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JOURNAL ARTICLE
Rong Chen, Alan Schumitzky, Alona Kryshchenko, Keith Nieforth, Michael Tomashevskiy, Shuhua Hu, Romain Garreau, Julian Otalvaro, Walter Yamada, Michael N Neely
Inspired from quantum Monte Carlo, by sampling discrete and continuous variables at the same time using the Metropolis-Hastings algorithm, we present a novel, fast, and accurate high performance Monte Carlo Parametric Expectation Maximization (MCPEM) algorithm. We named it Randomized Parametric Expectation Maximization (RPEM). We compared RPEM with NONMEM's Importance Sampling Method (IMP), Monolix's Stochastic Approximation Expectation Maximization (SAEM), and Certara's Quasi-Random Parametric Expectation Maximization (QRPEM) for a realistic two-compartment voriconazole model with ordinary differential equations using simulated data...
April 15, 2024: CPT: Pharmacometrics & Systems Pharmacology
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JOURNAL ARTICLE
Julian J Freen-van Heeren, Virginia Palomares Cabeza, David Cobeta Lopez, Domenique Kivits, Irma Rensink, Annelies W Turksma, Anja Ten Brinke
T cells are instrumental in protecting the host against invading pathogens and the development of cancer. To do so, they produce effector molecules such as granzymes, interleukins, interferons, and perforin. For the development and immunomonitoring of therapeutic applications such as cell-based therapies and vaccines, assessing T cell effector function is paramount. This can be achieved through various methods, such as 51 Cr release assays, flow cytometry, and enzyme-linked immune absorbent spot (ELISpot) assays...
2024: Methods in Molecular Biology
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JOURNAL ARTICLE
Julian J Freen-van Heeren
As part of the adaptive immune system, T cells are critical to maintain immune homeostasis. T cells provide protective immunity by killing infected cells and combatting cancerous cells. To do so, T cells produce and secrete effector molecules, such as granzymes, perforin, and cytokines such as tumor necrosis factor α and interferon γ. However, in immune suppressive environments, such as tumors, T cells gradually lose the capacity to perform their effector function. One way T cell effector function can be enhanced is through genetic engineering with tools such as clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)...
2024: Methods in Molecular Biology
#24
JOURNAL ARTICLE
Julian J Freen-van Heeren
Maintaining immune homeostasis is instrumental for host health. Immune cells, such as T cells, are instrumental for the eradication of pathogenic bacteria, fungi and viruses. Furthermore, T cells also play a major role in the fight against cancer. Through the formation of immunological memory, a pool of antigen-experienced T cells remains in the body to rapidly protect the host upon reinfection or retransformation. In order to perform their protective function, T cells produce cytolytic molecules, such as granzymes and perforin, and cytokines such as interferon γ and tumor necrosis factor α...
2024: Methods in Molecular Biology
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JOURNAL ARTICLE
Yongkang Xiao, Yu Hou, Huixue Zhou, Gayo Diallo, Marcelo Fiszman, Julian Wolfson, Li Zhou, Halil Kilicoglu, You Chen, Chang Su, Hua Xu, William G Mantyh, Rui Zhang
Non-pharmaceutical interventions (NPI) have great potential to improve cognitive function but limited investigation to discover NPI repurposing for Alzheimer's Disease (AD). This is the first study to develop an innovative framework to extract and represent NPI information from biomedical literature in a knowledge graph (KG), and train link prediction models to repurpose novel NPIs for AD prevention. We constructed a comprehensive KG, called ADInt, by extracting NPI information from biomedical literature. We used the previously-created SuppKG and NPI lexicon to identify NPI entities...
April 15, 2024: Scientific Reports
#26
JOURNAL ARTICLE
Jinxia Liu, Jane MacNaughtan, Annarein J C Kerbert, Theo Portlock, Javier Martínez Gonzalez, Yi Jin, Frederick Clasen, Abeba Habtesion, Huoyan Ji, Qin Jin, Alexandra Phillips, Francesco De Chiara, Ganesh Ingavle, Cesar Jimenez, Giacomo Zaccherini, Katherine Husi, Miguel Angel Rodriguez Gandia, Paul Cordero, Junpei Soeda, Lynda McConaghy, Jude Oben, Karen Church, Jia V Li, Haifeng Wu, Aarti Jalan, Pere Gines, Elsa Solà, Simon Eaton, Carrie Morgan, Michal Kowalski, Daniel Green, Amir Gander, Lindsey A Edwards, I Jane Cox, Helena Cortez-Pinto, Thomas Avery, Reiner Wiest, Francois Durand, Paolo Caraceni, Roberto Elosua, Joan Vila, Marco Pavesi, Vicente Arroyo, Nathan Davies, Rajeshwar P Mookerjee, Victor Vargas, Susan Sandeman, Gautam Mehta, Saeed Shoaie, Julian Marchesi, Agustín Albillos, Fausto Andreola, Rajiv Jalan
OBJECTIVE: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. DESIGN: Performance of Yaq-001 was evaluated in vitro . Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied...
April 15, 2024: Gut
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JOURNAL ARTICLE
Mitchell Wiebe, Kirsty Milligan, Joan Brewer, Alejandra M Fuentes, Ramie Ali-Adeeb, Alexandre G Brolo, Julian J Lum, Jeffrey L Andrews, Christina Haston, Andrew Jirasek
Radiation-induced lung injury (RILI) is a dose-limiting toxicity for cancer patients receiving thoracic radiotherapy. As such, it is important to characterize metabolic associations with the early and late stages of RILI, namely pneumonitis and pulmonary fibrosis. Recently, Raman spectroscopy has shown utility for the differentiation of pneumonitic and fibrotic tissue states in a mouse model; however, the specific metabolite-disease associations remain relatively unexplored from a Raman perspective. This work harnesses Raman spectroscopy and supervised machine learning to investigate metabolic associations with radiation pneumonitis and pulmonary fibrosis in a mouse model...
April 15, 2024: Analyst
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JOURNAL ARTICLE
Lisa Wilms, Martin Komainda, Dina Hamidi, Friederike Riesch, Juliane Horn, Johannes Isselstein
Virtual fencing (VF) is a modern fencing technology that requires the animal to wear a device (e.g. a collar) that emits acoustic signals to replace the visual cue of traditional physical fences (PF) and, if necessary, mild electric signals. The use of devices that provide electric signals leads to concerns regarding the welfare of virtually fenced animals. The objective of this review is to give an overview of the current state of VF research into the welfare and learning behavior of cattle. Therefore, a systematic literature search was conducted using two online databases and reference lists of relevant articles...
April 15, 2024: Journal of Animal Science
#29
JOURNAL ARTICLE
Kyle K Obana, Morgan E Hasegawa, John D Mueller, Alexander N Berk, Julian B Rimm, Jonathan C Horng, Bryan M Saltzman, Robert L Parisien, Lorrin S K Lee, David P Trofa
BACKGROUND: Surfing is an increasingly popular sport with a high propensity for both traumatic and atraumatic injuries. PURPOSE: To analyze the trends, etiologies, and diagnoses of lower extremity orthopaedic-related surfing injuries presenting to United States (US) emergency departments (EDs) within a 21-year study period. STUDY DESIGN: Descriptive epidemiology study. METHODS: The National Electronic Injury Surveillance System database was queried for data on lower extremity surfing injuries presenting to US EDs from January 1 to December 31, 2022...
April 2024: Orthopaedic Journal of Sports Medicine
#30
Ugo Sorrentino, Luigi M Romito, Barbara Garavaglia, Mario Fichera, Isabel Colangelo, Holger Prokisch, Juliane Winkelmann, Jan Necpal, Robert Jech, Michael Zech
BACKGROUND: Spinocerebellar ataxia 21 (SCA21) is a rare neurological disorder caused by heterozygous variants in TMEM240 . A growing, yet still limited number of reports suggested that hyperkinetic movements should be considered a defining component of the disease. CASE SERIES: We describe two newly identified families harboring the recurrent pathogenic TMEM240 p.Pro170Leu variant. Both index patients and the mother of the first proband developed movement disorders, manifesting as myoclonic dystonia and action-induced dystonia without co-occurring ataxia in one case, and pancerebellar syndrome complicated by action-induced dystonia in the other...
2024: Tremor and Other Hyperkinetic Movements
#31
Yihe Weng, Johann Kruschwitz, Laura M Rueda-Delgado, Kathy Ruddy, Rory Boyle, Luisa Franzen, Emin Serin, Tochukwu Nweze, Jamie Hanson, Alannah Smyth, Tom Farnan, Tobias Banaschewski, Arun L W Bokde, Sylvane Desrivières, Herta Flor, Antoine Grigis, Hugh Garavan, Penny Gowland, Andreas Heinz, Rüdiger Brühl, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Jane McGrath, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Nathalie Holz, Juliane H Fröhner, Michael N Smolka, Nilakshi Vaidya, Gunter Schumann, Henrik Walter, Robert Whelan
UNLABELLED: Substance use, including cigarettes and cannabis, is associated with poorer sustained attention in late adolescence and early adulthood. Previous studies were predominantly cross-sectional or under- powered and could not indicate if impairment in sustained attention was a consequence of substance- use or a marker of the inclination to engage in such behaviour. This study explored the relationship between sustained attention and substance use across a longitudinal span from ages 14 to 23 in over 1,000 participants...
April 5, 2024: bioRxiv
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JOURNAL ARTICLE
Katerina Mardilovich, Gregory Naylor, Linda Julian, Narisa Phinichkusolchit, Karen Keeshan, Karen Blyth, Michael F Olson
Apoptosis is characterized by membrane blebbing and apoptotic body formation. Caspase cleavage of ROCK1 generates an active fragment that promotes actin-myosin mediated contraction and membrane blebbing during apoptosis. Expression of caspase-resistant non-cleavable ROCK1 (Rock1 NC) prolonged survival of mice that rapidly develop B cell lymphomas due to Eµ-Myc transgene expression. Eµ-Myc; Rock1 NC mice had significantly fewer bone marrow cells relative to Eµ-Myc mice expressing wild-type ROCK1 (Rock1 WT), which was associated with altered cell cycle profiles...
April 15, 2024: Disease Models & Mechanisms
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JOURNAL ARTICLE
Carissa Bleker, Živa Ramšak, Andras Bittner, Vid Podpečan, Maja Zagorščak, Bernhard Wurzinger, Špela Baebler, Marko Petek, Maja Križnik, Annelotte van Dieren, Juliane Gruber, Leila Afjehi-Sadat, Wolfram Weckwert, Anže Županič, Markus Teige, Ute C Vothknecht, Kristina Gruden
Stress Knowledge Map (SKM, https://skm.nib.si) is a publicly available resource containing two complementary knowledge graphs describing current knowledge of biochemical, signalling, and regulatory molecular interactions in plants: a highly curated model of plant stress signalling (PSS, 543 reactions) and a large comprehensive knowledge network (CKN, 488,390 interactions). Both were constructed by domain experts through systematic curation of diverse literature and database resources. SKM provides a single entrypoint for plant stress response investigations and the related growth trade-offs as well as interactive exploration of current knowledge...
April 13, 2024: Plant communications
#34
JOURNAL ARTICLE
Daniel Pan, Julian W Tang
In June 2023, the UK began official hearings for its independent investigation into pandemic preparedness. Thus far, the inquiry has been told that planning has been wholly inadequate and that a future outbreak is inevitable. We present here four key problems that contributed to significant morbidity and mortality during the Coronavirus 2019 (COVID-19) pandemic over the past 3 years in the UK - and which will contribute to excess morbidity and mortality in the next outbreak. First, there was misunderstanding about what procedures were deemed as aerosol generating...
September 2023: Clinical Medicine: Journal of the Royal College of Physicians of London
#35
JOURNAL ARTICLE
Julian Swatler, Alicja Targońska, Laura Turos-Korgul, Grażyna Mosieniak, Katarzyna Piwocka
Extracellular vesicles (EVs) enable communication between cells and tissues and are implicated in modulation of tumor immunosuppression. Here, we present a protocol for isolating tumor-derived EVs and assessing their functional influence in cultures with different subsets of human T cells. We describe steps for differential ultracentrifugation, size exclusion chromatography, EVs quantification, and fluorescence-activated cell sorting of human T cells. We then detail procedures for culturing T cells with EVs and using high-resolution spectral flow cytometry phenotyping for the analysis thereof...
April 12, 2024: STAR protocols
#36
JOURNAL ARTICLE
Rodrigo Pommot Berto, Hanna Bugler, Gabriel Dias, Mateus Oliveira, Lucas Ueda, Sergio Dertkigil, Paula D P Costa, Leticia Rittner, Julian P Merkofer, Dennis M J van de Sande, Sina Amirrajab, Gerhard S Drenthen, Mitko Veta, Jacobus F A Jansen, Marcel Breeuwer, Ruud J G van Sloun, Abdul Qayyum, Cristobal Rodero, Steven Niederer, Roberto Souza, Ashley D Harris
PURPOSE: Use a conference challenge format to compare machine learning-based gamma-aminobutyric acid (GABA)-edited magnetic resonance spectroscopy (MRS) reconstruction models using one-quarter of the transients typically acquired during a complete scan. METHODS: There were three tracks: Track 1: simulated data, Track 2: identical acquisition parameters with in vivo data, and Track 3: different acquisition parameters with in vivo data. The mean squared error, signal-to-noise ratio, linewidth, and a proposed shape score metric were used to quantify model performance...
April 13, 2024: Magma
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JOURNAL ARTICLE
Lisanne A E M van Houtum, William F C Baaré, Christian F Beckmann, Josefina Castro-Fornieles, Charlotte A M Cecil, Juliane Dittrich, Bjørn H Ebdrup, Jörg M Fegert, Alexandra Havdahl, Manon H J Hillegers, Raffael Kalisch, Steven A Kushner, Isabelle M Mansuy, Signe Mežinska, Carmen Moreno, Ryan L Muetzel, Alexander Neumann, Merete Nordentoft, Jean-Baptiste Pingault, Martin Preisig, Andrea Raballo, John Saunders, Emma Sprooten, Gisela Sugranyes, Henning Tiemeier, Geeske M van Woerden, Caroline L Vandeleur, Neeltje E M van Haren
Over 50% of children with a parent with severe mental illness will develop mental illness by early adulthood. However, intergenerational transmission of risk for mental illness in one's children is insufficiently considered in clinical practice, nor is it sufficiently utilised into diagnostics and care for children of ill parents. This leads to delays in diagnosing young offspring and missed opportunities for protective actions and resilience strengthening. Prior twin, family, and adoption studies suggest that the aetiology of mental illness is governed by a complex interplay of genetic and environmental factors, potentially mediated by changes in epigenetic programming and brain development...
April 13, 2024: European Child & Adolescent Psychiatry
#38
REVIEW
Maxime Klimezak, Juliane Chaud, Anaïs Brion, Frédéric Bolze, Benoit Frisch, Béatrice Heurtault, Antoine Kichler, Alexandre Specht
The emerging field of photopharmacology is a promising chemobiological methodology for optical control of drug activities that could ultimately solve the off-target toxicity outside the disease location of many drugs for the treatment of a given pathology. The use of photolytic reactions looks very attractive for a light activated drug release but requires to develop photolytic reactions sensitive to red or NIR light excitation for better tissue penetration. In this review, we will present the concepts of triplet-triplet annihilation upconversion (TTA-UC) based photolysis and their recent in vivo applications for light induced drug delivery using photoactivatable nanoparticles (NPs)...
April 13, 2024: Advanced Healthcare Materials
#39
JOURNAL ARTICLE
Julian Bickel, Anne Szewczyk, Nadine Aboutara, Hilke Jungen, Alexander Müller, Benjamin Ondruschka, Stefanie Iwersen-Bergmann
A novel analytical method was developed for the simultaneous quantification of the R/S-enantiomers of amphetamine, methamphetamine, MDA and MDMA in hair samples using liquid chromatography-tandem mass spectrometry (LC-MS-MS). This method involved a straightforward derivatization step with dansyl chloride and the use of a chiral column, enabling the separation and quantification of all eight enantiomers in a single analysis. The method exhibited excellent linearity across a concentration range of 0.03-3.00 ng/mg for each enantiomer...
March 29, 2024: Journal of Analytical Toxicology
#40
JOURNAL ARTICLE
Laurent Peyrin-Biroulet, Marla C Dubinsky, Bruce E Sands, Julian Panés, Stefan Schreiber, Walter Reinisch, Brian G Feagan, Silvio Danese, Andres J Yarur, Geert R D'Haens, Martina Goetsch, Karolina Wosik, Michael Keating, Krisztina Lazin, Joseph Wu, Irene Modesto, Aoibhinn McDonnell, Lauren Bartolome, Séverine Vermeire
BACKGROUND AND AIMS: Pivotal trials in ulcerative colitis have historically excluded patients with isolated proctitis. Etrasimod is an oral, oncedaily, selective sphingosine 1phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis. This post hoc analysis assessed efficacy and safety of etrasimod 2 mg once daily in patients with isolated proctitis (centrally read) from the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials. METHODS: Patients, including those with isolated proctitis (<10 cm rectal involvement) who met all other inclusion criteria in ELEVATE UC 52 and ELEVATE UC 12, were randomised 2:1 to receive etrasimod or placebo...
April 13, 2024: Journal of Crohn's & Colitis
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