tbuckley/cabot-search huggingface dataset:
CrystalTac: Vision-Based Tactile Sensor Family Fabricated Via Rapid Monolithic Manufacturing
Authors: Wen Fan, Haoran Li, Dandan Zhang
Journal: Cyborg and Bionic Systems (2025)

Recently, vision-based tactile sensors (VBTSs) have gained popularity in robotics systems. The sensing mechanisms of most VBTSs can be categorized based on the type of tactile features they capture. Each category requires specific structural designs to convert physical contact into optical information. The complex architectures of VBTSs pose challenges for traditional manufacturing techniques in terms of design flexibility, cost-effectiveness, and quality stability. Previous research has shown that monolithic manufacturing using multimaterial 3-dimensional printing technology can address these challenges but fails to bridge the gap between the design phase and creation phase of VBTSs. Thereby, in this study, we introduce the CrystalTac family, a series of VBTSs designed with on-demand sensing mechanisms and fabricated through rapid monolithic manufacturing. Case studies on the CrystalTac family demonstrate their efficiency in targeted tasks involving tactile perception, along with impressive cost-effectiveness and design flexibility. The CrystalTac family aims to highlight the potential of rapid monolithic manufacturing techniques in VBTS development and inspire further research in tactile sensing and manipulation.
Real-world experience of bimekizumab for plaque psoriasis in adult patients with prior exposure to interleukin-17 inhibitors: A 52-week multicenter retrospective review
Authors: Siddhartha Sood, Alexander Rimke, Brian D Rankin, Abrahim Abduelmula, Jorge R Georgakopoulos, Khalad Maliyar, Ahmed Bagit, Fernejoy Leung, Alim R Devani, Ronald Vender, Jensen Yeung, Vimal H Prajapati
Journal: Journal of the American Academy of Dermatology (2025)
Integrating pharmacogenomics and cheminformatics with diverse disease phenotypes for cell type-guided drug discovery
Authors: Arda Halu, Sarvesh Chelvanambi, Julius L. Decano, Joan T. Matamalas, Mary Whelan, Takaharu Asano, Namitra Kalicharran, Sasha A. Singh, Joseph Loscalzo, Masanori Aikawa
Journal: Genome Medicine (2025)
Author Correction: Considerations in the search for epistasis
Authors: Marleen Balvert, Johnathan Cooper-Knock, Julian Stamp, Ross P. Byrne, Soufane Mourragui, Juami van Gils, Stefania Benonisdottir, Johannes Schlüter, Kevin Kenna, Sanne Abeln, Alfredo Iacoangeli, Joséphine T. Daub, Brian L. Browning, Gizem Taş, Jiajing Hu, Yan Wang, Elham Alhathli, Calum Harvey, Luna Pianesi, Sara C. Schulte, Jorge González-Domínguez, Erik Garrisson, Michael P. Snyder, Alexander Schönhuth, Letitia M. F. Sng, Natalie A. Twine
Journal: Genome biology (2025)
Author Correction: A multilineage screen identifies actionable synthetic lethal interactions in human cancers
Authors: Samson H. Fong, Brent M. Kuenzi, Nicole M. Mattson, John Lee, Kyle Sanchez, Ana Bojorquez-Gomez, Kyle Ford, Brenton P. Munson, Katherine Licon, Sarah Bergendahl, John Paul Shen, Jason F. Kreisberg, Prashant Mali, Jeffrey H. Hager, Michael A. White, Trey Ideker
Journal: Nature Genetics (2025)
Nanopore-based random genomic sampling for intraoperative molecular diagnosis
Authors: Francesco E. Emiliani, Abdol Aziz Ould Ismail, Edward G. Hughes, Gregory J. Tsongalis, George J. Zanazzi, Chun-Chieh Lin
Journal: Genome Medicine (2025)

Central nervous system tumors are among the most lethal types of cancer. A critical factor for tailored neurosurgical resection strategies depends on specific tumor types. However, it is uncommon to have a preoperative tumor diagnosis, and intraoperative morphology-based diagnosis remains challenging. Despite recent advances in intraoperative methylation classifications of brain tumors, accuracy may be compromised by low tumor purity. Copy number variations (CNVs), which are almost ubiquitous in cancer, offer highly sensitive molecular biomarkers for diagnosis. These quantitative genomic alterations provide insight into dysregulated oncogenic pathways and can reveal potential targets for molecular therapies. We develop iSCORED, a one-step random genomic DNA reconstruction method that enables efficient, unbiased quantification of genome-wide CNVs. By concatenating multiple genomic fragments into long reads, the method leverages low-pass sequencing to generate approximately 1–2 million genomic fragments within 1 h. This approach allows for ultrafast high-resolution CNV analysis at a genomic resolution of 50 kb. In addition, concurrent methylation profiling enables brain tumor methylation classification and identifies promoter methylation in amplified oncogenes, providing an integrated diagnostic approach. In our retrospective cohort of 26 malignant brain tumors, iSCORED demonstrated 100% concordance in CNV detection, including chromosomal alterations and oncogene amplifications, when compared to clinically validated assays such as Next-Generation Sequencing and Chromosomal Microarray. Furthermore, we validated iSCORED's real-time applicability in 15 diagnostically challenging primary brain tumors, achieving 100% concordance in detecting aberrant CNV detection, including diagnostic chromosomal gains/losses and oncogene amplifications (10/10). Of these, 14 out of 15 brain tumor methylation classifications aligned with final pathological diagnoses. This streamlined workflow—from tissue arrival to automatic generation of CNV and methylation reports—can be completed within 105 min. The iSCORED pipeline represents the first method capable of high-resolution CNV detection within the intraoperative timeframe. By combining CNV detection and methylation classification, iSCORED provides a rapid and comprehensive molecular diagnostic tool that can inform rapid clinical decision. The integrated approach not only enhances the accuracy of tumor diagnosis but also optimizes surgical planning and identifies potential molecular therapies, all within the critical intraoperative timeframe.
Exploring Integrin α5β1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights From Comprehensive Multicenter Preclinical Studies
Authors: Sarah-Eve Lemay, Mónica S. Montesinos, Yann Grobs, Tetsuro Yokokawa, Tsukasa Shimauchi, Manon Mougin, Charlotte Romanet, Mélanie Sauvaget, Sandra Breuils-Bonnet, Alice Bourgeois, Charlie Théberge, Andréanne Pelletier, Reem El Kabbout, Sandra Martineau, Keiko Yamamoto, Muzaffar Akram, Adrian S. Ray, Blaise Lippa, Bryan Goodwin, Fu-Yang Lin, Hua Wang, James E. Dowling, Min Lu, Qi Qiao, T. Andrew McTeague, Terence I. Moy, François Potus, Steeve Provencher, Olivier Boucherat, Sébastien Bonnet
Journal: Circulation (2025)

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by obliterative vascular remodeling of the small pulmonary arteries (PAs) and progressive increase in pulmonary vascular resistance leading to right ventricular failure. Although several drugs are approved for the treatment of PAH, mortality rates remain high. Accumulating evidence supports a pathological function of integrins in vessel remodeling, which are gaining renewed interest as drug targets. However, their role in PAH remains largely unexplored. METHODS: The expression of the RGD (arginylglycylaspartic acid)–binding integrin α5β1 was assessed in PAs, PA smooth muscle cells, and PA endothelial cells from patients with PAH and controls using NanoString, immunoblotting, and Mesoscale Discovery assays. RNA sequencing was conducted to identify gene networks regulated by α5β1 inhibition in PAH PA smooth muscle cells. The therapeutic efficacy of α5β1 inhibition was evaluated using a novel small molecule inhibitor and selective neutralizing antibodies in Sugen/hypoxia and monocrotaline rat models, with validation by an external contract research organization. Comparisons were made against standard-of-care therapies (ie, macitentan, tadalafil) and sotatercept and efficacy was assessed using echocardiographic, hemodynamic, and histological assessments. Ex vivo studies using human precision-cut lung slices were performed to further assess the effects of α5β1 inhibition on pulmonary vascular remodeling. RESULTS: We found that the arginine-glycine-aspartate RGD-binding integrin α5β1 is upregulated in PA endothelial cells and PA smooth muscle cells from patients with PAH and remodeled PAs from animal models. Blockade of the integrin α5β1 or depletion of the α5 subunit downregulated FOXM1 (forkhead box protein M1)–regulated gene networks, resulting in mitotic defects and inhibition of the pro-proliferative and apoptosis-resistant phenotype of PAH cells. We demonstrated that α5β1 integrin blockade safely attenuates pulmonary vascular remodeling and improves hemodynamics and right ventricular function and matched or exceeded the efficacy of standard of care and sotatercept in multiple preclinical models. Ex vivo studies further validated its potential in reversing advanced remodeling in human precision-cut lung slices. CONCLUSIONS: These findings establish α5β1 integrin as a pivotal driver of PAH pathology and we propose its inhibition as a novel, safe, and effective therapeutic strategy for PAH.
Healthcare use in 12–18-year-old adolescents vaccinated against SARS-CoV-2 versus unvaccinated in a national register-based Danish cohort
Authors: Selina Kikkenborg Berg, Helle Wallach-Kildemoes, Line Ryberg Rasmussen, Ulrikka Nygaard, Nina Marie Birk, Henning Bundgaard, Annette Kjær Ersbøll, Lau Caspar Thygesen, Susanne Dam Nielsen, Anne Vinggaard Christensen
Journal: Nature Human Behaviour (2025)
Targeting aldolase A in hepatocellular carcinoma leads to imbalanced glycolysis and energy stress due to uncontrolled FBP accumulation
Authors: Marteinn T. Snaebjornsson, Philipp Poeller, Daria Komkova, Florian Röhrig, Lisa Schlicker, Alina M. Winkelkotte, Adriano B. Chaves-Filho, Kamal M. Al-Shami, Carolina Dehesa Caballero, Ioanna Koltsaki, Felix C. E. Vogel, Roberto Carlos Frias-Soler, Ramona Rudalska, Jessica D. Schwarz, Elmar Wolf, Daniel Dauch, Ralf Steuer, Almut Schulze
Journal: Nature Metabolism (2025)

Abstract Increased glycolytic flux is a hallmark of cancer; however, an increasing body of evidence indicates that glycolytic ATP production may be dispensable in cancer, as metabolic plasticity allows cancer cells to readily adapt to disruption of glycolysis by increasing ATP production via oxidative phosphorylation. Using functional genomic screening, we show here that liver cancer cells show a unique sensitivity toward aldolase A (ALDOA) depletion. Targeting glycolysis by disrupting the catalytic activity of ALDOA led to severe energy stress and cell cycle arrest in murine and human hepatocellular carcinoma cell lines. With a combination of metabolic flux analysis, metabolomics, stable-isotope tracing and mathematical modelling, we demonstrate that inhibiting ALDOA induced a state of imbalanced glycolysis in which the investment phase outpaced the payoff phase. Targeting ALDOA effectively converted glycolysis from an energy producing into an energy-consuming process. Moreover, we found that depletion of ALDOA extended survival and reduced cancer cell proliferation in an animal model of hepatocellular carcinoma. Thus, our findings indicate that induction of imbalanced glycolysis by targeting ALDOA presents a unique opportunity to overcome the inherent metabolic plasticity of cancer cells.
Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies
Authors: Julie K. Jadlowsky, Elizabeth O. Hexner, Amy Marshall, Stephan A. Grupp, Noelle V. Frey, James L. Riley, Elizabeth Veloso, Holly McConville, Walter Rogal, Cory Czuczman, Wei-Ting Hwang, Yimei Li, Rachel M. Leskowitz, Olivia Farrelly, Jayashree Karar, Shannon Christensen, Julie Barber-Rotenberg, Avery Gaymon, Naomi Aronson, Wendy Bernstein, Jan Joseph Melenhorst, Aoife M. Roche, John K. Everett, Sonja A. Zolnoski, Alexander G. McFarland, Shantan Reddy, Angelina Petrichenko, Emma J. Cook, Carole Lee, Vanessa E. Gonzalez, Kathleen Alexander, Irina Kulikovskaya, Ángel Ramírez-Fernández, Janna C. Minehart, Marco Ruella, Saar I. Gill, Stephen J. Schuster, Adam D. Cohen, Alfred L. Garfall, Payal D. Shah, David L. Porter, Shannon L. Maude, Bruce L. Levine, Donald L. Siegel, Anne Chew, Stephen McKenna, Lester Lledo, Megan M. Davis, Gabriela Plesa, Friederike Herbst, Edward A. Stadtmauer, Pablo Tebas, Amanda DiNofia, Andrew Haas, Naomi B. Haas, Regina Myers, Donald M. O’Rourke, Jakub Svoboda, Janos L. Tanyi, Richard Aplenc, Jeffrey M. Jacobson, Andrew H. Ko, Roger B. Cohen, Carl H. June, Frederic D. Bushman, Joseph A. Fraietta
Journal: Nature Medicine (2025)
<scp>IL</scp>‐25 Enhances B Cell Responses in Type 2 Inflammation Through <scp>IL</scp>‐<scp>17RB</scp> Receptor
Authors: Semah Abdu, Jiao Xia, Huihui Yuan, Tiak Ju Tan, Janice A. Layhadi, Mohamed H. Shamji, Andrew N. J. McKenzie, Nora Haloob, Claire Hopkins, Grzegorz Woszczek, Stephen J. Till
Journal: Allergy (2025)

ABSTRACT Background Alarmin cytokine IL‐25 promotes type 2 inflammatory responses in disorders such as asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) and known targets include ILC2 and Th2 cells. However, other cellular targets for IL‐25 remain poorly defined. Objective To investigate induction and expression of IL‐25 receptor (IL‐17RB) by B cells and evaluate responsiveness of IL‐17RB‐expressing B cells to IL‐25 in vitro. Methods IL‐17RB expression, regulation and function on B cells were evaluated in peripheral blood‐derived B cells by flow cytometry and RT‐PCR, including in response to IgE‐inducing stimuli (anti‐CD40 mAb and IL‐4). Single‐cell RNA sequencing was used to compare IL‐17RB+ and IL‐17RB‐activated peripheral blood‐derived B cells. To evaluate B cell IL‐17RB expression within type 2 inflamed tissue, B cells were compared from nasal polyps, control turbinate tissue and matched peripheral blood. Results Activation of B cells with anti‐CD40 and IL‐4 increased IL‐17RB expression at both protein and mRNA level, which was further upregulated by IL‐25. B cells induced to express IL‐17RB responded to IL‐25 with enhanced antibody production. Single‐cell RNA‐sequencing showed that IL17RB+ activated B cells expressed higher levels of IGHE, CCL17 and CCL22 compared to IL17RB‐ B cells. B cells from nasal polyp tissue expressed higher levels of surface IL‐17RB compared with control tissue, correlating with patient‐reported CRSwNP severity (SNOT‐22). Conclusion Peripheral blood B cells activated under IgE‐inducing conditions express surface IL‐17RB, and tissue IL‐17RB+ B cells are increased in type 2 inflammation. IL‐17RB+ cells have a distinct transcriptional profile and respond to IL‐25 with enhanced antibody production, highlighting the IL‐25/IL‐17RB pathway as a potential therapeutic target for CRSwNP and other type 2 inflammatory disorders.
Unlocking novel T cell-based immunotherapy for hepatocellular carcinoma through neoantigen-driven T cell receptor isolation
Authors: Panagiota Maravelia, Haidong Yao, Curtis Cai, Daniela Nascimento Silva, Jennifer Fransson, Ola B Nilsson, Yong-Chen William Lu, Patrick Micke, Johan Botling, Francesca Gatto, Giulia Rovesti, Mattias Carlsten, Matti Sallberg, Per Stål, Carl Jorns, Marcus Buggert, Anna Pasetto
Journal: Gut (2025)

Background Tumour-infiltrating T cells can mediate both antitumour immunity and promote tumour progression by creating an immunosuppressive environment. This dual role is especially relevant in hepatocellular carcinoma (HCC), characterised by a unique microenvironment and limited success with current immunotherapy. Objective We evaluated T cell responses in patients with advanced HCC by analysing tumours, liver flushes and liver-draining lymph nodes, to understand whether reactive T cell populations could be identified despite the immunosuppressive environment. Design T cells isolated from clinical samples were tested for reactivity against predicted neoantigens. Single-cell RNA sequencing was employed to evaluate the transcriptomic and proteomic profiles of antigen-experienced T cells. Neoantigen-reactive T cells expressing 4-1BB were isolated and characterised through T-cell receptor (TCR)-sequencing. Results Bioinformatic analysis identified 542 candidate neoantigens from seven patients. Of these, 78 neoantigens, along with 11 hotspot targets from HCC driver oncogenes, were selected for ex vivo T cell stimulation. Reactivity was confirmed in co-culture assays for 14 targets, with most reactive T cells derived from liver flushes and lymph nodes. Liver flush-derived T cells exhibited central memory and effector memory CD4+ with cytotoxic effector profiles. In contrast, tissue-resident memory CD4+ and CD8+ T cells with an exhausted profile were primarily identified in the draining lymph nodes. Conclusion These findings offer valuable insights into the functional profiles of neoantigen-reactive T cells within and surrounding the HCC microenvironment. T cells isolated from liver flushes and tumour-draining lymph nodes may serve as a promising source of reactive T cells and TCRs for further use in immunotherapy for HCC.
The Gut Microbiome in Hyperuricemia and Gout
Authors: Robert Terkeltaub, Dylan Dodd
Journal: Arthritis & Rheumatology (2025)

Humans develop hyperuricemia via decreased urate elimination and excess urate production, consequently promoting monosodium urate crystal deposition and incident gout. Normally, approximately two thirds of urate elimination is renal. However, chronic kidney disease (CKD) and other causes of decreased renal urate elimination drive hyperuricemia in most with gout. This places more demand on elimination of urate via the gut, where diet, purine metabolism and microbiota intersect. Heritable impairment of urate transport into the gut is common, and promotes hyperuricemia, renal urate overload, and early onset and palpable tophaceous gout phenotypes. Lactobacilli, by sequestering and modifying ambient purines, are being studied for the potential to suppress diet‐induced urate generation and associated gout flares. Landmark preclinical studies recently revealed much higher‐capacity urate‐lowering effects of diverse, obligate and facultative anaerobic human and murine gut microbiota (predominantly of Bacillota phylum) termed purine‐degrading bacteria (PDB). A conserved gene cluster in PDB drives urate conversion to lactate or anti‐inflammatory short chain fatty acids (SCFA). When mice are rendered deficient in hepatic uricase to mimic human uricase absence, microbiota depletion rapidly elevates both cecal and serum urate, reversible by PDB administration. In healthy human volunteers with normal renal function, antibiotic‐induced gut microbiota depletion, decreases the urate‐lowering gene cluster unique to PDB and elevates fecal urate. Also, prior exposure to antibiotics with anaerobic coverage has been linked to heightened incident gout risk. Notably, intestinal dysbiosis that includes Bacillota depletion has been observed in gout cohorts. Therefore, the capacity of diverse gut bacterial strains to biochemically compensate for human limits in urate disposition suggests novel probiotic treatment approaches for gout with inadequate pharmacologic control of both flares and hyperuricemia. This is particularly so for severe CKD, which limits the options and maximal doses for use of conventional oral urate‐lowering drugs. image
Genetic context modulates aging and degeneration in the murine retina
Authors: Olivia J. Marola, Michael MacLean, Travis L. Cossette, Cory A. Diemler, Amanda A. Hewes, Alaina M. Reagan, Jonathan Nyandu Kanyinda, Daniel A. Skelly, Gareth R. Howell
Journal: Molecular Neurodegeneration (2025)

Abstract Background Age is the principal risk factor for neurodegeneration in both the retina and brain. The retina and brain share many biological properties; thus, insights into retinal aging and degeneration may shed light onto similar processes in the brain. Genetic makeup strongly influences susceptibility to age-related retinal disease. However, studies investigating retinal aging have not sufficiently accounted for genetic diversity. Therefore, examining molecular aging in the retina across different genetic backgrounds will enhance our understanding of human-relevant aging and degeneration in both the retina and brain—potentially improving therapeutic approaches to these debilitating conditions. Methods Transcriptomics and proteomics were employed to elucidate retinal aging signatures in nine genetically diverse mouse strains (C57BL/6J, 129S1/SvlmJ, NZO/HlLtJ, WSB/EiJ, CAST/EiJ, PWK/PhK, NOD/ShiLtJ, A/J, and BALB/cJ) across lifespan. These data predicted human disease-relevant changes in WSB and NZO strains. Accordingly, B6, WSB, and NZO mice were subjected to human-relevant in vivo examinations at 4, 8, 12, and/or 18M, including: slit lamp, fundus imaging, optical coherence tomography, fluorescein angiography, and pattern/full-field electroretinography. Retinal morphology, vascular structure, and cell counts were assessed ex vivo . Results We identified common molecular aging signatures across the nine mouse strains, which included genes associated with photoreceptor function and immune activation. Genetic background strongly modulated these aging signatures. Analysis of cell type-specific marker genes predicted age-related loss of photoreceptors and retinal ganglion cells (RGCs) in WSB and NZO, respectively. Fundus exams revealed retinitis pigmentosa-relevant pigmentary abnormalities in WSB retinas and diabetic retinopathy (DR)-relevant cotton wool spots and exudates in NZO retinas. Profound photoreceptor dysfunction and loss were confirmed in WSB. Molecular analyses indicated changes in photoreceptor-specific proteins prior to loss, suggesting photoreceptor-intrinsic dysfunction in WSB. In addition, age-associated RGC dysfunction, loss, and concomitant microvascular dysfunction were observed in NZO mice. Proteomic analyses revealed an early reduction in protective antioxidant processes, which may underlie increased susceptibility to DR-relevant pathology in NZO. Conclusions Genetic context is a strong determinant of retinal aging, and our multi-omics resource can aid in understanding age-related diseases of the eye and brain. Our investigations identified and validated WSB and NZO mice as improved preclinical models relevant to common retinal neurodegenerative diseases.