registry(PICURe)between September 1,2021,and August 31,*** patients were classified and compared according to their living status at the end of their PICU *** patients were evaluated by four experts in the field of pediatric infectiology and/or pediatric intensive *** imputability of SARS-CoV-2 as the cause of death was classified into four categories:certain,very probable,possible,or unlikely,and was defined by any of the first three *** There were 948 patients included of which 43 died(4.5%).From this,26 deaths(67%)could be attributed to SARS-CoV-2 infection,with an overall mortality rate of 2.8%.The imputability of death to SARS-CoV-2 was considered certain in only one case(O.1%).Deceased patients suffered more often from comorbidities,especially heart disease,neurological disorders,hematological disease,cancer,and *** of the deceased patients were admitted for pediatric inflam-matory multisystem syndrome(PIMS).Mortality risk factors were male gender,cardiac comorbidities,cancer,and acute respiratorydistress *** SARS-CoV-2 mortality in the French pediatric population was *** though the imputability of SARS-Cov-2 on mortality was considered in almost two-thirds of cases,this imputability was considered certain in only one case.

关键词： Death Pediatric intensive care unit SARS-CoV-2

The earliest evidence for a microblade adaptation in the remote,high altitude regions of the Tibetan Plateau

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Science China Earth Sciences 2024年第5期67卷 1561-1573页

作者： Yingshuai JIN Xiaoling ZHANG Shejiang WANG Junyi GE Wei HE Wa DA Yunyao TAN Ziyi YANG Christopher morgan Xing GAO Institute of Vertebrate Paleontology and Paleoanthropology Chinese Academy of SciencesBeijing 100044China University of the Chinese Academy of Sciences Beijing 100049China Cultural Relics Conservation Institute of the Xizang Autonomous Region Lhasa 850000China Nagqu Culture and Tourism Bureau Nagqu 852000China University of Nevada Reno 89557USA

Microblade assemblages are among the most common prehistoric archaeological materials found on the Tibetan Plateau(TP)and are thought to indicate large scale migration to and settlement of the *** microblade sites,however,have been systematically excavated,especially in the remotest,highest-elevation regions of the *** timing of the large-scale arrival,spread,and permanent settlement of people on the TP therefore remains *** this paper,we report on a recently excavated site,Locality 3 of the Nwya Devu Site(ND3),located at 4600 meters above sea level(masl),near the shore of Ngoin Lake,on the interior *** analyses reveal a fairly typical microblade technological orientation and two types of microblade cores:wedge-shaped and semi-conical,which are similar to those found throughout North *** Optically Stimulated Luminescence(OSL)dating and AMS^(14)C dating,the age of ND3 ranges from 11 to 10 *** date range indicates ND3 is the oldest microblade site yet recorded in the remote,high-elevation regions of the TP and thus provides important information about when and how hunter-gatherers using microblades began exploiting the higher altitudes of the *** together,studies at ND3 and throughout the TP suggest that a microblade adaptation is associated with the first prolonged human occupation of the plateau and that microblades played a significant role in mediating the risks and facilitating the mobility necessary to permanently inhabit the TP.

关键词： The interior of Tibetan Plateau Nwya Devu locality 3 Microblade Early Holocene High altitude adaption

Modelling Land Use/Land Cover Change of River Rwizi Catchment, South-Western Uganda Using GIS and Markov Chain Model

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Journal of Water Resource and Protection 2024年第2期16卷 181-206页

作者： Lauben Muhangane morgan Andama Faculty of Agriculture Uganda Martyrs University Nkozi Uganda Faculty of Science Muni University Arua Uganda

Analysis of catchment Land use/Land cover (LULC) change is a vital tool in ensuring sustainable catchment management. The study analyzed land use/land cover changes in the Rwizi catchment, south western Uganda from 1989-2019 and projected the trend by 2040. Landsat images, field observations, key informant interviews and focus group discussions were used to collect data. Changes in cropland, forestland, built up area, grazing land, wetland and open water bodies were analyzed in ArcGIS version 10.2.2 and ERDAS IMAGINE 14 software and a Markov chain model. All the LULC classes increased in area except grazing land. Forest land and builtup area between 2009-2019 increased by 370.03% and 229.53% respectively. Projections revealed an increase in forest land and builtup area by 2030 and only built up area by 2040. LULCC in the catchment results from population pressure, reduced soil fertility and high value of agricultural products.

关键词： Land Cover River Catchment Geographic Information System Markov Model Sustainable Land Management

Two-way communication: Volatile emission and uptake occur through the same barriers

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Molecular Plant 2023年第1期16卷 1-3页

作者： Joshua R.Widhalm Meng-Ling Shih John a.morgan Natalia Dudareva Department of Horticulture and Landscape Architecture Purdue UniversityWest LafayetteIN 47907USA Center for Plant Biology Purdue UniversityWest LafayetteIN 47907USA avidson School of Chemical Engineering Purdue UniversityWest LafayetteIN 47907USA Department of Biochemistry Purdue UniversityWest LafayetteIN 47907USA

Volatile organic compounds(VOCs)are released from aboveground organs into the atmosphere and/or from roots into the soil,allowing plants to communicate and interact with their environment,including with each ***-plant communication via VOCs includes intra-and inter-species signaling as well as within-plant *** some recipient tissues,for example,VOC perception encompasses storing the modified VOC for direct defense against herbivores(Sugimoto et al.,2014)or increasing tolerance to abiotic stresses(Zhao et al.,2020).In addition,or alternatively,perceived VOCs may initiate signaling cascades that prime plant defenses(Brosset and Blande,2022).In all cases,plant VOCs are first released into the environment before being taken up and perceived by the same or neighboring *** significant progress has been made over the last several years to elucidate how VOCs are released from plant cells,these studies have also revealed new questions about how communicated VOCs are imported across cellular *** reviews(Loreto and D’Auria,2022;Wang and Erb,2022)and a special issue(Vlot and Rosenkranz,2022)have proposed mechanisms for VOC perception and *** this Opinion piece,we shed light on the gaps in knowledge about VOC import and offer perspectives for future research aiming at understanding the molecular mechanisms underlying VOC-mediated communication in plants.

关键词： communicate soil barriers

Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19

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World Journal of Gastroenterology 2024年第31期30卷 3705-3716页

作者： Angus K Jacobs Steven D Morley Kay Samuel Katie morgan Lyndsey Boswell Timothy J Kendall David A Dorward Jonathan A Fallowfield Peter C Hayes John N Plevris Hepatology Laboratory University of EdinburghEdinburgh EH164SBUnited Kingdom Scottish National Blood Transfusion Service Jack Copland CentreEdinburgh EH144BEUnited Kingdom Institute for Regeneration and Repair University of EdinburghEdinburgh EH164UUUnited Kingdom Edinburgh Pathology University of EdinburghEdinburgh EH164SBUnited Kingdom

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and *** injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated *** of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell *** To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe *** ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel *** ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct ***,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in ***2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD *** A

关键词： Metabolic dysfunction-associated steatotic liver disease Angiotensin-converting enzyme 2 Immunohistochemistry COVID-19 COVID-19-associated cholangiopathy

Outcomes of critically ill children with pre-existing mental health conditions

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Pediatric Investigation 2024年第2期8卷 108-116页

作者： Conrad Krawiec morgan Cash Gary Ceneviva Zizhong Tian Shouhao Zhou Neal J.Thomas Department of Pediatrics Pediatric Critical Care MedicinePenn State Hershey Children's HospitalPennsylvaniaUSA Department of Public Health Sciences Division of Biostatistics and BioinformaticsPennsylvania State University College of MedicinePennsylvaniaUSA Department of Public Health_Sciences Pennsylvania State University College of MedicinePennsylvaniaUSA

Importance:Critically ill children with pre-existing mental health conditions may have an increased risk of poor health ***:We aimed to evaluate if pre-existing mental health conditions in critically ill pediatric patients would be associated with worse clinical outcomes,compared to children with no documented mental health ***:This retrospective observational cohort study utilized the TriNetX electronic health record database of critically ill subjects aged 12-18 *** were analyzed for demographics,pre-existing conditions,diagnostic,medication,procedural codes,and ***:From a dataset of 102027 critically ill children,we analyzed 1999 subjects(284[14.2%]with a pre-existing mental health condition and 1715[85.8%]with no pre-existing mental health condition).Multivariable analysis demonstrated that death within one year was associated with the presence of pre-existing mental health conditions(odds ratio 8.97[3.48-23.15],P<0.001),even after controlling for the presence of a complex chronic ***:The present study demonstrates that the presence of pre-existing mental health conditions was associated with higher odds of death within 1 year after receiving critical ***,the confidence interval was wide and hence,the findings are *** studies with a larger sample size may be necessary to evaluate the true long-term impact of children with pre-existing mental health conditions who require critical care services.

关键词： Critical care Psychiatry Psychology Public health