26 research outputs found
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.
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- Adamopoulos I. E.
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- Adolph T. E.
- Adornetto A.
- Aflaki E.
- Agam G.
- Agarwal A.
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- Agrewala J. N.
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- Aizawa S.
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- Akoumianaki T.
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- Al-Akra L.
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- Publication venue
- 'Informa UK Limited'
- Publication date
- 01/01/2021
- Field of study
Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial
- Author
- Abdelmalek Manal
- Abdelmalek Manal F
- Abrams Gary
- Aguilar Humberto
- Ahmed Aijaz
- Aigner Elmar
- Aithal Guruprasad
- Al-Shamma Sfa
- Ala Aftab
- Alazawi William
- Albillos Agustin
- Allison Michael
- Andrade Raul
- Andreone Pietro
- Angelico Mario
- Ankoma-Sey Victor
- Anstee Quentin
- Anstee Quentin M
- Anty Rodolphe
- Araya Victor
- Arenas Ruiz Juan Ignacio
- Arkkila Perttu
- Arora Marty
- Asselah Tarik
- Au Jennifer
- Ayonrinde Oyekoya
- Bailey Robert James
- Balakrishnan Maya
- Bambha Kiran
- Bansal Meena
- Barritt Sidney
- Bate John
- Beato Jorge
- Beckebaum Susanne
- Beckebaum Susanne
- Bedossa Pierre
- Behari Jaideep
- Bellot Pablo
- Ben Ari Ziv
- Bennett Michael
- Berenguer Marina
- Beretta-Piccoli Benedetta Terziroli
- Berg Thomas
- Bonacini Maurizio
- Bonet Lucia
- Borg Brian
- Bourliere Marc
- Boursier Jerome
- Boursier Jerome
- Bowman William
- Bradley David
- Brankovic Marija
- Braun Marius
- Bronowicki Jean-Pierre
- Bruno Savino
- Bugianesi Elisabetta
- Bugianesi Elisabetta
- Cai Cindy
- Calleja Panero José Luis
- Campagna Jason
- Carey Elizabeth
- Carmiel Michal
- Carrión Jose Antonio
- Cave Matthew
- Chagas Cristina
- Chami Tawfik
- Chang Alan
- Coates Allan
- Cobbold Jeremy
- Corey Kathleen
- Corless Lynsey
- Cortez-Pinto Helena
- Cortez-Pinto Helena
- Crespo Javier
- Cruz Pereira Oscar
- de Ledinghen Victor
- deLemos Andrew
- Diago Moises
- Dufour Jean-Francois
- Dufour Jean-François
- Dugalic Predrag
- Dunn Winston
- Elkhashab Magby
- Epstein Michael
- Escudero-Garcia Maria Desamparados
- Etzion Ohad
- Evans Larry
- Falcone Robert
- Fernandez Conrado
- Ferreira Jose
- Fink Scott
- Finnegan Kevin
- Firpi-Morell Roberto
- Floreani Annarosa
- Fontanges Thierry
- Ford Ryan
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- Fowell Andrew
- Fracanzani Anna Ludovica
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- Freilich Bradley
- Frias Juan
- Fuchs Michael
- Fuentes Javier
- Galambos Michael
- Gallegos Juan
- Geerts Anja
- Geier Andreas
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- George Jacob
- Ghali Maged
- Ghalib Reem
- Gholam Pierre
- Gines Pere
- Gitlin Norman
- Gluud Lise Lotte
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- Goff John
- Goodman Zachary
- Gordon Frederic
- Gordon Stuart
- Goria Odile
- Graupera Isabel
- Greer Shaun
- Grigorian Alla
- Gronbaek Henning
- Guillaume Maeva
- Gunaratnam Naresh
- Halegoua-De Marzio Dina
- Hameed Bilal
- Hametner Stephanie
- Hamilton James
- Harrison Stephen
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- Hartleb Marek
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- Herring Robert
- Heurich Eva
- Hezode Christophe
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- Jeffers Lennox
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- Jorge Rosa
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- Kayali Zeid
- Kechagias Stergios
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- Macedo Guilherme
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- Mathurin Philippe
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- Sheikh Muhammad
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- Sheridan David
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- Shiffman Mitchell
- Shringarpure Reshma
- Siddique Asma
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- Sigal Samuel
- Sikorska Katarzyna
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- Sinclair Marie
- Skoien Richard
- Solis Joel
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- Tam Edward
- Tetri Brent
- Thuluvath Paul
- Tobias Hillel
- Tomasiewicz Krzysztof
- Torres Dawn
- Trauner Michael
- Trautwein Christian
- Trotter James
- Trotter James
- Tsochatzis Emanuel
- Unitt Esther
- Uta Merle
- Vargas Victor
- Varkonyi Istvan
- Veitsman Ella
- Vespasiani Gentilucci Umberto
- Victor David
- Vierling John
- Vincent Catherine
- Vincze Aron
- von der Ohe Manfred
- Von Roenn Natasha
- Vuppalanchi Raj
- Waters Michael
- Watt Kymberly
- Weltman Martin
- Wieland Amanda
- Wiener Gregory
- Williams A Alonzo
- Williams J Jeffrey
- Wilson Jason
- Yataco Maria
- Yoshida Eric
- Younes Ziad
- Younossi Zobair M
- Yuan Liyun
- Zaru Luna
- Zivony Adam
- Zogg Donald
- Zoller Heinz
- Zoulim Fabien
- Zuckerman Eli
- Zuin Massimo
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2019
- Field of study
Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.
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- Abdel-Aziz AK
- Abdelfatah S
- Abdellatif M
- Abdoli A
- Abel S
- Abeliovich H
- Abildgaard MH
- Abudu YP
- Acevedo-Arozena A
- Adamopoulos IE
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- Adolph TE
- Adornetto A
- Aflaki E
- Agam G
- Agarwal A
- Aggarwal BB
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- Agostinis P
- Agrewala JN
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- Zaragoza P
- Zarbalis KS
- Zarebkohan A
- Zarrouk A
- Zeitlin SO
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- Zheng G
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- Zheng X-L
- Zheng Y
- Zheng Z-G
- Zhivotovsky B
- Zhong Q
- Zhou A
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- Zhou H
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- Zhou J
- Zhou J
- Zhou J
- Zhou J
- Zhou K
- Zhou R
- Zhou X-J
- Zhou Y
- Zhou Y
- Zhou Y
- Zhou Z
- Zhou Z-Y
- Zhu B
- Zhu C
- Zhu G-Q
- Zhu H
- Zhu H
- Zhu H
- Zhu W-G
- Zhu Y
- Zhu Y
- 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
Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world
- Author
- Abad Pedro
- Abbara Suhny
- Abbasi Taimur
- Abbott Brian
- Abdel Aziz Islam Shawky
- Abdulla Jawdat
- Abikhzer Gad
- Abohashem Shady
- Abougabal Mahasen
- Abramson Sandra
- Abrihan Paz
- Acuña Arturo Romero
- Affandi Erwin
- Afzal Muhammad Shehzad
- Agolti Mariela
- Agranovich Svetlana
- Aguadé-Bruix Santiago
- Aguero Roberto Nicolas
- Ahmed Hassan Mohamed Ismail
- Ahmed Taghreed
- Akhter Afroza
- Al Dhuhli Humoud
- Al Kindi Faiza
- Al-Abboud Tarek
- Al-Bulushi Naeema
- Al-Mallah Mouaz
- Alak Maria del Carmen
- Alam Edison
- Alaoui Nadia Ismaili
- Alasnag Mirvat
- Albadr Amjed
- Albalooshi Batool
- Albano Domenico
- Alberguina Lucia Graciela
- Albernaz Siqueira Maria Helena
- Alexanderson-Rosas Erick
- Alfaro Ana
- Ali Mohamed Mandour
- Alkadhi Hatem
- Alkandari Faridah
- Allam Adel
- Allarakha Mohammad Aaftaab
- Almeida Augusto
- Almousalli Omar
- Alongi Pierpaolo
- Alonso Omar
- Alves Togni Paulo Henrique
- Alves Wilson Furlan
- Ananthasubramaniam Karthikeyan
- Anderson Jill
- Andrade Jose Henrique
- Andrade Luciana
- Angelidis George
- Anselmi Carlos
- Ansheles Alexey
- Araújo Roberta
- Archontaki Aikaterini
- Arnone Gaspare
- Arnous Samer
- Arnson Yoav
- Arroñada Guillermo
- Arturo Harold
- Asano Hiroshi
- Ascani Sebastian Perez
- Asfour Ahmed
- Askew Jeffrey
- Assadi Majid
- Astesiano Alfredo
- Astesiano Andrea
- Attanasio Lea
- Atyani Said
- Ayala Sandra
- Ayetey Harold
- Ayodele Tolulope
- Azevedo Guilherme
- Bagatin Elisa
- Bailly Matthieu
- Baldari Sergio
- Balmer-Swain Mallory
- Bang Ji-In
- Banthia Nilesh
- Bar-Shalom Rachel
- Barette Rene
- Baric Ana
- Barneveld Peter
- Barragan Adriana Puente
- Barragan Erika
- Barroso Asela
- Basavaraj Ashok Gangasandra
- Batinic Tonci
- Batista Juan Felipe
- Batyrkhanov Daultai
- Bauckneht Matteo
- Baugh Dainia
- Bayer Richard R.
- Bedi Punit
- Bejai Shereen
- Ben-Rais Nozha
- Benedek Imre
- Benedek Theodora
- Benitez Luis
- Benlabgaa Rabie
- Bennie George
- Benteo Pablo
- Beretta Mario
- Berman Daniel S.
- Bernheim Adam
- Bertelli Paolo
- Bester Ria
- Bettencourt Nuno
- Better Nathan
- Better Nathan
- Beuzeville Scott
- Bezerra Sabbrina
- Bhagat Jinendra Kumar
- Bhargava Rishi
- Bhat Vivek
- Bhatia Mona
- Bhatti Sabha
- Biancardi Rodrigo
- Bianco Francesco
- Bieging Erik
- Biggans Thomas
- Bittencourt Marcio Sommer
- Blanco Isabel
- Blanco Juan
- Blankstein Ron
- Blankstein Ron
- Bloom Stephen
- Blue Sean
- Bluemke David
- Bluemke David A.
- Boktor Raef
- Bom Henry
- Bonelli Juan Manuel
- Bonfiglioli Rachele
- Boni Roberto
- Borges Andressa
- Bouyoucef Salah
- Branch Kelley
- Brandão Simone
- Bravo Paco
- Brothers Jessica
- Bruno Andrea
- Bruno Isabella
- Bråten Anders Tjellaug
- Budoff Matthew
- Buechel Ronny Ralf
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- Young Calum
- Younger John
- Younis Muhammad Numair
- Yu Jianqun
- Yuan Li
- Zaid Eed Abu
- Zakavi Seyed Rasoul
- Zapparoli Marcello
- Zavadovsky Konstantin
- Zeffiro Susana
- Zeidán Nahla
- Zerahn Bo
- Zgaljardic Michael
- Zhang Longjiang
- Zhang Tong
- Zhang Xiaoli
- Zhang Yong-Gao
- Zhu Li
- Zhuravlev Kirill
- Zoboli Stefania
- Zukotynski Katherine
- Zuluaga Alejandro
- Øvrehus Kristian Altern
- Štalc Monika
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2021
- Field of study
Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic.
Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality.
Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States.
Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis.
Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection
Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial
- Author
- Abdelmalek M
- Abdelmalek MF
- Abrams G
- Aguilar H
- Ahmed A
- Aigner E
- Aithal G
- Al-Shamma S
- Ala A
- Alazawi W
- Albillos A
- Allison M
- Andrade R
- Andreone P
- Angelico M
- Ankoma-Sey V
- Anstee Q
- Anstee QM
- Anty R
- Araya V
- Arenas Ruiz JI
- Arkkila P
- Arora M
- Asselah T
- Au J
- Ayonrinde O
- Bailey RJ
- Balakrishnan M
- Bambha K
- Bansal M
- Barritt S
- Bate J
- Beato J
- Beckebaum S
- Beckebaum S
- Bedossa P
- Behari J
- Bellot P
- Ben Ari Z
- Bennett M
- Berenguer M
- Beretta-Piccoli BT
- Berg T
- Bonacini M
- Bonet L
- Borg B
- Bourliere M
- Boursier J
- Boursier J
- Bowman W
- Bradley D
- Brankovic M
- Braun M
- Bronowicki J-P
- Bruno S
- Bugianesi E
- Bugianesi E
- Cai C
- Calleja Panero JL
- Campagna J
- Carey E
- Carmiel M
- Carrión JA
- Cave M
- Chagas C
- Chami T
- Chang A
- Coates A
- Cobbold J
- Corey K
- Corless L
- Cortez-Pinto H
- Cortez-Pinto H
- Crespo J
- Cruz Pereira O
- de Ledinghen V
- deLemos A
- Diago M
- Dufour J-F
- Dufour J-F
- Dugalic P
- Dunn W
- Elkhashab M
- Epstein M
- Escudero-Garcia MD
- Etzion O
- Evans L
- Falcone R
- Fernandez C
- Ferreira J
- Fink S
- Finnegan K
- Firpi-Morell R
- Floreani A
- Fontanges T
- Ford R
- Forrest E
- Fowell A
- Fracanzani AL
- Francque S
- Freilich B
- Frias J
- Fuchs M
- Fuentes J
- Galambos M
- Gallegos J
- Geerts A
- Geier A
- Geier A
- George J
- Ghali M
- Ghalib R
- Gholam P
- Gines P
- Gitlin N
- Gluud LL
- Gluud LL
- Goeser T
- Goff J
- Goodman Z
- Gordon F
- Gordon S
- Goria O
- Graupera I
- Greer S
- Grigorian A
- Gronbaek H
- Guillaume M
- Gunaratnam N
- Halegoua-De Marzio D
- Hameed B
- Hametner S
- Hamilton J
- Harrison S
- Harrison S
- Hartleb M
- Hassanein T
- Hellstern P
- Herring R
- Heurich E
- Hezode C
- Hinrichsen H
- Holland Fischer P
- Horsmans Y
- Huang J
- Häussinger D
- Jakiche A
- Jeffers L
- Jones B
- Jorge R
- Jorquera F
- Kahraman A
- Kaita K
- Karyotakis N
- Kayali Z
- Kechagias S
- Kepczyk T
- Khalili M
- Khallafi H
- Kluwe J
- Knapple W
- Knapple W
- Kohli A
- Korenblat K
- Kowdley K
- Kowdley KV
- Krag A
- Krause R
- Kremer A
- Krok K
- Krstic M
- Kugelmas M
- Kumar S
- Labarriere D
- Lai M
- Lampertico P
- Lawitz E
- Lawitz E
- Lee A
- Leroy V
- Lidofsky S
- Lim J
- Lim TH
- Lipkis D
- Little E
- Lonardo A
- Long M
- Loomba R
- Loomba R
- Lurie Y
- MacConell L
- Macedo G
- Makara M
- Maliakkal B
- Manns M
- Manousou P
- Mantry P
- Marchesini G
- Marinho C
- Marotta P
- Marschall H-U
- Mathurin P
- Mathurin P
- Mayo M
- Mazzella G
- Mazzella G
- McCullen M
- McLaughlin W
- Merriman R
- Modi A
- Molina E
- Montano-Loza A
- Montano-Loza AJ
- Monteverde C
- Moreea S
- Moreno C
- Morisco F
- Mubarak A
- Muellhaupt B
- Mukherjee S
- Muller K
- Müller T
- Nagorni A
- Naik J
- Neff G
- Nevah M
- Newsome P
- Newsome PN
- Nguyen-Khac E
- Noureddin M
- Oben J
- Olveira A
- Olveira A
- Orlent H
- Orr D
- Orr D
- Orr J
- Ortiz-Lasanta G
- Ozenne V
- Pandya P
- Paredes A
- Park J
- Patel J
- Patel K
- Patton H
- Peck-Radosavljevic M
- Petta S
- Pianko S
- Piekarska A
- Pimstone N
- Pockros P
- Pol S
- Porayko M
- Poulos J
- Pound D
- Pouzar J
- Presa Ramos J
- Pyrsopoulos N
- Rafiq N
- Ramji A
- Ratziu V
- Ratziu V
- Ravinuthala R
- Reddy K G G
- Reddy K R KR
- Reddy C
- Regenstein F
- Reindollar R
- Riera A
- Rinella M
- Rinella M
- Rivera Acosta J
- Robaeys G
- Roberts S
- Rodriguez-Perez F
- Romero-Gomez M
- Rubin R
- Rumi M
- Rushbrook S
- Rust C
- Ryan M
- Safadi R
- Said A
- Salminen K
- Samuel D
- Santoro J
- Sanyal A
- Sanyal AJ
- Sarkar S
- Schaeffer C
- Schattenberg J
- Schiefke I
- Schiff E
- Schmidt W
- Schneider J
- Schouten J
- Schultz M
- Sebastiani G
- Semela D
- Sepe T
- Shapiro D
- Sheikh A
- Sheikh M
- Sheikh MY
- Sheridan D
- Sheridan D
- Sherman K
- Shibolet O
- Shiffman M
- Shringarpure R
- Siddique A
- Sieberhagen C
- Sigal S
- Sikorska K
- Simon K
- Sinclair M
- Skoien R
- Solis J
- Sood S
- Souder B
- Spivey J
- Stal P
- Stinton L
- Strasser S
- Svorcan P
- Szabo G
- Talal A
- Tam E
- Tetri B
- Thuluvath P
- Tobias H
- Tomasiewicz K
- Torres D
- Trauner M
- Trautwein C
- Trotter J
- Trotter J
- Tsochatzis E
- Unitt E
- Uta M
- Vargas V
- Varkonyi I
- Veitsman E
- Vespasiani Gentilucci U
- Victor D
- Vierling J
- Vincent C
- Vincze A
- von der Ohe M
- Von Roenn N
- Vuppalanchi R
- Waters M
- Watt K
- Weltman M
- Wieland A
- Wiener G
- Williams A A
- Williams J J
- Wilson J
- Yataco M
- Yoshida E
- Younes Z
- Younossi ZM
- Yuan L
- Zaru L
- Zivony A
- Zogg D
- Zoller H
- Zoulim F
- Zuckerman E
- Zuin M
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2019
- Field of study
BACKGROUND
Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH.
METHODS
In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6.
FINDINGS
Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group).
INTERPRETATION
Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes.
FUNDING
Intercept Pharmaceuticals
Observation of gravitational waves from the coalescence of a 2.5−4.5 M⊙ compact object and a neutron star
- Author
- Abac Adrian
- Abbott R.
- Abouelfettouh I.
- Acernese F.
- Ackley Kendall
- Adhicary S.
- Adhikari Naresh
- Adhikari Rana X.
- Adkins V. K.
- Afif Ismail M.
- Agarwal Deepali
- Agathos Michalis
- Aghaei Abchouyeh Maryam
- Aguiar Odylio D.
- Aguilar I.
- Aiello Lorenzo
- Ain Anirban
- Ajith Parameswaran
- Akcay Sarp
- Akseli Hannuksela Otto
- Akutsu Tomotada
- Al-Jodah Ammar
- Al-Shammari S.
- Albanesi Simone
- Alex iandolo Guido
- Alfaidi Reem Atallah E
- Allocca Annalisa
- Alléné C.
- Altin Paul
- Alvarez-Lopez Sofia
- Amato Alex
- Amez-Droz L.
- Amorosi A.
- Amra C.
- Ananyeva A.
- Anderson Stuart
- Anderson Warren G.
- Andia Manuel
- Ando M.
- Andrade T.
- Andrea Prodi Giovanni
- Andres Nicolas
- Andric Tomislav
- Andrés Vallejo Peña Sergio
- Andrés-Carcasona Marc
- Anglin J.
- Anne Bizouard Marie
- Ansoldi Stefano
- Antelis Javier M.
- Antier Sarah
- Antoni Ramis Vidal Felip
- Antonietta Palaia Maria
- Antonio Font Roda Jose
- Aoumi M.
- Appavuravther E. Z.
- Appert S.
- Apple S. K.
- Arai Koji
- Araya Akito
- Araya Melody
- Areeda Joseph
- Argianas L.
- Arif Shaikh Md
- Aritomi N.
- Armato Federico
- Arnaud Nicolas
- Arogeti Megan
- Aronson Scott
- Arun K. G.
- Ashton Gregory
- Aso Yoichi
- Assiduo M.
- Aston S. M.
- Astone Pia
- Attadio Francesca
- Aubin Florian
- AVALLONE Guerino
- Azrad D.
- Babak Stanislav
- Badaracco Francesca
- Badger C.
- Bae Sangwook
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- Bagui E.
- Baier Jeremy
- Baiotti Luca
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- Barneo Pablo
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- Bartoletti A. M.
- Barton Mark Andrew
- Bartos I.
- Basak Soummyadip
- Basalaev Artem
- Bassiri Riccardo
- Basti Andrea
- Bates D. E.
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- Baxi P.
- Bayley Joseph
- Baylor Amanda
- Baynard II. P. A.
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- Bedakihale V. M.
- Beirnaert Freija
- Bejger Michał
- Belardinelli Daniele
- Bell Angus
- Benedetto V.
- Benoit William
- Bentley Joe
- Bera Sayantani
- Berbel Marina
- Bergamin Fabio
- Berger Beverly
- Bernuzzi Sebastiano
- Beroiz Martin
- Berry Christopher P. L.
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- Bertolini A.
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- Caudill S.
- Cavaglia Marco
- Cavalieri Roberto
- Cella Giancarlo
- Cerdá-Durán Pablo
- Cesarini Elisabetta
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- Chakraborty Pratik
- Chalathadka Subrahmanya Shreevathsa
- Chan M.
- Chandra K.
- Chang R. -J.
- Chao Shiuh
- Char Prasanta
- Charlton E. L.
- Charlton Philip
- Chassande-Mottin Eric
- Chatterjee Chayan
- Chatterjee Debarati
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- Chaty Sylvain
- Chatziioannou Katerina
- Chen A.
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- Chen Hsin-Yu
- Chen Junxin
- Chen K. H.
- Chen Y.
- Chen Yanbei
- Chen Yitian
- Cheng H. P.
- Chessa Piero
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- Chiadini Francesco
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- Choudhary Sunil
- Christensen Nelson
- Chua Sheon S. Y.
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- Chun Lung Chan Juno
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- Ciecieląg Paweł
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- Codazzo Elena
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- Colace Stefano
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- Conti Livia
- Corbitt Thomas
- Cordero-Carrión Isabel
- Corezzi S.
- Cornish Neil
- Corsi Alessandra
- Cortese Stefano
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- de rossi camilla
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- error error
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- Estellés Estrella Héctor
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- felicetti riccardo
- Fenyvesi Edit
- Ferguson Deborah
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- Figura Przemysław
- Fiori Alessio
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- Fuentes-Garcia Melina
- Fujii S.
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- Virgo Collaboration
- Virtuoso Andrea
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- Waratkar Gaurav
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- Washington N. Y.
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- 劉 國欽
- 都丸 隆行
- Publication venue
- Publication date
- 23/04/2024
- Field of study
4to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica
- Author
- Acosta Pedro
- Acurio R.
- Aguaded Ignacio
- Aguilar Ramon Adrián Paolo
- Aguillón Osma Osma
- Aller Castro José Manuel
- Alvarez Mendoza César Iván
- Ampuño Gary
- Arango Varela Sandra Sulay
- Arciniega G.
- Arévalo Bermeo Germán
- Avilés González Kevin Marcelo
- Ayala Carabajo Raquel
- Barrios D.
- Bermeo Naula Andrea Karina
- Bermeo A.
- Bonilla Agualongo Agustín Paul
- Bonilla A.
- Bustos González Juan Daniel
- Caamaño L.
- Caicedo S.
- Cajamarca Rivadeneira Ronald Enrique
- Calle Espinoza Carlos Julio
- Carabali Mariño Jenifer
- Carpio M.
- Castillo Guerrero John Mathews
- Cedeño Tello Alicia María
- Cedillo F.
- Cerrada Lozada Mariela
- Chacón J.
- Chicaiza J.
- Chiluisa-Utreras V.
- Chávez Carlos
- Coque S.
- Cos Farias Valeria Mishelle
- Cuellar Luz Angela
- Cuerva Pareja Carolina
- Cueva E.
- Cueva J.
- Cuzco Calle Irma
- Cárdenas David
- de la Nube Toral Sarmiento Adriana
- Domínguez Federico
- Duque Sarango Paola Jackeline
- Díaz Mónica
- Espinel Ramón
- Fernández de Córdoba Pedro
- Flores Noelia
- Fuentes Espinoza Pablo Gustavo
- Furlan Del Pezo Anggie Margarita
- Galarza Rodriguez Jose Luis
- Gallardo Sandoval Pedro Emilio
- Garabiza Castro Bella Del Rocío
- Garcés Villón Laura
- García C.
- Giovanny Cuzco Edgar
- González Rivera Pedro Luis
- Gordillo Manssur Fabián Alberto
- Guamán Seis Joseph Alexander
- Gómez M.
- Hernando Pérez Elena
- Hincapié Roberto Carlos
- Huerta Mónica
- Hurtado Isaza Sandra
- Inclán Diego
- Jaramillo F.
- Jenaro Río Cristina
- Jiménez Moposita Jorge
- Jurado V.
- Knezevich Palacios Alba Teresa
- Ladinez Gómez Erick Milton
- Lata J.
- León Michael
- Llerena Izquierdo Joe
- Llerena Paz Robinson Dimitri
- Loaiza Martínez María de Lourdes
- Lozano Garzón Carlos
- Lozano Zayda
- Lucín Castillo Virginia Carolina
- López Terán Adrián
- López Alfredo
- López R.
- Macancela J.
- Manzano Villafuerte Santiago
- Martínez Guashima Oswaldo
- Mediavilla Peñaherrera Emerson
- Mendieta Villalba Nadia Mercedes
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- Michinel Humberto
- Miranda Ramos Mónica
- Monsalve Artega Carlos
- Morales Ibarra Rafael
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- Moret Tatay Carmen
- Moya B.
- Moyano Rodriguez Diego
- Muñoz P.
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- Navas Ruilova Gustavo Ernesto
- Nieto-Londoño C.
- Nieto-Londoño César
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- Ocampo Alvarado Juan Carlos
- Orizaga Trejo José Antonio
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- Prieto Vélez Patsy Malena
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- Pérez Gosende Pablo Alberto
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- Ribadeneira Ramírez Jefferson
- Rivera Campoverde Néstor Diego
- Rodríguez Manuel
- Rojas Párraga Tania Catalina
- Rojas Zavala Víctor Emilio
- Romero Blacio Fernanda Yamileth
- Romero Paz Manuel de Jesús
- Romero Romero Byron Ramiro
- Romero-Rodríguez Luis Miguel
- Román Párraga Abel
- Rosero Toledo Karina
- Rosero Toledo Wendy
- Samaniego Raúl Arturo
- Santos Edgar Daniel
- Saquicela Victor Saquicela
- Serpa Andrade Luis Javier
- Silva Ariel Osvaldo
- Silva-Yumi Jorge
- Soberon D.
- Sumba N.
- Toapanta Toapanta Segundo Moisés
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- Torres Capuz Kevin Rolando
- Torres Toukoumidis Angel
- Uribe Yunda Diego Fernando
- Vaca I.
- Valdez Pérez María Eugenia
- Vega Ureta Nino Tello
- Veloz Mayorga Nancy
- Verdugo Romero Walter
- Viasus Germán
- Vidal Mogrovejo Paúl
- Vilches R.
- Villacrés Beltrán Fabián
- Villacrés Beltrán Fabián Isaac
- Vásquez Cevallos Leonel
- Vázquez Martínez Andrea
- Yambay Aulla Ines
- Zapata Narváez Diego
- Álvarez Guale Raúl
- Álvarez Guale Raúl Jimmy
- Álvarez C.
- Álvarez C.
- Ávalos Zambrano Rodrigo
- Publication venue
- Publication date
- 01/07/2018
- Field of study
Este volumen acoge la memoria académica de la Cuarta edición del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2017, desarrollado entre el 29 de noviembre y el 1 de diciembre de 2017 y organizado por la Universidad Politécnica Salesiana (UPS) en su sede de Guayaquil.
El Congreso ofreció un espacio para la presentación, difusión e intercambio de importantes investigaciones nacionales e internacionales ante la comunidad universitaria que se dio cita en el encuentro. El uso de herramientas tecnológicas para la gestión de los trabajos de investigación como la plataforma Open Conference Systems y la web de presentación del Congreso http://citis.blog.ups.edu.ec/, hicieron de CITIS 2017 un verdadero referente entre los congresos que se desarrollaron en el país.
La preocupación de nuestra Universidad, de presentar espacios que ayuden a generar nuevos y mejores cambios en la dimensión humana y social de nuestro entorno, hace que se persiga en cada edición del evento la presentación de trabajos con calidad creciente en cuanto a su producción científica.
Quienes estuvimos al frente de la organización, dejamos plasmado en estas memorias académicas el intenso y prolífico trabajo de los días de realización del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad al alcance de todos y todas
Ultralight vector dark matter search using data from the KAGRA O3GK run
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- Suzuki Takanori
- Swinkels Bas L.
- Sylvia Biscoveanu Andrea
- Syx A.
- Szczepańczyk Marek
- Szewczyk Paweł
- Sänger E. M.
- Sébastien Göttel Alexandre
- Tacca Matteo
- Tagoshi Hideyuki
- Tait Simon
- Tak Lun Tsang Terrence
- Takahashi Hirotaka
- Takahashi Ryutaro
- Takamori Akiteru
- Takatani K.
- Takeda Hiroki
- Takeda M.
- Takidera H.
- Talbot C.
- Talbot C. J.
- Tamaki M.
- Tamanini Nicola
- Tanabe D.
- Tanaka K.
- Tanaka Shuta
- Tanaka Takahiro
- Tanasijczuk A. J.
- Tang D.
- Tanioka Satoshi
- Tanner D. B.
- Tao Liu
- Tapia San Martín E. N.
- Tapia R. D.
- Tarafder R.
- Taranto C.
- Taruya Atsushi
- Tasson Jay
- Teloi M.
- Tenorio Rodrigo
- Themann H.
- Theodoropoulos A.
- Thirugnanasambandam M. P.
- Thomas M.
- Thomas P.
- Thompson Jonathan
- Thondapu S. R.
- Thorne K. A.
- Thrane E.
- Tissino Jacopo
- Tiwari A.
- tiwari shubhanshu
- Tiwari Srishti
- tiwari vaibhav
- Todd M. R.
- Toivonen Andrew
- Toland Karl
- Tolley Arthur E.
- Tomita K.
- Tomura Tomonobu
- Tong-Yu C.
- Toriyama A.
- Toropov Nikita
- Torres Forne Alejandro
- Torrie C. I.
- Toscani Martina
- Tosta e Melo Iara
- Tournefier Edwige
- TRAPANANTI Angela
- Travasso Flavio
- Traylor G.
- Trenado Juan
- Trevor M.
- Tripathee Aashish
- Troiano L.
- Trovato Agata
- Trozzo L.
- Trudeau R. J.
- Tso R.
- Tsuchida Satoshi
- Tsukada L.
- Tsutsui Takuya
- Turbang Kevin
- Turconi Margherita
- Turski C.
- Ubach Helena
- Ubhi A. S.
- Uchiyama Takashi
- Udall Rhiannon
- Uehara Tomoyuki
- Ueno Koh
- Unnikrishnan C. S.
- Ushiba Takafumi
- Vacatello Michele
- Vahlbruch Henning
- Vaidya Nina
- Vajente Gabriele
- Vajpeyi A.
- Valdes Guillermo
- Valencia J.
- Valentini Michele
- Vallejo-Peña S. A.
- Vallero S.
- Valsan Vinaya
- Valérie Martinez
- van Bakel N.
- van Beuzekom Martin
- van Dael Mathyn
- Van de Walle A.
- van den Brand Johannes
- Van Den Broeck C.
- van der Sluys Marc
- van Dongen Jesse
- Van Haevermaet Hans
- van Heijningen Joris
- van Putten Maurice
- Van Ranst Zeb
- van Remortel Nick
- Vander-Hyde D. C.
- Vandra K.
- Vanosky J.
- Vardaro M.
- Vargas A. F.
- varma vijay
- Vasuth Matyas
- vecchio alberto
- Vedovato G.
- Veitch John
- Veitch Peter
- Venikoudis S.
- Venneberg Jasper
- Verdier Patrice
- Verkindt Didier
- Verma B.
- Verma P.
- Verma Yogesh
- Vermeulen Sander M.
- Veske Doğa
- Vetrano F.
- Veutro A.
- Vibhute Ajay
- Viceré Andrea
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- Viets Aaron
- Vijaykumar Aditya
- Vilkha A.
- Villa-Ortega Verónica
- Vincent Erin
- Vinet J. -Y.
- Viret S.
- Virgo Collaboration
- Virtuoso Andrea
- Vitale Salvatore
- Vocca H.
- Voigt Daniel
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- von Wrangel J. S. A.
- Vyatchanin Sergey P.
- Wade L. E.
- Wade Madeline
- Wagner Katelyn
- Walet R. C.
- Walker M.
- Wallace G. S.
- Wallace L.
- Wang Haoyu
- Wang J. Z.
- Wang W. H.
- Wang Z.
- Waratkar Gaurav
- Ward R. L.
- Warner J.
- Was Michal
- Washimi Tatsuki
- Washington N. Y.
- Watarai D.
- Wayt K. E.
- Weaver B.
- Weaving C. R.
- Webster S. A.
- Weinert M.
- Weinstein Alan J.
- Weiss R.
- Weizmann Kiendrebeogo R.
- Weller C. M.
- Weller Robert
- Wellmann F.
- Wen L.
- Wette Karl
- Weßels P.
- Whelan John
- White D. D.
- Whiting Bernard F.
- Whittle Chris
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- Wu David S.
- Wu Hsun-Chung
- Wysocki Daniel
- Xiao Liting
- Xu Victoria
- Xu Yumeng
- Yaala M. Ben
- Yadav Nikesh
- Yakovlev Alexey
- Yamamoto Hiroaki
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- Yamamoto M.
- Yamamoto Takahiro
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- Yamamura S.
- Yamazaki Ryo
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- Yang Yi
- Yarbrough Zach
- Yeh S. -W.
- Yelikar A. B.
- Yeung S. M. C.
- Yin X.
- Yokoyama Jun'ichi
- Yokozawa T.
- Yoo Jooheon
- Yu Hang
- Yuzurihara Hirotaka
- Zadrożny A.
- Zahoor Jan Aasim
- Zannelli A. J.
- Zanolin M.
- Zeeshan M.
- Zelenova T.
- Zendri J. -P.
- Zeoli M.
- Zerrad M.
- Zevin Michael
- Zhang A. C.
- Zhang Jue
- Zhang L.
- Zhang Rui
- Zhang T.
- Zhang Ya
- Zhao C.
- Zhao Yue
- Zhao Yuhang
- Zheng Yanyan
- Zhong Haowen
- Zhong S.
- Zhou R.
- Zhu Zong-Hong
- Zucker M. E.
- Zweizig John
- Árpád Gergely László
- 劉 國欽
- 曹周键
- 都丸 隆行
- Publication venue
- Publication date
- 01/03/2024
- Field of study
Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM
Matrix metalloproteinase 10 is linked to the risk of progression to dementia of the Alzheimer's type
- Author
- Abdelnour Carla
- Aguilera Nuria
- Ahmad Shahzad
- Alarcón Martín Emilio
- Amin Najaf
- Andrade Fuentes Victor M
- Boada Merce
- Campos Martin Rafael
- Dalmasso Maria Carolina
- Espinosa Ana
- Esteban De Antonio Ester
- Frölich Lutz
- García Pablo
- Ikram M. Arfan
- Kleineidam Luca
- Kornhuber Johannes
- Lewczuk Piotr
- López Cuevas Rogelio
- Martino Adami Pamela Victoria
- Mauleón Ana
- Montrreal Laura
- Orellana Adelina
- Pablo Tartari Juan
- Parveen Kayenat
- Peters Oliver
- Rosende Roca Maitee
- Rüther Eckart
- Tarraga Lluis
- Vargas Liliana
- Wiltfang Jens
- Publication venue
- Oxford University Press
- Publication date
- 01/07/2022
- Field of study
Alzheimer's disease has a long asymptomatic phase that offers a substantial time window for intervention. Using this window of opportunity will require early diagnostic and prognostic biomarkers to detect Alzheimer's disease pathology at predementia stages, thus allowing identification of patients who will most probably progress to dementia of the Alzheimer's type and benefit from specific disease-modifying therapies. Consequently, we searched for CSF proteins associated with disease progression along with the clinical disease staging. We measured the levels of 184 proteins in CSF samples from 556 subjective cognitive decline and mild cognitive impairment patients from three independent memory clinic longitudinal studies (Spanish ACE, n = 410; German DCN, n = 93; German Mannheim, n = 53). We evaluated the association between protein levels and clinical stage, and the effect of protein levels on the progression from mild cognitive impairment to dementia of the Alzheimer's type. Mild cognitive impairment subjects with increased CSF level of matrix metalloproteinase 10 (MMP-10) showed a higher probability of progressing to dementia of the Alzheimer's type and a faster cognitive decline. CSF MMP-10 increased the prediction accuracy of CSF amyloid-β 42 (Aβ42), phospho-Tau 181 (P-Tau181) and total tau (T-Tau) for conversion to dementia of the Alzheimer's type. Including MMP-10 to the [A/T/(N)] scheme improved considerably the prognostic value in mild cognitive impairment patients with abnormal Aβ42, but normal P-Tau181 and T-Tau, and in mild cognitive impairment patients with abnormal Aβ42, P-Tau181 and T-Tau. MMP-10 was correlated with age in subjects with normal Aβ42, P-Tau181 and T-Tau levels. Our findings support the use of CSF MMP-10 as a prognostic marker for dementia of the Alzheimer's type and its inclusion in the [A/T/(N)] scheme to incorporate pathologic aspects beyond amyloid and tau. CSF level of MMP-10 may reflect ageing and neuroinflammation.Fil: Martino Adami, Pamela Victoria. University Of Cologne; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Orellana, Adelina. Instituto de Salud Carlos III; España. International University of Catalonia; EspañaFil: García, Pablo. International University of Catalonia; España. Instituto de Salud Carlos III; EspañaFil: Kleineidam, Luca. University Of Cologne; AlemaniaFil: Alarcón Martín, Emilio. International University of Catalonia; EspañaFil: Montrreal, Laura. International University of Catalonia; EspañaFil: Aguilera, Nuria. International University of Catalonia; EspañaFil: Espinosa, Ana. Fundació Ace; EspañaFil: Abdelnour, Carla. Fundació Ace; EspañaFil: Rosende Roca, Maitee. Fundació Ace; EspañaFil: Pablo Tartari, Juan. Fundació Ace; EspañaFil: Vargas, Liliana. Fundació Ace; EspañaFil: Mauleón, Ana. Fundació Ace; EspañaFil: Esteban De Antonio, Ester. Fundació Ace; EspañaFil: López Cuevas, Rogelio. Fundació Ace; EspañaFil: Dalmasso, Maria Carolina. University Of Cologne; Alemania. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; ArgentinaFil: Campos Martin, Rafael. University Of Cologne; AlemaniaFil: Parveen, Kayenat. University Of Cologne; AlemaniaFil: Andrade Fuentes, Victor M. University Of Cologne; AlemaniaFil: Amin, Najaf. University of Oxford; Reino UnidoFil: Ahmad, Shahzad. Erasmus MC; Países BajosFil: Ikram, M. Arfan. Erasmus MC; Países BajosFil: Lewczuk, Piotr. Universitat Erlangen-Nuremberg; AlemaniaFil: Kornhuber, Johannes. Universitat Erlangen-Nuremberg; AlemaniaFil: Peters, Oliver. University Hospital Of Białystok; PoloniaFil: Frölich, Lutz. Ruprecht Karls Universitat Heidelberg.; AlemaniaFil: Rüther, Eckart. Universität Göttingen; AlemaniaFil: Wiltfang, Jens. Universität Göttingen; AlemaniaFil: Tarraga, Lluis. Fundació Ace; EspañaFil: Boada, Merce. Fundació Ace; Españ
Matrix metalloproteinase 10 is linked to the risk of progression to dementia of the Alzheimer's type
- Author
- Abdelnour Carla
- Aguilera Nuria
- Ahmad Shahzad
- Alarcón-Martín Emilio
- Alegret Montserrat
- Amin Najaf
- Andrade Fuentes Victor M.
- Boada Merce
- Campos Martin Rafael
- Cano Amanda
- Dalmasso Maria Carolina
- De Rojas Itziar
- Espinosa Ana
- Esteban-De Antonio Ester
- Frölich Lutz
- García Pablo
- González Perez Antonio
- Hernández Isabel
- Ikram M. Arfan
- Jessen Frank
- Kleineidam Luca
- Kornhuber Johannes
- Lewczuk Piotr
- López-Cuevas Rogelio
- Maier Wolfgang
- Marquie Marta
- Martino Adami Pamela V.
- Mauleón Ana
- Montrreal Laura
- Orellana Adelina
- Pablo Tartari Juan
- Parveen Kayenat
- Peters Oliver
- Ramírez Alfredo
- Rosende-Roca Maitee
- Ruiz Agustín
- Rüther Eckart
- Sanabria Angela
- Schneider Anja
- Sáez Goñi María Eugenia
- Tarraga Lluis
- Valero Sergi
- Van Duijn Cornelia M.
- Vargas Liliana
- Wagner Michael
- Wiltfang Jens
- Publication venue
- 'Oxford University Press (OUP)'
- Publication date
- 01/01/2022
- Field of study
Alzheimer's disease has a long asymptomatic phase that offers a substantial time window for intervention. Using this window of opportunity will require early diagnostic and prognostic biomarkers to detect Alzheimer's disease pathology at predementia stages, thus allowing identification of patients who will most probably progress to dementia of the Alzheimer's type and benefit from specific disease-modifying therapies. Consequently, we searched for CSF proteins associated with disease progression along with the clinical disease staging. We measured the levels of 184 proteins in CSF samples from 556 subjective cognitive decline and mild cognitive impairment patients from three independent memory clinic longitudinal studies (Spanish ACE, n = 410; German DCN, n = 93; German Mannheim, n = 53). We evaluated the association between protein levels and clinical stage, and the effect of protein levels on the progression from mild cognitive impairment to dementia of the Alzheimer's type. Mild cognitive impairment subjects with increased CSF level of matrix metalloproteinase 10 (MMP-10) showed a higher probability of progressing to dementia of the Alzheimer's type and a faster cognitive decline. CSF MMP-10 increased the prediction accuracy of CSF amyloid-β 42 (Aβ42), phospho-Tau 181 (P-Tau181) and total tau (T-Tau) for conversion to dementia of the Alzheimer's type. Including MMP-10 to the [A/T/(N)] scheme improved considerably the prognostic value in mild cognitive impairment patients with abnormal Aβ42, but normal P-Tau181 and T-Tau, and in mild cognitive impairment patients with abnormal Aβ42, P-Tau181 and T-Tau. MMP-10 was correlated with age in subjects with normal Aβ42, P-Tau181 and T-Tau levels. Our findings support the use of CSF MMP-10 as a prognostic marker for dementia of the Alzheimer's type and its inclusion in the [A/T/(N)] scheme to incorporate pathologic aspects beyond amyloid and tau. CSF level of MMP-10 may reflect ageing and neuroinflammation