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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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Ponseti method treatment of neglected idiopathic clubfoot:Preliminary results of a multi-center study in Nigeria

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世界骨科杂志：英文版 2017年第8期8卷 624-630页

作者： Olayinka O Adegbehingbe Adeoye j Adetiloye Ladipo Adewole Dennis U Ajodo Nosirudeen Bello Oluwadare Esan Alex C hoover james Ior Omolade Lasebikan Owolabi Ojo Anthony Olasinde David Songden jose A Morcuende Department of Orthopedic Surgery and Traumatology Obafemi Awolowo University Gwarinpa General Hospital Federal Capital Territory Lagos State University College of Medicine Federal Medical Center Keffi Federal Medical Center Abeokuta Carver College of Medicine University of Iowa NKST Hospital Mkar National Orthopedic Hospital Federal Medical Center Owo Ekiti State Teaching Hospital

AIM To evaluate the effectiveness of the Ponseti method for initial correction of neglected clubfoot cases in multiple centers throughout *** Patient charts were reviewed through the International Clubfoot Registry for 12 different Ponseti clubfoot treatment centers and 328 clubfeet(225 patients) met inclusion criteria. All patients were treated by the method described by Ponseti including manipulation and casting with percutaneous Achilles tenotomy as *** A painless plantigrade foot was obtained in 255 feet(78%) without the need for extensive soft tissue release and/or bony *** We conclude that the Ponseti method is a safe, effective and low-cost treatment for initial correction of neglected idiopathic clubfoot presenting after walking age. Longterm follow-up will be required to assess outcomes.

关键词： Ponseti method Neglected clubfoot Nigeria Walking age

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The Disappearing Colorado River: Historic and Modern Attempts to Manage the Lifeline of the United States Southwest

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Open journal of Soil Science 2021年第11期11卷 538-566页

作者： Kenneth R. Olson james M. Lang Department of Natural Resources Urbana Illinois USA Department of Crop Sciences College of Agricultural Consumer and Environmental Sciences University of Illinois Urbana Illinois USA

Historic Native American and modern civilizations have been forcing the unstable use of the Colorado River and adjacent land resources for centuries. Much can be learned from past Native American cultures that created irrigation systems to offset low rainfall. These lessons learned can be applied to our modern civilization. We can learn a lot from their previous behavior and experiences and could apply the lessons learned to our current disappearing Colorado River situation. Little of the Colorado River water flow reaches the international border with Mexico near Yuma, Arizona. Intensive consumption, mostly in the United States, has dried up the lower 160 km of the river. Since the 1960s, the Colorado River has rarely flowed into the Gulf of California and when it does it becomes is a major international news event. The Colorado River Delta is drought prone and its headwater tributaries are a vital source of water for 40 million people. The Colorado River has whitewater rapids, canyons, and many United States National Parks. The tributary and river flow is managed by an extensive system of dams, aqueducts, and reservoirs. Most years the entire Colorado River flow is used for United States agricultural irrigation and domestic water supply purposes. The agricultural and urban needs in the United States are continuing to grow and it appears the days of Colorado River flowing into Mexico and the Gulf of California are numbered and declining every decade. The Colorado River is disappearing and restoration efforts appear to be too little too late. If the Colorado River valley is ever going to recover management lessons and failures learned from the Native Americans, including the Hohokam, must be applied. A balanced approach to water management is needed and must include aggressive conservation and efficiency measures.

关键词： Grand Canyon Hohokam Mexico-American War Gulf of California Salton Trough hoover Dam Glen Canyon Dam

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