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Therapeutics to harness the immune microenvironment in multiple myeloma

Cancer Drug Resistance 2022年第3期5卷 647-661页

作者： james j.Ignatz-Hoover james j.driscoll University Hospitals Seidman Cancer CenterClevelandOH 44106USA Department of Biochemistry Case Western Reserve UniversityClevelandOH 44106USA Hematopoietic and Immune Cancer Biology Program Case Comprehensive Cancer CenterCase Western Reserve UniversityClevelandOH 44106USA

Multiple myeloma(MM)remains an incurable,genetically heterogeneous disease characterized by the uncontrolled proliferation of transformed plasma cells nurtured within a permissive bone marrow(BM)*** therapies leverage the unique biology of MM cells and target the immune microenvironment that drives tumor growth and facilitates immune *** inhibitors and immunomodulatory drugs were initially introduced to complement and have now supplanted cytotoxic chemotherapy as frontline anti-myeloma ***,monoclonal antibodies,bispecific antibodies,and chimeric antigen receptor T cells were developed to revamp the immune system to overcome immune suppression and improve patient *** current MM therapies have markedly extended patient survival,acquired drug resistance inevitably emerges and drives disease *** logical progression for the next generation of MM therapies would be to design and validate agents that prevent and/or overcome acquired resistance to *** complex BM microenvironment promotes resistance to both current anti-myeloma agents and emerging *** cells are intertwined with a complex BM immune microenvironment that contributes to the development of adaptive drug ***,we describe recently FDA-approved and investigational anti-myeloma agents that directly or indirectly target the BM microenvironment to prevent or overcome drug *** effects of anti-myeloma agents may foster the development of rationally-designed drug cocktails that prevent BM-mediated resistance to immunotherapies.

关键词： Multiple myeloma drug resistance proteasome inhibitors immunomodulators immunotherapeutics adaptive resistance bone marrow microenvironment

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An analytical model to estimate the time delay to reach spontaneous ignition considering heat loss in oil reservoirs

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Petroleum Science 2024年第4期21卷 2469-2474页

作者： james j.Sheng Er-Long Yang College of Petroleum Engineering Northeast Petroleum University

During air injection into an oil reservoir, an oxidation reaction generates some heat to raise the reservoir temperature. When the reservoir temperature reaches an ignition temperature, spontaneous ignition occurs. There is a time delay from the injection to ignition. There are mixed results regarding the feasibility of spontaneous ignition in real-field projects and in laboratory experiments. No analytical model is available in the literature to estimate the oxidation time required to reach spontaneous ignition with heat *** paper discusses the feasibility of spontaneous ignition from theoretical points and experimental and field project observations. An analytical model considering heat loss is proposed. Analytical models with and without heat loss investigate the factors that affect spontaneous ignition. Based on the discussion and investigations, we find that it is more difficult for spontaneous ignition to occur in laboratory experiments than in oil reservoirs; spontaneous ignition is strongly affected by the initial reservoir temperature, oil activity, and heat loss; spontaneous ignition is only possible when the initial reservoir temperature is high, the oil oxidation rate is high, and the heat loss is low.

关键词： Spontaneous ignition Time delay Air injection Heat loss Low temperature oxidation Combustion

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Evaluating reservoir suitability for large-scale hydrogen storage:A preliminary assessment considering reservoir properties

Energy Geoscience

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Energy Geoscience 2024年第4期5卷 198-211页

作者： Chinedu j.Okere james j.Sheng Chinedu Ejike Bob L.Herd Department of Petroleum Engineering Texas Tech UniversityLubbockTX79409United States Mewbourne School of Petroleum and Geological Engineering University of OklahomaOK73019United States

With rising demand for clean energy,global focus turns to finding ideal sites for large-scale underground hydrogen storage(UHS)in depleted petroleum reservoirs.A thorough preliminary reservoir evaluation before hydrogen(H_(2))injection is crucial for UHS success and *** criteria for UHS often emphasize economics and chemistry,neglecting key reservoir *** study introduces a comprehensive framework for the reservoir-scale preliminary assessment,specifically tailored for long-term H_(2) storage within depleted gas *** evaluation criteria encompass critical components,including reservoir geometry,petrophysical properties,tectonics,and formation *** illustrate the practical application of this approach,we assess the Barnett shale play reservoir *** assessment unfolds through three key stages:(1)A systematic evaluation of the reservoir's properties against our comprehensive screening criteria determines its suitability for H_(2) storage.(2)Using both homogeneous and multilayered gas reservoir models,we explore the feasibility and efficiency of H_(2) *** phase involves an in-depth examination of reservoir behavior during the injection stage.(3)To enhance understanding of UHS performance,sensitivity analyses investigate the impact of varying reservoir dimensions and injection/production *** findings reveal the following:(a)Despite potential challenges associated with reservoir compaction and aquifer support,the reservoir exhibits substantial promise as an H_(2) storage site.(b)Notably,a pronounced increase in reservoir pressure manifests during the injection stage,particularly in homogeneous reservoirs.(c)Furthermore,optimizing injection-extraction cycle efficiency can be achieved by augmenting reservoir dimensions while maintaining a consistent *** ensure a smooth transition to implementation,further comprehensive investigations are advised,including experimental and numerical studies to address

关键词： Site selection Underground hydrogen storage Preliminary evaluation Depleted petroleum reservoirs Reservoir assessment

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Insm1:orchestrating cellular mimicry in the thymus medulla

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Cellular & Molecular Immunology 2024年第4期21卷 414-416页

作者： K.D.james j.E.Cowan UCL Institute of Immunity and Transplantation The Pears BuildingRowland Hill StreetLondonNW32PPUK

The thymus is the primary production site for a functional and self-tolerant T-cell *** establishment of immune tolerance is mediated by the generation and presentation of tissue-restricted self-antigens(TRAs)by medullary thymic epithelial cells(mTECs),which screen T-cell receptors for self-reactivity to eliminate autoreactive T *** studies have extended our understanding of mTEC heterogeneity by examining the mechanisms by which mTECs mimic the peripheral self[1].

关键词： medullary eliminate restricted

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What diameter?What height?Influence of measures of average tree size on area-based allometric volume relationships

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Forest Ecosystems 2024年第1期11卷 100-109页

作者： Yilin Wang john A.Kershaw Mark j.Ducey Yuan Sun james B.McCarter Integrated Forest Mensuration and Systems Analysis Laboratory Faculty of Forestry and Environmental ManagementUniversity of New BrunswickFrederictonNBCanada Department of Natural Resources and the Environment University of New HampshireDurhamNHUSA College of Forestry Nanjing Forestry UniversityNanjing210037China Scientific Programmer RayonierYuleeFLUSA

Volume is an important attribute used in many forest management *** from 83 fixed-area plots located in central New Brunswick,Canada,are used to examine how different measures of stand-level diameter and height influence volume prediction using a stand-level variant of Honer's(1967)volume *** density was included in the models(Volume=f(Diameter,Height,Density))choice of diameter measure was more important than choice of height *** density was not included(Volume=f(Diameter,Height)),the opposite was *** models with density included,moment-based estimators of stand diameter and height performed better than all other *** models without density,largest tree estimators of stand diameter and height performed better than other *** overall best equation used quadratic mean diameter,Lorey's height,and density(root mean square error=5.26 m^3·ha^(-1);1.9%relative error).The best equation without density used mean diameter of the largest trees needed to calculate a stand density index of 400 and the mean height of the tallest 400 trees per ha(root mean square error=32.08 m^(3)·ha^(-1);11.8%relative error).The results of this study have some important implications for height subsampling and LiDAR-derived forest inventory analyses.

关键词： Allometric relationships Stand structure Volume estimation Stand-level attributes

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Radiofrequency ablation versus microwave ablation for colorectal liver metastases:long-term results of a retrospective cohort surgical experience

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Hepatobiliary Surgery and Nutrition 2024年第5期13卷 759-770,I0001页

作者： Ali Gunduz Sarioglu Chase j.Wehrle Ege Akgun Arturan Ibrahimli james F.Bena Eren Berber Department of Endocrine Surgery Cleveland ClinicClevelandOHUSA Department of General Surgery Cleveland ClinicClevelandOHUSA Department of Quantitative Health Sciences Cleveland ClinicClevelandOHUSA

Background:Ablation is an alternative treatment modality for selected patients with colorectal liver metastases(CRLMs).Although initially widely performed via radiofrequency ablation(RFA),more recently,microwave ablation(MWA)is being preferred due to its perceived superiority in creating the ablation *** aim of this study is to compare the long-term efficacy of these two modalities performed ***:Patients undergoing surgical liver ablation from 2005-2023 at a tertiary center by a single surgeon for CRLM were included in a retrospective institutional review board-approved *** were compared using Wilcoxon,Chi-square,Kaplan-Meier,and Cox multivariate regression *** data are presented as median(interquartile range).Results:There were a total of 242 *** RFA was done in 121 patients with 303 lesions and laparoscopic MWA in 121 patients with 300 *** was no difference between the groups regarding operative time(161 vs.147 minutes,respectively,P=0.4),perioperative morbidity(3%vs.8%,respectively,P=0.2)or hospital stay(1 vs.1 day,P=0.05).Local recurrence(LR)per lesion with at least 1 year of imaging follow-up was 29%in the RFA and 13%in the MWA group(P<0.001).Based on univariate survival analysis,tumor size,blood vessel proximity,ablation margin,and ablation modality were independent predictors of *** control these variables,direct matching was *** cohort included 189 ***-Meier analysis of these cohorts showed increased LR-free survival in the MWA group *** RFA group(P=0.005).Conclusions:This large study confirms our initial observation that local tumor control rate is better after MWA ***.

关键词： Colorectal cancer liver metastasis liver ablation radiofrequency ablation(RFA) microwave ablation(MWA) local recurrence(LR)

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Outcomes following minimally invasive dorsal cheilectomy for hallux rigidus:A systematic review

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World journal of Orthopedics 2024年第6期15卷 585-592页

作者： Katherine Esser james j Butler Mackenzie Roof Nathaniel P Mercer Michael C Harrington Alan P Samsonov Andrew j Rosenbaum john G Kennedy Department of Orthopaedic Surgery University of Toledo Medical Center University of Toledo College of Medicine and Life SciencesToledoOH 43614United States Department of Orthopedic Surgery NYU Langone HealthNew YorkNY 10002United States Department of Orthopedic Surgery Albany Medical CenterAlbanyNY 12208United States

BACKGROUND Cheilectomy of the 1^(st)metatarsophalangeal joint(MTPj)is one of the most common procedures for the management of hallux ***,there is no consensus regarding outcomes following minimally invasive dorsal cheilectomy(MIDC)for the management of hallux *** To evaluate outcomes following MIDC for the management of hallux *** During November 2023,the PubMed,EMBASE and Cochrane Library databases were systematically reviewed to identify clinical studies examining outcomes following MIDC for the management of hallux *** Six studies were *** total,348 patients(370 feet)underwent MIDC for hallux rigidus at a weighted mean follow-up of 37.9±16.5 *** distribution of patients by Coughlin and Shurna's classification was recorded in 4 studies as follows:Ⅰ(58 patients,27.1%),Ⅱ(112 patients,52.3%),Ⅲ(44 patients,20.6%).Three studies performed an additional 1^(st)MTPj arthroscopy and debridement following *** intra-articular bone debris was observed in 100%of patients in 1 *** weighted mean American orthopedic foot and ankle society score improved from a preoperative score of 68.9±3.2 to a postoperative score of *** complication rate was 8.4%,the most common of which was persistent joint pain and ***-two failures(8.7%)were ***-three secondary procedures(8.9%)were performed at a weighted mean time of 8.6±3.2 months following the index *** This systematic review demonstrated improvements in subjective clinical outcomes together with a moderate complication rate following MIDC for the management of hallux rigidus at short-term follow-up.A moderate reoperation rate at short-term follow-up was *** marked heterogeneity between included studies and paucity of high quality comparative studies limits the generation of any robust conclusions.

关键词： Minimally invasive dorsal cheilectomy Hallux rigidus The first metatarsophalangeal joint Cheilectomy Minimally invasive surgery

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The risk of prostate cancer on incidental finding of an avid prostate uptake on 2-deoxy-2-[^(18)F]fluoro-D-glucose positron emission tomography/computed tomography for non-prostate cancer-related pathology:A single centre retrospective study

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Asian journal of Urology 2024年第1期11卷 33-41页

作者： Anthony Franklin Troy Gianduzzo Boon Kua David Wong Louise McEwan james Walters Rachel Esler Matthew j.Roberts Geoff Coughlina john W.Yaxley Department of Urology The Wesley HospitalBrisbaneQLDAustralia Wesley Medical Research BrisbaneQLDAustralia School of Medicine The University of QueenslandBrisbaneQLDAustralia Department of Radiology Wesley Medical ImagingBrisbaneQLDAustralia Department of Urology Royal Brisbane and Women's HospitalBrisbaneQLDAustralia

Objective:To review the risk of prostate cancer(PCa)in men with incidentally reported increased intraprostatic uptake at 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography(18F-FDG PET/CT)ordered at Department of Urology,The Wesley Hospital,Brisbane,QLD,Australia for non-PCa related ***:Retrospective analysis of consecutive men between August 2014 and August 2019 presenting to a single institution for 18F-FDG PET/CT for non-prostate related conditions was *** were classified as benign,indeterminate,or malignant depending of the results of prostate-specific antigen(PSA),PSA velocity,biopsy histopathology,and three-Tesla(3 T)multiparametric MRI(mpMRI)Prostate Imaging Reporting and Data System score,or gallium-68-prostate-specific membrane antigen(68Ga-PSMA)PET/CT ***:Three percent(273/9122)of men demonstrated 18F-FDG avidity within the ***-five percent(231/273)were further investigated,including with PSA tests(227/231,98.3%),3 T mpMRI(68/231,29.4%),68Ga-PSMA PET/CT(33/231,14.3%),and prostate biopsy(57/231,24.7%).Results were considered benign in 130/231(56.3%),indeterminate in 31/231(13.4%),and malignant in 70/231(30.3%).PCa was identified in 51/57(89.5%)of the men who proceeded to biopsy,including 26/27(96.3%)men with Prostate Imaging Reporting and Data System scores 4-5 mpMRI and six men with a positive 68Ga-PSMA PET/*** most common Gleason score on biopsy was greater than or equal to 4+5(14/51,27.5%).68Ga-PSMA PET/CT was concordant with the 18F-FDG findings in 26/33(78.8%).All 13 men with a positive concordant 18F-FDG,3 T mpMRI,and 68Ga-PSMA PET/CT had PCa on *** was no statistically significant difference in the 18F-FDG maximum standardized uptake value between the benign or malignant groups(5.7 vs.6.1;p=0.580).Conclusion:In this study,after an incidental finding of an avid intraprostatic lesion on 18F-FDG PET/CT,70 of the 231 cases(30.3%;0.8%of the entire cohort)had results c

关键词： Prostatecancer Positionemission tomography Multiparametric magneticresonance imaging Prostatebiopsy

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Ranking environmental and edaphic attributes driving soil microbial community structure and activity with special attention to spatial and temporal scales

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mLife 2024年第1期3卷 21-41页

作者： Vadakattu V.S.R.Gupta james M.Tiedje CSIRO Agriculture&Food UrrbraeSouth AustraliaAustralia Centre for Microbial Ecology Michigan State UniversityEast LansingMichiganUSA

The incredibly complex soil microbial communities at small scales make their analysis and identification of reasons for the observed structures *** community structure is mainly a result of the inoculum(dispersal),the selective advantages of those organisms under the habitat-based environmental attributes,and the ability of those colonizers to sustain themselves over *** soil is protective,and its microbial inhabitants have long adapted to varied soil conditions,significant portions of the soil microbial community structure are likely ***,a substantial portion of the community will not correlate to often measured soil *** suggest that the drivers be ranked on the basis of their importance to the fundamental needs of the microbes:(i)those that supply energy,i.e.,organic carbon and electron acceptors;(i)environmental effectors or stressors,i.e.,pH,salt,drought,and toxic chemicals;(ii)macro-organism associations,i.e.,plants and their seasonality,animals and their fecal matter,and soil fauna;and(iv)nutrients,in order,N,P,and probably of lesser importance,other micronutrients,and *** relevance of drivers also varies with spatial and time scales,for example,aggregate to field to regional,and persistent to dynamic populations to transcripts,and with the extent of phylogenetic difference,hence phenotypic differences in organismal *** present a summary matrix to provide guidance on which drivers are important for particular studies,with special emphasis on a wide range of spatial and temporal scales,and illustrate this with genomic and population(rRNA gene)data from selected studies.

关键词： abundance community structure diversity functional microbiome microorganisms

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Lipid nanoparticles deliver mRNA to the blood-brain barrier

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Nano Research 2024年第10期17卷 9126-9134页

作者： Yanina Kuzminich Avraham Shakked Randi Calkins Sebastian Rudden Camille jones jessie Doan Bora jang Elisa Schrader Echeverri Ryan Zenhausern Liming Lian David Loughrey Hannah E.Peck Rachelle Wiese Dorothy Koveal Philip j.Santangelo james E.Dahlman George C.Woodruff School of Mechanical Engineering Georgia Institute of TechnologyAtlantaGA 30332USA Parker H.Petit Institute for Bioengineering and Biosciences Georgia Institute of TechnologyAtlantaGA 30332USA Wallace H.Coulter Department of Biomedical Engineering Emory University School of Medicine and Georgia Institute of TechnologyAtlantaGA 30332USA

Lipid nanoparticles(LNPs)have delivered RNA to hepatocytes in patients after intravenous *** clinical data support efforts to design LNPs that transfect cells in the central nervous system(CNS).However,delivery to the CNS has been difficult,in large part because quantifying on-target delivery alongside common off-target cell types in adult mice remains *** we report methods to isolate different cell types from the CNS,and subsequently present mRNA delivery readouts using a liver-detargeted *** data suggest that LNPs without targeting ligands can transfect cerebral endothelial cells in mice after intravenous *** the difficulty of crossing the blood-brain barrier,they also underscore the value of quantifying delivery in the CNS with cell-type resolution instead of whole-tissue resolution.

关键词： lipid nanoparticle mRNA nanomedicine central nervous system blood-brain barrier

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