1.CORRIGENDUM: Epigenetic modulation inhibits epithelial-mesenchymal transition-driven fibrogenesis and enhances characteristics of chemically-derived hepatic progenitors
Michael ADISASMITA ; Hyomin K LEE ; Yohan AN ; Myounghoi KIM ; Michael Girma MAMO ; Junho K. HUR ; Dongho CHOI ; Ji Hyun SHIN ; Yun Kyung JUNG
Annals of Surgical Treatment and Research 2024;106(6):370-370
2.Epigenetic modulation inhibits epithelial-mesenchymal transition-driven fibrogenesis and enhances characteristics of chemically-derived hepatic progenitors
Michael ADISASMITA ; Hyomin K LEE ; Yohan AN ; Myounghoi KIM ; Michael Girma MAMO ; Junho K. HUR ; Dongho CHOI ; Ji Hyun SHIN ; Yun Kyung JUNG
Annals of Surgical Treatment and Research 2024;106(5):274-283
Purpose:
One of the novel cell sources of cell-based liver regenerative medicine is human chemically-derived hepatic progenitors (hCdHs). We previously established this cell by direct hepatocyte reprogramming with a combination of small molecules (hepatocyte growth factor, A83-01, CHIR99021). However, there have been several issues concerning the cell’s stability and maintenance, namely the occurrences of epithelial-mesenchymal transition (EMT) that develop fibrotic phenotypes, resulting in the loss of hepatic progenitor characteristics. These hepatic progenitor attributes are thought to be regulated by SOX9, a transcription factor essential for hepatic progenitor cells and cholangiocytes.
Methods:
To suppress the fibrotic phenotype and improve our long-term hCdHs culture technology, we utilized the epigenetic modulating drugs DNA methyltransferase inhibitor (5-azacytidine) and histone deacetylase inhibitor (sodium butyrate) that have been reported to suppress and revert hepatic fibrosis. To confirm the essential role of SOX9 to our cell, we used clustered regularly interspaced short palindromic repeats-interference (CRISPRi) to repress the SOX9 expression.
Results:
The treatment of only 5-azacytidine significantly reduces the fibrosis/mesenchymal marker and EMT-related transcription factor expression level in the early passages. Interestingly, this treatment also increased the hepatic progenitor markers expression, even during the reprogramming phase. Then, we confirmed the essential role of SOX9 by repressing the SOX9 expression with CRISPRi which resulted in the downregulation of several essential hepatic progenitor cell markers.
Conclusion
These results highlight the capacity of 5-azacytidine to inhibit EMT-driven hepatic fibrosis and the significance of SOX9 on hepatic progenitor cell stemness properties.
3.Mobile Real-time Tracking of Acute Stroke Patients and Instant, Secure Inter-team Communication - the Join App.
Stephan A MUNICH ; Lee A TAN ; Danilo M NOGUEIRA ; Kiffon M KEIGHER ; Michael CHEN ; R Webster CROWLEY ; James J CONNERS ; Demetrius K LOPES
Neurointervention 2017;12(2):69-76
PURPOSE: The primary correlate to survival and preservation of neurologic function in patients suffering from an acute ischemic stroke is time from symptom onset to initiation of therapy and reperfusion. Communication and coordination among members of the stroke team are essential to maximizing efficiency and subsequently early reperfusion. In this work, we aim to describe our preliminary experience using the Join mobile application as a means to improve interdisciplinary team communication and efficiency. MATERIALS AND METHODS: We describe our pilot experience with the initiation of the Join mobile application between July 2015 and July 2016. With this application, a mobile beacon is transported with the patient on the ambulance. Transportation milestone timestamps and geographic coordinates are transmitted to the treating facility and instantly communicated to all treatment team members. The transport team / patient can be tracked en route to the treating facility. RESULTS: During our pilot study, 62 patients were triaged and managed using the Join application. Automated time-stamping of critical events, geographic tracking of patient transport and summary documents were obtained for all patients. Treatment team members had an overall favorable impression of the Join application and recommended its continued use. CONCLUSION: The Join application is one of several components of a multi-institutional, interdisciplinary effort to improve the treatment of patients with acute ischemic stroke. The ability of the treatment team to track patient transport and communicate with the transporting team may improve reperfusion time and, therefore, improve neurologic outcomes.
Ambulances
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Humans
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Mobile Applications
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Pilot Projects
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Reperfusion
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Stroke*
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Transportation
4.Amplification of distinct α-synuclein fibril conformers through protein misfolding cyclic amplification.
Byung Chul JUNG ; Yoon Ju LIM ; Eun Jin BAE ; Jun Sung LEE ; Min Sun CHOI ; Michael K LEE ; He Jin LEE ; Yoon Suk KIM ; Seung Jae LEE
Experimental & Molecular Medicine 2017;49(4):e314-
Amyloid fibril formation has been implicated in the pathogenesis of neurodegenerative diseases. Fibrillation generates numerous conformers. Presumably, the conformers may possess specific biological properties, thus providing a biochemical framework for strains of prions. However, the precise relationship between various fibril conformers and their pathogenic functions has not been determined because of limited accessibility to adequate amounts of fibrils from tissue samples. α-Synuclein is one such protein, and it has been implicated in Parkinson disease. Using a technique known as protein misfolding cyclic amplification, originally developed for amplifying prions, we established a procedure through which the amplification of α-synuclein fibrils is possible. With a trace amount of seeds, we succeeded in amplifying α-synuclein fibrils. The replication of the seeds was faithful in terms of conformation even after multiple rounds of cyclic amplification. Moreover, two transgenic mouse strains each representing a distinct synucleinopathy were used to investigate different conformers by using this technique. The amplified α-synuclein fibrils derived from the tissue extracts of these two strains led to the production of two different fibril conformers with distinct proteinase K digestion profiles. Together, our results demonstrated that a trace amount of α-synuclein fibrils in tissue extracts could be amplified with their conformations conserved. This procedure should be useful in amplifying α-synuclein fibrils from the brains and body fluids of patients afflicted with synucleinopathies and may serve as a potential diagnostic tool for Parkinson disease and other synucleinopathies.
Amyloid
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Animals
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Body Fluids
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Brain
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Digestion
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Endopeptidase K
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Humans
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Mice
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Mice, Transgenic
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Neurodegenerative Diseases
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Parkinson Disease
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Prions
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Tissue Extracts
5.Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality
Thanh N. NGUYEN ; Muhammad M. QURESHI ; Piers KLEIN ; Hiroshi YAMAGAMI ; Mohamad ABDALKADER ; Robert MIKULIK ; Anvitha SATHYA ; Ossama Yassin MANSOUR ; Anna CZLONKOWSKA ; Hannah LO ; Thalia S. FIELD ; Andreas CHARIDIMOU ; Soma BANERJEE ; Shadi YAGHI ; James E. SIEGLER ; Petra SEDOVA ; Joseph KWAN ; Diana Aguiar DE SOUSA ; Jelle DEMEESTERE ; Violiza INOA ; Setareh Salehi OMRAN ; Liqun ZHANG ; Patrik MICHEL ; Davide STRAMBO ; João Pedro MARTO ; Raul G. NOGUEIRA ; ; Espen Saxhaug KRISTOFFERSEN ; Georgios TSIVGOULIS ; Virginia Pujol LEREIS ; Alice MA ; Christian ENZINGER ; Thomas GATTRINGER ; Aminur RAHMAN ; Thomas BONNET ; Noémie LIGOT ; Sylvie DE RAEDT ; Robin LEMMENS ; Peter VANACKER ; Fenne VANDERVORST ; Adriana Bastos CONFORTO ; Raquel C.T. HIDALGO ; Daissy Liliana MORA CUERVO ; Luciana DE OLIVEIRA NEVES ; Isabelle LAMEIRINHAS DA SILVA ; Rodrigo Targa MARTÍNS ; Letícia C. REBELLO ; Igor Bessa SANTIAGO ; Teodora SADELAROVA ; Rosen KALPACHKI ; Filip ALEXIEV ; Elena Adela CORA ; Michael E. KELLY ; Lissa PEELING ; Aleksandra PIKULA ; Hui-Sheng CHEN ; Yimin CHEN ; Shuiquan YANG ; Marina ROJE BEDEKOVIC ; Martin ČABAL ; Dusan TENORA ; Petr FIBRICH ; Pavel DUŠEK ; Helena HLAVÁČOVÁ ; Emanuela HRABANOVSKA ; Lubomír JURÁK ; Jana KADLČÍKOVÁ ; Igor KARPOWICZ ; Lukáš KLEČKA ; Martin KOVÁŘ ; Jiří NEUMANN ; Hana PALOUŠKOVÁ ; Martin REISER ; Vladimir ROHAN ; Libor ŠIMŮNEK ; Ondreij SKODA ; Miroslav ŠKORŇA ; Martin ŠRÁMEK ; Nicolas DRENCK ; Khalid SOBH ; Emilie LESAINE ; Candice SABBEN ; Peggy REINER ; Francois ROUANET ; Daniel STRBIAN ; Stefan BOSKAMP ; Joshua MBROH ; Simon NAGEL ; Michael ROSENKRANZ ; Sven POLI ; Götz THOMALLA ; Theodoros KARAPANAYIOTIDES ; Ioanna KOUTROULOU ; Odysseas KARGIOTIS ; Lina PALAIODIMOU ; José Dominguo BARRIENTOS GUERRA ; Vikram HUDED ; Shashank NAGENDRA ; Chintan PRAJAPATI ; P.N. SYLAJA ; Achmad Firdaus SANI ; Abdoreza GHOREISHI ; Mehdi FARHOUDI ; Elyar SADEGHI HOKMABADI ; Mazyar HASHEMILAR ; Sergiu Ionut SABETAY ; Fadi RAHAL ; Maurizio ACAMPA ; Alessandro ADAMI ; Marco LONGONI ; Raffaele ORNELLO ; Leonardo RENIERI ; Michele ROMOLI ; Simona SACCO ; Andrea SALMAGGI ; Davide SANGALLI ; Andrea ZINI ; Kenichiro SAKAI ; Hiroki FUKUDA ; Kyohei FUJITA ; Hirotoshi IMAMURA ; Miyake KOSUKE ; Manabu SAKAGUCHI ; Kazutaka SONODA ; Yuji MATSUMARU ; Nobuyuki OHARA ; Seigo SHINDO ; Yohei TAKENOBU ; Takeshi YOSHIMOTO ; Kazunori TOYODA ; Takeshi UWATOKO ; Nobuyuki SAKAI ; Nobuaki YAMAMOTO ; Ryoo YAMAMOTO ; Yukako YAZAWA ; Yuri SUGIURA ; Jang-Hyun BAEK ; Si Baek LEE ; Kwon-Duk SEO ; Sung-Il SOHN ; Jin Soo LEE ; Anita Ante ARSOVSKA ; Chan Yong CHIEH ; Wan Asyraf WAN ZAIDI ; Wan Nur Nafisah WAN YAHYA ; Fernando GONGORA-RIVERA ; Manuel MARTINEZ-MARINO ; Adrian INFANTE-VALENZUELA ; Diederik DIPPEL ; Dianne H.K. VAN DAM-NOLEN ; Teddy Y. WU ; Martin PUNTER ; Tajudeen Temitayo ADEBAYO ; Abiodun H. BELLO ; Taofiki Ajao SUNMONU ; Kolawole Wasiu WAHAB ; Antje SUNDSETH ; Amal M. AL HASHMI ; Saima AHMAD ; Umair RASHID ; Liliana RODRIGUEZ-KADOTA ; Miguel Ángel VENCES ; Patrick Matic YALUNG ; Jon Stewart Hao DY ; Waldemar BROLA ; Aleksander DĘBIEC ; Malgorzata DOROBEK ; Michal Adam KARLINSKI ; Beata M. LABUZ-ROSZAK ; Anetta LASEK-BAL ; Halina SIENKIEWICZ-JAROSZ ; Jacek STASZEWSKI ; Piotr SOBOLEWSKI ; Marcin WIĄCEK ; Justyna ZIELINSKA-TUREK ; André Pinho ARAÚJO ; Mariana ROCHA ; Pedro CASTRO ; Patricia FERREIRA ; Ana Paiva NUNES ; Luísa FONSECA ; Teresa PINHO E MELO ; Miguel RODRIGUES ; M Luis SILVA ; Bogdan CIOPLEIAS ; Adela DIMITRIADE ; Cristian FALUP-PECURARIU ; May Adel HAMID ; Narayanaswamy VENKETASUBRAMANIAN ; Georgi KRASTEV ; Jozef HARING ; Oscar AYO-MARTIN ; Francisco HERNANDEZ-FERNANDEZ ; Jordi BLASCO ; Alejandro RODRÍGUEZ-VÁZQUEZ ; Antonio CRUZ-CULEBRAS ; Francisco MONICHE ; Joan MONTANER ; Soledad PEREZ-SANCHEZ ; María Jesús GARCÍA SÁNCHEZ ; Marta GUILLÁN RODRÍGUEZ ; Gianmarco BERNAVA ; Manuel BOLOGNESE ; Emmanuel CARRERA ; Anchalee CHUROJANA ; Ozlem AYKAC ; Atilla Özcan ÖZDEMIR ; Arsida BAJRAMI ; Songul SENADIM ; Syed I. HUSSAIN ; Seby JOHN ; Kailash KRISHNAN ; Robert LENTHALL ; Kaiz S. ASIF ; Kristine BELOW ; Jose BILLER ; Michael CHEN ; Alex CHEBL ; Marco COLASURDO ; Alexandra CZAP ; Adam H. DE HAVENON ; Sushrut DHARMADHIKARI ; Clifford J. ESKEY ; Mudassir FAROOQUI ; Steven K. FESKE ; Nitin GOYAL ; Kasey B. GRIMMETT ; Amy K. GUZIK ; Diogo C. HAUSSEN ; Majesta HOVINGH ; Dinesh JILLELA ; Peter T. KAN ; Rakesh KHATRI ; Naim N. KHOURY ; Nicole L. KILEY ; Murali K. KOLIKONDA ; Stephanie LARA ; Grace LI ; Italo LINFANTE ; Aaron I. LOOCHTAN ; Carlos D. LOPEZ ; Sarah LYCAN ; Shailesh S. MALE ; Fadi NAHAB ; Laith MAALI ; Hesham E. MASOUD ; Jiangyong MIN ; Santiago ORGETA-GUTIERREZ ; Ghada A. MOHAMED ; Mahmoud MOHAMMADEN ; Krishna NALLEBALLE ; Yazan RADAIDEH ; Pankajavalli RAMAKRISHNAN ; Bliss RAYO-TARANTO ; Diana M. ROJAS-SOTO ; Sean RULAND ; Alexis N. SIMPKINS ; Sunil A. SHETH ; Amy K. STAROSCIAK ; Nicholas E. TARLOV ; Robert A. TAYLOR ; Barbara VOETSCH ; Linda ZHANG ; Hai Quang DUONG ; Viet-Phuong DAO ; Huynh Vu LE ; Thong Nhu PHAM ; Mai Duy TON ; Anh Duc TRAN ; Osama O. ZAIDAT ; Paolo MACHI ; Elisabeth DIRREN ; Claudio RODRÍGUEZ FERNÁNDEZ ; Jorge ESCARTÍN LÓPEZ ; Jose Carlos FERNÁNDEZ FERRO ; Niloofar MOHAMMADZADEH ; Neil C. SURYADEVARA, MD ; Beatriz DE LA CRUZ FERNÁNDEZ ; Filipe BESSA ; Nina JANCAR ; Megan BRADY ; Dawn SCOZZARI
Journal of Stroke 2022;24(2):256-265
Background:
and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year.
Methods:
We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020).
Results:
There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths.
Conclusions
During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.