tbuckley/cabot-search huggingface dataset:
Altered immune landscape of cervical lymph nodes reveals Epstein-Barr virus signature in multiple sclerosis
Authors: Joona Sarkkinen, Dawit A. Yohannes, Nea Kreivi, Pia Dürnsteiner, Alexandra Elsakova, Jani Huuhtanen, Kirsten Nowlan, Goran Kurdo, Riikka Linden, Mika Saarela, Pentti J. Tienari, Eliisa Kekäläinen, Maria Perdomo, Sini M. Laakso
Journal: Science Immunology (2025)

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and Epstein-Barr virus (EBV) infection is a prerequisite for developing the disease. However, the pathogenic mechanisms that lead to MS remain to be determined. Here, we characterized the immune landscape of deep cervical lymph nodes (dcLNs) in newly diagnosed untreated patients with MS (pwMS) using fine-needle aspirations. By combining single-cell RNA sequencing and cellular indexing of transcriptomes and epitopes by sequencing, we observed increased memory B cells and reduced germinal center B cells with decreased clonality in pwMS. Double-negative memory B cells were increased in pwMS that transcriptionally resembled B cells with a lytic EBV infection. Moreover, EBV-targeting memory CD8 T cells were detected in a subset of pwMS. We also detected increased EBV DNA in dcLNs and elevated viral loads in patient saliva. These findings suggest that EBV-driven B cell dysregulation is a critical mechanism in MS pathogenesis.
Genomic signals of ecogeographic adaptation in a wild relative are associated with improved wheat performance under drought stress
Authors: Moses Nyine, Dwight Davidson, Elina Adhikari, Marshall Clinesmith, Huan Wang, Alina Akhunova, Allan Fritz, Eduard Akhunov
Journal: Genome biology (2025)

Prioritizing wild relative diversity for improving crop adaptation to emerging drought-prone environments is challenging. Here, we combine the genome-wide environmental scans (GWES) in wheat diploid ancestor Aegilops tauschii (Ae. tauschii) with allele testing in the genetic backgrounds of adapted cultivars to identify diversity for improving wheat adaptation to water-limiting conditions. We evaluate the adaptive allele effects in Ae. tauschii-wheat introgression lines phenotyped for multiple traits under irrigated and water-limiting conditions using both unmanned aerial system-based imaging and conventional approaches. The GWES show that climatic gradients alone explain more than half of genomic variation in Ae. tauschii, with many alleles associated with climatic factors in Ae. tauschii being linked with improved performance of introgression lines under water-limiting conditions. We find that the most significant GWES signals associated with temperature annual range in the wild relative are linked with reduced canopy temperature in introgression lines and increased yield. Our results suggest that introgression of climate-adaptive alleles from Ae. tauschii has the potential to improve wheat performance under water-limiting conditions, and that variants controlling physiological processes responsible for maintaining leaf temperature are likely among the targets of adaptive selection in a wild relative. Adaptive variation uncovered by GWES in wild relatives has the potential to improve climate resilience of crop varieties.
Sequence chunking through neural encoding of ordinal positions
Authors: Nai Ding
Journal: Trends in Cognitive Sciences (2025)

Grouping sensory events into chunks is an efficient strategy to integrate information across long sequences such as speech, music, and complex movements. Although chunks can be constructed based on diverse cues (e.g., sensory features, statistical patterns, internal knowledge) recent studies have consistently demonstrated that the chunks constructed by different cues are all tracked by low-frequency neural dynamics. Here, I review evidence that chunking cues drive low-frequency activity in modality-dependent networks, which interact to generate chunk-tracking activity in broad brain areas. Functionally, this work suggests that a core computation underlying sequence chunking may assign each event its ordinal position within a chunk and that this computation is causally implemented by chunk-tracking neural activity during predictive sequence chunking.
Endothelial c-REL orchestrates atherosclerosis at regions of disturbed flow through crosstalk with TXNIP-p38 and non-canonical NF-κB pathways
Authors: Blanca Tardajos Ayllon, Neil Bowden, Celine Souilhol, Hazem Darwish, Siyu Tian, Carrie Duckworth, D Mark Pritchard, Suowen Xu, Jon Sayers, Sheila Francis, Jovana Serbanovic-Canic, Fiona Oakley, Paul C Evans
Journal: Cardiovascular Research (2025)

Atherosclerosis initiation at sites of disturbed blood flow involves heightened inflammation coupled to excessive endothelial cell (EC) proliferation. Here, we unveil the pivotal role of c-REL, a member of the NF-κB transcription factor family, in orchestrating these processes by driving dual pathological inflammatory and cell cycle pathways. Analysis of cultured EC and murine models revealed enrichment and activation of c-REL at atherosusceptible sites experiencing disturbed flow. Transcriptome analysis, extensively validated in vitro and in vivo, demonstrates that endothelial c-REL drives inflammation via a TXNIP-p38 MAP kinase signalling pathway and enhances proliferation through a non-canonical NFKB2-p21 pathway. Consistent with its pivotal role in EC pathology, genetic deletion of c-Rel in EC significantly reduces plaque burden in hypercholesterolemic mice. These findings underscore the fundamental role of c-REL in endothelial responses to disturbed flow and highlight therapeutic targeting of endothelial c-REL as a potential strategy for atherosclerosis treatment.
Combination locoregional and systemic therapies in hepatocellular carcinoma
Authors: Bin-Yan Zhong, Wenzhe Fan, Justin J Guan, Zhenwei Peng, Zhongzhi Jia, Haojie Jin, Zhi-Cheng Jin, Jian-Jian Chen, Hai-Dong Zhu, Gao-Jun Teng
Journal: The Lancet. Gastroenterology & hepatology (2025)
Emerging evidence-based role for external-beam radiation therapy in hepatocellular carcinoma
Authors: Stephanie O Dudzinski, Neil B Newman, Jeff McIntyre, Reena Engineer, Nina N Sanford, Jennifer Y Wo, Jinsil Seong, Chandan Guha, Daniel T Chang, Theodore S Hong, Laura A Dawson, Eugene J Koay, Ethan B Ludmir
Journal: The Lancet. Gastroenterology & hepatology (2025)
Impact of Endoscopic Ultrasound-guided biliary drainage on the management of difficult biliary cannulation in patients with distal malignant biliary obstruction
Authors: Marco Spadaccini, Cecilia Binda, Aurelio Mauro, Romain Legros, Matteo Colombo, Carmelo Marco Giacchetto, Marta Andreozzi, Silvia Carrara, Daryl Ramai, Jérémie Albouys, Stefano Mazza, Chiara Coluccio, Antonio Facciorusso, Carlo Fabbri, Andrea Anderloni, Cesare Hassan, Jeremie Jacques, Alessandro Repici, Alessandro Fugazza
Journal: Endoscopy (2025)

Background: Biliary drainage (BD) in patients with distal malignant biliary obstruction (DMBO) implies a higher risk of difficult biliary cannulation (DBC) during endoscopic retrograde cholangiopancreatography (ERCP). After standard cannulation failure, the endoscopist may proceed with advanced cannulation techniques and/or, with endoscopic ultrasound-guided biliary drainage (EUS-BD). Materials: This was a retrospective study of consecutive patients with DMBO and dilated common bile duct (CBD, &gt; 12mm) that underwent ERCP for endoscopic BD in four European centers. The rates of DBC, technical and, clinical success, and procedure-related adverse events (AEs) were assessed. The predictive factors for AEs were also investigated through regression analysis. EUS-BD approach was considered as first option after standard cannulation failure or as final option after advanced cannulation failure. Results: A total of 1016 patients with DMBO were included in the study, with 524(51.6%) matching the definition of DBC. Clinical success was achieved in 956 cases (94.1%). One-hundred-sixty-seven patients (16,4%) experienced procedural-related AEs. Subjects with DBC showed a higher risk for AEs (p = 0.003), however, patients undergoing “early” EUS-BD showed a risk of AEs comparable to those managed with standard cannulation (p = 0.3776). The attempt of any advanced cannulation technique was independently associated with the occurrence of AEs (p = 0.001). Conclusions: The risk of AEs is higher in patients with DMBO, and DBC, this appears to be mainly related to the advanced cannulation techniques. In patients with dilated CBD (&gt;12mm) “early” EUS-BD may minimize the risk of adverse events.
Endoscopic Vacuum Therapy for the Management of Non-Variceal Upper Gastrointestinal Bleeding: A Valuable Resource for the Endoscopist’s Toolbox
Authors: Paulo Ferreira Mega, Eduardo Guimarães Hourneaux de Moura, Alexandre Moraes Bestetti, Daryl Ramai, Atul Kumar, Ludhmila Abrahão Hajjar, Christopher C. Thompson, Diogo Turiani Hourneaux de Moura
Journal: Endoscopy (2025)

Endoscopic Vacuum Therapy (EVT) is a well-established method for managing gastrointestinal perforations. During the COVID epidemic, case reports demonstrated the effective use of EVT in controlling COVID related diffuse duodenal bleeding. Due to its unique mechanism of action, this approach may also be effective for other types of Non-Variceal Upper Gastrointestinal Bleeding (NVUGIB). This study aims to assess EVT in the treatment of NVUGIB. This retrospective analysis of a prospectively collected database includes patients who underwent EVT for the treatment of NVUGIB. The primary outcome was clinical success. Secondary outcomes included technical success and safety. Subgroup analysis comparing outcomes for patients with and without COVID was conducted. A total of 19 patients underwent EVT for NVUGIB, with 57.9% having failed other therapies. Technical success occurred in all patients, and clinical success was achieved in 89.5%. There was no difference in clinical success rates between patients with or without COVID (88% versus 91%, respectively). No procedure-related adverse events occurred. EVT appears to be safe and effective in the management of NVUGIB. This approach could be particularly useful in refractory or diffuse bleeding. Larger studies are warranted to validate these findings.
Regional‐Specific Decellularized Meniscus Extracellular Matrix Elastic Nanofiber Aerogels Regulate Meniscal Regeneration and Vascularization
Authors: Moran Huang, Yangfan Ding, Jize Dong, Guoqi Li, Guojian Fu, Jinhui Pang, Yaying Sun, Shanxing Zhang, Jinglei Wu, Jiwu Chen
Journal: Advanced Healthcare Materials (2025)

Abstract The meniscus is a heterogeneous structure with spatial distribution of cells and vessels. Promoting meniscus healing remains challenging, especially in its avascular inner region. The ideal repair mode shall promote meniscus repair while maintaining local avascularity to prevent pathological changes from vascular invasion. Given the natural biochemical components of native meniscus, decellularized meniscus extracellular matrix (dmECM) shows promise for meniscus repair. Compared to homogeneous dmECM, regional‐specific dmECM (RS‐dmECM) appears to offer greater potential for constructing heterogeneous meniscus structures. Furthermore, there is currently no study on the effects of RS‐dmECM on vascularization. Thus, RS‐dmECM is prepared and found dmECM‐Outer induced stem cells fibrochondrogenic differentiation, while dmECM‐Inner induced the chondrogenic differentiation and inhibited angiogenesis through suppressing the peroxisome proliferators‐activated receptors signaling pathway. Subsequently, regional‐specific poly(lactic acid)/gelatin/dmECM elastic 3D nanofiber aerogels (PG‐dmECM) are fabricated to repair meniscal avascular area defects in a rabbit model. The PG‐Outer promotes meniscal fibrocartilage regeneration without a significant effect on vascular invasion. In contrast, the PG‐Inner achieves meniscal cartilage regeneration and inhibits vascular invasion. Moreover, the compressive stress can reach 117 kPa, comparable to that of the avascular area. This PG‐Inner may have the potential to promote meniscal cartilage regeneration and prevent pathological changes within the avascular area.
Corrigendum to ‘Optimal electrical stimulation boosts stem cell therapy in nerve regeneration’ [Biomaterials 181 (2018) 18758]
Authors: Jian Du, Gehua Zhen, Huanwen Chen, Shuming Zhang, Liming Qing, Xiuli Yang, Gabsang Lee, Hai-Quan Mao, Xiaofeng Jia
Journal: Biomaterials (2025)
Tetrodotoxin Delivery Pen Safely Uses Potent Natural Neurotoxin to Manage Severe Cutaneous Pain
Authors: Yuhao Cai, Qi Li, Ajay K. Banga, Ursula Wesselmann, Chao Zhao
Journal: Advanced Healthcare Materials (2025)

Abstract Clinically available therapies often inadequately address severe chronic cutaneous pain due to short anesthetic duration, insufficient intensity, or side effects. This study introduces a pen device delivering tetrodotoxin (TTX), a potent neurotoxin targeting nerve voltage‐gated sodium channels, as a safe and effective topical anesthetic to treat severe chronic cutaneous pain. Chemical permeation enhancers, such as sodium dodecyl sulfate (SDS) and limonene (LIM), are incorporated to enhance TTX skin permeability. The device ensures precise TTX dosing down to the nanogram level, essential to avoid TTX overdose. In rats, the pen device treatment produces TTX‐dose‐dependent anesthetic effectiveness. An administration of 900 ng of TTX with SDS and LIM to the rat back skin produces a 393.25% increase (measurement limit) in the nociceptive skin pressure threshold, and the hypoalgesia lasts for 11.25 h, outperforming bupivacaine (28 µg), of which are 25.24% and under 1 h. Moreover, the pen device provides on‐demand therapy for multiple treatments, consistently achieving prolonged anesthesia over ten sessions (1 treatment per day) without noted toxicity. Furthermore, a single topical administration of 16 µg of TTX exhibits no TTX‐related toxicity in rats. The TTX delivery pen paves the way for clinical trials, offering a promising solution for severe cutaneous pain.
Viscoelastic HyA Hydrogel Promotes Recovery of Muscle Quality and Vascularization in a Murine Model of Delayed Rotator Cuff Repair
Authors: Morgan R. Pfaff, Aboubacar Wague, Michael Davies, Anouk R. Killaars, Derek Ning, Steven Garcia, Anthony Nguyen, Prashant Nuthalapati, Mengyao Liu, Xuhui Liu, Brian T. Feeley, Kevin E. Healy
Journal: Advanced Healthcare Materials (2025)

Abstract Rotator cuff tears are common musculotendinous injuries with a high risk of permanent functional disability. Following surgical repair, sub‐optimal patient outcomes are directly correlated with poor muscle quality; namely, injury site fatty infiltration, fibrosis, and muscle atrophy. Muscle resident fibro‐adipogenic progenitor cells (FAPs) have been identified as key regulators of post‐injury skeletal muscle regeneration and repair by maintaining a pro‐myogenic environment. In this work, human FAPs (hFAPs) were encapsulated into hyaluronic acid (HyA)‐based hydrogels functionalized with bsp‐RGD(15) cell adhesion peptide, heparin, and a matrix metalloproteinase (MMP)‐cleavable crosslinker. Hydrogel‐encapsulated hFAPs increased expression of the pro‐myogenic marker UCP1 and production of the anti‐inflammatory cytokine IL‐10 while downregulating the expression of the fibrotic marker αSMA over time. A murine model of unilateral rotator cuff transection, denervation, and delayed repair was treated with the HyA hydrogel or PBS and compared to a contralateral, non‐injured control limb. Muscle histology 6 weeks post‐repair revealed that the hydrogel reduced fibrosis, FI, and muscle atrophy while supporting vascularization of the injured tissue region. Collectively, these results suggest that the HyA hydrogel alone can promote muscle regeneration in a clinically relevant delayed repair model of rotator cuff tear, which is hypothesized due to controlled FAP differentiation into pro‐myogenic lineages.
Metastable Calcium Phosphate Cluster‐Involved Mineralization Process Regulated by a Dual Biomolecule System Toward the Application in Dentinal Tubules Occlusion
Authors: Xiaochen Xu, Nan Luo, Jing Ru, Hua Zeng, Xiaohao Liu, Shuo Tan, Feng Chen, Bing‐Qiang Lu, Xi Chen
Journal: Advanced Healthcare Materials (2025)

Dentin hypersensitivity caused by the exposure of dentinal tubules is affecting a significant portion of the population. With promising prospects, the biomimetic mineralization materials used in treating dentin hypersensitivity are expected to possess a metastable characteristic, for which they can easily penetrate the tubules and the surrounding tissues, but then occlude them via a transformation of size and phase immediately. Herein, this study develops a metastable calcium phosphate cluster (MCPC)-involved mineralization process, which is regulated by dual biological macromolecules: bovine serum albumin (BSA) and poly-L-lysine (PLL). BSA functions to stabilize the primary calcium phosphate clusters; PLL further tunes the cluster's evolution (toward larger and crystalline particles) into a metastable fashion, and meanwhile inhibits the local bacteria. Upon treatments, the system generates amorphous MCPC with ultrasmall size (1-2 nm); then they enter the deep dentinal tubules, subsequently aggregate and crystalline into immobile larger particles, which finally seal the exposed dentinal tubules. The effective occlusion of dentinal tubules as well as significant antibacterial performance are confirmed both in vivo and in vitro. This study has devised not only a regulatory approach for the evolution of mineralization-active clusters but also established an efficient method for managing dentin hypersensitivity.
Mechano‐Lysis in Whole Blood Clots: On How Mechanics Affect Clot Lysis, and How Lysis Affects Clot Mechanics
Authors: Grace N. Bechtel, Gabriella P. Sugerman, Tatum Eades, Zuzanna Malinowska, Adam M. Bush, Hamidreza Saber, Sapun H. Parekh, Manuel K. Rausch
Journal: Advanced Healthcare Materials (2025)

Thromboembolic diseases are a significant cause of mortality and are clinically treated enzymatically with tissue plasminogen activator (tPA). Interestingly, prior studies in fibrin fibers and fibrin gels have demonstrated that thrombolysis may be mechanically sensitive. This study aims to expand mechano-lytic studies to whole blood clots. Furthermore, this study investigates not only how mechanics impacts lysis but also how lysis impacts mechanics. Therefore, clots made from whole human blood are exposed to tPA while the clots are either stretched or unstretched. After, the resulting degree of clot lysis is measured by weighing the clots and by measuring the concentration of D-dimer in the surrounding bath. Additionally, each clot's mechanical properties are measured. This study finds that mechanical stretch accelerates loss in clot weight but does not impact the lysis rate as measured by D-dimer. Moreover, lysis not only removes clot volume but also reduces the remaining clot's stiffness and toughness. In summary, tPA-induced lysis of whole clot appears mechanically insensitive, but stretch reduces clot weight. Furthermore, results show that thrombolysis weakens clot. This suggests that thrombolysis may increase the risk of secondary embolizations but may also ease clot removal during thrombectomy, for example.
Mosaic loss of chromosome Y characterises late-onset rheumatoid arthritis and contrasting associations of polygenic risk score based on age at onset
Authors: Shunsuke Uchiyama, Yuki Ishikawa, Katsunori Ikari, Suguru Honda, Keiko Hikino, Eiichi Tanaka, Yoichiro Kamatani, Takahisa Gono, Giulio Genovese, Masataka Kuwana, Chikashi Terao
Journal: Annals of the Rheumatic Diseases (2025)

Mosaic chromosomal alterations (mCAs) increase with age and are associated with age-related diseases. The association between mCAs and rheumatoid arthritis (RA), particularly late-onset RA (LORA), has not been explored. mCAs were detected in peripheral blood samples from 2 independent Japanese datasets (Set 1: 2107 RA cases and 86,998 controls; Set 2: 2359 RA cases and 86,998 controls). The associations between mCAs and RA were evaluated in each dataset using logistic regression models and meta-analysis. In each dataset, the effect sizes of mosaic loss of Y (mLOY) and polygenic risk score (PRS) of RA in males was evaluated, and a meta-analysis was subsequently performed. The interaction between mLOY and PRS was assessed. These models were applied separately to RA, LORA, and young-onset RA (YORA). mLOY increased significantly in LORA (odds ratio [OR] = 1.43, P = .0070). We observed a negative association between mLOY and YORA (OR = 0.66, P = .0034). On the other hand, we found consistently negative associations of autosomal mCAs or mosaic loss of X with RA, LORA, and YORA. The PRS effect sizes were lower for LORA than for YORA. mLOY with a high cell fraction strengthened the association between PRS and LORA (P = .0036), whereas the association with YORA was independent of mLOY. LORA was characterised by the presence of a high burden of mLOY. The observed interaction between mLOY and PRS in LORA, but not in YORA, supports different gene-environment interactions between the subsets. These data suggest that distinct pathophysiological mechanisms underlie the development of LORA and YORA.
Physiological effects of nasal high flow therapy during exercise in patients with chronic obstructive pulmonary disease: A crossover randomised controlled trial
Authors: Tristan Bonnevie, Francis-Edouard Gravier, Pauline Smondack, Emeline Fresnel, Isabelle Rivals, Helena Brunel, Yann Combret, Clément Médrinal, Guillaume Prieur, Fairuz Boujibar, Thomas Similowski, Jean-François Muir, Antoine Cuvelier, Maxime Patout
Journal: Pulmonology (2025)

KEYWORDS: Chronic obstructive pulmonary diseaseconstant workload exercise testingwork of breathingpulmonary rehabilitation
Discrepancies in Beta‐Lactam Antibiotics Cross‐Reactivity: Implications for Clinical Practice
Authors: Evelien Maria Hutten, Maja Bulatović Ćalasan, Jason Anthony Trubiano, Rick Gert‐Jan Pleijhuis, Ingrid Terreehorst
Journal: Allergy (2025)

ABSTRACT Background In patients with a beta‐lactam antibiotic (BA) allergy label, avoidance of the whole group of BAs leads to displacement of first‐line therapies potentially influencing patient outcomes and antimicrobial resistance. Studies previously published on BA cross‐reactivity use different sets of BA and seem to contain conflicting recommendations on safe BA alternatives in case of (suspected) BA allergy. Methods The objectives were (i) to identify discrepancies between studies regarding cross‐allergy in BA and (ii) to identify research gaps. The tables and errata of 4 studies (Romano et al., Trubiano et al., Zagursky et al., SWAB‐guideline by Wijnakker et al.) were evaluated and compared head‐to‐head. Results A total of 51 antibiotics were covered by the four authors, theoretically leading to 2550 potential recommendations regarding alternatives in case of specific allergies. Internal discrepancies existed in 2 tables. Since none of the tables included all 51 BAs, in 356 situations data were lacking regarding specific alternatives. In 1104 situations, only one author gave advice about a specific alternative. Harmony and disharmony between authors could be evaluated in 1090 cases. The advice regarding alternative BAs was 696 times in harmony (482 safe, 214 unsafe), while discrepancies were found in 394 cases. This led to a different advice (safe vs. unsafe) in 272 cases or 69%. Conclusion Disharmony between authors was identified in 36% of the cases. In 69%, this led to a clinically relevant, different advice. This indicates the need for synchronisation of cross‐reactivity tables and answering remaining research gaps.
Telemedicine-based integrated management of atrial fibrillation in village clinics: a cluster randomized trial
Authors: Ming Chu, Shimeng Zhang, Jinlong Gong, Shu Yang, Gang Yang, Xingxing Sun, Dan Wu, Yaodongqin Xia, Jincheng Jiao, Xiafeng Peng, Zhihang Peng, Li Hong, Zhirong Wang, Mingfang Li, Gregory Y. H. Lip, Minglong Chen, Yutao Guo, Xinfeng Liu, Shanshan Lu
Journal: Nature Medicine (2025)