tbuckley/cabot-search huggingface dataset:
The airway epithelium: an orchestrator of inflammation, a key structural barrier and a therapeutic target in severe asthma
Authors: Richard J. Russell, Louis-Philippe Boulet, Christopher E. Brightling, Ian D. Pavord, Celeste Porsbjerg, Del Dorscheid, Asger Sverrild
Journal: European Respiratory Journal (2024)

Asthma is a disease of heterogeneous pathology, typically characterised by excessive inflammatory and bronchoconstrictor responses to the environment. The clinical expression of the disease is a consequence of the interaction between environmental factors and host factors over time, including genetic susceptibility, immune dysregulation and airway remodelling. As a critical interface between the host and the environment, the airway epithelium plays an important role in maintaining homeostasis in the face of environmental challenges. Disruption of epithelial integrity is a key factor contributing to multiple processes underlying asthma pathology. In this review, we first discuss the unmet need in asthma management and provide an overview of the structure and function of the airway epithelium. We then focus on key pathophysiological changes that occur in the airway epithelium, including epithelial barrier disruption, immune hyperreactivity, remodelling, mucus hypersecretion and mucus plugging, highlighting how these processes manifest clinically and how they might be targeted by current and novel therapeutics.
Aging phenotype in AD brain organoids: Track to success and challenges
Authors: Muhammad Kamal Hossain, Hyung-Ryong Kim, Han Jung Chae
Journal: Ageing Research Reviews (2024)

Alzheimer's disease (AD) poses a complex challenge, with abnormal protein accumulation in the brain causing memory loss and cognitive decline. Traditional models fall short in AD research, prompting interest in 3D brain organoids (BOs) from human stem cells. These findings hold promise for unveiling the mechanisms of AD, especially in relation to aging. However, an understanding of the aging impact of AD remains elusive. BOs offer insight but face challenges. This review delves into the role of BOs in deciphering aging-related AD and acknowledges limitations. Strategies to enhance BOs for accurate aging modeling in AD brains are suggested. Strengthened by molecular advancements, BOs have the potential to uncover the aging phenotype, advancing AD research.
Off‐the‐Shelf Synthetic Biodegradable Grafts Transform In Situ into a Living Arteriovenous Fistula in a Large Animal Model
Authors: Paul J. Besseling, Wojciech Szymczyk, Martin Teraa, Raechel J. Toorop, Dan Jing Wu, Rob C. H. Driessen, Arturo M. Lichauco, Henk M. Janssen, Melanie van de Kaa, Krista den Ouden, Petra M. de Bree, Joost O. Fledderus, Carlijn V. C. Bouten, Gert J. de Borst, Patricia Y. W. Dankers, Marianne C. Verhaar
Journal: Advanced Healthcare Materials (2024)

Current vascular access options require frequent interventions. In situ tissue engineering (TE) may overcome these limitations by combining the initial success of synthetic grafts with long-term advantages of autologous vessels by using biodegradable grafts that transform into autologous vascular tissue at the site of implantation. Scaffolds (6 mm-Ø) made of supramolecular polycarbonate-bisurea (PC-BU), with a polycaprolactone (PCL) anti-kinking-coil, are implanted between the carotid artery and jugular vein in goats. A subset is bio-functionalized using bisurea-modified-Stromal cell-derived factor-1α (SDF1α) derived peptides and ePTFE grafts as controls. Grafts are explanted after 1 and 3 months, and evaluated for material degradation, tissue formation, compliance, and patency. At 3 months, the scaffold is resorbed and replaced by vascular neo-tissue, including elastin, contractile markers, and endothelial lining. No dilations, ruptures, or aneurysms are observed and grafts are successfully cannulated at termination. SDF-1α-peptide-biofunctionalization does not influence outcomes. Patency is lower in TE grafts (50%) compared to controls (100% patency), predominantly caused by intimal hyperplasia. Rapid remodeling of a synthetic, biodegradable vascular scaffold into a living, compliant arteriovenous fistula is demonstrated in a large animal model. Despite lower patency compared to ePTFE, transformation into autologous and compliant living tissue with self-healing capacity may have long-term advantages.
ARID1A orchestrates SWI/SNF-mediated sequential binding of transcription factors with ARID1A loss driving pre-memory B cell fate and lymphomagenesis
Authors: Darko Barisic, Christopher R. Chin, Cem Meydan, Matt Teater, Ioanna Tsialta, Coraline Mlynarczyk, Amy Chadburn, Xuehai Wang, Margot Sarkozy, Min Xia, Sandra E. Carson, Santo Raggiri, Sonia Debek, Benedikt Pelzer, Ceyda Durmaz, Qing Deng, Priya Lakra, Martin Rivas, Christian Steidl, David W. Scott, Andrew P. Weng, Christopher E. Mason, Michael R. Green, Ari Melnick
Journal: Cancer Cell (2024)
US Food and Drug Administration Approval Summary: Talazoparib in Combination With Enzalutamide for Treatment of Patients With Homologous Recombination Repair Gene-Mutated Metastatic Castration-Resistant Prostate Cancer
Authors: Brian L. Heiss, Elaine Chang, Xin Gao, Tien Truong, Michael H. Brave, Erik Bloomquist, Ankit Shah, Salaheldin Hamed, Jeffrey Kraft, Haw-Jyh Chiu, Tiffany K. Ricks, Amy Tilley, William F. Pierce, Liuya Tang, Abdelrahmman Abukhdeir, Shyam Kalavar, Reena Philip, Shenghui Tang, Richard Pazdur, Laleh Amiri-Kordestani, Paul G. Kluetz, Daniel L. Suzman
Journal: Journal of Clinical Oncology (2024)

The US Food and Drug Administration (FDA) approved talazoparib with enzalutamide for first-line treatment of patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).
Meningeal lymphatics can influence stroke outcome
Authors: Gou Young Koh, Donald M. McDonald
Journal: The Journal of Experimental Medicine (2024)

Meningeal lymphatics are conduits for cerebrospinal fluid drainage to lymphatics and lymph nodes in the neck. In this issue of JEM, Boisserand et al. (https://doi.org/10.1084/jem.20221983) provide evidence that expansion of meningeal lymphatics protects against ischemic stroke.
Emerging Strategies for Beta Cell Encapsulation for Type 1 Diabetes Therapy
Authors: Mette Steen Toftdal, Lars Groth Grunnet, Menglin Chen
Journal: Advanced Healthcare Materials (2024)

Abstract Diabetes is a prevalent chronic disease affecting millions of people globally. To address this health challenge, advanced beta cell therapy using biomaterials‐based macroscale, microscale, and nanoscale encapsulation devices must tackle various obstacles. First, overcoming foreign body responses is a major focus of research. Strategies such as immunomodulatory materials and physical immunoshielding are investigated to reduce the immune response and improve the longevity of the encapsulated cells. Furthermore, oxygenating strategies, such as the use of oxygen‐releasing biomaterials, are developed to improve oxygen diffusion and promote cell survival. Finally, yet importantly, promoting vascularization through the use of angiogenic growth factors and the incorporation of pre‐vascularized materials are also explored to enhance nutrient and oxygen supply to the encapsulated cells. This review seeks to specifically highlight the emerging research strategies developed to overcome these challenges using micro and nanoscale biomaterial encapsulation devices. Continuously improving and refining these strategies make an advance toward realizing the improved therapeutic potential of the encapsulated beta cells.
Randomized trials of multicancer screening tests: augmenting their ability to identify a genuine mortality benefit
Authors: Noel S Weiss
Journal: JNCI Journal of the National Cancer Institute (2024)

Randomized trials of the efficacy of multicancer early detection, by means of measurement of cell-free DNA and/or protein biomarkers in peripheral blood specimens, will attempt to document a difference in cancer mortality between persons assigned to intervention and control arms. Their ability to do so is limited by the relatively low rate of death from individual forms of cancer, the relatively low sensitivity of the tests currently being used, and the use of other cancer screening modalities among trial participants. However, if those same blood specimens also could be obtained from control arm participants in a given trial and then tested for the same markers, with results not known (or not made available) until the conclusion of follow-up for cancer mortality, it would be possible to compare mortality from given forms of cancer between test-positive individuals whose results were known and not known during the course of the trial. Such an analysis addresses the impact of a stimulus to offer targeted diagnostic testing, potentially leading to early treatment, against cancer mortality. Among persons who screen as positive, it should provide a relatively more sensitive means of gauging a possible mortality benefit resulting from multicancer screening.
Offline: Towards Shangri-La
Authors: Richard Horton
Journal: The Lancet (2024)

The subject on the menu was trust, or rather the "alarming lack of trust in government, institutions, science, and within society". Post-pandemic, trust has become a fashionable accessory in the wardrobe of global health. The quantity of trust within a society was an important predictor of whether countries succeeded in navigating COVID-19. In a place I cannot describe, with people I cannot name, our goal was to explore how to bridge the trust deficit. (Note to hosts: trust cannot be sustained without transparency.) Here is a brief summary of our conversation.
A randomized double-blinded trial to assess recurrence of systemic allergic reactions following COVID-19 mRNA vaccination
Authors: Muhammad B Khalid, Ellen Zektser, Eric Chu, Min Li, Joanna Utoh, Patrick Ryan, Hanna S Loving, Roa Harb, Robbie Kattappuram, Lindsay Chatman, Stella Hartono, Estefania Claudio-Etienne, Guangping Sun, Edward P Feener, Zhongbo Li, Samuel K Lai, Quang Le, Lawrence B Schwartz, Jonathan J Lyons, Hirsh Komarow, Zhao-Hua Zhou, Haniya Raza, Maryland Pao, Karen Laky, Steven M Holland, Erica Brittain, Pamela A Frischmeyer-Guerrerio
Journal: Journal of Allergy and Clinical Immunology (2024)
Low physical function following cancer diagnosis is associated with higher mortality risk in postmenopausal women
Authors: Paola Gonzalo-Encabo, Alexi Vasbinder, Jennifer W Bea, Kerryn W Reding, Deepika Laddu, Michael J LaMonte, Marcia L Stefanick, Candyce H Kroenke, Su Yon Jung, Aladdin H Shadyab, Michelle J Naughton, Manali I Patel, Juhua Luo, Hailey R Banack, Yangbo Sun, Michael S Simon, Christina M Dieli-Conwright
Journal: JNCI Journal of the National Cancer Institute (2024)

Postmenopausal women with cancer experience an accelerated physical dysfunction beyond what is expected through aging alone due to cancer and its treatments. The aim of this study was to determine whether declines in physical function after cancer diagnosis are associated with all-cause mortality and cancer-specific mortality.
Intravitreal aflibercept 8 mg in diabetic macular oedema (PHOTON): 48-week results from a randomised, double-masked, non-inferiority, phase 2/3 trial
Authors: David M Brown, David S Boyer, Diana V Do, Charles C Wykoff, Taiji Sakamoto, Peter Win, Sunir Joshi, Hani Salehi-Had, András Seres, Alyson J Berliner, Sergio Leal, Robert Vitti, Karen W Chu, Kimberly Reed, Rohini Rao, Yenchieh Cheng, Wei Sun, Delia Voronca, Rafia Bhore, Ursula Schmidt-Ott, Thomas Schmelter, Andrea Schulze, Xin Zhang, Boaz Hirshberg, George D Yancopoulos, Sobha Sivaprasad, Prema Abraham, Christopher Aderman, Kunihiko Akiyama, Daniel V. Alfaro, Fareed A. Ali, Payam Amini, Andres Emanuelli Anzalotta, György Bátor, Ivan Batlle, Adam Berger, Ramanath Bhandari, William Bridges, Christian Brinkmann, Jamin Brown, Stuart Burgess, Jorge Calzada, Antonio Capone Jr., Dana Cervena, Steven Charles, Nauman Chaudhry, David Chow, W. Lloyd Clark, Paul Conrad III, Matthew Cunningham, Hajir Dadgostar, Amr Dessouki, Dana Deupree, Christopher Devine, David Eichenbaum, Jan Ernest, Nicolas Feltgen, Moss Fenberg, Philip Ferrone, Ronald Frenkel, Scott Friedman, Julie Gasperini, Adam Gerstenblith, Ghassan Ghorayeb, Michel Giunta, Mitchell Goff, Liliya Golas, Joseph M. Googe Jr., Jordana Goren Fein, Curtis Hagedorn, Akira Hagiwara, Paul Hahn, Richard Hairston, Jason Handza, Vivienne Hau, Ken Hayashi, Jeffrey Heier, Vrinda Hershberger, Patrick Higgins, Yoshio Hirano, Shigeru Honda, Yasuko Ikegami, Yuichiro Ishida, Isao Ishikawa, Kiyoshi Ishii, Eric P. Jablon, Atul Jain, Yuichi Kaji, Kapil Kapoor, Ágnes Kerényi, Kazuhiro Kimura, Genichiro Kishino, Katalin Kiss, Takashi Kitaoka, James M. Klancnik, Namie Kobayashi, Jiro Kogo, Vladimir Korda, Erik Kruger, Sentaro Kusuhara, Wilfredo Lara, Ketan Laud, Seong Lee, James Luu, Dennis Marcus, Calvin Mein, Annal Meleth, Tibor Milibák, Yoshinori Mitamura, Toshinori Murata, Sumiyo Noge, Hajime Onoe, James Osher, András Papp, Justin Parschauer, Sugat Patel, Sunil Patel, Matthew Pezda, Ashkan Pirouz, Pradeep Prasad, Omar Punjabi, Llewelyn Rao, Richard Roe, Ramin Schadlu, Eric Schneider, Ankur Shah, Milan Shah, Sandeep Shah, Sumit Shah, Ashish Sharma, Veeral Sheth, Masahiko Shimura, Lawrence Singerman, Georg Spital, Robert Stoltz, Eric Suan, Kiyoshi Suzuma, Hidenori Takahashi, Yoshihiro Takamura, Masaru Takeuchi, Jeffrey Tan, Benjamin Thomas, Edit Tóth,-Molnár, Tetsuo Ueda, Hiroaki Ushida, Attila Vajas, Deepali Varma, Balázs Varsányi, Miroslav Veith, Pamela Weber, Raymond Wee, Geoff Williams, Haruhiko Yamada, Yoshihiro Yonekawa, Shigeo Yoshida
Journal: The Lancet (2024)
Ocular Mucous Membrane Pemphigoid
Authors: Raul E. Ruiz-Lozano, Maria F. Colorado-Zavala, Eugenia M. Ramos-Dávila, Manuel E. Quiroga-Garza, Nadim S. Azar, Hazem M. Mousa, Julio C. Hernández-Camarena, Sandra S. Stinnett, Melissa Daluvoy, Terry Kim, Maite Sainz-de-la-Maza, Russell P. Hall, Alejandro Rodriguez-Garcia, Victor L. Perez
Journal: Ophthalmology (2024)
Oral peptide therapeutics for diabetes treatment: State-of-the-art and future perspectives
Authors: Bingwen Ding, Zhu Zhu, Cong Guo, Jiaxin Li, Yong Gan, Miaorong Yu
Journal: Acta Pharmaceutica Sinica B (2024)

Diabetes, characterized by hyperglycemia, is a major cause of death and disability worldwide. Peptides, such as insulin and glucagon-like peptide-1 (GLP-1) analogs, have shown promise as treatments for diabetes due to their ability to mimic or enhance insulin's actions in the body. Compared to subcutaneous injection, oral administration of anti-diabetic peptides is a preferred approach. However, biological barriers significantly reduce the efficacy of oral peptide therapeutics. Recent advancements in drug delivery systems and formulation techniques have greatly improved the oral delivery of peptide therapeutics and their efficacy in treating diabetes. This review will highlight (1) the benefits of oral anti-diabetic peptide therapeutics; (2) the biological barriers for oral peptide delivery, including pH and enzyme degradation, intestinal mucosa barrier, and biodistribution barrier; (3) the delivery platforms to overcome these biological barriers. Additionally, the review will discuss the prospects in this field. The information provided in this review will serve as a valuable guide for future developments in oral anti-diabetic peptide therapeutics.
Bringing innovative wound care polymer materials to the market: Challenges, developments, and new trends
Authors: Pegah Sanjarnia, Matías L. Picchio, Agustin N. Polegre Solis, Katharina Schuhladen, Patricia M. Fliss, Nikolaos Politakos, Lutz Metterhausen, Marcelo Calderón, Ernesto R. Osorio-Blanco
Journal: Advanced Drug Delivery Reviews (2024)
Smart exosomes enhance PDAC targeted therapy
Authors: Justin F. Creeden, Jonathan Sevier, Jian-Ting Zhang, Yakov Lapitsky, F. Charles Brunicardi, Ge Jin, John Nemunaitis, Jing-Yuan Liu, Andrea Kalinoski, Donald Rao, Shi-He Liu
Journal: Journal of Controlled Release (2024)

Exosomes continue to attract interest as a promising nanocarrier drug delivery technology. They are naturally derived nanoscale extracellular vesicles with innate properties well suited to shuttle proteins, lipids, and nucleic acids between cells. Nonetheless, their clinical utility is currently limited by several major challenges, such as their inability to target tumor cells and a high proportion of clearance by the mononuclear phagocyte system (MPS) of the liver and spleen. To overcome these limitations, we developed "Smart Exosomes" that co-display RGD and CD47p110–130 through CD9 engineering (ExoSmart). The resultant ExoSmart demonstrates enhanced binding capacity to αvβ3 on pancreatic ductal adenocarcinoma (PDAC) cells, resulting in amplified cellular uptake in in vitro and in vivo models and increased chemotherapeutic efficacies. Simultaneously, ExoSmart significantly reduced liver and spleen clearance of exosomes by inhibiting macrophage phagocytosis via CD47p110–130 interaction with signal regulatory proteins (SIRPα) on macrophages. These studies demonstrate that an engineered exosome drug delivery system increases PDAC therapeutic efficacy by enhancing active PDAC targeting and prolonging circulation times, and their findings hold tremendous translational potential for cancer therapy while providing a concrete foundation for future work utilizing novel peptide-engineered exosome strategies.
Genomic Analyses Capture the Human-Induced Demographic Collapse and Recovery in a Wide-Ranging Cervid
Authors: Camille Kessler, Aaron B A Shafer
Journal: Molecular Biology and Evolution (2024)

The glacial cycles of the Quaternary heavily impacted species through successions of population contractions and expansions. Similarly, populations have been intensely shaped by human pressures such as unregulated hunting and land use changes. White-tailed and mule deer survived in different refugia through the Last Glacial Maximum, and their populations were severely reduced after the European colonization. Here, we analyzed 73 resequenced deer genomes from across their North American range to understand the consequences of climatic and anthropogenic pressures on deer demographic and adaptive history. We found strong signals of climate-induced vicariance and demographic decline; notably, multiple sequentially Markovian coalescent recovers a severe decline in mainland white-tailed deer effective population size (Ne) at the end of the Last Glacial Maximum. We found robust evidence for colonial overharvest in the form of a recent and dramatic drop in Ne in all analyzed populations. Historical census size and restocking data show a clear parallel to historical Ne estimates, and temporal Ne/Nc ratio shows patterns of conservation concern for mule deer. Signatures of selection highlight genes related to temperature, including a cold receptor previously highlighted in woolly mammoth. We also detected immune genes that we surmise reflect the changing land use patterns in North America. Our study provides a detailed picture of anthropogenic and climatic-induced decline in deer diversity and clues to understanding the conservation concerns of mule deer and the successful demographic recovery of white-tailed deer.
The use of serum methotrexate level as an assessment of biochemical drug adherence in psoriasis
Authors: Amelle G Ra, Zoe Littlewood, Anne Barton, Brian Keevil, Malcolm McTaggart, Richard B Warren, James Bluett
Journal: British Journal of Dermatology (2024)

Psoriasis is a common inflammatory skin condition affecting approximately 2–3% of people worldwide. Methotrexate (MTX) is a cheap and effective drug that is often recommended as the first-choice systemic agent for psoriasis. Around 40–50% of patients achieve a good response; however, mechanisms of nonresponse are poorly understood. It is not known whether biochemical MTX adherence in patients with psoriasis is suboptimal and requires intervention. Our aim was to audit biochemical MTX adherence using a sensitive liquid chromatography–tandem mass spectrometry in patients prescribed oral MTX for the treatment of psoriasis at our tertiary dermatology centre. Ethical approval for this audit was not required as confirmed by the Health Research Authority.
Smooth muscle cell-specific matrix metalloproteinase 3 deletion reduces osteogenic transformation and medial artery calcification
Authors: Yangzhouyun Xie, Tonghui Lin, Ying Jin, Alexa G Berezowitz, Xue-Lin Wang, Jinny Lu, Yujun Cai, Raul J Guzman
Journal: Cardiovascular Research (2024)

Vascular calcification is highly prevalent in atherosclerosis, diabetes, and chronic kidney disease. It is associated with increased morbidity and mortality in patients with cardiovascular disease. Matrix metalloproteinase 3 (MMP-3), also known as stromelysin-1, is part of the large matrix metalloproteinase family. It can degrade extracellular matrix components of the arterial wall including elastin, which plays a central role in medial calcification. In this study, we sought to determine the role of MMP-3 in medial calcification.
From virtual patients to digital twins in immuno-oncology: lessons learned from mechanistic quantitative systems pharmacology modeling
Authors: Hanwen Wang, Theinmozhi Arulraj, Alberto Ippolito, Aleksander S Popel
Journal: npj Digital Medicine (2024)

Virtual patients and digital patients/twins are two similar concepts gaining increasing attention in health care with goals to accelerate drug development and improve patients' survival, but with their own limitations. Although methods have been proposed to generate virtual patient populations using mechanistic models, there are limited number of applications in immuno-oncology research. Furthermore, due to the stricter requirements of digital twins, they are often generated in a study-specific manner with models customized to particular clinical settings (e.g., treatment, cancer, and data types). Here, we discuss the challenges for virtual patient generation in immuno-oncology with our most recent experiences, initiatives to develop digital twins, and how research on these two concepts can inform each other.