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Wyświetlanie 1-10 z 43
Tytuł:
Network analysis of neuropsychiatric, cognitive, and functional complications of stroke : implications for novel treatment targets
Autorzy:
Lam, Ben
Sachdev, Perminder S.
Chen, Christopher
Traykov, Latchezar
Oestreich, Lena K.L.
Desmond, David W.
Klimkowicz-Mrowiec, Aleksandra
Wright, Paul
Di Biase, Maria A.
Mok, Alice H.
van Oostenbrugge, Robert
Crawford, John D.
Bordet, Régis
Yu, Kyung‐Ho
O'Sullivan, Michael J.
Lee, Minwoo
Staals, Julie E.A.
Lo, Jessica W.
Köhler, Sebastian
Zalesky, Andrew
Opis:
Aim: Recovery from stroke is adversely affected by neuropsychiatric complications, cognitive impairment, and functional disability. Better knowledge of their mutual relationships is required to inform effective interventions. Network theory enables the conceptualization of symptoms and impairments as dynamic and mutually interacting systems. We aimed to identify interactions of poststroke complications using network analysis in diverse stroke samples. Methods: Data from 2185 patients were sourced from member studies of STROKOG (Stroke and Cognition Consortium), an international collaboration of stroke studies. Networks were generated for each cohort, whereby nodes represented neuropsychiatric symptoms, cognitive deficits, and disabilities on activities of daily living. Edges characterized associations between them. Centrality measures were used to identify hub items. Results: Across cohorts, a single network of interrelated poststroke complications emerged. Networks exhibited dissociable depression, apathy, fatigue, cognitive impairment, and functional disability modules. Worry was the most central symptom across cohorts, irrespective of the depression scale used. Items relating to activities of daily living were also highly central nodes. Follow-up analysis in two studies revealed that individuals who worried had more densely connected networks than those free of worry (CASPER [Cognition and Affect after Stroke: Prospective Evaluation of Risks] study: S = 9.72, P = 0.038; SSS [Sydney Stroke Study]: S = 13.56, P = 0.069). Conclusion: Neuropsychiatric symptoms are highly interconnected with cognitive deficits and functional disabilities resulting from stroke. Given their central position and high level of connectedness, worry and activities of daily living have the potential to drive multimorbidity and mutual reinforcement between domains of poststroke complications. Targeting these factors early after stroke may have benefits that extend to other complications, leading to better stroke outcomes.
Dostawca treści:
Repozytorium Uniwersytetu Jagiellońskiego
Artykuł
Tytuł:
Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting
Autorzy:
Sharma, Pankaj
Woo, Daniel
Wong, Tien Y.
Beecham, Ashley H.
Cole, John W.
Thijs, Vincent
Griswold, Michael E.
Gudnason, Vilmundur
Montine, Thomas J.
Liewald, David
Maillard, Pauline
McWhirter, Rebekah
Kittner, Steven J.
Launer, Lenore J.
Hernández, Maria del C. Valdés
Aggarwal, Neelum T.
Wardlaw, Joanna M.
Rosand, Jonathan
van der Graaf, Yolanda
Brodaty, Henry
Adams, Hieab H.H.
Rexrode, Kathy
Thomson, Russell
Deary, Ian J.
Romero, Jose R.
Wittfeld, Katharina
Dichgans, Martin
Hofer, Edith
Tzourio, Christophe
Schmidt, Helena
Hopewell, Jemma C.
Schellenberg, Gerard D.
Satizabal, Claudia L.
International Stroke Genetics Consortium,
Rice, Kenneth
Longstreth, W.T.
Asselbergs, Folkert W.
Knopman, David S.
DeStefano, Anita L.
Srikanth, Velandai
Sachdev, Perminder S.
Beekman, Marian
Wright, Clinton B.
Starr, John M.
Armstrong, Nicola J.
Chouraki, Vincent
Jern, Christina
Schofield, Peter R.
van der Lee, Sven J.
Uh, Hae-Won
Saba, Yasaman
Worrall, Bradford B.
Hosten, Norbert
Benavente, Oscar R.
Callisaya, Michele
Schilling, Sabrina
Stott, David J.
van Duijn, Cornelia M.
Kjartansson, Olafur
Yamaguchi, Shuhei
Zhu, Yi-Cheng
Slagboom, Eline
Kaffashian, Sara
Rothwell, Peter M.
Amouyel, Philippe
DeCarli, Charles
Nabika, Toru
Uitterlinden, André G.
Kato, Norihiro
Amin, Najaf
Grewal, Raji P.
Chauhan, Ganesh
Rich, Stephen S.
McArdle, Patrick F.
Johnson, Julie A.
Trompet, Stella
van der Grond, Jeroen
Mitchell, Braxton D.
Gottesman, Rebecca F.
Sargurupremraj, Muralidharan
Phan, Thanh
Mather, Karen A.
Ames, David
Rajan, Kumar B.
Grabe, Hans J.
Jimenez-Conde, Jordi
Pera, Joanna
Meschia, James F.
Sacco, Ralph L.
Blanton, Susan H.
Beva, Steve
Wen, Wei
Kwok, John B.
Psaty, Bruce M.
von Sarnowski, Bettina
Seshadri, Sudha
Ikram, Mohammad K.
Liao, Jiemin
Pulit, Sara L.
de Bakker, Paul I.W.
Windham, B. Gwen
Stroke Genetics Network,
Moran, Chris
Wong, Quenna
Smith, Albert Vernon
Melander, Olle
Luciano, Michelle
Aparicio, Hugo J.
Bastin, Mark E.
Ford, Ian
Traylor, Matthew
Muñoz Maniega, Susana
Vernooij, Meike W.
Jukem, J. Wouter
Fornage, Myriam
Bis, Joshua C.
Thalamuthu, Anbupalam
Levi, Christopher
Geerlings, Mirjam I.
Rotter, Jerome I.
Arnett, Donna K.
Wasssertheil-Smoller, Sylvia
Markus, Hugh S.
Chen, Christopher
Słowik, Agnieszka
Mazoyer, Bernard
Beecham, Gary W.
Evans, Denis A.
Ikram, Mohammad A.
Völker, Uwe
Debette, Stéphanie
Rundek, Tatjana
Malik, Rainer
Hofman, Albert
Lopez, Oscar L.
Teumer, Alexander
Deelen, Joris
Lemmens, Robin
Lee, Jin-Moo
Chong, Elizabeth
De Jager, Philip L.
Schmidt, Reinhold
Cheng, Ching-Yu
Lindgren, Arne
Sudlow, Cathie L.M.
Rutten-Jacob, Loes C.A.
van der Lugt, Aad
Boncoraglio, Giorgio B.
Takeuchi, Fumihiko
Mosley, Thomas H.
METASTROKE,
Wright, Margaret J.
Hilal, Saima
Jian, Xueqiu
Dostawca treści:
Repozytorium Uniwersytetu Jagiellońskiego
Artykuł
Tytuł:
Augmenting precision medicine via targeted RNA-Seq detection of expressed mutations
Autorzy:
Pabón-Peña, Carlos
Scherer, Andreas
Łabaj, Paweł
Mason, Christopher E.
Lucas, Anne Bergstrom
Li, Jianying
Gong, Binsheng
Johann, Donald J.
Richmond, Todd A.
Mozsary, Christopher
Butler, Daniel
Ebrahim Sahraeian, Sayed Mohammad
Jones, Wendell
Maestro, Roberta
Xu, Joshua
Willey, James C.
Bushel, Pierre R.
Li, Dan
Pan, Bohu
Kusko, Rebecca
Novoradovskaya, Natalia
Kreil, David P.
Chen, Guangchun
Foox, Jonathan
Tilgner, Hagen U.
Opis:
In precision medicine, DNA-based assays are currently necessary but not always sufficient for predicting therapeutic efficacy of cancer drugs based on the mutational findings in a patient’s tumor specimen. Most drugs target proteins, but it is challenging and not yet cost-effective to perform high-throughput proteomics profiling, including mutational analysis, on cancer specimens. RNA may be an effective mediator for bridging the "DNA to protein divide" and provide more clarity and therapeutic predictability for precision oncology. While RNA sequencing (RNA-seq) has been increasingly used alongside DNA cancer mutation screening panels to assess the impact of variants on gene transcript expression and splicing, comprehensive evaluations of RNA panels and the integration of expressed mutation data analytics to supplement DNA panels are still limited. In this study, we conducted targeted RNA-seq on a reference sample set for expressed variant detection to explore its potential capability to complement DNA variant results or detect variants independently. The results indicated that, with a carefully controlled false positive rate ensuring high accuracy, RNA-seq uniquely identified variants with significant pathological relevance that were missed by DNA-seq, demonstrating its potential to uncover clinically actionable mutations. On the other hand, while some variants were detected by both approaches, others were missed by one or the other, reflecting either the nature of these variants or limitations of the bioinformatics tools used. Variants missed by RNA-seq are often not expressed or expressed at very low levels, suggesting they may be of lower clinical relevance. Incorporating RNA-seq into clinical biomarker panels will ultimately advance precision medicine and improve patient outcomes by improving the strength and reliability of somatic mutation findings for clinical diagnosis, prognosis and prediction of therapeutic efficacy.
Dostawca treści:
Repozytorium Uniwersytetu Jagiellońskiego
Artykuł
Tytuł:
Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell-engaging antibody, in relapsed or refractory large B-cell lymphoma : dose expansion in a phase I/II trial
Autorzy:
Cheah, Chan Y.
van der Poel, Marjolein
Thieblemont, Catherine
Kim, Tae Min
Cota Stirner, Mariana
Feldman, Tatyana
Kilavuz, Nurgul
Poon, Michelle Limei
Do, Young Rok
Ahmadi, Tahamtan
Jurczak, Wojciech
Phillips, Tycel
Elliott, Brian
Chiu, Christopher
Sacchi, Mariana
Gasiorowski, Robin
Hutchings, Martin
Ghesquieres, Herve
Clausen, Michael Roost
Chen, Menghui
Lugtenburg, Pieternella J.
Lewis, David John
Cunningham, David
Opis:
Purpose: Epcoritamab is a subcutaneously administered CD3xCD20 T-cell–engaging, bispecific antibody that activates T cells, directing them to kill malignant CD20+ B cells. Single-agent epcoritamab previously demonstrated potent antitumor activity in dose escalation across B-cell non-Hodgkin lymphoma subtypes. Patients and Methods: In the dose-expansion cohort of a phase I/II study (ClinicalTrials.gov identifier: NCT03625037), adults with relapsed or refractory CD20+ large B-cell lymphoma and at least two prior therapy lines (including anti-CD20 therapies) received subcutaneous epcoritamab in 28-day cycles (once weekly step-up doses in weeks 1-3 of cycle 1, then full doses once weekly through cycle 3, once every 2 weeks in cycles 4-9, and once every 4 weeks in cycle 10 and thereafter) until disease progression or unacceptable toxicity. The primary end point was overall response rate by the independent review committee. Results: As of January 31, 2022, 157 patients were treated (median age, 64 years [range, 20‐83]; median of three [range, 2-11] prior therapy lines; primary refractory disease: 61.1%; prior chimeric antigen receptor (CAR) T-cell exposure: 38.9%). At a median follow-up of 10.7 months, the overall response rate was 63.1% (95% CI, 55.0 to 70.6) and the complete response rate was 38.9% (95% CI, 31.2 to 46.9). The median duration of response was 12.0 months (among complete responders: not reached). Overall and complete response rates were similar across key prespecified subgroups. The most common treatment-emergent adverse events were cytokine release syndrome (49.7%; grade 1 or 2: 47.1%; grade 3: 2.5%), pyrexia (23.6%), and fatigue (22.9%). Immune effector cell–associated neurotoxicity syndrome occurred in 6.4% of patients with one fatal event. Conclusion: Subcutaneous epcoritamab resulted in deep and durable responses and manageable safety in highly refractory patients with large B-cell lymphoma, including those with prior CAR T-cell exposure.
Dostawca treści:
Repozytorium Uniwersytetu Jagiellońskiego
Artykuł
Wyświetlanie 1-10 z 43

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