82 research outputs found
Investigating Homology between Proteins using Energetic Profiles
- Author
- A Pascual-Garcia
- AG Murzin
- AJ Oakley
- AL Lee
- AL Lehninger
- AR Fersht
- C Sander
- CB Anfinsen
- CC Huang
- CD Mol
- CM Wood
- CR Babu
- D Kern
- DM Ford
- DR Bickel
- DW Li
- F Poy
- G Hernandez
- G Spraggon
- H Pan
- J Vertrees
- J Vertrees
- J Vertrees
- J Vertrees
- JA D'Aquino
- James O. Wrabl
- JB Thoden
- JB Thoden
- JD Dunitz
- JF Andersen
- JM Chandonia
- JO Wrabl
- JO Wrabl
- JO Wrabl
- JS Milne
- K Lim
- K Natarajan
- K Sharp
- KA Henzler-Wildman
- KY Hwang
- L Holm
- L Liu
- L Swint-Kruse
- LN Kinch
- M Morra
- N Tokuriki
- NV Grishin
- O Jardetzky
- PA Alexander
- PA Alexander
- PA Alexander
- R Kolodny
- R Li
- R Lumry
- R Thom
- RI Sadreyev
- RR Krug
- SA Larson
- SJ Benkovic
- SK Katti
- SS Taylor
- ST Whitten
- SW Englander
- T Hamma
- T Liu
- TL Creighton
- TP Schrank
- V Alva
- V Guillet
- Vijay S. Pande
- Vincent J. Hilser
- VJ Hilser
- VJ Hilser
- VJ Hilser
- VJ Hilser
- W Kabsch
- W Kabsch
- WH Press
- X Tao
- Y Bai
- Y Papanikolau
- Publication venue
- Public Library of Science
- Publication date
- 01/03/2010
- Field of study
Accumulated experimental observations demonstrate that protein stability is often preserved upon conservative point mutation. In contrast, less is known about the effects of large sequence or structure changes on the stability of a particular fold. Almost completely unknown is the degree to which stability of different regions of a protein is generally preserved throughout evolution. In this work, these questions are addressed through thermodynamic analysis of a large representative sample of protein fold space based on remote, yet accepted, homology. More than 3,000 proteins were computationally analyzed using the structural-thermodynamic algorithm COREX/BEST. Estimated position-specific stability (i.e., local Gibbs free energy of folding) and its component enthalpy and entropy were quantitatively compared between all proteins in the sample according to all-vs.-all pairwise structural alignment. It was discovered that the local stabilities of homologous pairs were significantly more correlated than those of non-homologous pairs, indicating that local stability was indeed generally conserved throughout evolution. However, the position-specific enthalpy and entropy underlying stability were less correlated, suggesting that the overall regional stability of a protein was more important than the thermodynamic mechanism utilized to achieve that stability. Finally, two different types of statistically exceptional evolutionary structure-thermodynamic relationships were noted. First, many homologous proteins contained regions of similar thermodynamics despite localized structure change, suggesting a thermodynamic mechanism enabling evolutionary fold change. Second, some homologous proteins with extremely similar structures nonetheless exhibited different local stabilities, a phenomenon previously observed experimentally in this laboratory. These two observations, in conjunction with the principal conclusion that homologous proteins generally conserved local stability, may provide guidance for a future thermodynamically informed classification of protein homology
Contemporary experience with high-dose interleukin-2 therapy and impact on survival in patients with metastatic melanoma and metastatic renal cell carcinoma
- Author
- A Hauschild
- Ajjai Alva
- Asim Amin
- B Escudier
- BI Rini
- BI Rini
- Brendan Curti
- C Robert
- C Robert
- C Robert
- C Robert
- David F. McDermott
- DF McDermott
- DY Heng
- EM Allen Van
- FD Birkhauser
- FS Hodi
- G Fyfe
- GA Daniels
- GA McArthur
- Gerald Miletello
- Gregory A. Daniels
- H Shi
- HL Kaufman
- Hong Hua
- Howard L. Kaufman
- J Larkin
- James N. Lowder
- Janice P. Dutcher
- John M. Kirkwood
- Joseph I. Clark
- K Trunzer
- KT Flaherty
- M Hanzly
- MA Morse
- MA Postow
- Mayer Fishman
- MB Atkins
- Michael A. Morse
- Michael K. K. Wong
- Neeraj Agarwal
- O Hamid
- R Payne
- R Siegel
- Ralph J. Hauke
- Rene Gonzalez
- RI Fisher
- RJ Motzer
- RJ Motzer
- Sandra Aung
- Sanjiv S. Agarwala
- SL Topalian
- Theodore F. Logan
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Effects of surface application of calcium-magnesium silicate and gypsum on soil fertility and sugarcane yield
- Author
- ADAMS F
- ALCARDE J.A
- ALVA A.K
- ALVAREZ V. V.H
- AMARAL A.S
- CAIRES E.F
- CAIRES E.F
- CAIRES E.F
- CAIRES E.F
- CAIRES E.F
- Carlos Alexandre Costa Crusciol
- CARVALHO J.M
- CARVALHO R
- CARVALHO-PUPATTO J.G
- CASAGRANDE J.C
- CASAGRANDE J.C
- CASTRO G.S.A
- CORREA J.C
- CRUSCIOL C.A.C
- DATNOFF E
- FASSBENDER H.W
- FERNANDES A.C
- ILER R.K
- JACKSON M.L
- James Mabry McCray
- KORNDÖRFER G.H
- MALAVOLTA E
- MORELLI S.L
- OATES K.M
- OLIVEIRA E.L
- OLIVEIRA L.A
- OLMOS I.L.J.
- Otavio Bagiotto Rossato
- PAVAN M
- PRADO R.M
- PRADO R.M
- PULZ A.L
- QUAGGIO J.A
- Raffaella Rossetto
- RAIJ B.van
- RAIJ B.van
- RAIJ B.van
- REEVE N.G
- Rodrigo Foltran
- ROSOLEM C.A
- SILVA N.M
- SORATTO R.P
- SORATTO R.P
- SPIRONELLO A
- TRIVELIN P.C.O
- VITTI G.C
- VON UEXKÜLL H.R
- WINSLOW M.D
- ZAMBROSI F.C.B
- Publication venue
- 'FapUNIFESP (SciELO)'
- Publication date
- Field of study
Synergistic combination of cytotoxic chemotherapy and cyclin-dependent kinase 4/6 inhibitors in biliary tract cancers
- Author
- Abdelrahman Amro M
- Ahn Daniel H
- Alva-Ruiz Roberto
- Arora Mansi
- Baker Alexander T
- Barrett Michael T
- Bekaii-Saab Tanios S
- Bogenberger James M
- Borad Mitesh J
- Braggio Esteban
- Buetow Kenneth H
- Chen Xianfeng
- Dumbauld Chelsae R
- Egan Jan B
- Eskelinen Eeva-Liisa
- Gamb Scott I
- Kosiorek Heidi E
- Leiting Jennifer L
- Mansfield Aaron S
- Meurice Nathalie
- Nagalo Bolni Marius
- Roberts Lewis R
- Salomao Marcela A
- Serrano Uson Junior Pedro Luiz
- Sonbol Mohamad B
- Truty Mark J
- Yonkus Jennifer
- Zhou Yumei
- Publication venue
- 'Wiley'
- Publication date
- 27/10/2022
- Field of study
Background and aims: Biliary tract cancers (BTCs) are uncommon, but highly lethal, gastrointestinal malignancies. Gemcitabine/cisplatin is a standard-of-care systemic therapy, but has a modest impact on survival and harbors toxicities, including myelosuppression, nephropathy, neuropathy, and ototoxicity. Whereas BTCs are characterized by aberrations activating the cyclinD1/cyclin-dependent kinase (CDK)4/6/CDK inhibitor 2a/retinoblastoma pathway, clinical use of CDK4/6 inhibitors as monotherapy is limited by lack of validated biomarkers, diffident preclinical efficacy, and development of acquired drug resistance. Emerging studies have explored therapeutic strategies to enhance the antitumor efficacy of CDK4/6 inhibitors by the combination with chemotherapy regimens, but their mechanism of action remains elusive.Approach and results: Here, we report in vitro and in vivo synergy in BTC models, showing enhanced efficacy, reduced toxicity, and better survival with a combination comprising gemcitabine/cisplatin and CDK4/6 inhibitors. Furthermore, we demonstrated that abemaciclib monotherapy had only modest efficacy attributable to autophagy-induced resistance. Notably, triplet therapy was able to potentiate efficacy through elimination of the autophagic flux. Correspondingly, abemaciclib potentiated ribonucleotide reductase catalytic subunit M1 reduction, resulting in sensitization to gemcitabine.Conclusions: As such, these data provide robust preclinical mechanistic evidence of synergy between gemcitabine/cisplatin and CDK4/6 inhibitors and delineate a path forward for translation of these findings to preliminary clinical studies in advanced BTC patients.</p
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
- Author
- A. -G. Wu
- A. C. Ma
- A. K. Au
- Abdel-Aziz A. K.
- Abdelfatah S.
- Abdellatif M.
- Abdoli A.
- Abel S.
- Abeliovich H.
- Abildgaard M. H.
- Abudu Y. P.
- Acevedo-Arozena A.
- Adamopoulos I. E.
- Adeli K.
- Adolph T. E.
- Adornetto A.
- Aflaki E.
- Agam G.
- Agarwal A.
- Aggarwal B. B.
- Agnello M.
- Agostinis P.
- Agrewala J. N.
- Agrotis A.
- Aguilar P. V.
- Ahmad S. T.
- Ahmed Z. M.
- Ahumada-Castro U.
- Aits S.
- Aizawa S.
- Akkoc Y.
- Akoumianaki T.
- Akpinar H. A.
- Al-Abd A. M.
- Al-Akra L.
- Al-Gharaibeh A.
- Alaoui-Jamali M. A.
- Alberti S.
- Alcocer-Gomez E.
- Alessandri C.
- Ali M.
- Alim Al-Bari M. A.
- Aliwaini S.
- Alizadeh J.
- Almacellas E.
- Almasan A.
- Alonso A.
- Alonso G. D.
- Altan-Bonnet N.
- Altieri D. C.
- Alvarez E. M. C.
- Alves da Costa C.
- Alves S.
- Alzaharna M. M.
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- Ambrosio S.
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- Ammanathan V.
- An Z.
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- Publication venue
- 'Informa UK Limited'
- Publication date
- 01/01/2021
- Field of study
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.
- Author
- Abdel-Aziz AK
- Abdelfatah S
- Abdellatif M
- Abdoli A
- Abel S
- Abeliovich H
- Abildgaard MH
- Abudu YP
- Acevedo-Arozena A
- Adamopoulos IE
- Adeli K
- Adolph TE
- Adornetto A
- Aflaki E
- Agam G
- Agarwal A
- Aggarwal BB
- Agnello M
- Agostinis P
- Agrewala JN
- Agrotis A
- Aguilar PV
- Ahmad ST
- Ahmed ZM
- Ahumada-Castro U
- Aits S
- Aizawa S
- Akkoc Y
- Akoumianaki T
- Akpinar HA
- Al-Abd AM
- Al-Akra L
- Al-Gharaibeh A
- Alaoui-Jamali MA
- Alberti S
- Alcocer-Gómez E
- Alessandri C
- Ali M
- Alim Al-Bari MA
- Aliwaini S
- Alizadeh J
- Almacellas E
- Almasan A
- Alonso A
- Alonso GD
- Altan-Bonnet N
- Altieri DC
- Alves da Costa C
- Alves S
- Alzaharna MM
- Amadio M
- Amantini C
- Amaral C
- Ambrosio S
- Amer AO
- Ammanathan V
- An Z
- Andersen SU
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- Angelini S
- Ann D
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- Arévalo M-A
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- Aschner M
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- Atanasov AG
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- Zhong Q
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- Zhu B
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- Zhu G-Q
- Zhu H
- Zhu H
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- Zhu W-G
- Zhu Y
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- Zhuang H
- Zhuang X
- Zientara-Rytter K
- Zimmermann CM
- Ziviani E
- Zoladek T
- Zong W-X
- Zorov DB
- Zorzano A
- Zou W
- Zou Z
- Zou Z
- Zuryn S
- Zwerschke W
- Álvarez ÉMC
- Ávalos Y
- Önal G
- Üstün S
- Čolić M
- Đokić J
- Žerovnik E
- Publication venue
- 'Informa UK Limited'
- Publication date
- 01/01/2021
- Field of study
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field
Canagliflozin and renal outcomes in type 2 diabetes and nephropathy
- Author
- A Kaldun Nossuli
- Aamir Jamal
- Adalbert Schiller
- Adam Cheifetz
- Adarsh Daswani
- Adeera Levin
- Adline Ghazi
- Adrian Guinsburg
- Adriana Cif
- Adriana Gabriela Onaca
- Adriana Ilavska
- Adriana Villarino
- Agarwal R.
- Agnieszka Starzec
- Ahmed Arif
- Ahmed Awad
- Aiping Yin
- Akimichi Asano
- Alan Jackson
- Alan McMahon
- Alan Perlman
- Alberto Di Carlo
- Alberto Esquenazi
- Alejandra Oviedo
- Alejandro Valdes Depeda
- Aleksandra Kendereski
- Alex Valenzuela
- Alexander Dreval
- Alexander Gonzalez
- Alexander Shinkov
- Alexander Turchin
- Alexandre Klein
- Alfonso Soto Gonzalez
- Alfred Penfornis
- Alfredo Chew Wong
- Alfredo Wassermann
- Ali Torshizi
- Alicia Chilito
- Alina Agafyina
- Alison Dawson
- Alva Hansraj
- Amer Al-Karadsheh
- Amorin Remus Popa
- Amrendra Kumar
- Amy Sprague
- Ana Limos
- Ana Maria Cusumano
- Ana Maria Elosegui
- Anabella Amigo
- Anatoliy Kazmirchuk
- Andrea Phillips
- Andrea Stella
- Andreas Maddux
- Andrej Dzupina
- Andres Alvarisqueta
- Andrew Johnson
- Andrew O'Shaughnessy
- Andrew Steele
- Andrian Yakov
- Andrzej Januszewicz
- Andrzej Madej
- Angelina Angelova
- Anibal Gastaldi
- Anil Gupta
- Anita Bhajan Manocha
- Anjanette Tan
- Anna Kaminska
- Anna Maria Veronelli
- Anna Strzelecka
- Anna Zateyshchikova
- Anselmo Bordonava
- Antanas Navickas
- Anthony Gunstone
- Anthony Roberts
- Antonio Ceriello
- Antonio Galan Serrano
- Antonio Scafuto Scotton
- Antonio Terrelonge
- Antônio Roberto Chacra
- Anupama Gowda
- Arjun D Sinha
- Armando Perez
- Ashot Mkrtumyan
- Atanas Koundurdjiev
- Augusto Vallejos
- Aurelian-Emil Ranetti
- Ayim Akyea-Djamson
- Aysha Badat
- Bakris G.
- Baldev Singh
- Barbara Greco
- Barbara Kaczmarek
- Barbara Rewerska
- Barry M Brenner
- Belia Martin Del Camp Blanco
- Bernard Zinman
- Bertrand Cariou
- Bertrand Dussol
- Bhasker Mehta
- Bhimavarapu Sudhakar
- Björn Paschen
- Bompoint S.
- Borys Mankovskyy
- Botond Csiky
- Boyan Nonchev
- Brenner B. M.
- Brett Kissela
- Brian Nichol
- Bruce Neal
- Bruce Trippe
- Bruno Geloneze Neto
- Bull S.
- Byung-Wan Lee
- C B Keshavamurthy
- Cannon C. P.
- Capuano G.
- Carlo Giorda
- Carlos Alberto Cuneo
- Carlos Arauz-Pacheco
- Carlos Barrera
- Carlos Perez
- Carmel Hawley
- Carmen Crisan
- Carol Pollock
- Carolyn Droste
- Caroucel Chuateco
- Caryl David
- Cecilia Garcia Ballesteros
- Cecilia Jimeno
- Celso Amodeo
- Cesar Javier Zaidman
- Cesar Yoiti Hayashida
- Chamberlain Obialo
- Chang-Hsun Hsieh
- Charles Cook
- Charles Kaupke
- Charytan D. M.
- Chek Loong Loh
- Chen Leia
- Cheol-Young Park
- Chih-Ching Lin
- Christopher P Cannon
- Christy Yao
- Chu P. -L.
- Chwen-Tzuei Chang
- Chye Lee Gan
- Clara Barrios
- Claude Galphin
- Claudia Goycoa
- Claudia Moreira de Brito
- Clodoaido Caringal
- Cristian Serafinceanu
- Cristina Toarba
- Cristobal Morales Portillo
- Csaba Kovesdy
- Cynthia Bowman-Stroud
- Cynthia Christiano
- Cynthia Mustieles Rocha
- Cyrus Desouza
- Cássio Slompo Ramos
- Dagmar Bartaskova
- Dale Crawford Allison
- Dalia Kozloviene
- Dan Scharfstein
- Dana Cosma
- Daniel Coyne
- Daniel Hiser
- Daniel Kolansky
- Daniel Panarotto
- Daniel Pella
- Daniel Weiner
- Daniil Chizhov
- Dariusz Sowinski
- Darren K McGuire
- Davesh Sennik
- David C Wheeler
- David Cherney 3rd
- David Gorson
- David Johnson
- David M Charytan
- David Packham
- David Scott
- David Wheeler
- De Zeeuw D.
- Debbie Cohen-Stein
- Debbie Mascaro
- Deepak Koppolu
- Dennis Levinson
- Derek Lewis
- Detian Li
- Devasmita Dev
- Devesh Patel
- Dewan Deepak
- Dick de Zeeuw
- Diego Aizenberg
- Dinesh Jain
- Dinesh Khullar
- Diogo Belo
- Dmitry Zateyshshikov
- Domenico Santoro
- Domingos d'Avila
- Donald Brandon
- Donald Fraser
- Dong-Wan Chae
- Dora Inés Molina de Salazar
- Dorota Mlodawska-Choluj
- Doru Negru
- Edgar Arcos
- Edoardo Mannucci
- Eduardo Farias
- Edward Watson
- Edwards R.
- Egle Gaupsiene
- Egle Urbanaviciene
- Ekaterina Velichkova
- Elena Christofides
- Elena Grineva
- Elena Kolmakova
- Elena Shutemova
- Eleonora Harcsa
- Elizabeth Barranco
- Elizabeth Gelersztein
- Elizabeth Kern
- Elizete Keitel
- Eloisa Tellez Chavez
- Emanuela Orsi
- Emil Martinka
- Emyr Davies
- Enrique Gonzalez
- Eric Alamartine
- Eric Hernandez Triana
- Eric Thervet
- Erick Turcios Juarez
- Esteban Cercos
- Eugenia Galindo-Ramos
- Eva Peterfai
- Evaly Chen
- Evandro de Souza Portes
- Evgueniy Vazelov
- Fabian Otreras
- Fabiana Loss de Carvalho Contieri
- Fabio Malberti
- Fadi Saba
- Fadlo Fraige Filho
- Favio Edmundo Enriquez Sosa
- Fayzal Ahmed
- Ferdinando Carlo Sasso
- Fernanco Augusto Alves da Costa
- Fernanda Cristina Camelo Sanches
- Fernando Cereto Castro
- Fernando Flores Lozano
- Fernando Jimenez Florez
- Fernando Krynski
- Fernando M Edwin
- Fernando Thomé
- Fernando Trespalacios
- Florence Santos
- Florencia Kraft
- Fracisco Javier Gonzalez Martinez
- Fran Morren
- Franciso Jose Tinahones Madueno
- Frank Eder
- Franklin Joseph
- Franklin Paul Haase
- Frantisek Saudek
- François Dubé
- François Madore
- Freemu Varghese
- Gabriela Cecilia Coloma
- Gabriela Genova-Hristova
- Gabriele von Ingersleben
- Gaetano Serviddio
- Galina Nagibovich
- Gary Meininger
- Gema Fernandez Fresnedo
- Georg Plassmann
- George Bakris
- George Hon
- George Newman
- Gerald DaRoza
- Gerald Keightley
- Gerry Tan
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- Giovanni Frascà
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- Heerspink H. J. L.
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- Suely Keiko Kohara
- Sun Kim
- Sun-Hee Park
- Sunil Sheth
- Susumu Kashine
- Svetlana Goykhman
- Svitlana D Bilyk
- Swee Win Lam
- Sylvia Rosas
- Sylvia Shaw
- Szilard Vasas
- Sérgio Alberto Cunha Vêncio
- Sérgio Yamada
- Tadashi Iitsuka
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- Takashi Wada
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- Tamara Malek Marin
- Tamas Oroszlan
- Tara Chang
- Tareq Nassar
- Tarissa Beatrice Zanata Petry
- Tatiana Koroleva
- Tatiana Morugova
- Tatiana Raskina
- Tatyana Zykova
- Te-Lin Hsia
- Terue Sakakibara
- Tetiana Zlova
- Tetsuji Niiya
- Tetyana Pertseva
- Tiago Schuch
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- Tom Christensen
- Tom Greene
- Tomas Drasnar
- Tomas Smith Casabella
- Tonatiu Diaz Escalante
- Toshihiko Yanase
- Toshio Kawada
- Vadym Vizir
- Vanassa Ratnasingam
- Venessa Tsang
- Venkata Behara
- Vera Klokocnikova
- Vera Krane
- Veronica Anghel
- Veselka Genadieva
- Vesna Popovic-Radinovic
- Viacheslav Marasaev
- Victor Commendatore
- Victor Saavedra Gajardo
- Vijayaraman Arutchelvam
- Viktor Margaritov
- Viktor Zaviriukha
- Viktoria Andreeva
- Vimladhevi Govender
- Vincent Pichette
- Vincent Woo
- Vira Tseluyko
- Virginia Esther Visco
- Vivek Sood
- Vivekan Jha
- Vladimir Dobronravov
- Vladimir Khirmanov
- Vladimir Tesar
- Vlado Perkovic
- Volker Burst
- Volodymyr Botsyurko
- Walter Guillermo Douthat
- Walter Pharr
- Wasim Hanif
- Wataru Yumita
- Wayne H-H Sheu
- Wayne Turner
- Wei Yen Kong
- Weihong Song
- Weiping Lu
- Wendy Lane
- Wenge Li
- Wheeler D. C.
- Wladmir Saporito
- Xuemei Li
- Xueqing Yu
- Yamil Canaan
- Yan Ren
- Yannick Le Meur
- Yaozhong Kong
- Yasuro Kumeda
- Yasushi Wakida
- Yavin Y.
- Yeong Hoon Kim
- Yevgeniya Svyshchenko
- Young Min Cho
- Yulia Samoylova
- Yung-Chuan Lu
- Yuriy Mostovoy
- Yuriy Shwartz
- Yvette Ethel Yap
- Zaynab Abejuela
- Zdravko Kamenov
- Zeid Khitan
- Zhang H.
- Zinman B.
- Zishan Ali
- Zuzana Ochodnicka
- Ângela Regina Nazario Sabbag
- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2019
- Field of study
BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years
Corporate Political Speech, Political Extortion, and the Competition for Corporate Charters
- Author
- Alan R Palmiter
- B Merritt
- B Merritt
- B Merritt
- B Merritt
- Bill Ainsworth
- Cary
- Coffee
- Coffee
- Cornell L Rev
- Cornell L Rev
- Curtis Alva
- Daniel R Fischel
- Del Const Art
- Edward A See Also
- Eisenberg Melvin Aron
- Elizabeth Corcoran
- Elizabeth Corcoran
- Ferrell Bebchuk
- Ferrell Bebchuk
- Fisch
- Fischel Easterbrook
- Fred S Mcchesney
- Ginsburg
- J Del
- J Del
- J L Romano
- J Stephen
- J Stephen
- James D Cox
- Jeffrey N Gordon
- Jeffrey Taylor
- Jeffrey Taylor
- L Cardozo
- L Emory
- L Harv
- L Yale
- L Yale
- L Yale
- L Yale
- Leo E See
- Leslie Eaton
- Lucian Arye Bebchuk
- Marcel See
- Mark Simon
- Miller Macey
- Miller Macey
- N Amir
- Paul G Mahoney
- Ralph K Winter
- Richard W Painter
- Robert H. Sitkoff
- Roberta Romano
- Romano
- Romano
- Romano
- Romano
- See
- See
- See
- See Bill Mcallister
- See Carney
- See Macey
- See Romano
- Soft Kangas
- Stephen Choi
- Strauss
- Strine
- Strine
- William L Cary
- Yale L J At
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2003
- Field of study
Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study
- Author
- A. Mohammed Kalakwa
- A. Nemer Ayoub
- Abantanga Francis A.
- Abatli Safa' Jamal
- Abbas Wisam
- Abbo Olivier
- Abdelbaqi Reem
- Abdelhady Dina Sobhy
- Abdelhafez Mohammad Omar Mohammad
- Abdelhamid Sultan S.
- Abdelmaksoud Sherif
- Abdelmoumen Roua
- Abdelmutalib Fakereldeen
- Abdul-Mumin Alhassan
- Abduljawad Fatima Mousa
- Abdullah Fizan
- Abdullah Mohd Yusof bin
- Abdulraheem Nurudeen
- Abdulrahman Alaa
- Abdulsalam Moruf Adekunle
- Abdunomonovich Dekhkonboev Avazjon
- Aboelela Ahmed
- Abouheba Mohamed
- Abrahamsson Kate
- Abrunhosa Matias Marcia
- Abu-Nejmah Fawzi
- Abuajaila Abdulsalam
- Abuattaya Adham Ashraf
- Abubakar Auwal M
- Abueideh Ahmad
- Abuhayyeh Husam Aldean
- Abuhlega Ma'aly A.
- Abukhalaf Sadi
- Abumunshar Ali Abdelhay
- Acuna Gaston
- Adams Stephen
- Adamu Sani
- Adanan Mohd Fitri Shukri bin Mohamed
- Adawi Ihda
- Adawi Samer
- Adawy Ahmad
- Ade-Ajayi Niyi
- Adegboyega Rilwan
- Ademuyiwa Adesoji
- Adesanya Opeoluwa
- Adhiwidjaja Cathline Freya
- Adofo-Ansong Nana
- Agboola Titiloye Hannah
- Agelebe Efeturi
- Aguilar Aguilar Faye
- Aguilar Gargurevich Prince Pamela
- Aguirre-Lopez Pastor
- Agulham Miguel Angelo
- Ahmad Hira
- Ahmad Zahidah Adlynee Haji
- Ahmed Hazem
- Ahmed Mahmoud Abdelfattah
- Ajai Olalekan Temitope
- Ajao Emmanuel Akinlabi
- Ajiboye Olalekan S.
- Ajrami Yara
- Ajwa Ahmad Elian Abu
- Akan M. Eren
- Akhbari Melika
- Akhter Nadeem
- Akova Fatih
- Al-Attar Hala M.
- Al-Halbouni Layana
- Al-Mamun Abdullah
- Al-Mayoof Ali Farooq
- Al-Momani Hashem M.
- Al-Mouakeh Ahmad
- Al-Rayyes Maisara
- Al-saleem Hasan Subhi Hasan Abu
- Al-Salhi Ashraf Ayman
- Al-Shwaikh Samar H.
- Al-Slaibi Ibrahim
- Al-Taher Raed Nael
- Al-Taher Raed Nael
- Al-Tammam Hiba
- Alakaloko Felix
- Alamrain Abdulwhhab Ayman Abu
- Alanguia Chipana Cathy Lee
- Alattas Khalid
- Alberto Carlos
- Albozidi Aya
- Alcántara Elvyn
- ALDIRAWI MOHAMMED A. M.
- Alebbini Mohanad Mutasem
- Alfoghi Mabroka
- Algabri Hayder Nadhim Obaid
- Alglaib Mohammed Meftah
- Alhamid Ahmad
- Alhamid Aos
- Alhassan Priscilla
- Ali Hassan
- Ali Karim Osamy
- Ali Liza
- Ali Mansour
- Alijla Sharif
- Alijla Sharif S.
- Aliwisat Ahmad Hasan
- Aljaboo Hajir
- Aljadidi Wesal Omar F. Saied
- Aljarad Ziad
- Alkareem Raghad mohammad abdu
- Almada Suad Ahmed
- Almadhoun Walaa
- Almasri Murad
- Almeida Aguiar Arthur
- Almeida Giovana
- Almengar Inas
- Almohamady Hisham
- Almosaibli Mohammad
- Almusleh Tasneem Fathi Hasan
- Alnaeri Ali
- Alnahhal Khaled
- Alonso Verónica
- Alosta Hasan Mustafa
- Alqarajeh Firas
- Alqor Mohammad Omar Ibrahim
- Alsaadi Nijmeh Nasser
- Alsaggaf Ameen
- Alsaied Amer
- Alser Mohammed
- Alser Osaid H.
- Alshaikhkhalil Haya Abdulnasser Ali
- Alshehri Abdullah
- Altaweel Ahmed
- Altın Merve
- Altokhais Tariq
- Altomi Mohamed
- Alturki Fahad
- Alvarado Zelada Jackelyne
- Alves Dutra da Silva Érika
- Alwadia Soha Marwan Salem
- Alwaggaa Nouriyah Ali
- Alzamari Ainaa Ata Mohammad
- Alzate Gallego Edgar
- Alzeer Asmahan Mohammad Suliman
- Alzerei Sulaiman T.
- Alzraikat Sayel H.
- Alzubair Afnan
- Alzughayyar Tareq Z.
- Amad Mohamed
- Amado Fernando
- Amaechi Chukwubinyelum
- Amah Christopher Chim
- Amarin Justin Z.
- Amarin Marzouq
- Ambriz-González Gabriela
- Ameh Emmanuel
- Amjad Muhammad Bin
- Amoabin Afua Amoabin
- Anatole Nzanzu
- Anatole Nzanzu Kipata
- Anaya Dominguez Marlene
- Anaya Firas
- Andrade Jerhy
- Andreussi Lorna
- Anicama Elias Rocio
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- Osuigwe Andrew N
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- Rivera Altamirano Porfirio
- Rivera Alvarez Julio
- Roberts Charles A.
- Roberts Kiera
- Roberts Rebecca
- Rojas Nair
- Rolle Udo
- Romano Piero Giovanni
- Romero Manteola Enrique
- Roszkiewicz Anna
- Ruan Weiwei
- Rudolfson Niclas
- Ruiz de Temiño Bravo Mercedes
- Ruzgar Nensi
- Rygl Michal
- S. Alkali Yahya
- Saad Alshaimaa M.
- Saad Mahmoud M.
- Sabbatini Stella
- Sabic Adnan
- Sabti Shahad
- Sadagurschi Mariana
- Sadek Kareem
- Sadek Mirna
- Safa Nadia
- Sahnoun Lassaad
- Salah Mohammed
- Salawu Morayo Monsurat
- Salazar Karla
- Saldaña Lily
- Saleem Ayesha
- Saleem Muhammad
- Saleh Amr
- Saleh Mahmoud
- Salem Hosni khairy
- Salha Aya Azmi Shehda
- Salim Jamal Mohammed
- Salinas Barreto Juan Jose
- Salinas Vicente
- Salö Martin
- Samad Lubna
- Samadi Dr. Ahmad Zia
- Samanez Obeso Angel
- Samarah Yasmeen Ahmad
- Samarakkody Udaya
- Samy Doaa
- Sanchez Valladares Pablo
- Sanchez Alberto
- Sanchez Beatriz
- Sanchez Janina
- Sanchez Nancy
- Santana Ortiz Rafael
- Saousen Benmanseur
- Sara Nabti
- Saracevic Adna
- Sarhan Osama Abdul Kareem
- Sarıhan Haluk
- Sarkaz Taher L.
- Sartori Giovanoni Lais
- Sayeed Fatema
- Sbaih Mahmoud Fuad
- Scalabre Aurelien
- Scherl Humberto
- Schmedding Andrea
- Segura Calle Carlos
- Sehic Anesa
- Sehwiel Abrar Shaheen
- Sekyere Owusu
- Selak Nejra
- Semensato Carloni Isabela Cristina
- Sempertegui Denisse
- Serban Andreea Madalina
- Serezo Belen
- Sevdalis Nick
- Seyi-Olajide Justina
- Sferco Carlos Ariel
- Shabana Osaid Shaher
- Shahbal Swaleh
- Shaheen Ahmad Ashraf
- Shaheen Nureddin
- Shaklawoon Aisha
- Shalaby Amr
- Shalaby Hanin
- Shalluf Hawa Ahmed
- Shan Cheah Hui
- Sharabati Fadwa
- Sharabati Mutassem
- Sharif Muhammad
- Sharif Randa Alamen M
- Shaw Kenneth
- Shehada Mohammed
- Shehu Ibrahim
- Sheir Hesham
- Sherer Karen
- Sherzad Ajmal
- Shiha Eman Abu
- Shikha Anas
- Shinondo Patricia
- Shnishah Aya Essam
- Shokri Hajer Ali
- Shonubi Amo
- Shoubaki Ali
- Shu Qiang
- Shyaka Gashugi Ian
- Siddiqui Sabina M
- Sidler Daniel
- Sigalet David
- Sihem Brahimi
- Sikwete Guigui
- Siles Hinojosa Alexander
- Silva Beltrán Nathalia
- Silva dos Santos Carla
- Silva Ferreira dos Santos Marília
- Silva Elisângela
- Silva Julian
- Silva Karina Ilheu da
- Silva Yanina
- Sim Marcus
- Simeon Turatsinze
- Simon Soledad
- Sindi Omar
- Singer Georg
- Singh Michael
- Sivaraj Jayaram
- Sivasubramaniam Mithila
- Siyotula Thozama
- Slavkovi Andjelka
- Slavkovic Milan
- Smith Emily Rose
- Soares de Fraga José Carlos
- Sobrero Helena
- Soccorso Giampiero
- Sokolovic Emir
- Sola Juan
- Solanki Meghna
- Soliman Nourhan Akram
- Son Joonhyuk
- Song Eung song
- Soomro Aqil
- Sotelo Sanchez Jennifer
- Souhem Touabti
- Soula Enas
- Souza Barros Beatriz
- Souza Machado Ana Beatriz
- Sowe Babucarr
- Sriniworn Anan
- St-Louis Etienne
- St-Vil Dickens
- Stark Domitille
- Stojanovic Miona
- Stringer Mark
- Strumila Arunas
- Sueiras Ines
- Sulca Cruzado Gladys Johana
- Suleiman Faruk
- Sultana Sadia
- Suradi Haya H.
- Sutcliffe Jonathan
- Suzana Trein Cristine
- Suzen Alev
- Svensson Emma
- Svirsky Alexander
- Swessi Hisham
- Syed Shahnoor
- Syovata Francisa
- Szklarz Maria Tatiana
- Sánchez Paredes Vicente
- Sönmez Kaan
- T Shajin
- T. Sambo Yusuf
- Tababa Osama
- Tabari Ahmad Khaleghnejad
- Tabiri Stephen
- Tadesse Amezene
- Tahyneh Abdulraheem Adnan Abdulraheem
- Takrouney Mohammed Hamada
- Talat Nabila
- Tallaa Mohamed Anwer El
- Tamada Horácio
- Tamaddun Hafatin Fairos bt
- Tang Weibing
- Tanimola Adebayo Gbenga
- Tanming Patchareeporn
- Tanny Sharman Tan
- Tantush Sara Abobaker
- Tarabishi Ahmad Sankari
- Tarek Ahmed
- Tarmohamed Murad
- Tarniba Sara Ali
- Tarrado Xavier
- Tasker David
- Teague Warwick
- Telles Leila
- Temilade Bolarinwa Bolanle
- Teo Rufinah
- Teran Araceli
- Terzic Sabina
- Testoni Daniela
- Thaiwatcharamas Kanokrat
- Thiessen Jesh
- Thomas Amy Hughes
- Thomas Gordon
- Thomas Mark C
- Thompson Hannah
- Till Holger
- Tillig Bernd
- Tinoco Guzmán Nestor Julien
- Tobor Szymon
- Toczewski Krystian
- Tom Alan
- Toplicic Djordje
- Toral Eliana
- Torres Miranda Cesar
- Torres Picón Cintya Maria de Jesus
- Torres-Canchala Laura
- Toselli Luzia
- Touabti Souhem
- Toufik Iaiche Achour
- Tovar Gutierrez Natalia
- Trainba Sara
- Trigoso Mori Fernando
- Trindade Deyl Rafael
- Trojanová Barbora
- Trypens Agata
- Tumi Mohamed
- Tuyishime Eugene
- Türkyılmaz Canan
- Türkyılmaz Zafer
- Ubhi Harmony
- Ugwu Jideofor O
- Ugwunne Chuka A
- Ulasi Ikechukwu
- Ullrich Sarah
- Vacek Jonathan
- Vaitkiene Agota
- Valencia Santiago
- Valeria Pelussi
- Valerio-Vazquez Rafael
- Vanis Nedim
- Vaquila Justo
- Varela Maria Florencia
- Vasquez Matos Juan Pedro
- Vatta Fabrizio
- Vega Centen Stephany
- Velaña Junior
- Vellusamy V Muthualhagi M
- Venant Ntakarutimana
- Venkatraman Soundappan Sannappa
- Verdeata Roxana
- Verduga Ivan
- Verduga Leonardo
- Vergara Carolina
- Verkauskas Gilvydas
- Veronica Sofficci
- Vervoort Dominique
- Vianney Butoyi Jean Marie
- Vida Lucian
- Vidal Cristian R. Zalles
- Vierboom Liam
- Villalba Villalba Araceli
- Villegas Silva Raúl
- Vinskaite Asta
- Vos Corné de
- Vosoughi Armin
- Wafa Tamer
- Walker Gregor
- Wang Jinhu
- Wang Peng
- Waseem Basma
- Weeratunga Naveen
- Weiszewsk Alicja
- Wen Gang
- Werneck Raposo Juliana
- Wester Tomas
- Wijekoon Naveen
- Wilke Alexandra
- Williams Isabelle
- Williams Omolara
- Williams Regan
- Win Win Sabai Phyu
- Wishah Bisan D. M.
- Wishah Nidal
- Wissanji Hussein
- Wolak Przemyslaw
- Wolny Agnieszka
- Wong Janice
- Wong Marilyn
- Wright Naomi Jane
- Wu Guowei
- Wyrzykowski Dariusz
- Xiaodong Guo
- Xie Hua
- Yacoub Mina A.
- Yaghi Bashar
- Yaghi Dua Hasan
- Yalcinkaya Ali
- Yang Hee-Beom
- Yanis Ahmad H.
- Yanowsky Reyes Guillermo
- Yao Yang
- Yapo Benjamin
- Yarza Fernández Jessica
- Yeniay Aslı Öztürk
- Yola Mariya Mukhtar
- Yong Feng
- Youn Joong Kee
- Yousuf Hina
- Yu Mengnan
- Yu Raisa
- Yuen Quah Soong
- Yuldashev Rustam Z.
- Yunus Aayenah
- Za'nouneh Faris J. Abu
- Zaghlol Louay Y.
- Zahari Dato' Dr Zakaria bin
- Zain Mostafa
- Zaman Azrina SK
- Zanellato Josiane Bernartt
- Zarwawi Ahmad Zulhisyam bin
- Zea-Salazar Luis Enrique
- Zeinelabdeen Ali
- Zhao Xiaoxia
- Zhu Jianming
- Zhu Libin
- Zidan Mazen
- Zivanovic Dragoljub
- Zottis Barcelos Fabricio
- Zreeg Dafer abdulhakim . S.
- Zurikat Rajai O.
- Zvizdic Nada
- Zvizdic Zlatan
- Çekiç Bahanur
- Çelik Müge
- Özçelik Zerrin
- Şeref Kıvanç
- Šafus Antonín
- Škvařil Jan
- Štichhauer Radek
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2021
- Field of study
Summary
Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally.
Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies
have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of
the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income
countries globally, and identified factors associated with mortality.
Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to
hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis,
exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a
minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical
status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary
intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause,
in-hospital mortality for all conditions combined and each condition individually, stratified by country income status.
We did a complete case analysis.
Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital
diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal
malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome
countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male.
Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3).
Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income
countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups).
Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome
countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries;
p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients
combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11],
p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20
[1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention
(ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety
checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed
(ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of
parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65
[0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality.
Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome,
middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will
be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger
than 5 years by 2030
A NEW GILIA (POLEMONIACEAE) FROM LIMESTONE OUTCROPS IN THE SOUTHERN SIERRA NEVADA OF CALIFORNIA
- Publication venue
- Berkeley,California Botanical Society.
- Publication date
- Field of study
Volume: 45Start Page: 137End Page: 14
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