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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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Osteoarticular lesions of the Shoulder Girdle by Hippopotamus Bite: Highly Septic lesion

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Open Journal of Orthopedics 2024年第2期14卷 114-121页

作者： jr Pierre Germain Ochou Achié Jean Régis Akobe Yao Aboh Ganyn robert Arnaud Assere Kouamé Jean-Eric Kouassi Adelaïde Aya Natacha Kouassi Ibrahim Soumahoro Zolopégué Marcel Soro Sédi loues De Randolphe Akpro Gbalé Yannick Blé Kouamé Innocent M’bra loukou Blaise Yao Bada Juste léopold NiaoréSery Koffi léopold Krah Michel Kodo Department of Orthopaedic and Traumatological Surgery Bouaké University Hospital Bouaké Ivory Coast Raoul Follereau Institute Manikro Centre Bouaké Ivory Coast

Hippopotamus bites are rare in medical consultations, despite several studies exposing their aggressive character. A case of a hippopotamus bite on the shoulder of a fisherman has been reported. In addition to the osteoarticular aspect representing a therapeutic problem, the infectious aspect was marked by sepsis, with a death in less than 48 hours. Based on this observation, a protocol for the initial management of large animal bites was submitted.

关键词： Bite Hippopotamus Septic Shock

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A review of potential conservation and fisheries benefits of breaching four dams in the lower Snake River(Washington,USA)

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Water Biology and Security 2022年第2期1卷 10-22页

作者： Adam J.Storch Howard A.Schaller Charles E.Petrosky robert l.vadas.jr. Benjamin J.Clemens Gary Sprague Norman Mercado-Silva Brett Roper Michael J.Parsley Edward Bowles robert M.Hughes Jay A.Hesse Oregon Department of Fish and Wildlife Ocean Salmon and Columbia River Program17330 Southeast Evelyn StreetClackamasOR 97015USA U.S.Fish and Wildlife Service 911 Northeast 11th AvenuePortlandOR 97232USA Idaho Department of Fish and Game 600 South Walnut StreetBoiseID 83707USA Unaffiliated OlympiaWAUSA Oregon Department of Fish and Wildlife Corvallis Research Lab28655 Hwy 34CorvallisOR 97333USA National Marine Fisheries Service 650 Capitol MallSacramentoCA 95814USA Centro de Investigacion en Biodiversidad y Conservacion Universidad Autonoma del Estado de MorelosAv.Universidad 1001Col.ChamilpaC.P.62209CuernavacaMorelosMexico National Stream and Aquatic Ecology Center U.S.Forest Service860 North 1200 EastLoganUT 84321USA Independent Fisheries Consultant 191 Sooter RoadUnderwoodWA 98651USA Oregon Department of Fish and Wildlife 4034 Fairview Industrial Drive SoutheastSalemOR 97302USA Amnis Opes Institute 2895 Southeast Glenn StreetCorvallisOR 97333USA Department of Fisheries Wildlife&Conservation Sciences104 Nash HallCorvallisOR 97331USA Nez Perce Tribe Department of Fisheries Resources Management 120 Beaver GradeLapwaiID 83540USA

Abundances of important and imperiled fishes of the Snake River Basin continue to *** assessed the rationale for breaching the four lower Snake River Basin dams to prevent complete loss of these fishes,and to maximize their likelihood of *** summarize the science surrounding Sockeye Salmon(Oncorhynchus nerka),Chinook Salmon(***),steelhead(***),Bull Trout(Salvelinus confluentus),White Sturgeon(Acipenser transmontanus),and Pacific lamprey(Entosphenus tridentatus).From this,we drew ten conclusions:(1)development of the Columbia River System(including the Snake River Basin)has converted mainstem rivers into reservoirs,altering fish behavior and survival;(2)most populations currently record their lowest abundance;(3)the Columbia River System dams reduce productivity of diadromous fishes in the highest-quality spawning grounds that could buffer against future climate dynamics;(4)past actions have done little to reduce impacts or precipitate recovery;(5)the Columbia River System constrains survival and productivity of salmon,steelhead and Bull Trout;(6)Snake River Basin salmon and steelhead remain at high extinction risk;(7)eliminating migration impediments and improving mainstem habitats are essential for maintaining genetic diversity and improving Bull Trout persistence;(8)the lower Snake River Basin dams preclude passage of adult White Sturgeon,constraining gene flow and recruitment;(9)the lower Snake River Basin dams impede dramatically passage of adult and juvenile Pacific lamprey,and(10)Snake River Basin Pacific lamprey is at high risk of *** the four lower Snake River Basin dams is an action likely to prevent extirpation and extinction of these *** from the Columbia River System can inform conservation in other impounded rivers.

关键词： Bull trout Impoundment Pacific lamprey Salmon Steelhead White sturgeon

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Envita’s Precision Cancer Care: 35-Fold Improvement in Response Rates

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Journal of Cancer Therapy 2024年第4期15卷 99-120页

作者： Sheba Goklany John C. Oertle III Ronald Matthias jr. Daniel Warren David Medina Rory Sears robert Zieve Kendra Quart Christopher Aussems Jon Moma Shannon Miller Zach Poteet Conner Coffin Courtney Middleton Erika Ware Phylicia Zarnosky Julie Nowak Winlove Suasin Daniel Conway Chad Burk Ruth Tan-lim Dino Prato Envita Medical Centers Scottsdale AZ USA

New clinical approaches are imperative beyond the widely adopted National Comprehensive Cancer Network (NCCN) guidelines, utilized by prominent cancer institutions. Cancer is the leading cause of death among individuals younger than 85 years within the United States. Despite significant technological advances, including the expenditure of hundreds of billions, treatment outcomes and overall survival have not notably improved for most types of advanced cancer over the last several decades. Over the past 24 years, Envita Medical Centers has pioneered a unique form of personalized treatment approach for late-stage and refractory cancer patients, introducing groundbreaking innovations in the field. Our integrated algorithm utilizes advanced genomics, transcriptomics, and highly tailored immunotherapy, resulting in remarkable outcome improvements. This study presents Envita’s innovative personalized treatment algorithms and examines the response outcomes of 199 late-stage cancer patients treated at Envita Medical Centers over a two-year period. Compared to standard of care and palliative chemotherapy, Envita’s treatment demonstrated a remarkable 35-fold improvement in overall response rates (Figure 1). Moreover, 88% of the patients, the majority presenting with Stage 3 or 4 cancer, experienced a 43-fold improvement in quality of life with minimal side effects, as compared to standard of care chemotherapy and palliative care. This revolutionary success is attributed to Envita’s personalized therapeutic algorithms, which incorporate customized immunotherapy. Envita’s precision care approach has also achieved a 100% better response rate compared to over 65 global chemotherapy clinical trials with more than 2700 patients. The results from this study suggest that a wider utilization of Envita’s personalized approach can significantly benefit patients with late-stage and refractory cancer.

关键词： Envita Medical Centers late-stage Cancer Overall Response Rate Quality of life Circulating Tumor Cells (CTCs) Mutant Allele Frequency (MAF) Precision Care

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language development : an introduction / robert E. Owens, jr. 5th ed.

Language development : an introduction / Robert E. Owens, Jr...

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2001年

作者： robert E. Owens jr.

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Impact of a physician-supervised exercise-nutrition program with testosterone substitution in partial androgen-deficient middle-aged obese men

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Journal of Geriatric Cardiology 2011年第4期8卷 201-206页

作者： Ernst R Schwarz robert D Willix jr Cenegenics Education and Research Foundation Las Vegas and Heart Institute of Southern CaliforniaBeverly Hills348 S Oakhurst DrBeverly HillsCA 90212USA

Background Partial androgen deficiency syndrome in the aging male is associated with signs of aging such as a development of abdominal obesity,sexual dysfunction,increase body fat,weight gain and the development of cardiac *** We assessed the outcome of a commercially available physician supervised nutrition and exercise program with concomitant testosterone replacement therapy in middle age obese men with partial androgen deficiency in order to reduce cardiac risks *** Fifty-six self referred men without diabetes mellitus,hypertension,or cardiovascular disease(ages 52.3±7.8 years)were randomly selected from a large *** weight,body fat composition,fasting glucose,hemoglobin A1c and fasting lipid levels,as well as free and total testosterone levels were *** patients were assessed and followed 6–18 months after initiation of the *** program consisted of a low glycemic load balanced nutrition diet,a recommended structured daily exercise program of 30–60 minutes,as well as once to twice weekly intramuscular testosterone injections(113.0±27.8 mg).Results At follow up,weight was reduced from 233.9±30.0 pounds(lbs)to 221.3±25.1 lbs(Pl body fat was 27.1%±5.2%vs.34.3%±5.7%at baseline(Plucose was reduced from 95.3±14.4 mg/dl to 87.5±12.6 mg/dl(Pl cholesterol was reduced from 195.4±33.0 mg/dl to 172.7±35.0 mg/dl(Plinically significant adverse events were *** Testosterone replacement therapy in middle aged obese men with partial androgen deficiency appeared safe and might have promoted the effects of a weight reduction diet and daily exercise program as long as an adequate physician supervision and follow up was *** combination therapy significantly reduced coronary risk factors such as glucose intolerance and hyperlipidemia.

关键词： aging heart disease androgen deficiency testosterone

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Assemblage-based biomonitoring of freshwater ecosystem health via multimetric indices:A critical review and suggestions for improving their applicability

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Water Biology and Security 2022年第3期1卷 28-42页

作者： robert l.vadas.jr. robert M.Hughes Yeon Jae Bae Min Jeong Baek Orestes Carlos Bello Gonzáles Marcos Callisto Débora ReisdeCarvalho Kai Chen Maria T.Ferreira Pablo Fierro Jon S.Harding Dana M.Infante C.J.Kleynhans Diego R.Macedo Isabela Martins Norman Mercado Silva Nabor Moya Susan J.Nichols Paulo S.Pompeu Renata Ruaro Deborah R.O.Silva R.Jan Stevenson Bianca de Freitas Terra Christa Thirion Douglas Ticiani lizhu Wang Chris O.Yoder 2909 Boulevard Rd SEOlympiaWA98501-3971USA Amnis Opes Institute 2895 SE GlennCorvallisOR97333USA Department of Fisheries Wildlife&Conservation SciencesOregon State UniversityCorvallisOR97331USA Division of Environmental Science&Ecological Engineering Korea University145 Anam-roSeongbuk-guSeoul02841South Korea National Institute of Biological Resources Ministry of Environment42 Hwangyeong-roSeo-guIncheon22689South Korea Centro de Investigacion en Biodiversidad y Conservacion Universidad Autonoma del Estado de Morelos1001Col.ChamilpaC.P62209CuernavacaMorelosMexico Departamento de Genética Ecologia e EvoluçaoInstituto de Ciências BiologicaUniversidade Federal de Minas GeraisAvenida Ant^onio Carlos 6627CEP31270-901Belo HorizonteMGBrazil Departamento de Ecologia e Conservaçao Universidade Federal de Lavras37200-900LavrasMGBrazil State Key laboratory of Marine Resource Utiliization in South China Sea Hainan UniversityHaikou570228China Forest Research Centre&Associate laboratory TERRA University of LisbonTapada da Ajuda1349-017LisbonPortugal Instituto de Ciencias Marinas y limnologicas Universidad Austral de ChileValdiviaChile School of Biological Sciences University of CanterburyPrivate Bag 4800Christchurch8140New Zealand Department of Fisheries&Wildlife Michigan State University1405 South Harrison Road#318East LansingMI48823USA Department of Water Affairs and Forestry(retired) 8th Avenue 771Wonderboom South0084PretoriaSouth Africa Departamento de Geografia Instituto de GeociênciasUniversidade Federal de Minas GeraisAvenida Antônio Carlos 6627CEP31270-901Belo HorizonteMGBrazil Instituto Guaicuy 109 Rua BrasopolisBelo HorizonteMG31150-170Brazil Centro de Investigación en Biodiversidad y Conservación Universidad Autónoma del Estado de MorelosAvenida Universidad 1001Col.ChamilpaC.P.62209CuernavacaMorelosMexico Instituto Experimental de Biología Universidad San Francisco Xavier de ChuquisacaSucreBolivia Centre for Applied Water Science Un

Freshwater biota are more comprehensive and direct indicators of biological impacts,and more meaningful to the public than water quality or physical habitat *** biotic data and the multiple biological indicators developed from them offer a much richer array of data for assessing the impacts of pollution controls than a limited set of physical or chemical *** recent decades,assemblage-based assessments by ecologists,environmental scientists,and water quality agencies have been employed globally for determining the condition of,and threats to,freshwater ecosystems.A key step in this advance has been the development of multimetric indices(MMIs)or indices of biotic integrity(IBIs)based on quantitative assessments of algae,macrophyte,macroinvertebrate,fish or riparian bird *** Europe,where biological assemblages are mandated for assessing freshwater ecosystem health,many indices are ***,the proliferation of MMIs globally has not always occurred through the application of rigorous study designs and monitoring protocols,nor have they always effectively incorporated functional metrics,stressor assessments,and statistical ***,in this review,we discuss eleven major concerns with the development and application(including logistical limitations)of multimetric indicators based on freshwater biota to encourage more rigorous and widely applicable(transferable)MMI use and ***,our concerns focus on reference conditions;sampling effort,methods,and season;trophic guild definition;metric comprehensiveness,options,screening and scoring;and MMI *** could also benefit from increased attention to ecological mechanisms and metric development,to further improve our understanding of anthropogenic impacts as well as rehabilitation effects on freshwater ecosystems *** closer attention to study designs,ecological mechanisms and metric development should further improve our understa

关键词： IBI MMI Fish Macroinvertebrates Algae Streams Rivers lakes Wetlands Biological monitoring

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Andropause and the development of cardiovascular disease presentationmore than an epi-phenomenon

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Journal of Geriatric Cardiology 2011年第1期8卷 35-43页

作者： Emst R. Schwarz Anita Phan robert D. Willix jr Cedars Sinai Heart Institute Cedars Sinai Medical Center 8700 Beverly Boulevard Suite 6215 Los Angeles CA 90048 USA Cenegenics Medical Institute 851 Rampart Blvd. Las Vegas NV 89145 USA

Andropause 指男荷尔蒙的概括衰落，包括在中年、老化的人的睾丸激素和 dehydroepiandrosterone。在荷尔蒙的这衰落在身体作文与象消沉，性欲的损失，性机能障碍，和变化那样的变化被联系了。老化与许多伴随物被联系了疾病，特别地心血... 详细信息

Andropause 指男荷尔蒙的概括衰落，包括在中年、老化的人的睾丸激素和 dehydroepiandrosterone。在荷尔蒙的这衰落在身体作文与象消沉，性欲的损失，性机能障碍，和变化那样的变化被联系了。老化与许多伴随物被联系了疾病，特别地心血管的疾病，并且尽管 andropause 被相关到老化，在雄激素的减小和象动脉粥样硬化和心失败那样的长期的疾病的发展之间的一种原因的关系一直不是还信服地建立了。在另一方面，增加数据出现了那在心血管的疾病前进上揭示了雄激素的底层的效果。作为一个例子，睾丸激素的底层被连接了到冠的动脉疾病的更高的发生。被用于 andropausal 人减轻男经绝期的症状的荷尔蒙代替治疗是否能停止心血管的疾病的前进，仍然保持争论地讨论了，首先由于设计得好的、使随机化的控制试用的缺乏。至少为症状改进，在 andropausal 人的雄激素代替治疗的使用可以临床上被显示，并且与适当管理并且列在后面在上面可以证明关于在更高的年龄的心血管的健康的完整的保藏有益。

关键词：心血管疾病男性雄激素替代疗法 EPI 动脉粥样硬化冠状动脉疾病随机对照试验雄性激素

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North American Tunneling 2012 Proceedings Har/Cdr

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2012年

作者： Matthew Fowler robert Palermo robert Pintabona Michael Smithson jr

ISBN: (纸本)9780873353618

North American Tunneling is the premier forum to discuss new trends and developments in underground construction in North America. With every conference, the number of attendees and breadth of topics has grown. This collection of papers presented at the highly regarded 2012 North American Tunneling Conference records many of the tremendous advances that have been made in the delivery of more cost-effective and less disruptive solutions to the underground infrastructure needs of North America. With more than 100 papers from engineers, contractors, owners, suppliers, manufacturers, and others in the industry, the proceedings documents the progress being made in the methods, practices, and technologies used in underground infrastructure. The authors share the latest case histories, expertise, lessons learned, and real-world applications from around the globe on a wide range of topics including Better geologic characterization methods for predicting TBM advance rates, Corrosion protection for sewer tunnels, Tunnel ventilation design, TBM modifi cations for the world’s second deepest civil works tunnel, Alternative project delivery approaches and risk allocation, and Structural designs for large highway tunnels. Whether it is Panama’s first wastewater tunnel, TBMs for mine development in Montana, tunnel excavation assessment in Seattle, marine site investigation in Ireland, design of an underground line in Berlin, groundwater infiltration reduction in Atlanta, storm tunnel emergency rehabilitation in Minneapolis, or blasting parameters in Manhattan, you will learn about the latest projects and practices in this ever-changing industry

关键词： proceedings tunneling american north

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Spatial literary Studies in China

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文艺理论研究 2023年第3期 107-107页

作者：方英 robert T.Tally jr 不详

本书着眼于向国际学术界展示中国“文学空间研究”的大致现状、前沿探索和重要成果,突出了中国学者在这个领域的理论、话语建构和批评模式探索,彰显了中国立场与自信;兼顾中外、古今理论资源和文学分析,形成了中、西文学研究的对话与互... 详细信息

本书着眼于向国际学术界展示中国“文学空间研究”的大致现状、前沿探索和重要成果,突出了中国学者在这个领域的理论、话语建构和批评模式探索,彰显了中国立场与自信;兼顾中外、古今理论资源和文学分析,形成了中、西文学研究的对话与互补,具有一定程度的历史纵深和地理广度;包括理论研究、概念梳理、文本分析、文学史重构、数字地图、人文地理等多种角度,基本上勾勒出中国文学空间研究的主要轮廓。

关键词：文学空间文学史重构话语建构人文地理文本分析数字地图前沿探索概念梳理

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