tbuckley/cabot-search huggingface dataset:
St Andrews Referral Delay in Skin Cancer (StARDISC): A study of keratinocyte skin cancer time to treatment, growth, invasiveness, British Association of Dermatologists risk factors and excision adequacy
Authors: Ben H Miranda, Shahab Shahid, Anna Correiro, Jufen Zhang, Sebastian Kosasih, Naguib El-Muttardi
Journal: British Journal of Dermatology (2025)

Abstract Background British Association of Dermatologists (BAD) guidelines for basal (BCC) and squamous (SCC) cell skin carcinomas are distinct; there is however a paucity of evidence relating to their histopathological behaviour over time, with management guidelines. Objectives To investigate the effect of lesion time on keratinocyte skin cancer (KSC) growth, development of high-risk factors according to BAD guidelines, and excision margin adequacy. Further aims included investigating the impact of the presence of high or very-high-risk histological parameters on excision rates and clearance margins. Methods A cohort study was undertaken on a random sample of patients referred to our Plastic Surgery Skin Cancer Centre with BCC and SCC from January to June 2019 inclusive. Data collected included patient demographics, referral source, lesion time (first appearance to treatment), histological data, excision margins and skin cancer risk as defined by BAD guidelines. Results There were 728 patients included (397 male, 331 female, median age=77 years), who underwent 872 KSC excisions (BCC=454, SCC=418). Longer lesion time was associated with increased BCC (p&amp;lt;0.001, p=0.001) and SCC (p&amp;lt;0.001, p&amp;lt;0.001) surface area and thickness at multivariable regression. The likelihood of developing very-high-risk histological parameters increased with SCC lesion time, including diameter &amp;gt;40mm (p&amp;lt;0.001), thickness &amp;gt;6mm (p&amp;lt;0.001) and total number of very-high-risk factors (p&amp;lt;0.001). SCCs with lesion durations &amp;gt;3 months had greater median surface areas (706.9mm2 vs. 295.3mm2; p&amp;lt;0.001), and thicknesses (3.5mm vs. 3mm; p&amp;lt;0.001), than those with durations ≤3 months); the same was found for median BCC surface area (263.9mm2 vs. 131.9mm2; p&amp;lt;0.001). A general trend in decreasing BCC and SCC adequate excision rates was observed with increasing numbers of high or very-high-risk parameters. Conclusions Increasing lesion time resulted in increased KSC thickness and surface area, and increased presence of BAD high-risk factors, in SCC far more than BCC; this had a negative impact on surgical excision margins. Crucially, lesion time was significantly associated with increased SCC thickness (but not BCC) at 3 months. Our results support BAD guidance on KSC, which identifies the highest risk lesions and informs the practice of skin cancer units.
Positioning Imatinib for Pulmonary Arterial Hypertension: A Dose Finding Phase 2 Study
Authors: Alexander M.K. Rothman, Sofia Villar, Jennifer Middleton, Andreas A. Roussakis, Frances Varian, Hamza Zafar, Martin Law, Jane Apperley, Imke H. Bartelink, Medhat M. Said, Juan A. Delgado-SanMartin, David G. Kiely, Luke Howard, Mark Toshner, S John Wort, Martin R Wilkins
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Imatinib 400mg daily reduces pulmonary vascular resistance and improves exercise capacity in patients with pulmonary arterial hypertension. Concerns about safety and tolerability limit its use. To identify a safe and tolerated dose of oral imatinib between 100mg and 400mg daily and evaluate its efficacy. Oral imatinib was added to the background therapy of 17 patients with pulmonary arterial hypertension, including 13 implanted with devices providing daily measurements of cardiopulmonary haemodynamics and physical activity. The first patient started on 100mg daily. The next 12 patients, recruited serially, started on 200mg, 300mg or 400mg daily, following a Continuous Reassessment Method sequence. An extension cohort (patients 14 to 17) received 100mg or 200mg daily. The Continuous Assessment Method recommended starting dose was 200mg daily. The most common side effect was nausea. Imatinib reduced mean pulmonary artery pressure (-6.5 mmHg, 95%CI -2.4 to -10.6, P<0.01) and total pulmonary resistance (-2.8 Wood Units, 95%CI -1.5 to -4.2, P<0.001) with no significant change in cardiac output. The reduction in total pulmonary resistance was dose and exposure-dependent; the reduction from baseline with imatinib 200mg daily was -20.3% (95%CI -14.3 to -26.3%). Total pulmonary resistance and night heart rate declined steadily over the first 28 days of treatment and remained below baseline up to 40 days following imatinib withdrawal. Oral imatinib 200mg daily is well tolerated as an add-on treatment in pulmonary arterial hypertension. A delay in the return of cardiopulmonary haemodynamics to baseline was observed after stopping imatinib. Clinical trial registration available at www. gov, ID: NCT04416750 This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Mutation of SMARCA4 Induces Cancer Cell-Intrinsic Defects in the Enhancer Landscape and Resistance to Immunotherapy
Authors: Yawen Wang, Ismail M. Meraz, Md Qudratullah, Sasikumar Kotagiri, Yanyan Han, Yuanxin Xi, Jing Wang, Kadir C. Akdemir, Jack A. Roth, Yonathan Lissanu
Journal: Cancer Research (2025)

Abstract Cancer genomic studies have identified frequent alterations in genes encoding components of the SWI/SNF chromatin remodeling complex, including SMARCA4 and ARID1A. Importantly, clinical reports indicate that SMARCA4-mutant lung cancers respond poorly to immunotherapy and have dismal prognosis. Here, we corroborated the clinical findings by using immune-humanized, syngeneic, and genetically engineered mouse models of lung cancer harboring SMARCA4 deficiency. Specifically, models with SMARCA4 loss showed decreased response to anti-PD1 immunotherapy associated with significantly reduced infiltration of dendritic cells and CD4+ T cells into the tumor microenvironment. SMARCA4 loss in tumor cells led to profound downregulation of STING1, IL1B, and other components of the innate immune system, as well as inflammatory cytokines that are required for efficient recruitment and activity of immune cells. The deregulation of gene expression was caused by cancer cell-intrinsic reprogramming of the enhancer landscape with marked loss of chromatin accessibility at enhancers of genes involved in innate immune response, such as STING1, IL1B, type I interferon, and inflammatory cytokines. Interestingly, the transcription factor NF-κB binding motif was enriched in enhancers that lose accessibility upon SMARCA4 deficiency. Furthermore, SMARCA4 and NF-κB co-occupied the same genomic loci on enhancers associated with STING1 and IFNB1, indicating a functional interplay between SMARCA4 and NF-κB. Taken together, these findings provide the mechanistic basis for the poor response of SMARCA4-mutant tumors to immunotherapy and establish a functional link between SMARCA4 and NF-κB in innate immune and inflammatory gene expression regulation.
SMYD3 Activates Fatty Acid β-oxidation to Promote Self-Renewal of Leukemia Stem Cells
Authors: Min Zhou, Zihao Wu, Fen Wei, Chen Duan, Xiaoying Lin, Waiyi Zou, Chang Liu, Jingxuan Pan, Yanli Jin
Journal: Cancer Research (2025)

Abstract The development of BCR-ABL tyrosine kinase inhibitors (TKIs) has revolutionized disease management of chronic myeloid leukemia (CML). However, the persistence of leukemia stem cells (LSCs) remains a major barrier to curing CML, highlighting the urgent need to identify the regulators supporting LSCs. In this study, we validated the critical role of the histone methyltransferase SET and MYND domain containing 3 (SMYD3) in the maintenance of LSCs in CML. SMYD3 was overexpressed in CML LSCs and enhanced the survival and self-renewal properties of human primary CD34+ CML cells. Loss of SMYD3 blocked leukemogenesis and impaired the self-renewal and disease reconstitution abilities of LSCs in mice without affecting normal hematopoiesis. SMYD3 stimulated fatty acid β-oxidation (FAO) in LSCs by activating the FABP5/PPARD/CPT1A signaling axis in a methyltransferase activity-dependent manner. Blocking CPT1A-mediated FAO reduced the function of human CML LSCs in vitro and depleted LSCs in vivo. These findings shed light on the role of histone lysine methylation-mediated FAO in the maintenance of LSCs and suggest that SMYD3 may serve as a therapeutic target for treating patients with CML.
Prodrug-designed nanocarrier co-delivering chemotherapeutic and vascular disrupting agents with exceptionally high drug loading capacity
Authors: Huicong Zhou, Zhaofan Yang, Guanyu Jin, Lanqing Wang, Yuanzhen Su, Hao Liu, Hai Sun, Lingwei Xue, Liwei Mi, Irina A Veselova, Mingqiang Li, Shixian Lv, Xuesi Chen
Journal: Journal of Controlled Release (2025)
PROTAC-loaded nanocapsules degrading BRD4 for radio-chemotherapy sensitization in glioblastoma
Authors: Yun Guo, Mingzhu Fang, Shilin Zhang, Zheng Zhou, Zonghua Tian, Haoyu You, Yun Chen, Jingyi Zhou, Xiaobao Yang, Yunke Bi, Chen Jiang, Tao Sun
Journal: Acta Pharmaceutica Sinica B (2025)
Clinical presentation and prognosis of acute symptomatic pulmonary embolism in patients with concomitant upper-extremity versus lower-extremity deep vein thrombosis
Authors: Álvaro Dubois-Silva, Behnood Bikdeli, David Jiménez, Cristina Barbagelata-López, Carmen Fernández-Capitán, Andris Skride, Khanh Quoc Pham, José Antonio Porras, Nazaret Pacheco-Gómez, Manuel Monreal
Journal: Thorax (2025)

Background The impact of deep vein thrombosis (DVT) location on acute pulmonary embolism (PE) prognosis remains uncertain. Methods Using the Registro Informatizado de Enfermedad TromboEmbólica registry, we assessed 30-day and 90-day outcomes in patients with acute symptomatic PE and concomitant upper-extremity (UEDVT) versus lower-extremity DVT (LEDVT). Cox regression was employed for analysis, and standardised differences (SRD) were used for reporting clinical characteristics to minimise type I error overinflation. The primary outcome was 30-day all-cause mortality, with secondary outcomes including 90-day mortality, fatal PE, venous thromboembolism (VTE) recurrences, and major bleeding. Results Among 21 617 patients with PE (March 2001–April 2023), 508 had UEDVT, and 21 109 had LEDVT. Patients with UEDVT were younger (SRD: 0.231), more often had cancer (SRD: 0.395) or non-central PEs (SRD: 0.445), but less frequently had raised troponin levels (SRD: 0.376) or right ventricle dysfunction (SRD: 0.249). Thirty-day mortality was higher in UEDVT compared with LEDVT (7.3% vs 3.5%; p&lt;0.001), with similar trends at 90 days (14% vs 6.0%) and in subgroup analysis in patients without cancer. Increased rates of PE-related mortality, VTE recurrences and major bleeding were noted in patients with UEDVT at both 30 and 90 days. UEDVT was associated with a higher risk for 30-day (adjusted HR (aHR): 1.49; 95% CI 1.04 to 2.13) and 90-day (aHR: 1.52; 95% CI 1.15 to 2.00) all-cause mortality on multilevel multivariable analysis. Conclusions Patients with concomitant UEDVT experienced worse short-term outcomes, including higher mortality, despite fewer clinical signs of PE severity compared with LEDVT. These findings suggest that unrecognised patient characteristics might influence prognosis, warranting further research.
Lateral Walking Gait Recognition and Hip Angle Prediction using a Dual-Task Learning Framework
Authors: Mingxiang Luo, Meng Yin, Jinke Li, Ying Li, Worawarit Kobsiriphat, Hongliu Yu, Tiantian Xu, Xinyu Wu, Wujing Cao
Journal: Cyborg and Bionic Systems (2025)

Lateral walking exercise is beneficial for the hip abductor enhancement. Accurate gait recognition and continuous hip joint angle prediction are essential for the control of exoskeletons. We propose a dual-task learning framework, the "Twin Brother" model, which fuses convolutional neural network (CNN), long short-term memory (LSTM), neural networks (NNs), and the squeezing-elicited attention mechanism to classify the lateral gait stage and estimate the hip angle from electromyography (EMG) signals. The EMG signals of 6 muscles from 10 subjects during lateral walking were collected. Four gait phases were recognized, and the hip angles of both legs were continuously estimated. The sliding window length of 250 ms and the sliding increment of 3 ms were determined by the requirements of response time and recognition accuracy of the real-time system. We compared the performance of CNN-LSTM, CNN, LSTM, support vector machine, NN, K-nearest neighbor, and the "Twin Brother" models. The "Twin Brother" model achieved a recognition accuracy (mean ± SD) of 98.81% ± 0.14%. The model's predicted root mean square error (RMSE) for the left and right hip angles are 0.9183° ± 0.024° and 1.0511° ± 0.027°, respectively, where the R 2 are 0.9853 ± 0.006 and 0.9808 ± 0.008. The accuracy of recognition and estimation are both better than comparative models. For gait phase percentage prediction, RMSE and R 2 predicted by the model can reach 0.152° ± 0.014° and 0.986 ± 0.011, respectively. These results demonstrate that the method can be applied to lateral walking gait recognition and hip joint angle prediction.
Electrode Arrays for Detecting and Modulating Deep Brain Neural Information in Primates: a Review
Authors: Siyu Zhang, Yilin Song, Shiya Lv, Luyi Jing, Mingchuan Wang, Yu Liu, Wei Xu, Peiyao Jiao, Suyi Zhang, Mixia Wang, Juntao Liu, Yirong Wu, Xinxia Cai
Journal: Cyborg and Bionic Systems (2025)

Primates possess a more developed central nervous system and a higher level of intelligence than rodents. Detecting and modulating deep brain activity in primates enhances our understanding of neural mechanisms, facilitates the study of major brain diseases, enables brain–computer interactions, and supports advancements in artificial intelligence. Traditional imaging methods such as magnetic resonance imaging, positron emission computed tomography, and scalp electroencephalogram are limited in spatial resolution. They cannot accurately capture deep brain signals from individual neurons. With the progress of microelectromechanical systems and other micromachining technologies, single-neuron level detection and stimulation technology in rodents based on microelectrodes has made important progress. However, compared with rodents, human and nonhuman primates have larger brain volume that needs deeper implantation depth, and the test object has higher safety and device preparation requirements. Therefore, high-resolution devices suitable for long-term detection in the brains of primates are urgently needed. This paper reviewed electrode array devices used for electrophysiological and electrochemical detections in primates’ deep brains. The research progress of neural recording and stimulation technologies was introduced from the perspective of electrode type and device structures, and their potential value in neuroscience research and clinical disease treatments was discussed. Finally, it is speculated that future electrodes will have a lot of room for development in terms of flexibility, high resolution, deep brain, and high throughput. The improvements in electrode forms and preparation process will expand our understanding of deep brain neural activities, and bring new opportunities and challenges for the further development of neuroscience.
AI-powered evaluation of lung function for diagnosis of interstitial lung disease
Authors: Daniela Gompelmann, Maximilian Robert Gysan, Paul Desbordes, Julie Maes, Karolien Van Orshoven, Maarten De Vos, Markus Steinwender, Erich Helfenstein, Corina Marginean, Nicolas Henzi, Peter Cerkl, Patrick Heeb, Stephan Keusch, Gianluca Calderari, Paul von Boetticher, Bernhard Baumgartner, Daiana Stolz, Marioara Simon, Helmut Prosch, Wim Janssens, Marko Topalovic
Journal: Thorax (2025)

Background The diagnosis of interstitial lung disease (ILD) can pose a challenge as the pulmonary function test (PFT) is only minimally affected at the onset. To improve early diagnosis, this study aims to explore the potential of artificial intelligence (AI) software in assisting pulmonologists with PFT interpretation for ILD diagnosis. The software provides an automated description of PFT and disease probabilities computed from an AI model. Study methods In study phase 1, a cohort of 60 patients, 30 of whom had ILD, were retrospectively diagnosed by 25 pulmonologists (8 junior physicians and 17 experienced pneumologists) by evaluating a PFT (body plethysmography and diffusion capacity) and a short medical history. The experts screened the cohort twice, without and with the aid of AI (ArtiQ.PFT, V.1.4.0, ArtiQ, BE) software and provided a primary diagnosis and up to three differential diagnoses for each case. In study phase 2, 19 pulmonologists repeated the protocol after using ArtiQ.PFT for 4–6 months. Results Overall, AI increased the diagnostic accuracy for various lung diseases from 41.8% to 62.3% in study phase 1. Focusing on ILD, AI improved the detection of lung fibrosis as the primary diagnosis from 42.8% without AI to 72.1% with AI (p&lt;0.0001). Phase 2 yielded a similar outcome: using AI increased ILD diagnosis based on primary diagnosis (53.2% to 75.1%; p&lt;0.0001). ILD detections without AI support significantly increased between phase 1 and phase 2 (p=0.028) but not with AI (p=0.24). Interpretation This study shows that AI-based decision support on PFT interpretation improves accurate and early ILD diagnosis.
Curative Application of Immunotherapy in Untreated Head and Neck and Nasopharynx Cancer
Authors: Marshall Posner
Journal: JAMA (2025)

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Robotic Ultrasound Scanning End-effector with Adjustable Constant Contact Force
Authors: Zehao Wu, Xianli Wang, Yuning Cao, Weijian Zhang, Qingsong Xu
Journal: Cyborg and Bionic Systems (2025)

In modern medical treatment, ultrasound scanning provides a radiation-free medical imaging method for the diagnosis of soft tissues via skin contact. However, the exerted contact force heavily relies on the skill and experience of the operator, which poses great inspection instability. This article reports on a robotic ultrasound scanning system with a constant-force end-effector. Its uniqueness is the introduction of a hybrid active-passive force control approach to maintaining a constant contact force between the ultrasound probe and the continually changing surface. In particular, the passive constant-force mechanism provides strong buffering to the force variation. The active force control system improves flexibility and provides long-stroke positioning. Experimental tests on both silicone models and human volunteers demonstrate the capability of the proposed robotic ultrasound scanning system for obtaining qualified ultrasound images with high repeatability. Moreover, the ease of operation of the robotic US scanning system is verified. This work provides a promising method to assist doctors in conducting better and cushier ultrasound scanning imaging.
Submicron-sized superantigen biomimetic liposomes with highly efficient pulmonary accumulation to remodel local immune microenvironment for cancer chemoimmunotherapy
Authors: Bochuan Yuan, Feng Zhang, Qiucheng Yan, Wanmei Wang, Zhangyu Li, Lina Du, Yiguang Jin, Fei Xie
Journal: Acta Pharmaceutica Sinica B (2025)
Methodological Considerations to Enhance the Relevance of Causal Observational Research in the Field of Kidney Disease
Authors: Antoine Créon, Juan Jesus Carrero, Edouard L. Fu
Journal: Journal of the American Society of Nephrology (2025)

The recent study published in JASN by Cheng et al.1 examines the impact of initiating statin therapy in patients with kidney failure. However, several aspects of the study warrant closer examination to ensure that the findings meaningfully inform clinical practice. First, focusing on incident statin users limits the study's relevance because most patients already use statins or have cardiovascular disease at the time of kidney failure. Of 26,933 individual patients, only 3019 were eligible, and 17% of them initiated statins. A more clinically meaningful question would be whether patients with kidney failure should continue or stop statins, similar to previous studies that have explored the withdrawal of renin-angiotensin system inhibitors in advanced kidney disease.2 In addition, the inability to distinguish between patients on dialysis and nondialysis patients is problematic because these groups may respond differently to statins. It is also unclear whether kidney transplant recipients were included and how transplantation during follow-up was handled. Second, several analytical choices violate the principles of target trial emulation, even though the study reports to implement this framework. A key aspect of this approach is that three aspects need to be aligned at one moment in time: meeting eligibility criteria, assigning treatment strategies, and commencing follow-up.3 Misalignment of these elements introduces biases.3 Here, the authors' exclusion of patients who experienced an outcome during the first year of follow-up introduces selection bias. In addition, the requirement to have a follow-up visit after baseline introduces immortal time because patients must survive to the first follow-up to be included. These issues, which may have contributed to the low incidence of outcomes observed in the study, impede accurate estimation of absolute risks. Finally, by censoring patients upon death and applying censoring weights, the findings reflect the effect of statin use in an unrealistic hypothetical scenario where no individuals ever die, which, in causal terms, corresponds to the controlled direct effect.4 A causal estimand that would be more relevant for decision making would be the total effect of statin use on cardiovascular disease, which is the composite of the direct effect and the effect mediated by the competing risk of death. We believe that addressing these methodological considerations would enhance the robustness of the findings and their relevance to patient care. Future research may benefit from a design that better reflects real-world clinical practice, aligns with target trial emulation principles, and targets clinically meaningful estimands when dealing with competing risks.
Socioeconomic Status—Another Piece in the Puzzle of Access to Transplant
Authors: Daniel M. Guidot, Lisa M. McElroy
Journal: JAMA Network Open (2025)

Carli J. Lehr, MD, PhD; Lyla Mourany, MS; Paul Gunsalus, MS; Johnie Rose, MD, PhD; Maryam Valapour, MD, MPP; Jarrod E. Dalton, PhD