tbuckley/cabot-search huggingface dataset:
Dual modulation of amyloid beta and tau aggregation and dissociation in Alzheimer’s disease: a comprehensive review of the characteristics and therapeutic strategies
Authors: Yunkwon Nam, Soo Jung Shin, Vijay Kumar, Jihyeon Won, Sujin Kim, Minho Moon
Journal: Translational Neurodegeneration (2025)

Abstract Alzheimer’s disease (AD) is not a single-cause disease; rather, it is a complex neurodegenerative disease involving multiple pathological pathways influenced by various risk factors. Aggregation and accumulation of amyloid beta (Aβ) and tau are the most prominent features in the brains of AD patients. Aggregated Aβ and tau exert neurotoxic effects in the central nervous system, contributing to the pathogenesis and progression of AD. They also act synergistically to cause neurodegeneration, resulting in memory loss. In this context, dual inhibition of Aβ and tau aggregation, or dissociation of these two aggregates, is considered promising for AD treatment. Recently, dual inhibitors capable of simultaneously targeting the aggregation and dissociation of both Aβ and tau have been investigated. Specific amino acid domains of Aβ and tau associated with their aggregation/dissociation have been identified. Subsequently, therapeutic agents that prevent aggregation or promote disaggregation by targeting these domains have been identified/developed. In this review, we summarize the major domains and properties involved in Aβ and tau aggregation, as well as the therapeutic effects and mechanisms of agents that simultaneously regulate their aggregation and dissociation. This comprehensive review may contribute to the design and discovery of next-generation dual-targeting drugs for Aβ and tau, potentially leading to the development of more effective therapeutic strategies for AD.
Haem biosynthesis regulates BCAA catabolism and thermogenesis in brown adipose tissue
Authors: Dylan J. Duerre, Julia K. Hansen, Steven V. John, Annie Jen, Noah D. Carrillo, Hoang Bui, Yutong Bao, Matias Fabregat, J. Leon Catrow, Li-Yu Chen, Katherine A. Overmyer, Evgenia Shishkova, Quentinn Pearce, Mark P. Keller, Richard A. Anderson, Vincent L. Cryns, Alan D. Attie, James E. Cox, Joshua J. Coon, Jing Fan, Andrea Galmozzi
Journal: Nature Metabolism (2025)
Transmission dynamics of the 2022 mpox epidemic in New York City
Authors: Jonathan E. Pekar, Yu Wang, Jade C. Wang, Yucai Shao, Faten Taki, Lisa A. Forgione, Helly Amin, Tyler Clabby, Kimberly Johnson, Lucia V. Torian, Sarah L. Braunstein, Preeti Pathela, Enoma Omoregie, Scott Hughes, Marc A. Suchard, Tetyana I. Vasylyeva, Philippe Lemey, Joel O. Wertheim
Journal: Nature Medicine (2025)

Abstract The 2022 global mpox epidemic was caused by transmission of MPXV clade IIb, lineage B.1 through sexual contact networks, with New York City (NYC) experiencing the first and largest outbreak in the United States. By performing phylogeographic analysis of MPXV genomes sampled from 757 individuals in NYC between April 2022 and April 2023, and 3,287 MPXV genomes sampled around the world, we identify over 200 introductions of MPXV into NYC with at least 84 leading to onward transmission. These infections primarily occurred among men who have sex with men, transgender women and nonbinary individuals. Through a comparative analysis with HIV in NYC, we find that both MPXV and HIV genomic cluster sizes are best fit by scale-free distributions, and that people in MPXV clusters are more likely to have previously received an HIV diagnosis and be a member of a recently growing HIV transmission cluster. We model MPXV transmission through sexual contact networks and show that highly connected individuals would be disproportionately infected at the start of an epidemic, which would likely result in the exhaustion of the most densely connected parts of the network, and, therefore, explain the rapid expansion and decline of the NYC outbreak. By coupling the genomic epidemiology of MPXV and HIV with epidemic modeling, we demonstrate that the transmission dynamics of MPXV in NYC can be understood by general principles of sexually transmitted pathogens.
Escitalopram for agitation in Alzheimer’s dementia: a randomized controlled phase 3 trial
Authors: Tarek K. Rajji, Sheriza N. Baksh, David M. Shade, Zahinoor Ismail, Amer M. Burhan, Hamid R. Okhravi, Prasad R. Padala, Paul B. Rosenberg, Lon S. Schneider, Anton P. Porsteinsson, Constantine G. Lyketsos
Journal: Nature Medicine (2025)
Prospective, multicenter validation of a platform for rapid molecular profiling of central nervous system tumors
Authors: Areeba Patel, Kirsten Göbel, Sebastian Ille, Felix Hinz, Natalie Schoebe, Henri Bogumil, Jochen Meyer, Michelle Brehm, Helin Kardo, Daniel Schrimpf, Artem Lomakin, Michael Ritter, Pauline Göller, Paul Kerbs, Lisa Pfeifer, Stefan Hamelmann, Christina Blume, Franziska M. Ippen, Natalie Berghaus, Philipp Euskirchen, Leonille Schweizer, Claus Hultschig, Nadine Van Roy, Jo Van Dorpe, Joni Van der Meulen, Siebe Loontiens, Franceska Dedeurwaerdere, Henning Leske, Skarphéðinn Halldórsson, Graeme Fox, Simon Deacon, Inswasti Cahyani, Nadine Holmes, Satrio Wibowo, Rory Munro, Dan Martin, Abid Sharif, Mark Housley, Robert Goldspring, Sebastian Brandner, Somak Roy, Jürgen Hench, Stephan Frank, Andreas Unterberg, Violaine Goidts, Natalie Jäger, Simon Paine, Stuart Smith, Christel Herold-Mende, Wolfgang Wick, Stefan M. Pfister, Einar O. Vik-Mo, Andreas von Deimling, Sandro Krieg, David TW Jones, Matthew Loose, Matthias Schlesner, Martin Sill, Felix Sahm
Journal: Nature Medicine (2025)

Molecular data integration plays a central role in central nervous system (CNS) tumor diagnostics but currently used assays pose limitations due to technical complexity, equipment and reagent costs, as well as lengthy turnaround times. We previously reported the development of Rapid-CNS2, an adaptive-sampling-based nanopore sequencing workflow. Here we comprehensively validated and further developed Rapid-CNS2 for intraoperative use. It now offers real-time methylation classification and DNA copy number information within a 30-min intraoperative window, followed by comprehensive molecular profiling within 24 h, covering the complete spectrum of diagnostically and therapeutically relevant information for the respective entity. We validated Rapid-CNS2 in a multicenter setting on 301 archival and prospective samples including 18 samples sequenced intraoperatively. To broaden the utility of methylation-based CNS tumor classification, we developed MNP-Flex, a platform-agnostic methylation classifier encompassing 184 classes. MNP-Flex achieved 99.6% accuracy for methylation families and 99.2% accuracy for methylation classes with clinically applicable thresholds across a global validation cohort of more than 78,000 frozen and formalin-fixed paraffin-embedded samples spanning five different technologies. Integration of these tools has the potential to advance CNS tumor diagnostics by providing broad access to rapid, actionable molecular insights crucial for personalized treatment strategies. Application of a nanopore sequencing workflow for real-time analysis of brain tumors results in molecular classification within a 30-minute intraoperative window, followed by comprehensive profiling within 24 hours.
AI-guided precision parenteral nutrition for neonatal intensive care units
Authors: Thanaphong Phongpreecha, Marc Ghanem, Jonathan D Reiss, Tomiko Oskotsky, Samson J Mataraso, Davide De Francesco, S Momsen Reincke, Camilo Espinosa, Philip Chung, Taryn Ng, Jean M Costello, Jennifer A Sequoia, Sheila Razdan, Feng Xie, Eloise Berson, Yeasul Kim, David Seong, May Y Szeto, Faith Myers, Hannah Gu, John Feister, Courtney P Verscaj, Laura A Rose, Lucas W Y Sin, Boris Oskotsky, Jacquelyn Roger, Chi-Hung Shu, Sayane Shome, Liu K Yang, Yuqi Tan, Steven Levitte, Ronald J Wong, Brice Gaudillière, Martin S Angst, Thomas J Montine, John A Kerner, Roberta L Keller, Gary M Shaw, Karl G Sylvester, Janene Fuerch, Valerie Chock, Shabnam Gaskari, David K Stevenson, Marina Sirota, Lawrence S Prince, Nima Aghaeepour
Journal: Nature Medicine (2025)

One in ten neonates are admitted to neonatal intensive care units, highlighting the need for precise interventions. However, the application of artificial intelligence (AI) in guiding neonatal care remains underexplored. Total parenteral nutrition (TPN) is a life-saving treatment for preterm neonates; however, implementation of the therapy in its current form is subjective, error-prone and resource-consuming. Here, we developed TPN2.0—a data-driven approach that optimizes and standardizes TPN using information collected routinely in electronic health records. We assembled a decade of TPN compositions (79,790 orders; 5,913 patients) at Stanford to train TPN2.0. In addition to internal validation, we also validated our model in an external cohort (63,273 orders; 3,417 patients) from a second hospital. Our algorithm identified 15 TPN formulas that can enable a precision-medicine approach (Pearson's R = 0.94 compared to experts), increasing safety and potentially reducing cost. A blinded study (n = 192) revealed that physicians rated TPN2.0 higher than current best practice. In patients with high disagreement between the actual prescriptions and TPN2.0, standard prescriptions were associated with increased morbidities (for example, odds ratio = 3.33; P value = 0.0007 for necrotizing enterocolitis), while TPN2.0 recommendations were linked to reduced risk. Finally, we demonstrated that TPN2.0 employing a transformer architecture enabled guideline-adhering, physician-in-the-loop recommendations that allow collaboration between the care team and AI. An artificial intelligence model defines a data-driven set of total parenteral nutrition compositions to assist clinicians in personalized treatment of neonates in intensive care and is able to adapt recommendations to patient status, with validation from large external cohorts and a blinded reader study.
The Role of Basement Membrane Thickening in Airway Physiology and Immunopathology of Severe Asthma
Authors: Matthew H. Liu, Teal S Hallstrand
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

"The Role of Basement Membrane Thickening in Airway Physiology and Immunopathology of Severe Asthma." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
The Saga of Equitable Oxygen Saturation Measurement Continues: The Role of Arterial Blood Gases
Authors: Christopher F Chesley, George L Anesi
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

"The Saga of Equitable Oxygen Saturation Measurement Continues: The Role of Arterial Blood Gases." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Water, Water, Everywhere, Nor Any Drop to Drink – Beware of Mycobacteria
Authors: Tavs Qvist, Andrew Bush, Michal Shteinberg
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

"Water, Water, Everywhere, Nor Any Drop to Drink – Beware of Mycobacteria." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
The Rapidly Evolving Landscape of Asthma Therapies Is Exhilarating, Yet a Lack of Innovation in Clinical Trial Design Makes Feasibility A Real Concern
Authors: Njira Lugogo
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

"The Rapidly Evolving Landscape of Asthma Therapies Is Exhilarating, Yet a Lack of Innovation in Clinical Trial Design Makes Feasibility A Real Concern." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
<sup>18</sup> F-Labeled Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography in Staging and Restaging Patients With Breast Cancer
Authors: David Groheux, Sofia C. Vaz, Lioe-Fee de Geus-Oei, Elizabeth H. Dibble, Gary A. Ulaner, Gary J.R. Cook, Elif Hindié, Philip Poortmans, Ritse M. Mann, Heather Jacene, John P. Pilkington Woll, Isabel T. Rubio, Marie-Jeanne Vrancken Peeters, Stephanie L. Graff, Fatima Cardoso
Journal: Journal of Clinical Oncology (2025)
Role and mechanisms of histone methylation in osteogenic/odontogenic differentiation of dental mesenchymal stem cells
Authors: Meijun Hu, Zhipeng Fan
Journal: International Journal of Oral Science (2025)

Abstract Dental mesenchymal stem cells (DMSCs) are pivotal for tooth development and periodontal tissue health and play an important role in tissue engineering and regenerative medicine because of their multidirectional differentiation potential and self-renewal ability. The cellular microenvironment regulates the fate of stem cells and can be modified using various optimization techniques. These methods can influence the cellular microenvironment, activate disparate signaling pathways, and induce different biological effects. “Epigenetic regulation” refers to the process of influencing gene expression and regulating cell fate without altering DNA sequences, such as histone methylation. Histone methylation modifications regulate pivotal transcription factors governing DMSCs differentiation into osteo-/odontogenic lineages. The most important sites of histone methylation in tooth organization were found to be H3K4, H3K9, and H3K27. Histone methylation affects gene expression and regulates stem cell differentiation by maintaining a delicate balance between major trimethylation sites, generating distinct chromatin structures associated with specific downstream transcriptional states. Several crucial signaling pathways associated with osteogenic differentiation are susceptible to modulation via histone methylation modifications. A deeper understanding of the regulatory mechanisms governing histone methylation modifications in osteo-/odontogenic differentiation and immune-inflammatory responses of DMSCs will facilitate further investigation of the epigenetic regulation of histone methylation in DMSC-mediated tissue regeneration and inflammation. Here is a concise overview of the pivotal functions of epigenetic histone methylation at H3K4, H3K9, and H3K27 in the regulation of osteo-/odontogenic differentiation and renewal of DMSCs in both non-inflammatory and inflammatory microenvironments. This review summarizes the current research on these processes in the context of tissue regeneration and therapeutic interventions.
NGS-based IG/TR rearrangement profiling in acute lymphoblastic leukemia: age dependence of immunogenetic maturation
Authors: Michaela Kotrova, Constantin Proske, Nikos Darzentas, Anna Laqua, Britta Kehden, Jan Christian Kässens, Sonja Bendig, Saskia Kohlscheen, Monika Szczepanowski, Wiebke Wessels, Željko Antić, Christiane Pott, Matthias Ritgen, Jacques J.M. van Dongen, Nicola Gökbuget, Guranda Chitadze, Anke Bergmann, Lorenz Bastian, Claudia D. Baldus, Gunnar Cario, Martin Schrappe, Stefan Schwartz, Julia Alten, Rolf Koehler, Monika Brüggemann
Journal: Blood (2025)
Destabilization of PF4-antigenic complexes in heparin-induced thrombocytopenia
Authors: Lubica Rauova, Khalil Bdeir, Ann H Rux, Manu Thomas Kalathottukaren, Jenna Oberg, Chanel C. La, David Thiam En Lim, Vincent M Hayes, Gavin T. Koma, Amrita Sarkar, Mortimer Poncz, Jayachandran N Kizhakkedathu, Douglas B. Cines
Journal: Blood (2025)
Tracking clusterin expression in hematopoietic stem cells reveals their heterogeneous composition across the lifespan
Authors: Shuhei Koide, Motohiko Oshima, Takahiro Kamiya, Zhiqian Zheng, Zhaoyi Liu, Ola Rizq, Akira Nishiyama, Koichi Murakami, Yuta Yamada, Yaeko Nakajima-Takagi, Bahityar Rahmutulla, Atsushi Kaneda, Kazuaki Yokoyama, Nozomi Yusa, Seiya Imoto, Fumihito Miura, Takashi Ito, Tomohiko Tamura, Claus Nerlov, Masayuki Yamashita, Atsushi Iwama
Journal: Blood (2025)
US Population Size and Outcomes of Adults on Liver Transplant Waiting Lists
Authors: Tomohiro Tanaka, George Wehby, Mark Vander Weg, Keith Mueller, David Axelrod
Journal: JAMA Network Open (2025)

Importance Disparities in organ supply and demand led to geographic inequities in the score-based liver transplant (LT) allocation system, prompting a change to allocation based on acuity circles (AC) defined by fixed distances. However, fixed distances do not ensure equivalent population size, potentially creating new sources of disparity. Objective To estimate the association between population size around LT centers and waiting list outcomes for critically ill patients with chronic end-stage liver disease and high Model for End-stage Liver Disease (MELD) scores or acute liver failure (ALF). Design, Setting, and Participants This US nationwide retrospective cohort study included adult (aged ≥18 years) candidates for deceased donor LT wait-listed between June 18, 2013, and May 31, 2023. Follow-up was completed June 30, 2023. Participants were divided into pre-AC and post-AC groups. Exposure Population size within defined radii around each LT center (150 nautical miles [nm] for participants with high MELD scores and 500 nm for those with ALF) based on AC allocation policy. Main Outcomes and Measures LT candidate waiting list mortality and dropout rate were analyzed using generalized linear mixed-effect models with random intercepts for center and listing date before and after AC implementation. Fine-Gray competing risk regression, accounting for clustering, was used as a secondary model. Results The study analyzed 6142 LT candidates (1581 with ALF and 4561 with high MELD scores) during the pre-AC era and 4344 candidates (749 with ALF and 3595 with high- MELD scores) in the post-AC era, for a total of 10 486 participants (6331 male [60.5%]; mean [SD] age, 48.5 [7.1] years). In the high-MELD cohort, being listed at a center in the lowest tertile of population size was associated with increased waiting list mortality in the AC era (adjusted odds ratio [AOR], 1.68; 95% CI, 1.14-2.46). Doubling of the population size was associated with a 34% reduction in the odds of mortality or dropout (AOR, 0.66; 95% CI, 0.49-0.90). These results were consistent with those of the extended Fine-Gray models and were also corroborated by multiple sensitivity analyses. However, there were no significant population density–associated disparities in the ALF cohort. Conclusions and Relevance In this retrospective nationwide cohort study, being wait-listed in less populated regions was associated with greater mortality among critically ill LT candidates with high MELD scores, underscoring the limitations of allocation systems based purely on fixed distances.
Five-Year Functional Outcomes Among Patients Surviving Aneurysmal Subarachnoid Hemorrhage
Authors: Ho Seok Lee, Min Kyun Sohn, Jongmin Lee, Deog Young Kim, Yong-Il Shin, Gyung-Jae Oh, Yang-Soo Lee, Min Cheol Joo, So Young Lee, Min-Keun Song, Junhee Han, Jeonghoon Ahn, Young-Hoon Lee, Dae Hyun Kim, Young-Taek Kim, Yun-Hee Kim, Won Hyuk Chang
Journal: JAMA Network Open (2025)

Importance Longitudinal changes in functional levels can provide valuable information about disability. However, longitudinal outcomes in aneurysmal subarachnoid hemorrhage (aSAH) have not been well reported, which could provide insight into appropriate management and information for patients experiencing disability. Objective To investigate the 5-year prognosis and functional outcomes of patients with aSAH. Design, Setting, and Participants This retrospective cohort study used data of patients with aSAH from the Korean Stroke Cohort for Functioning and Rehabilitation study up to 5 years after onset. Data were collected from August 2012 through May 2015 in 9 different hospitals in Korea. Data were analyzed from September 2023 through January 2024. Exposure Patients with aSAH surviving at least 7 days after onset. Main Outcomes and Measures Assessments were performed serially from 7 days to 5 years after onset. Prognosis, measured by the modified Rankin scale (mRS) in terms of positive outcome (mRS score of 0 or 1), and mortality were analyzed. In addition, sequential functional outcomes were assessed using the Functional Independence Measure (FIM) in survivors of aSAH at 5 years after onset. Multiple imputation method was used to handle missing data. Wilcoxon signed-rank test and paired t test were used to analyze differences in functional measurements between each follow-up period. Additionally, a generalized mixed-effects model was used to analyze the longitudinal trajectory of the FIM. Results A total of 338 patients with aSAH (mean [SD] age, 56.3 [13.0] years; 207 female [61.2%]) were included. Among survivors of aSAH at 7 days, the 5-year mortality rate was 8.3% (28 participants). The distribution of mRS significantly improved until 4 years and then plateaued, with 180 (53.3%) and 77 (22.8%) patients reporting an mRS score of 0 and 1, respectively. FIM showed a significant improvement up to 4 years (mean [SD] score, 118.9 [18.7]) and then plateaued. Conclusions and Relevance In this cohort study, the functional outcomes in patients with aSAH continued to improve up to 4 years after onset, with the majority of participants showing favorable outcomes without significant disability, suggesting that proper long-term assessment is needed and appropriate management should be emphasized to maximize potential outcomes of patients with aSAH.
Corrigendum to ‘Innovative injectable, self-healing, exosome cross-linked biomimetic hydrogel for cartilage regeneration’ [Journal of Controlled Release, Volume 381 (2025), 113608].
Authors: Chenlin Tu, Xiang Gao, Hong Zheng, Rui Huang, Fengkai Yang, Yeying Dong, Kaipeng Jing, Thomas Groth, Mingyan Zhao
Journal: Journal of Controlled Release (2025)