tbuckley/cabot-search huggingface dataset:
Dual Self‐Assembly of Puerarin and Silk Fibroin into Supramolecular Nanofibrillar Hydrogel for Infected Wound Treatment
Authors: Dan Yang, Wei Zhao, Shengyu Zhang, Yu Liu, Jingmei Teng, Yuxi Ma, Rongjian Huang, Hua Wei, Hailan Chen, Jiantao Zhang, Jing Chen
Journal: Advanced Healthcare Materials (2024)

The treatment of infected wounds remains a challenging biomedical problem. Some bioactive small-molecule hydrogelators with unique rigid structures can self-assemble into supramolecular hydrogels for wound healing. However, they are still suffered from low structural stability and bio-functionality. Herein, a supramolecular hydrogel antibacterial dressing with a dual nanofibrillar network structure is proposed. A nanofibrillar network created by a small-molecule hydrogelator, puerarin extracted from the traditional Chinese medicine Pueraria, is interconnected with a secondary macromolecular silk fibroin nanofibrillar network induced by Ga ions via charge-induced supramolecular self-assembly. The resulting hydrogel features adequate mechanical strength for sustainable retention at wounds. Good biocompatibility and efficient bacterial inhibition are obtained when the Ga ion concentration is 0.05%. Otherwise, the substantial release of Ga ions and puerarin endows the hydrogel with excellent hemostatic and antioxidative properties. In vivo, evaluation of a mouse-infected wound model demonstrates that its healing effect outperformed that of a commercially available silver-containing wound dressing. The experimental group successfully achieves a 100% wound closure rate on day 10. This study sheds new light on the design of nanofibrillar hydrogels based on supramolecular self-assembly of naturally derived bioactive molecules as well as their clinical use for treating chronic infected wounds.
Neoadjuvant nivolumab or nivolumab plus LAG-3 inhibitor relatlimab in resectable esophageal/gastroesophageal junction cancer: a phase Ib trial and ctDNA analyses
Authors: Ronan J. Kelly, Blair V. Landon, Ali H. Zaidi, Dipika Singh, Jenna V. Canzoniero, Archana Balan, Russell K. Hales, K. Ranh Voong, Richard J. Battafarano, Blair A. Jobe, Stephen C. Yang, Stephen Broderick, Jinny Ha, Kristen A. Marrone, Gavin Pereira, Nisha Rao, Aryan Borole, Katerina Karaindrou, Zineb Belcaid, James R. White, Suqi Ke, Ali I. Amjad, Benny Weksler, Eun Ji Shin, Elizabeth Thompson, Kellie N. Smith, Drew M. Pardoll, Chen Hu, Josephine L. Feliciano, Valsamo Anagnostou, Vincent K. Lam
Journal: Nature Medicine (2024)

Abstract Gastroesophageal cancer dynamics and drivers of clinical responses with immune checkpoint inhibitors (ICI) remain poorly understood. Potential synergistic activity of dual programmed cell death protein 1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) inhibition may help improve immunotherapy responses for these tumors. We report a phase Ib trial that evaluated neoadjuvant nivolumab (Arm A, n = 16) or nivolumab–relatlimab (Arm B, n = 16) in combination with chemoradiotherapy in 32 patients with resectable stage II/stage III gastroesophageal cancer together with an in-depth evaluation of pathological, molecular and functional immune responses. Primary endpoint was safety; the secondary endpoint was feasibility; exploratory endpoints included pathological complete (pCR) and major pathological response (MPR), recurrence-free survival (RFS) and overall survival (OS). The study met its primary safety endpoint in Arm A, although Arm B required modification to mitigate toxicity. pCR and MPR rates were 40% and 53.5% for Arm A and 21.4% and 57.1% for Arm B. Most common adverse events were fatigue, nausea, thrombocytopenia and dermatitis. Overall, 2-year RFS and OS rates were 72.5% and 82.6%, respectively. Higher baseline programmed cell death ligand 1 (PD-L1) and LAG-3 expression were associated with deeper pathological responses. Exploratory analyses of circulating tumor DNA (ctDNA) showed that patients with undetectable ctDNA post-ICI induction, preoperatively and postoperatively had a significantly longer RFS and OS; ctDNA clearance was reflective of neoantigen-specific T cell responses. Our findings provide insights into the safety profile of combined PD-1 and LAG-3 blockade in gastroesophageal cancer and highlight the potential of ctDNA analysis to dynamically assess systemic tumor burden during neoadjuvant ICI that may open a therapeutic window for future intervention. ClinicalTrials.gov registration: NCT03044613 .
Heterogeneity and predictors of the effects of AI assistance on radiologists
Authors: Feiyang Yu, Alex Moehring, Oishi Banerjee, Tobias Salz, Nikhil Agarwal, Pranav Rajpurkar
Journal: Nature Medicine (2024)

Abstract The integration of artificial intelligence (AI) in medical image interpretation requires effective collaboration between clinicians and AI algorithms. Although previous studies demonstrated the potential of AI assistance in improving overall clinician performance, the individual impact on clinicians remains unclear. This large-scale study examined the heterogeneous effects of AI assistance on 140 radiologists across 15 chest X-ray diagnostic tasks and identified predictors of these effects. Surprisingly, conventional experience-based factors, such as years of experience, subspecialty and familiarity with AI tools, fail to reliably predict the impact of AI assistance. Additionally, lower-performing radiologists do not consistently benefit more from AI assistance, challenging prevailing assumptions. Instead, we found that the occurrence of AI errors strongly influences treatment outcomes, with inaccurate AI predictions adversely affecting radiologist performance on the aggregate of all pathologies and on half of the individual pathologies investigated. Our findings highlight the importance of personalized approaches to clinician–AI collaboration and the importance of accurate AI models. By understanding the factors that shape the effectiveness of AI assistance, this study provides valuable insights for targeted implementation of AI, enabling maximum benefits for individual clinicians in clinical practice.
Human lung cancer harbors spatially organized stem-immunity hubs associated with response to immunotherapy
Authors: Jonathan H. Chen, Linda T. Nieman, Maxwell Spurrell, Vjola Jorgji, Liad Elmelech, Peter Richieri, Katherine H. Xu, Roopa Madhu, Milan Parikh, Izabella Zamora, Arnav Mehta, Christopher S. Nabel, Samuel S. Freeman, Joshua D. Pirl, Chenyue Lu, Catherine B. Meador, Jaimie L. Barth, Mustafa Sakhi, Alexander L. Tang, Siranush Sarkizova, Colles Price, Nicolas F. Fernandez, George Emanuel, Jiang He, Katrina Van Raay, Jason W. Reeves, Keren Yizhak, Matan Hofree, Angela Shih, Moshe Sade-Feldman, Genevieve M. Boland, Karin Pelka, Martin J. Aryee, Mari Mino-Kenudson, Justin F. Gainor, Ilya Korsunsky, Nir Hacohen
Journal: Nature Immunology (2024)
Biomimetic Platelet‐Cloaked Nanoparticles for the Delivery of Anti‐Inflammatory Curcumin in the Treatment of Atherosclerosis
Authors: Flavia Fontana, Giuseppina Molinaro, Sofia Moroni, Giulia Pallozzi, Mónica P. A. Ferreira, Rubén Pareja Tello, Khalil Elbadri, Giulia Torrieri, Alexandra Correia, Marianna Kemell, Luca Casettari, Christian Celia, Hélder A. Santos
Journal: Advanced Healthcare Materials (2024)

Atherosclerosis still represents a major driver of cardiovascular diseases worldwide. Together with accumulation of lipids in the plaque, inflammation is recognized as one of the key players in the formation and development of atherosclerotic plaque. Systemic anti-inflammatory treatments are successful in reducing the disease burden, but are correlated with severe side effects, underlining the need for targeted formulations. In this work, curcumin is chosen as the anti-inflammatory payload model and further loaded in lignin-based nanoparticles (NPs). The NPs are then coated with a tannic acid (TA)- Fe (III) complex and further cloaked with fragments derived from platelet cell membrane, yielding NPs with homogenous size. The two coatings increase the interaction between the NPs and cells, both endothelial and macrophages, in steady state or inflamed status. Furthermore, NPs are cytocompatible toward endothelial, smooth muscle and immune cells, while not inducing immune activation. The anti-inflammatory efficacy is demonstrated in endothelial cells by real-time quantitative polymerase chain reaction and ELISA assay where curcumin-loaded NPs decrease the expression of Nf-κb, TGF-β1, IL-6, and IL-1β in lipopolysaccharide-inflamed cells. Overall, due to the increase in the cell-NP interactions and the anti-inflammatory efficacy, these NPs represent potential candidates for the targeted anti-inflammatory treatment of atherosclerosis.
Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia
Authors: Mathieu Membrez, Eugenia Migliavacca, Stefan Christen, Keisuke Yaku, Jennifer Trieu, Alaina K. Lee, Francesco Morandini, Maria Pilar Giner, Jade Stiner, Mikhail V. Makarov, Emma S. Garratt, Maria F. Vasiloglou, Lucie Chanvillard, Emilie Dalbram, Amy M. Ehrlich, José Luis Sanchez-Garcia, Carles Canto, Leonidas G. Karagounis, Jonas T. Treebak, Marie E. Migaud, Ramin Heshmat, Farideh Razi, Neerja Karnani, Afshin Ostovar, Farshad Farzadfar, Stacey K. H. Tay, Matthew J. Sanders, Karen A. Lillycrop, Keith M. Godfrey, Takashi Nakagawa, Sofia Moco, René Koopman, Gordon S. Lynch, Vincenzo Sorrentino, Jerome N. Feige
Journal: Nature Metabolism (2024)

Abstract Mitochondrial dysfunction and low nicotinamide adenine dinucleotide (NAD + ) levels are hallmarks of skeletal muscle ageing and sarcopenia 1–3 , but it is unclear whether these defects result from local changes or can be mediated by systemic or dietary cues. Here we report a functional link between circulating levels of the natural alkaloid trigonelline, which is structurally related to nicotinic acid 4 , NAD + levels and muscle health in multiple species. In humans, serum trigonelline levels are reduced with sarcopenia and correlate positively with muscle strength and mitochondrial oxidative phosphorylation in skeletal muscle. Using naturally occurring and isotopically labelled trigonelline, we demonstrate that trigonelline incorporates into the NAD + pool and increases NAD + levels in Caenorhabditis elegans , mice and primary myotubes from healthy individuals and individuals with sarcopenia. Mechanistically, trigonelline does not activate GPR109A but is metabolized via the nicotinate phosphoribosyltransferase/Preiss–Handler pathway 5,6 across models. In C. elegans , trigonelline improves mitochondrial respiration and biogenesis, reduces age-related muscle wasting and increases lifespan and mobility through an NAD + -dependent mechanism requiring sirtuin. Dietary trigonelline supplementation in male mice enhances muscle strength and prevents fatigue during ageing. Collectively, we identify nutritional supplementation of trigonelline as an NAD + -boosting strategy with therapeutic potential for age-associated muscle decline.
miR-430 regulates zygotic mRNA during zebrafish embryogenesis
Authors: Danielson Baia Amaral, Rhonda Egidy, Anoja Perera, Ariel A Bazzini
Journal: Genome biology (2024)

Early embryonic developmental programs are guided by the coordinated interplay between maternally inherited and zygotically manufactured RNAs and proteins. Although these processes happen concomitantly and affecting gene function during this period is bound to affect both pools of mRNAs, it has been challenging to study their expression dynamics separately.
Calr type 1/like mutation in myelofibrosis is the most prominent predictor of momelotinib drug survival and longevity without transplant
Authors: Ayalew Tefferi, Animesh Pardanani, Kebede H. Begna, Aref Al-Kali, William J. Hogan, Mark R. Litzow, Rhett P. Ketterling, Kaaren K. Reichard, Naseema Gangat
Journal: Blood Cancer Journal (2024)

Calr type 1
Red/NIR‐I‐Fluorescence Carbon Dots Based on Rhein with Active Oxygen Scavenging and Colitis Targeting for UC Therapeutics
Authors: Jiashan Xia, Jiayu Wang, Fengyuan Liu, Zhiqiong Chen, Changmei Chen, Xiangshu Cheng, Yu Chao, Yue Wang, Tao Deng
Journal: Advanced Healthcare Materials (2024)

Ulcerative colitis (UC) is a chronic inflammatory disease with uncontrolled inflammation and demage to the intestinal barrier. Rhein, a bioactive compound in traditional Chinese medicine, has anti-inflammatory and intestinal repair effect. However, their clinical application is limited by their hydrophobicity and poor bioavailability. L-arginine, as a complement to NO, has synergistic and attenuating effects. In this paper, red/NIR-I fluorescent carbon dots based on rhein and doped with L-arginine (RA-CDs), which are synthesized by a hydrothermal process without any organic solvents, are reported. RA-CDs preserve a portion of the functional group of the active precursor, increase rhein solubility, and emit red/NIR-I light for biological imaging. In vitro experiments show that RA-CDs scavenge excessive reactive oxygen species (ROS), protect cells from oxidative stress, and enable the fluorescence imaging of inflamed colons. In a DSS-induced UC mouse model, both delayed and prophylactic treatment with RA-CDs via intraperitoneal and tail vein injections alleviate UC severity by reducing intestinal inflammation and restoring the intestinal barrier. This study highlights a novel strategy for treating and imaging UC with poorly soluble small-molecule drugs.
Non-coronary peripheral arterial complications in people with type 2 diabetes: a Swedish retrospective cohort study
Authors: Araz Rawshani, Björn Eliasson, Jan Boren, Naveed Sattar, Deepak Bhatt, Linn El-Khalili, Joakim Nordanstig, Tarik Avdic, Joshua A. Beckman, Hertzel C. Gerstein, Darren K. McGuire, Elmir Omerovic, Aidin Rawshani
Journal: The Lancet Regional Health - Europe (2024)

Few studies have explored long-term trends and risk factors for peripheral arterial complications in type 2 diabetes compared to the general population. Our research focuses on identifying optimal risk factors, their significance, risk associated with multifactorial risk factor control, and trends for these complications in diabetic patients versus general controls.
Clinical effectiveness of a multitarget urine DNA test for urothelial carcinoma detection: a double-blinded, multicenter, prospective trial
Authors: Junlong Wu, Yuda Lin, Kaiwei Yang, Xiao Liu, Huina Wang, Tingting Yu, Ran Tao, Jing Guo, Libin Chen, Huanqing Cheng, Feng Lou, Shanbo Cao, Wei Yu, Hailong Hu, Dingwei Ye
Journal: Molecular Cancer (2024)

Abstract Urine-based testing is promising for noninvasive diagnosis of urothelial carcinoma (UC) but has suboptimal sensitivity for early-stage tumors. Herein, we developed a multitarget urine tumor DNA test, UI-Seek, for UC detection and evaluated its clinical feasibility. The prediction model was developed in a retrospective cohort ( n = 382), integrating assays for FGFR3 and TERT mutations and aberrant ONECUT2 and VIM methylation to generate a UC-score. The test performance was validated in a double-blinded, multicenter, prospective trial ( n = 947; ChiCTR2300076543) and demonstrated a sensitivity of 91.37% and a specificity of 95.09%. The sensitivity reached 75.81% for low-grade Ta tumors and exceeded 93% in high-grade Ta and higher stages (T1 to T4). Simultaneous identification of both bladder and upper urinary tract tumors was enabled with sensitivities exceeding 90%. No significant confounding effects were observed regarding benign urological diseases or non-UC malignancies. The test showed improved sensitivities over urine cytology, the NMP22 test, and UroVysion FISH alongside comparable specificities. The single-target accuracy was greater than 98% as confirmed by Sanger sequencing. Post-surgery UC-score decreased in 97.7% of subjects. Overall, UI-Seek demonstrated robust performance and considerable potential for the early detection of UC.
Multi-slice spatial transcriptome domain analysis with SpaDo
Authors: Bin Duan, Shaoqi Chen, Xiaojie Cheng, Qi Liu
Journal: Genome biology (2024)

With the rapid advancements in spatial transcriptome sequencing, multiple tissue slices are now available, enabling the integration and interpretation of spatial cellular landscapes. Herein, we introduce SpaDo, a tool for multi-slice spatial domain analysis, including modules for multi-slice spatial domain detection, reference-based annotation, and multiple slice clustering at both single-cell and spot resolutions. We demonstrate SpaDo's effectiveness with over 40 multi-slice spatial transcriptome datasets from 7 sequencing platforms. Our findings highlight SpaDo's potential to reveal novel biological insights in multi-slice spatial transcriptomes.
DANCE: a deep learning library and benchmark platform for single-cell analysis
Authors: Jiayuan Ding, Renming Liu, Hongzhi Wen, Wenzhuo Tang, Zhaoheng Li, Julian Venegas, Runze Su, Dylan Molho, Wei Jin, Yixin Wang, Qiaolin Lu, Lingxiao Li, Wangyang Zuo, Yi Chang, Yuying Xie, Jiliang Tang
Journal: Genome biology (2024)

DANCE is the first standard, generic, and extensible benchmark platform for accessing and evaluating computational methods across the spectrum of benchmark datasets for numerous single-cell analysis tasks. Currently, DANCE supports 3 modules and 8 popular tasks with 32 state-of-art methods on 21 benchmark datasets. People can easily reproduce the results of supported algorithms across major benchmark datasets via minimal efforts, such as using only one command line. In addition, DANCE provides an ecosystem of deep learning architectures and tools for researchers to facilitate their own model development. DANCE is an open-source Python package that welcomes all kinds of contributions.
LOX-1 and MMP-9 Inhibition Attenuates the Detrimental Effects of Delayed rt-PA Therapy and Improves Outcomes After Acute Ischemic Stroke
Authors: Kajsa Arkelius, Trevor S. Wendt, Henrik Andersson, Anaële Arnou, Michael Gottschalk, Rayna J. Gonzales, Saema Ansar
Journal: Circulation Research (2024)

BACKGROUND: Acute ischemic stroke triggers endothelial activation that disrupts vascular integrity and increases hemorrhagic transformation leading to worsened stroke outcomes. rt-PA (recombinant tissue-type plasminogen activator) is an effective treatment; however, its use is limited due to a restricted time window and hemorrhagic transformation risk, which in part may involve activation of MMPs (matrix metalloproteinases) mediated through LOX-1 (lectin-like oxLDL [oxidized low-density lipoprotein] receptor 1). This study’s overall aim was to evaluate the therapeutic potential of novel MMP-9 (matrix metalloproteinase 9) ± LOX-1 inhibitors in combination with rt-PA to improve stroke outcomes. METHODS: A rat thromboembolic stroke model was utilized to investigate the impact of rt-PA delivered 4 hours poststroke onset as well as selective MMP-9 (JNJ0966) ±LOX-1 (BI-0115) inhibitors given before rt-PA administration. Infarct size, perfusion, and hemorrhagic transformation were evaluated by 9.4-T magnetic resonance imaging, vascular and parenchymal MMP-9 activity via zymography, and neurological function was assessed using sensorimotor function testing. Human brain microvascular endothelial cells were exposed to hypoxia plus glucose deprivation/reperfusion (hypoxia plus glucose deprivation 3 hours/R 24 hours) and treated with ±tPA and ±MMP-9 ±LOX-1 inhibitors. Barrier function was assessed via transendothelial electrical resistance, MMP-9 activity was determined with zymography, and LOX-1 and barrier gene expression/levels were measured using qRT-PCR (quantitative reverse transcription PCR) and Western blot. RESULTS: Stroke and subsequent rt-PA treatment increased edema, hemorrhage, MMP-9 activity, LOX-1 expression, and worsened neurological outcomes. LOX-1 inhibition improved neurological function, reduced edema, and improved endothelial barrier integrity. Elevated MMP-9 activity correlated with increased edema, infarct volume, and decreased neurological function. MMP-9 inhibition reduced MMP-9 activity and LOX-1 expression. In human brain microvascular endothelial cells, LOX-1/MMP-9 inhibition differentially attenuated MMP-9 levels, inflammation, and activation following hypoxia plus glucose deprivation/R. CONCLUSIONS: Our findings indicate that LOX-1 inhibition and ± MMP-9 inhibition attenuate negative aspects of ischemic stroke with rt-PA therapy, thus resulting in improved neurological function. While no synergistic effect was observed with simultaneous LOX-1 and MMP-9 inhibition, a distinct interaction is evident.
Puzzling phenomenon: adult-onset cancer predisposition and pediatric cancer
Authors: Michaela Kuhlen, Thomas G. Hofmann, Monika M. Golas
Journal: Trends in cancer (2024)

Pathogenic variants (PVs) in DNA repair–linked adult-onset cancer predisposition genes, including double heterozygosity, are increasingly identified in pediatric patients with cancer. Their role in childhood cancer, however, remains poorly understood. Integrating comprehensive tumor analysis is integral for understanding the contribution of such PVs in cancer development and personalized cancer care.
Using Effect Scores to Characterize Heterogeneity of Treatment Effects
Authors: Guanbo Wang, Patrick J. Heagerty, Issa J. Dahabreh
Journal: JAMA (2024)

This JAMA Guide to Statistics and Methods article explains effect score analyses, an approach for evaluating the heterogeneity of treatment effects, and examines its use in a study of oxygen-saturation targets in critically ill patients.
Your Mileage May Vary
Authors: Derek C. Angus
Journal: JAMA (2024)

Kevin G. Buell, MBBS; Alexandra B. Spicer, MS; Jonathan D. Casey, MD, MSc; Kevin P. Seitz, MD, MSc; Edward T. Qian, MD, MSc; Emma J. Graham Linck, MS; Wesley H. Self, MD, MPH; Todd W. Rice, MD, MSc; Pratik Sinha, MBChB, PhD; Paul J. Young, MD, PhD; Matthew W. Semler, MD, MSc; Matthew M. Churpek, MD, MPH, PhD