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Tissue-specific Tregs in cancer metastasis:opportunities for precision immunotherapy

cellular & Molecular Immunology 2022年第1期19卷 33-45页

作者： Laura A.Huppert Michael D.Green Luke Kim christine chow Yan Leyfman Adil I.Daud james c.lee Division of Hematology/Oncology Department of MedicineUniversity of CaliforniaSan FranciscoSan FranciscoCAUSA Department of Radiation Oncology University of Michigan School of MedicineAnn ArborMIUSA Veterans Affairs Ann Arbor Healthcare System Ann ArborMIUSA University of california San Francisco School of MedicineSan FranciscoCAUSA Penn State college of Medicine HersheyPAUSA Parker Institute for cancer Immunotherapy San FranciscoCAUSA

Decades of advancements in immuno-oncology have enabled the development of current immunotherapies,which provide longterm treatment responses in certain metastatic cancer ***,cures remain infrequent,and most patients ultimately succumb to treatment-refractory metastatic *** insights suggest that tumors at certain organ sites exhibit distinctive response patterns to immunotherapy and can even reduce antitumor immunity within anatomically distant tumors,suggesting the activation of tissue-specific immune tolerogenic mechanisms in some cases of therapy *** immune cells known as regulatory T cells(Tregs)are present within all tissues in the body and coordinate the suppression of excessive immune activation to curb autoimmunity and maintain immune *** the high volume of research on Tregs,the findings have failed to reconcile tissue-specific Treg functions in organs,such as tolerance,tissue repair,and regeneration,with their suppression of local and systemic tumor immunity in the context of immunotherapy *** improve the understanding of how the tissue-specific functions of Tregs impact cancer immunotherapy,we review the specialized role of Tregs in clinically common and challenging organ sites of cancer metastasis,highlight research that describes Treg impacts on tissue-specific and systemic immune regulation in the context of immunotherapy,and summarize ongoing work reporting clinically feasible strategies that combine the specific targeting of Tregs with systemic cancer *** knowledge of Tregs in the framework of their tissue-specific biology and clinical sites of organ metastasis will enable more precise targeting of immunotherapy and have profound implications for treating patients with metastatic cancer.

关键词： Tissue Tregs Immunotherapy Organ-specific tolerance Metastasis cancer

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预防性中央区淋巴结清扫治疗甲状腺乳头状癌的利与弊

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中国普通外科杂志 2014年第5期23卷 567-574页

作者： Anthony R.Glover Justin S.Gundara Olov Norlén james c.lee Stan B.Sidhu 冯铁成李新营澳大利亚悉尼大学皇家北岸医院科林医学研究所肿瘤遗传学实验室澳大利亚悉尼大学皇家北岸医院内分泌外科

对甲状腺乳头状癌(PTc)的患者是否行预防性的中央区淋巴结清扫(pcND)是存在争议的。相比于其他恶性肿瘤而言,PTc患者有较好的整体生存率,但由于淋巴结的转移而导致局部复发也是治疗的一个难点。与颈侧区淋巴结转移不同,中央区淋巴结转... 详细信息

对甲状腺乳头状癌(PTc)的患者是否行预防性的中央区淋巴结清扫(pcND)是存在争议的。相比于其他恶性肿瘤而言,PTc患者有较好的整体生存率,但由于淋巴结的转移而导致局部复发也是治疗的一个难点。与颈侧区淋巴结转移不同,中央区淋巴结转移在术前评估中不易被发现,并且第1次术后如中央区的病灶复发或残留可能需再次手术治疗,但是出现手术并发症的风险将增加。由于中央区淋巴结在位置上属于甲状腺切除术的区域内,所以行pcND可以减少复发的风险及再次手术的需要,但也需要衡量患者的风险及获益。笔者将通过长期的治疗效果来讨论pcND的优势及劣势,同时也将对pcND的合理性,单或双侧pcND的指征及常规行pcND和复发再手术的比较进行讨论。分子标志物在高危患者中的应用及患者术后生存质量的研究也有所提及。

关键词：甲状腺肿瘤颈淋巴结清扫术肿瘤转移

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comparing four machine learning algorithms for household non-intrusive load monitoring

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Energy and AI 2024年第3期17卷 206-219页

作者： Thomas lee Young james Gopsill Maria Valero Sindre Eikevåg Ben Hicks University of Bristol UK

The combination of Machine Learning (ML), smart energy meters, and availability of household appliance energy profile data has opened new opportunities for Non-Intrusive Load Monitoring (NILM). However, the number of options makes it challenging in selecting optimal combinations for different energy applications, which requires studies to examine their *** paper contributes one such study that investigated four established ML approaches – K Nearest Neighbour (KNN), Support Vector Machine (SVM), eXtreme Gradient Boosting (XGBoost) and convolutional Neural Network (cNN) – and their performance in classifying appliance events from Alternating current (Ac) and Root Mean Square (RMS) energy data where the sampling frequency and training dataset set size was varied (10 Hz–1 kHz and 50–2000 examples per class, respectively). The computational expense during training, testing and storage was also assessed and evaluated with reference to real-world *** cNN classifier trained on Ac data at 500 Hz and 11,000 examples gave the best F1-score (0.989) followed by the KNN classifier (0.940). The storage size required by the cNN models was 3̃MB, which is very close to fitting on cost-effective embedded system microcontrollers. This would prevent high-rate data needing to be sent to the cloud as analysis could be performed on edge computing Internet-of-Things (IoT) devices.

关键词： NILM ML Edge computing Signal processing Smart meters

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Exposure of juvenile chinook salmon to effluent from a large urban wastewater treatment *** *** responses

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Aquaculture and Fisheries 2024年第3期9卷 355-366页

作者： Suzanne c.Ball james P.Meador c.Andrew james Jenifer K.McIntyre Washington State University School of the EnvironmentPuyallup Research and Extension Center2606 W Pioneer AvePuyallupWA98371USA Dept.of Environmental and Occupational Health Sciences School of Public Health4225 Roosevelt Way NESuite 100SeattleWA98105-6099USA University of Washington Tacoma Center for Urban Waters326 East D StreetTacomaWA98421-1801USA

Wastewater treatment plants release complex mixtures of chemicals into the aquatic environment as wastewater effluent(WWE);however,the effects of these mixtures are still poorly *** salmon(Oncorhynchus tshawytscha)are a culturally important species in the Pacific Northwest and are a vital food resource for southern resident killer whales(Orcinus orca)that are listed as‘critically endangered’under the *** Species Act(ESA).chinook populations have declined drastically in this region and have failed to show significant recovery despite regional-to-federal efforts,resulting in many populations being listed as threatened under the *** source of stress to juvenile chinook is chemical pollution from WWE during their outmigration along river corridors and residency in *** this study,we investigated effects of WWE on juvenile chinook health in a ten-day exposure to dilutions of WWE from 0.1%to 20%.At the end of the exposure,we measured endpoints associated with endocrine disruption,brain function,osmoregulation,stress,and *** to WWE significantly(α=0.1 for all analyses)induced vitellogenesis,indicating endocrine system *** saw significant reductions in plasma glucose,an indication of stress,and brain Na+/K+-ATPase(NKA)activity,an enzyme essential for neuronal ***,metabolism was affected as evidenced by altered total protein,cholesterol,and albumin in plasma,a drastic decrease in whole body lipid content,and a significant increase in visible liver *** compared contaminant concentrations in exposure water with effects concentrations from the literature for chemicals known to induce vitellogenin or inhibit brain *** most contaminants,concentrations in exposure waters were several orders of magnitude below effects concentrations in the *** exception was estrogenic hormones,which were detected at similar concentrations in this study compared to concentrations in other studies tha

关键词： Wastewater effluent chinook salmon Toxicity Sodium potassium ATPase Vitellogenin Physiology Metabolism Glucose

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Exposure of juvenile chinook salmon to effluent from a large urban wastewater treatment *** *** profiling

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Aquaculture and Fisheries 2024年第3期9卷 367-377页

作者： james P.Meador Suzanne c.Ball c.Andrew james Jenifer K.McIntyre Dept.of Environmental and Occupational Health Sciences School of Public Health4225 Roosevelt Way NESuite 100SeattleWA98105-6099USA Washington State University School of the EnvironmentPuyallup Research and Extension Center2606 W Pioneer AvePuyallupWA98371USA University of Washington Tacoma Center for Urban Waters326 East D StreetTacomaWA98421-1801USA

Targeted metabolomic analysis was conducted on juvenile chinook salmon exposed for 10 days to wastewater effluent(WWE)from a large urban treatment *** included five dilutions of WWE(20%,5.3%,1.4%,0.4%,and 0.1%)and a control with 7 replicates per *** was extracted from fish and analyzed via liquid chromatography–mass spectrometry(Lc-MS)for 361 endogenous metabolites,of which 185 were ***-versus-treatment comparisons identified several metabolites that were associated with altered biochemical pathways observed for all treatments,including several that are important for energy generation and *** altered pathways are crucial for fish health and may be an early indicator of potential adverse effects on growth,reproduction,behavior,and immune *** ocean-type chinook salmon spend several days to weeks in the nearshore estuary where they may encounter high concentrations of WWE *** are exposed to a wide range of potent pharmaceuticals,personal care products,and industrial compounds from WWE that have the potential to affect physiological homeostasis and disrupt their normal life cycle.

关键词： Wastewater effluent Metabolomics Physiology chinook salmon Pharmaceuticals Metabolic pathways Estuary

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The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

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Bone Research 2024年第2期12卷 289-301页

作者： Heeseog Kang Amy L.Strong Yuxiao Sun Lei Guo conan Juan Alec c.Bancroft Ji Hae choi chase A.Pagani Aysel A.Fernandes Michael Woodard Juhoon lee Sowmya Ramesh Aaron W.james David Hudson Kevin N.Dalby Lin Xu Robert J.Tower Benjamin Levi center for Organogenesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Plastic Surgery Department of SurgeryUniversity of MichiganAnn ArborMI 48109USA Quantitative Biomedical Research center Peter O’Donnell Jr.School of Public HealthUniversity of Texas SouthwesternDallasTX 75390USA Department of Orthopedics and Sports Medicine University of WashingtonSeattleWA 98195USA Division of chemical Biology and Medicinal chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Pathology Johns Hopkins UniversityBaltimoreMD 21218USA

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(EcM)organization and downstream processes of cell fate after musculoskeletal injury remains to be ***(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal *** andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote ***,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPcs)contributes to pathologic bone formation remain to ***,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell ***-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen EcM organizationis the most highly up-regulated biological process in *** mesenchymal cell-specific deletion of Hif1α(Hoxa11-creER^(T2);Hif1a^(fl/fl))significantly mitigated HO in ***-seq analysis of these Hoxa11-creER^(T2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of ***,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPcs is most highly impacted by HIF-1α*** a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPcssignificantly decreased osteogenic differentiation and glycolytic *** suggests that the HIF-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPc *** results suggest that the HIF-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.

关键词： metabolism skeletal aberrant

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Signaling pathways in osteogenesis and osteoclastogenesis:Lessons from cranial sutures and applications to regenerative medicine

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Genes & Diseases 2015年第1期2卷 57-68页

作者： Justin B.Maxhimer james P.Bradley Justine c.lee Division of Plastic and Reconstructive Surgery UCLA David Geffen School of MedicineCAUSA Division of Plastic and Reconstructive Surgery Temple University/St.Christopher’s Hospital for ChildrenPAUSA Division of Plastic and Reconstructive Surgery Greater Los Angeles VA Healthcare SystemUSA

One of the simplest models for examining the interplay between bone formation and resorption is the junction between the cranial *** only roughly a quarter of patients diagnosed with craniosynostosis have been linked to known genetic disturbances,the molecular mechanisms elucidated from these studies have provided basic knowledge of bone *** work has translated to methods and advances in bone tissue *** this review,we examine the current knowledge of cranial suture biology derived from human craniosynostosis syndromes and discuss its application to regenerative medicine.

关键词： craniosynostosis OPG Osteoclast RANK RANKL Tissue engineering Osteogenesis Signaling

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Synthesis of carbon nitride in potassium hydroxide molten salt for efficient uranium extraction from radioactive wastewater

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Frontiers of Environmental Science & Engineering 2024年第8期18卷 89-99页

作者： Shuang Liu Junhan Luo Daniel-james Maguire Liyuan Zheng Zhe Wang Yuexiang Lu Institute of Nuclear and New Energy Technology Tsinghua UniversityBeijing 100084China Nuclear Research Institute for Future Technology and Policy Seoul National UniversitySeoul 08826Republic of Korea Department of Earth Sciences University of CambridgeCambridge CB23EQUK The MOE Key Laboratory of Resources and Environmental System Optimization College of Environmental Science and EngineeringNorth China Electric Power UniversityBeijing 102206China

Photocatalysis-assisted removal of uranium has been proven as an effective method for the elimination of radioactive pollution from *** this work,carbon nitride materials were synthesized in potassium hydroxide(KOH)molten salt and applied to photocatalytic uranyl *** materials were confirmed to possess the triazine-s-heptazine structure by NMR,XPS and UV-Vis characterization,and exhibited a wider visible light absorption than graphitic carbon nitride(g-c_(3)N_(4)).The photocatalytic activity of the carbon nitride materials was tailored by varying the precursor mass *** carbon nitride obtained at 80%melamine as precursor(K-cN-80)exhibited the highest photocatalytic extraction ability and its photocatalytic reaction rate is 6.6 times faster than that of g-c_(3)N_(4).The influence of sacrificial agents was studied and the results showed that triethanolamine inhibited U(Ⅵ)photoreduction,but methanol can accelerate U(Ⅵ)photoreduction by consuming photogenerated *** unary KOH molten salt synthesis method has exceptional potential applications in the preparation of carbon nitrides,and the obtained products showed potential in extracting U(Ⅵ)from aqueous solutions for use in nuclear fuel industry and for U(Ⅵ)environmental pollution cleanup.

关键词： Uranium carbon nitride Molten salt Photocatalysis Radioactive wastewater

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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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Handheld bedside ultrasound in the diagnosis of myocarditis

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World Journal of Emergency Medicine 2024年第1期15卷 73-74页

作者： Frank Wheeler Robin Lahr james Espinosa Alan Lucerna Henry Schuitema Department of Emergency Medicine Rowan University School of Osteopathic MedicineStratford 08084USA Emergency Medicine Residency Program Jeff erson HealthStratford 08084USA Department of Emergency Medicine and Associate chief Medical Offi cer Stratford 08084USA

Myocarditis is a disease process that every emergency physician fears *** severity can be mild to life-threatening,and many cases are likely undetected because they are subclinical with nonspecifi c signs.[1]Subtle cardiac signs may be overshadowed by systemic symptoms of the underlying infectious ***,myalgias,lethargy,symptoms commonly associated with viral syndrome,can mask the life-threatening myocarditis that may be *** fact,in the United States Myocarditis Treatment Trial,almost 90%of patients reported symptoms consistent with a viral prodrome.[2]Ammirati et al[3]reported that 27%of patients with myocarditis had either reduced left ventricular ejection fraction,ventricular arrhythmias,or low cardiac ***,we present a case report,in which handheld point-of-care ultrasound was utilized at the bedside to aid in the critical diagnosis of *** the additional information provided through this imaging modality,this patient was able to be transferred to the appropriate tertiary care facility in an expeditious manner and receive possible defi nitive treatment.

关键词： diagnosis myocarditis Fever

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