tbuckley/cabot-search huggingface dataset:
Prospective 18-Month Study of Bimatoprost Intracameral Implant in Patients with Open-Angle Glaucoma or Ocular Hypertension in US Clinical Practice
Authors: Eric Mann, Jeffrey A. Kammer, Gagan Sawhney, Jella An, Erica C. Werts, Vanessa Vera, Marcos Rivas, Hongxin Lai, Sadhana Sonparote, E. Randy Craven
Journal: Drugs (2025)

Bimatoprost implant 10 µg (Durysta) is an intracameral biodegradable implant that releases bimatoprost to lower intraocular pressure (IOP). The purpose of this study was to prospectively collect effectiveness and safety data after administration of the implant in patients with open-angle glaucoma or ocular hypertension. This phase IV, multicenter, prospective, observational, open-label, 18-month study (ARGOS) enrolled adult patients with open-angle glaucoma or ocular hypertension who were scheduled to receive the bimatoprost implant in one or both eyes. Data collected included IOP, use of topical IOP-lowering medications, treatment-emergent adverse events, and central corneal endothelial cell density. The primary endpoint was the proportion of primary (first-treated) eyes that received no additional (new) IOP-lowering treatment per standard medical care through month 6 after the implant administration. A total of 217 patients (341 eyes) were enrolled, and 132 patients (60.8%) and 203 eyes (59.5%) completed the study. Most patients were on topical IOP-lowering medication before receiving the implant. After implant administration, the proportion of primary eyes that had received no additional treatment was 88.6% (95% confidence interval 86.6–90.6) at month 6 (primary endpoint) and remained high throughout the follow-up: 83.7% (95% confidence interval 80.2–87.3) at month 12 and 77.7% (95% confidence interval 73.4–82.1) at month 18. Intraocular pressure was reduced after implant administration, with mean changes in IOP from baseline at follow-up visits ranging from − 1.0 to − 2.0 mm Hg. The mean number of topical IOP-lowering medications used was also reduced, from 1.8 at baseline to 0.9 at month 12 and 1.0 at month 18. Increased IOP and dry eye were the most common ocular treatment-emergent adverse events. The mean percentage change in central corneal endothelial cell density from baseline at month 18 (central reading center evaluation) was − 3.47%. In qualitative interviews, most patients (84%, 21/25) reported overall satisfaction with their treatment outcomes. The bimatoprost implant helped control IOP and decrease topical medication use. Throughout the 18 months after implant administration, an estimated 77.7% of eyes required no new added medication for IOP management. Patient-reported outcomes were favorable, and the safety profile of the implant was acceptable. ClinicalTrials.gov identifier NCT04647214, registered 23 November, 2020.
Glioma-White Matter Tract Interactions: A dMRI-Based Three-Tier Classification and Its Clinical Relevance
Authors: Jie Hu, Hongbo Bao, Xing Liu, Shengyu Fang, Zeya Yan, Zihan Wang, Renwu Zhang, Ruiyang Wang, Tingting Pu, Chao Li, Zaixu Cui, Tao Jiang, Yinyan Wang
Journal: Neuro-Oncology (2025)

Abstract Background This study proposed a classification system for the interaction between gliomas and white matter tracts, exploring its potential associations with clinical characteristics, tumor pathological subtypes, and patient outcomes. Methods Clinical data and diffusion MRI from 360 glioma patients who underwent craniotomy were analyzed. Using automatic fiber tractography, glioma-tract relationships were categorized into three types: displacement, infiltration, and disruption. Double immunohistochemical staining for IDH and MBP was performed on neuronavigation-guided tissue samples to validate the imaging-based classifications. The clinical implications of these classifications on the extent of tumor resection, postoperative motor function, and survival outcomes were evaluated. Results Among the patients, 35 (9.7%) were categorized as displacement type, 283 (78.6%) as infiltration type, and 42 (11.7%) as disruption type. Disruption-type tracts were predominantly associated with IDH wild-type gliomas (87.2%), significantly higher than infiltration (28.5%) and displacement types (23.5%) (P &amp;lt; 0.001). Displacement and infiltration types were more common in IDH-mutant gliomas (P &amp;lt; 0.001). Displacement-type tracts were significantly associated with higher rates of complete tumor resection compared to infiltration types (P = 0.015). In corticospinal tract involved cases, displacement-type tumors demonstrated no significant postoperative motor strength changes, whereas infiltration (P &amp;lt; 0.001) and disruption types (P = 0.013) were highly associated with postoperative motor deficits. Histological results aligned with dMRI-based classifications. Conclusions This dMRI-based classification of glioma-tract interactions is significantly associated with tumor pathology, resection outcomes, functional prognosis, and survival, providing a valuable tool for personalized and precise surgical planning.
Improving uptake of lung cancer screening: an observational study on the impact of timed appointments and reminders
Authors: Amyn Bhamani, Sindhu Bhaarrati Naidu, Tanya Patrick, Lavanya Anandan, Kiran Desai, Fanta Bojang, Priyam Verghese, Paul Robinson, Shivani Patel, Ricky Thakrar, Arjun Nair, Neal Navani, Sam M Janes
Journal: Thorax (2025)

Lung cancer screening (LCS) reduces lung cancer-related mortality; however, uptake remains low compared with other cancer screening programmes. In this observational study, we report the impact of timed appointments and reminders on participation in our regional LCS programme. Initial uptake of timed appointments was 53.0% (n=17 274/32 593), higher than previously reported in the UK, while initial uptake of open invitations was 29.8% (n=10 246/34 371). Among initial non-responders, 17.5% (n=4263/24 400) completed triage following a reminder. The increased participation following reminders only partially offset the significant difference in initial uptake between the two appointment types. Timed appointments and reminders are strongly advocated to increase participation in national LCS programmes.
Targeting adenosine enhances immunotherapy in MSS colorectal cancer with EGFRvIII mutation
Authors: Fei Sun, Fangzhen Yao, Chunting Zeng, Yang Zhao, Bishan Liang, Shaowei Li, Yawen Wang, Qijing Wu, Yulu Shi, Zhiqi Yao, Jiao Wang, Yu Jiang, Chunhui Gu, Qiong Huang, Wangjun Liao, Na Huang, Chunlin Wang, Xiaoxiang Rong, Jing Wu, Yujing Tan, Jianjun Peng, Yong Li, Min Shi
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Patients with microsatellite stable (MSS) colorectal cancer (CRC) often display resistance to immunotherapy. Epidermal growth factor receptor (EGFR)-targeted therapies have shown potential in enhancing immunotherapy, yet clinical benefits remain unfulfilled, which may relate to inadequate patient stratification. Methods Circulating tumor cells and tumor tissues were collected from multicenter cohorts of patients with CRC receiving cetuximab to analyze EGFR variant type III (EGFRvIII) expression and immune infiltration. Syngeneic mouse models of EGFRvIII CRC were used to investigate the combined efficacy of adenosine inhibition and antiprogrammed cell death protein 1 (anti-PD-1). Results EGFRvIII mutations are found in about 10% of MSS CRC and are associated with poor response to cetuximab therapy. EGFRvIII-mutated patients with CRC exhibit an adenosine-mediated immunosuppressive tumor microenvironment (TME) subtype. Combination therapy with adenosine inhibitors remodels the TME, reversing cetuximab resistance and enhancing anti-PD-1 efficacy in EGFRvIII CRC. Conclusions Our findings identified EGFRvIII-positive CRC as a distinct subtype characterized by adenosine-mediated immunosuppressive TME. Targeting adenosine significantly improved the efficacy of anti-PD-1 in MSS CRC.
Stretch regulation of β2-Adrenoceptor signalling in cardiomyocytes requires caveolae
Authors: Jiarong Fu, Catherine Mansfield, Ivan Diakonov, Aleksandra Judina, Matthew Delahaye, Navneet Bhogal, Jose L Sanchez-Alonso, Timothy Kamp, Julia Gorelik
Journal: Cardiovascular Research (2025)

Abstract Aims Caveolin-3 is essential for the formation of caveolae in cardiomyocytes. Caveolar microdomains have been shown to regulate the distribution of signalling proteins such as beta-adrenoceptors (βAR) and may act as membrane reserves to protect the cell from damage during the mechanical stretch. Myocardial stretch occurs during haemodynamic overload and may be normal (e.g. exercise) or pathological (e.g. heart failure); therefore, it is important to understand the effect of stretch on signalling pathways associated with mechanosensitive structures, such as caveolae. In this study, we investigate the role of caveolae in regulating the effect of stretch on βAR-signalling. Methods and results We used osmotic swelling of isolated rat ventricular cardiomyocytes as a method to stretch the cell membrane and investigate the effect of βAR stimulation on cyclic adenosine monophosphate (cAMP) activity and contractility. βAR response was measured using a Förster Resonance Energy Transfer reporter for the second messenger cAMP and using CytoCypher for the measurement of cell contractility. β1AR and β2AR blockers were used to selectively allow stimulation of β2AR and β1AR, respectively. We also investigated the effect of stretch on βAR response to isoprenaline stimulation in left ventricular trabeculae dissected from control and cardiac-specific caveolin-3 knock-out mice (Cav3KO). Stretching trabeculae produces increased baseline adenylyl cyclase activity and a higher level of cAMP and a greater β2AR-induced positive inotropy after stimulation of the β2AR but not β1AR, by isoprenaline. Similar findings were confirmed for isolated myocytes subjected to hypoosmotic conditions. In isolated cardiomyocytes, caveolae depletion using methyl-beta-cyclodextrin or Cav3KO abolished the increase in β2AR response induced by stretch. Conclusion Our study reveals a stretch-regulation of the β2AR signalling pathway, which requires functional caveolae. This indicates caveolae are mechanosensitive membrane domains that undergo structural and functional changes in response to stretch, thus leading to mechanical regulation of caveolae-associated signalling pathways.
Long-Term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: a 4-Year, Phase 3, Open-Label Study
Authors: Evan S Dellon, David A Katzka, Vincent A Mukkada, Margaret H Collins, Gary W Falk, Camilla A Richmond, Brian Terreri, Manoj Thakur, Mena Boules, Bridgett Goodwin, Ikuo Hirano
Journal: Clinical Gastroenterology and Hepatology (2025)
Spironolactone reduces the risk of low-dose oral minoxidil-induced edema in women with female pattern hair loss.
Authors: Juan Jimenez-Cauhe, Rocio Gil-Redondo, David Saceda-Corralo, Adrian Imbernon-Moya, Angela Hermosa-Gelbard, Daniel Ortega-Quijano, Cristina Pindado-Ortega, Diego Buendia-Castaño, Sergio Vaño-Galvan
Journal: Journal of the American Academy of Dermatology (2025)
Outcomes after radical endoscopic resection of high-risk T1 esophageal adenocarcinoma: an international multicenter retrospective cohort study
Authors: Man Wai Chan, Rehan Haidry, Benjamin Norton, Massimiliano di Pietro, Andreas V. Hadjinicolaou, Maximilien Barret, Paul Doumbe Mandengue, Stefan Seewald, Raf Bisschops, Philippe Nafteux, Michael J. Bourke, Sunil Gupta, Pradeep Mundre, Arnaud Lemmers, Clémence Vuckovic, Oliver Pech, Philippe Leclercq, Emmanuel Coron, Sybren L Meijer, Jacques Bergman, Roos E. Pouw
Journal: Endoscopy (2025)

Introduction Post-endoscopic resection (ER) management of high-risk T1 esophageal adenocarcinoma (EAC) is debated, with conflicting reports on lymph node metastases (LNM) We aimed to assess outcomes following radical ER for high-risk T1 EAC. Methods We identified patients who underwent radical ER (tumor-negative deep margin) of high-risk T1 EAC, followed by surgery or endoscopic surveillance, between 2008-2019 across 11 international centers. Results In total, 106 patients (86 men, 70 ±11 years) were included. Of these, 26 patients (64 ±11 yrs) underwent additional surgery, with residual T1 EAC in 5 (19%) and LNM in 2 (8%) cases. After median 47 (IQR 32-79) months follow-up, 2/26 (8%) developed LNM/distant metastasis (DM), with 1 (4%) EAC-related death. There was 1/26 (4%) unrelated death and 4/26 (15%) were lost to follow-up. Eighty patients (71 ±9 yrs) entered endoscopic surveillance. Over 46 (IQR 25-59) months follow-up, 5/80 (6%) developed LNM/DM, with 4/80 (5%) EAC-related deaths. There were 15/80 (19%) unrelated deaths, and 10/80 (13%) were lost to follow-up. Overall rates during follow-up were 6% (95% CI 2-12) for LNM, 7% (95% CI 3-13) for LNM/DM, 5% (95% CI 2-11) for EAC-related mortality, and 20% (95% CI 13-29) for overall mortality. Conclusion Our findings present low rates of LNM after radical ER of high-risk T1 EAC, consistent with other endoscopy-focused studies. Post-surgical patients are still at risk for metastasis and disease-specific mortality. These results suggest that endoscopic surveillance is suitable for selected cases, but further prospective studies are needed to refine patient selection and confirm optimal outcomes.
First-in-human evaluation of memory-like NK cells with an IL-15 super-agonist and CTLA-4 blockade in advanced head and neck cancer
Authors: Roman M. Shapiro, Michal Sheffer, Matthew A. Booker, Michael Y. Tolstorukov, Grace C. Birch, Moshe Sade-Feldman, Jacy Fang, Shuqiang Li, Wesley Lu, Michela Ansuinelli, Remy Dulery, Mubin Tarannum, Joanna Baginska, Nishant Dwivedi, Ashish Kothari, Livius Penter, Yasmin Z. Abdulhamid, Isabel E. Kaplan, Dinh Khanhlinh, Ravindra Uppaluri, Robert A. Redd, Sarah Nikiforow, John Koreth, Jerome Ritz, Catherine J. Wu, Robert J. Soiffer, Glenn J. Hanna, Rizwan Romee
Journal: Journal of Hematology & Oncology (2025)

Cytokine induced memory-like natural killer (CIML NK) cells combined with an IL-15 super-agonist (N-803) are a novel modality to treat relapsed/refractory head and neck cancer. We report data from a phase I trial of haploidentical CIML NK cells combined with N-803 with or without ipilimumab (IPI) in relapsed/refractory head and neck cancer patients after a median of 6 prior lines of therapy. The trial adhered to a 3 + 3 dose de-escalation design, with primary endpoint being safety. High-resolution immunophenotypic and transcriptional profiling characterized the NK cells and their interacting partners in vivo. The primary safety endpoint was established, with dose-limiting toxicity in 1/10 patients. A transient disease control rate correlated with donor NK cell expansion, the latter occurring irrespective of IPI. The combination of CIML NK cells with N-803 and IPI was associated with increased early NK cell proliferation, contraction of Treg: Tcon, rapid recovery of recipient CD8+ T cells, and subsequent accelerated rejection of donor NK cells. CIML NK cells combined with N-803 and ipilimumab to treat head and neck cancer is safe, and associated with a more proliferative NK cell phenotype. However, the combination leads to reduced HLA mismatched NK cell persistence, resulting in an important limitation affecting NK cell combination therapies in clinical trials. These results inform evaluation of CIML NK therapy for advanced malignancies, with considerations for combination with IPI. NCT04290546.
Personalized decision making for coronary artery disease treatment using offline reinforcement learning
Authors: Peyman Ghasemi, Matthew Greenberg, Danielle A. Southern, Bing Li, James A. White, Joon Lee
Journal: npj Digital Medicine (2025)

Choosing optimal revascularization strategies for patients with obstructive coronary artery disease (CAD) remains a clinical challenge. While randomized controlled trials offer population-level insights, gaps remain regarding personalized decision-making for individual patients. We applied off-policy reinforcement learning (RL) to a composite data model from 41,328 unique patients with angiography-confirmed obstructive CAD. In an offline setting, we estimated optimal treatment policies and evaluated these policies using weighted importance sampling. Our findings indicate that RL-guided therapy decisions outperformed physician-based decision making, with RL policies achieving up to 32% improvement in expected rewards based on composite major cardiovascular events outcomes. Additionally, we introduced methods to ensure that RL CAD treatment policies remain compatible with locally achievable clinical practice models, presenting an interpretable RL policy with a limited number of states. Overall, this novel RL-based clinical decision support tool, RL4CAD, demonstrates potential to optimize care in patients with obstructive CAD referred for invasive coronary angiography.
Respiratory Exacerbations and Lung Function Decline in People with Smoking History and Normal Spirometry
Authors: Spyridon Fortis, Matthew Strand, Surya P Bhatt, Patrick Ten Eyck, Linder Wendt, Trisha Parekh, MeiLan K. Han, John E Hokanson, Gregory Kinney, Jeffrey L. Curtis, Russell P. Bowler, Emily S. Wan, Ken M Kunisaki, Chris H. Wendt, Elizabeth Regan, Mark Dransfield, James D Crapo, Edwin K Silverman, Alejandro P. Comellas
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

The impact of respiratory exacerbation on chronic obstructive pulmonary disease (COPD) is well established. The effects of respiratory exacerbations in people with cigarette smoking but normal spirometry are unknown. To assess the association of respiratory exacerbations with lung function decline and mortality in people with normal spirometry and current or former cigarette smoking history. We analyzed data from COPDGene participants with ≥10 pack-years cigarette smoking and normal spirometry at enrollment (Visit 1) defined as post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ≥lower limit of normal (LLN) and FEV1 ≥LLN. We examined whether respiratory exacerbations occurring between Visits 1 and the 5-year follow-up visit (Visit 2) were associated with FEV1 decline, and all-cause mortality. Among 2,939 participants with cigarette smoking history and normal lung function at Visit 1, each additional exacerbation between visit 1 and 2 was associated with a 2.96 ml/year FEV1 decline (95%CI 1.81 to 4.12; P<0.001) at Visit 2. Experiencing ≥1 severe exacerbation between Visits 1 and 2 was associated with 14.6 ml/year FEV1 decline relative to those with no severe exacerbations (95% CI 8.56 to 20.6; P<0.001). Individuals with ≥1 severe exacerbation between Visits 1 and 2 had increased mortality compared to those with no severe exacerbations (17.1% vs. 9.8%; adjusted hazard ratio 1.97;95% CI 1.40 to 2.77; P<0.001). Respiratory exacerbations in people with cigarette smoking but normal spirometry were associated lung function decline. Experiencing a severe respiratory exacerbation was associated with increased mortality.
Harnessing Prazosin for Tumors: Liposome Hybrid Nanovesicles Activate Tumor Immunotherapy via Autophagy Inhibition
Authors: Xinyang Xuanyuan, Wenshang Liu, Min Jiang, Xin Zhang, BeiBei Wen, Rui Zheng, Ning Yao, Tinglin Zhang, Yu Feng, Chaofeng Qiao, Huiqi Zhang, Dong Luo, Sa Feng, Meng Li, Jie Gao, Zhengmao Lu
Journal: Biomaterials (2025)
Corrigendum to “Construction of nanofibrous scaffolds with interconnected perfusable microchannel networks for engineering of vascularized bone tissue” [Bioact. Mater. 6 (2021),3254–3268]
Authors: Jiani Gu, Qiangian Zhang, Mengru Geng, Weizhong Wang, Jin Yang, Atta Ur Rehman Khan, Haibo Du, Zhou Sha, Xiaojun Zhou, Chuanglong He
Journal: Bioactive Materials (2025)
Improving musculoskeletal care with AI enhanced triage through data driven screening of referral letters
Authors: Tjardo Daniël Maarseveen, Herman Kasper Glas, Josien Veris-van Dieren, Erik van den Akker, Rachel Knevel
Journal: npj Digital Medicine (2025)

Abstract Musculoskeletal complaints account for 30% of GP consultations, with many referred to rheumatology clinics via letters. This study developed a Machine Learning (ML) pipeline to prioritize referrals by identifying rheumatoid arthritis (RA), osteoarthritis, fibromyalgia, and patients requiring long-term care. Using 8044 referral letters from 5728 patients across 12 clinics, we trained and validated ML models in two large centers and tested their generalizability in the remaining ten. The models were robust, with RA achieving an AUC-ROC of 0.78 (CI: 0.74–0.83), osteoarthritis 0.71 (CI: 0.67–0.74), fibromyalgia 0.81 (CI: 0.77–0.85), and chronic follow-up 0.63 (CI: 0.61–0.66). The RA-classifier outperformed manual referral systems, as it prioritised RA over non-RA cases ( P &lt; 0.001 ), while the manual referral system could not differentiate between the two. The other classifiers showed similar prioritisation improvements, highlighting the potential to enhance care efficiency, reduce clinician workload, and facilitate earlier specialized care. Future work will focus on building clinical decision-support tools.
Switching between medicare advantage and traditional medicare for individuals newly diagnosed with cancer 2015-2019
Authors: Helen M Parsons, Samuel J Greenwald, Stephanie Jarosek, Sayeh Nikpay, Roxanne M Clark, Nathan Shippee, Carrie Henning-Smith, Lindsey Enewold
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Background Medicare Advantage (MA) plans may offer more benefits and lower costs relative to Traditional Medicare (TM), but may also provide narrower provider networks and pre-authorization requirements. We explore the impact of a cancer diagnosis on switching between MA and TM after diagnosis. Methods We used the 2015-2019 Surveillance, Epidemiology and End Results-Medicare data to examine patterns of switching between MA and TM after cancer relative to those without cancer. We used binomial generalized estimating equations to evaluate the cancer and sociodemographic characteristics of those with higher probabilities of switching. Results Among those initially enrolled in MA plans (39.27% of those with vs 40.79% without cancer), 3.76% of individuals with cancer switched to TM compared to 2.23% without cancer. For those initially enrolled in TM, 2.96% of individuals with cancer switched to MA vs 4.35% without cancer. Multivariable analyses demonstrated that, among individuals starting in MA, a cancer diagnosis was associated with a 52.02% increase in switching relative to those without cancer, whereas among those starting in TM, a cancer diagnosis was associated with a 26.90% reduction in switching. Younger individuals, males, dual-eligible, those with more comorbidities, rural-dwellers, and those living in zip codes with higher education and income levels also had higher probabilities of switching from MA to TM. Conclusions Prior to diagnosis, MA enrollment is comparable between individuals with and without cancer. However, after diagnosis, individuals with cancer have higher probability of switching from MA to TM and lower probability of switching from TM to MA.
Engineering sialylated N-glycans on adeno-associated virus capsids for targeted gene delivery and therapeutic applications
Authors: Weixuan Zhao, Jinhuan Luo, Fudi Wang, Yingying Shi, Jiawen Zhang, Yuanjie Zhang, Yingbo Li, Xinchen Wang, Yingying Chen, Xiaohui Zhang, Xiaoyang Wang, Yu Mu, Dezhong Ji, Sulong Xiao, Qi Wang, Lihe Zhang, Chuanling Zhang, Demin Zhou
Journal: Journal of Controlled Release (2025)
Efficacy and safety of intravenous nerinetide initiated by paramedics in the field for acute cerebral ischaemia within 3 h of symptom onset (FRONTIER): a phase 2, multicentre, randomised, double-blind, placebo-controlled study
Authors: Jim Christenson, Michael D Hill, Richard H Swartz, Corey Adams, Oscar Benavente, Leanne K Casaubon, Sheldon Cheskes, Aravind Ganesh, Jonathan Dave Garman, Cameron Harris, Devin R Harris, Kathy Heard, Sandra Jenneson, Yatika Kohli, Michelle Leroux, Diana Mayor-Nunez, George Medvedev, Manu Mehdiratta, Laurie J Morrison, Johanna Maria Ospel, Sarah Pennington, Yael Perez, Daniel Selchen, Alexander Stebner, John Tallon, Aleksander Tkach, Pieter Richard Verbeek, Michael Tymianski
Journal: The Lancet (2025)