tbuckley/cabot-search huggingface dataset:
Facts and hopes of CD40 agonists as a cancer immunotherapy
Authors: John C. McVey, Gregory L. Beatty
Journal: Clinical Cancer Research (2025)

Abstract CD40 agonists are a promising class of immunotherapeutic agents that potentiate both innate and adaptive immunity. This review examines the established facts and prospects of CD40 agonists in cancer immunotherapy. CD40, a co-stimulatory receptor of the TNF receptor superfamily, is found on antigen-presenting cells. CD40 activation licenses dendritic cells to prime tumor-specific T cells, polarizes macrophages to a pro-inflammatory phenotype, activates B cells, and facilitates tumor fibrosis remodeling. Preclinical models demonstrate the significant potential of CD40 agonists to induce anti-tumor immunity, leading to the development of various CD40-activating therapeutics, including monoclonal antibodies, recombinant CD40L, and ectopic expression of CD40L via gene transfer. While clinical trials show modest antitumor activity, some patients experience durable responses, especially when CD40 agonists are combined with other therapies such as immune checkpoint inhibitors and chemotherapy. These combinations, tested in traditionally difficult-to-treat cancers like pancreatic cancer, provide hope for improved outcomes. Current research focuses on refining CD40 agonist therapies through novel combination strategies, improving patient selection, and the development of tumor-targeted CD40 agonists and Fc-engineered antibodies which aim to enhance efficacy while mitigating toxicity. However, significant challenges remain, particularly in identifying patients most likely to benefit from CD40 immunotherapy and understanding resistance mechanisms. Addressing these challenges is crucial for guiding effective combination strategies and optimizing treatment outcomes. By examining both established facts and ongoing developments, this review provides a comprehensive overview of the status and potential of CD40 agonists in cancer immunotherapy.
Precision Endocrine Therapy in Endometrial Cancer: Has its time finally come?
Authors: Vikas Garg, Amit M. Oza
Journal: Clinical Cancer Research (2025)

Abstract Endocrine therapy (ET) has been underexplored in endometrial cancer (EC). Emerging data suggest that combining ET with CDK4/6 inhibitors improve outcomes in EC. This commentary complements a recent CCR manuscript and reviews opportunities to improve precision ET, and the potential to overcome resistance mechanisms associated with ET failure.
A systematic review with a Burden of Proof meta-analysis of health effects of long-term ambient fine particulate matter (PM2.5) exposure on dementia
Authors: Xinmei Huang, Jaimie Steinmetz, Elizabeth K. Marsh, Aleksandr Y. Aravkin, Charlie Ashbaugh, Christopher J. L. Murray, Fanghan Yang, John S. Ji, Peng Zheng, Reed J. D. Sorensen, Sarah Wozniak, Simon I. Hay, Susan A. McLaughlin, Vanessa Garcia, Michael Brauer, Katrin Burkart
Journal: Nature Aging (2025)

Abstract Previous studies have indicated increased dementia risk associated with fine particulate matter (PM 2.5 ) exposure; however, the findings are inconsistent. In this systematic review, we assessed the association between long-term PM 2.5 exposure and dementia outcomes using the Burden of Proof meta-analytic framework, which relaxes log-linear assumptions to better characterize relative risk functions and quantify unexplained between-study heterogeneity (PROSPERO, ID CRD42023421869). Here we report a meta-analysis of 28 longitudinal cohort studies published up to June 2023 that investigated long-term PM 2.5 exposure and dementia outcomes. We derived risk–outcome scores (ROSs), highly conservative measures of effect size and evidence strength, mapped onto a 1–5-star rating from ‘weak and/or inconsistent evidence’ to ‘very strong and/or consistent evidence’. We identified a significant nonlinear relationship between PM 2.5 exposure and dementia, with a minimum 14% increased risk averaged across PM 2.5 levels between 4.5 and 26.9 µg m −3 (the 15th to 85th percentile exposure range across included studies), relative to a reference of 2.0 µg m −3 ( n = 49, ROS = 0.13, two stars). We found a significant association of PM 2.5 with Alzheimer’s disease ( n = 12, ROS = 0.32, three stars) but not with vascular dementia. Our findings highlight the potential impact of air pollution on brain aging.
Vestibular neurons link motion sickness, behavioural thermoregulation and metabolic balance in mice
Authors: Longlong Tu, Xing Fang, Yongjie Yang, Meng Yu, Hailan Liu, Hesong Liu, Na Yin, Jonathan C. Bean, Kristine M. Conde, Mengjie Wang, Yongxiang Li, Olivia Z. Ginnard, Qingzhuo Liu, Yuhan Shi, Junying Han, Yi Zhu, Makoto Fukuda, Qingchun Tong, Benjamin Arenkiel, Mingshan Xue, Yang He, Chunmei Wang, Yong Xu
Journal: Nature Metabolism (2025)
When I use a word . . . The longest medical words
Authors: Jeffrey K Aronson
Journal: BMJ (2025)

I define a long word as one that is at least 10 letters and four syllables long. These are arbitrary criteria. However, in trying to find the very longest such words, particularly medical ones, I find that my efforts have been thwarted by the occurrence of exceptionally long concatenations that cannot be properly described as words at all, in the usual sense of the word. So, in order to find some very long medical words, I shall have to try harder and perhaps set my sights lower, regarding the lengths of the words I seek.
Author Correction: Mitochondrial respiratory complex IV deficiency recapitulates amyotrophic lateral sclerosis
Authors: Man Cheng, Dan Lu, Kexin Li, Yan Wang, Xiwen Tong, Xiaolong Qi, Chuanzhu Yan, Kunqian Ji, Junlin Wang, Wei Wang, Huijiao Lv, Xu Zhang, Weining Kong, Jian Zhang, Jiaxin Ma, Keru Li, Yaheng Wang, Jingyu Feng, Panpan Wei, Qiushuang Li, Chengyong Shen, Xiang-Dong Fu, Yuanwu Ma, Xiaorong Zhang
Journal: Nature Neuroscience (2025)
Blood lead levels in children 5–7–years from the Republic of Georgia—a feasibility study on lead surveillance using volumetric absorptive microsampling
Authors: Charlotta Rylander, Erik Eik Anda, Ciprian Mihai Cirtiu, Tamar Jankhoteli, Nino Dzotsenidze, Vladimer Ghetia, Eka Adamia, Paata Imnadze, Tinatin Manjavidze
Journal: Environmental Health Perspectives (2025)

For years, children in the Republic of Georgia, have experienced elevated blood lead levels (BLLs). From September 2023 to April 2024, the National Center for Disease Control and Public Health in Georgia piloted a national surveillance program for lead in children in two western regions of the country, using volumetric absorptive microsampling (VAMS) to measure BLLs.
Erratum: Naldemedine for Opioid-Induced Constipation in Patients With Cancer: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial
Authors: Jun Hamano, Takahiro Higashibata, Takaomi Kessoku, Shinya Kajiura, Mami Hirakawa, Shunsuke Oyamada, Keisuke Ariyoshi, Takeshi Yamada, Yoshiyuki Yamamoto, Yasuyuki Takashima, Kosuke Doki, Masato Homma, Bryan J. Mathis, Tsumugi Jono, Tomoki Ogata, Kosuke Tanaka, Yuki Kasai, Michihiro Iwaki, Akiko Fuyuki, Atsushi Nakajima, Ryuji Hayashi, Takayuki Ando, Naoki Izawa, Yuko Kobayashi, Yoshiki Horie, Tatsuya Morita
Journal: Journal of Clinical Oncology (2025)
Response to Comments on Maddaloni et al. Osteoprotegerin, Osteopontin, and Osteocalcin Are Associated With Cardiovascular Events in Type 2 Diabetes: Insights From EXSCEL. Diabetes Care 2025;48:235–242
Authors: Ernesto Maddaloni, Maggie Nguyen, Svati H. Shah, Rury R. Holman
Journal: Diabetes Care (2025)
Allo-HCT refined ELN 2022 risk classification: validation of the Adverse-Plus risk group in AML patients undergoing allogeneic hematopoietic cell transplantation within the Spanish Group for Hematopoietic Cell Transplantation (GETH-TC)
Authors: Carlos Jiménez-Vicente, Jordi Esteve, Mónica Baile-González, Estefanía Pérez-López, Carmen Martin Calvo, Clara Aparicio, Itziar Oiartzabal Ormategi, Albert Esquirol, Felipe Peña-Muñoz, Sara Fernández-Luis, Inmaculada Heras Fernando, Ana Pilar González-Rodríguez, Alberto López-García, Jose Luis López-Lorenzo, Tamara Torrado, Adolfo Jesús Sáez Marín, Cynthia Acosta Fleytas, Lucía García, Sara Villar, Silvia Filaferro, Pascual Balsalobre, María Jesús Pascual Cascón, María Queralt Salas
Journal: Blood Cancer Journal (2025)

This multicenter retrospective study by GETH-TC validates the prognostic value of the Allo-HCT Refined ELN 2022 risk classification in allografted AML patients. The new classification refines the ELN 2022 risk classification, dividing adverse-risk patients into two subgroups: Adv-Plus (AdvP), including those with complex karyotype, MECOM (EVI1) rearrangement, or TP53 mutations/del(17p), and an additional adverse group (Adv*). The study included 651 AML patients treated with at least one line of anthracycline-based induction therapy and in complete remission. According to the Allo-HCT Refined ELN 2022 risk classification, 19.4% (n = 126) patients were classified into the Favorable (Fav) risk, 38.1% (n = 248) into the Intermediate (Int) risk, 27.2% (n = 177) in the Adv* and 15.4% (n = 100) in the AdvP. Outcomes were significantly poorer for patients allocated in the AdvP risk group (5-year OS rate: 32.3%, 5-year LFS rate: 24.3%, both p < 0.001 with the rest of subgroups) and a higher CIR (5-year CIR: 64.3%, p < 0.001). Patients in the Adv* risk group had similar outcomes than patients in the Int risk group (5-year OS rate: 70.2% vs. 66.7%, p = 0.69, 5-year LFS rate: 63.8% vs. 55.9%, p = 0.33). Multivariate analysis confirmed the dismal outcomes for AdvP patients for OS: Hazard Ratio (HR) = 3.05, and LFS: HR = 2.66, both p < 0.001. Our findings validate the Allo-HCT Refined ELN 2022 classification as a robust prognostic tool, particularly highlighting the poor outcomes for the AdvP subgroup.
Colorectal cancer incidence following a negative colonoscopy in fecal immunochemical test-based screening: a nationwide cohort study after 8 years of screening in Denmark
Authors: Pernille T. Larsen, Susanne F. Jørgensen, Morten Rasmussen, Berit Andersen, Amanda J. Cross, Sisse H. Njor
Journal: Endoscopy (2025)

Abstract Screening participants with a positive fecal immunochemical test (FIT) result and a subsequent negative colonoscopy are quarantined from the Danish bowel cancer screening program for 8 years. This recommendation is based on evidence from settings other than FIT-based screening, but referral of this evidence is not necessarily sufficient. We estimated the colorectal cancer (CRC) risk among these FIT-positive/colonoscopy-negative individuals and compared it with the risk in a historical unscreened population. Using national health registers in Denmark, we compared 29 936 participants with a positive FIT but negative colonoscopy with 720 850 randomly selected unscreened controls born 9 years earlier (ratio 1:24). Controls were assigned a pseudo-colonoscopy date 9 years prior to the negative colonoscopy group. We examined cases per 10 000 person-years and estimated relative risks (RR) and 95%CIs for CRC. After 8 years’ follow-up, CRC risk was lower among FIT-positive/colonoscopy-negative participants compared with controls (RR 0.72, 95%CI 0.61–0.84). By age group and sex, the lower risk was only evident for women and men in their 60s (RR 0.67 [95%CI 0.47–0.96] and RR 0.65 [95%CI 0.48–0.88], respectively) and men in their 70s (RR 0.60 [95%CI 0.44–0.84]). The overall risk for CRC was lower for individuals with a positive FIT but negative colonoscopy compared with unscreened controls. However, the lower risk might not justify 8 years of quarantine, especially for women and younger age groups. Individualized screening is warranted and transfer of evidence from non-FIT screening should be done carefully.
Antegrade bilateral metal stent deployment under endoscopic ultrasound guidance for hepatic hilar obstruction using locking stent technique
Authors: Takeshi Ogura, Yuki Uba, Nobuhiro Hattori, Kimi Bessho, Hiroki Nishikawa
Journal: Endoscopy (2025)

Endoscopic ultrasound-guided biliary drainage (EUS-BD) has been widely performed for distal biliary obstruction. Due to improvements in devices and techniques, EUS-BD has recently been indicated for hepatic hilar biliary obstruction (HBO). In cases of surgically altered anatomy, right hepatic biliary drainage using the bridging technique is needed to perform bilateral biliary drainage because the access route is from the left hepatic bile duct [1]. After the bridging technique, a metal stent should be deployed at the periphery of the bile duct to obtain sufficient drainage area. However, if metal stent deployment at the periphery of the bile duct is performed, stent dislocation can occur because the length of the metal stent is short in the hepatic site [2] [3]. To prevent this adverse event, a sufficient length of stent in the hepatic site should be obtained. Technical tips for EUS-BD for HBO using the previously described locking stent technique [4] to prevent stent dislocation and obtain sufficient drainage area are described.
An innovative technique for closing a post-endoscopic submucosal dissection ulcer to prevent early dehiscence, the muscle-grasping clip with line pulley securing technique
Authors: Shinya Nagae, Ryoju Negishi, Kohei Ono, Yohei Minato, Deepak Madhu, Hideyuki Chiba, Ken Ohata
Journal: Endoscopy (2025)

Endoscopic submucosal dissection (ESD) is a standard treatment for early gastrointestinal cancer, but carries risks of delayed bleeding and perforation. Endoscopic closure of the post-ESD ulcer can reduce these risks [1]. We previously reported the "clip with line pulley securing" (CLiPS) technique [2] [3] [4], a simple cost-effective method that allows closure without scope reinsertion. Mucosa-to-mucosa closure may however result in early dehiscence, particularly in large mucosal defects. To address this limitation, we developed a modified technique, the muscle-grasping CLiPS (M-CLiPS) technique ([Fig. 1]).
Scraping away technique under cholangioscopy using an improved forceps biopsy device for Mirizzi syndrome
Authors: Takeshi Ogura, Takafumi Kanadani, Nobuhiro Hattori, Kimi Bessho, Hiroki Nishikawa
Journal: Endoscopy (2025)

Mirizzi syndrome is a relatively rare disease that causes inflammation of the common bile duct due to an impacted gallstone in the neck of the gallbladder or cystic duct. It occurs in about 1–2% of patients with cholelithiasis [1] [2]. The gold standard treatment for Mirizzi syndrome is surgical resection. An alternative technique is electrohydraulic lithotripsy (EHL) under endoscopic retrograde cholangiopancreatography (ERCP) guidance. However, EHL can be indicated if the stone is visible on cholangioscopy. However, in cases of stones coated by gallbladder mucosa, this technique might not be indicated. Recently, an improved forceps biopsy device for the SpyGlass DS was released (SpyBite MAX; Boston Scientific, Marlborough, Massachusetts, USA), with microteeth on the tip of the forceps that improve the tissue gripping force. Technical tips for EHL using this forceps biopsy device, which is called the "scraping-away technique," to treat Mirizzi syndrome are described.
Over-the-wire lumen-apposing metal stent for the management of a chronic fistula after one-anastomosis gastric bypass
Authors: Vincenzo Bove, Loredana Gualtieri, Maria Valeria Matteo, Martina De Siena, Valerio Pontecorvi, Cristiano Spada, Ivo Boskoski
Journal: Endoscopy (2025)

Gastro-gastric fistulas are uncommon complications of bariatric bypass surgery, but their management can be challenging [1] [2] [3]. We report a case of chronic gastro-gastric fistula after one-anastomosis gastric bypass (OAGB) treated with a lumen-apposing metal stent (LAMS), with the aim of presenting a viable treatment solution to the initial problem.
Underwater compression hemostasis method for active bleeding in underwater endoscopic submucosal dissection
Authors: Mitsuru Nagata
Journal: Endoscopy (2025)

Active bleeding during underwater endoscopic submucosal dissection (U-ESD) in saline can cause visual field loss [1]. The field can be visualized by changing to under gas conditions, and hemostasis can be achieved using a knife or hemostatic forceps. However, this approach may cause a large amount of blood to mix with the saline, and deaeration and saline replacement are required before the resumption of U-ESD. Moreover, if active bleeding occurs on the gravity side where U-ESD can be suitable [2], blood accumulation due to gravity makes identifying the bleeding point difficult even under gas conditions, missing appropriate timing for hemostasis.
A novel technique for gastrostomy tube replacement following post-radiotherapy esophageal atresia: the joint forces of double endoscopy
Authors: Zeliang Yang, Yong Liu, Shun He, Hongqing Li, Wang Guiqi
Journal: Endoscopy (2025)

Percutaneous endoscopic gastrostomy provides a safe and effective minimally invasive surgical route, thus ensuring long-term enteral nutritional support therapy [1]. Patients with esophageal cancer may develop scars from long-term radiotherapy, causing complete esophageal obstruction and difficulties in replacing gastrostomy tubes. Our center utilizes a new approach to replacing gastrostomy tubes by incising the atretic segment of the esophagus through transoral and transgastric fistula bimodality ([Video 1]).
Removing a large pedunculated colonic polyp using a loop anchored with clips at the root
Authors: Zhang Tao, Chao Lan, Min Huang, Tengwei Deng, Qingyu Zeng, Jie Liu, Luli Hu
Journal: Endoscopy (2025)

Compared with conventional polypectomy after adrenaline injection, loop-assisted polypectomy is considered more effective and has less post-procedural bleeding in endoscopic resection of large pedunculated colonic polyps [1]. However, postpolypectomy bleeding still exists after loop-assisted polypectomy because the loop slips off the stalk or a thin stalk is transected by the loop after polypectomy [2]. We used two clips to fasten the loop at the root to avoid the stalk slipping or transecting in a large pedunculated colonic polyp. Moreover, we removed the polyp successfully without postpolypectomy bleeding, and the stalk disappeared one month later.
Synthetic bone marrow images augment real samples in developing acute myeloid leukemia microscopy classification models
Authors: Jan-Niklas Eckardt, Ishan Srivastava, Zizhe Wang, Susann Winter, Tim Schmittmann, Sebastian Riechert, Miriam Eva Helena Gediga, Anas Shekh Sulaiman, Martin M. K. Schneider, Freya Schulze, Christian Thiede, Katja Sockel, Frank Kroschinsky, Christoph Röllig, Martin Bornhäuser, Karsten Wendt, Jan Moritz Middeke
Journal: npj Digital Medicine (2025)

Abstract High-quality image data is essential for training deep learning (DL) classifiers, yet data sharing is often limited by privacy concerns. We hypothesized that generative adversarial networks (GANs) could synthesize bone marrow smear (BMS) images suitable for classifier training. BMS from 1251 patients with acute myeloid leukemia (AML), 51 patients with acute promyelocytic leukemia (APL), and 236 stem cell donors were digitized, and synthetic images were generated using StyleGAN2-Ada. In a blinded visual Turing test, eight hematologists achieved 63% accuracy in identifying synthetic images, confirming high image quality. DL classifiers trained on real data achieved AUROCs of 0.99 across AML, APL, and donor classifications, with performance remaining above 0.95 even when incrementally substituting real data for synthetic samples. Adding synthetic data to real training data offered performance gains for an exceptionally rare disease (APL). Our study demonstrates the usability of synthetic BMS data for training highly accurate image classifiers in microscopy.
Carcinogenicity of automotive gasoline and some oxygenated gasoline additives
Authors: Michelle C Turner, Lode Godderis, Pascal Guénel, Nancy Hopf, Betzabet Quintanilla-Vega, Sheila C Soares-Lima, Sunisa Chaiklieng, Juliana Da Silva, Silvia Fustinoni, Min Gi, Julia E Heck, François Huaux, Gunnar Johanson, Jorunn Kirkeleit, Kirill Kirsanov, Lorenzo Richiardi, João Paulo Teixeira, Andrea Terron, Jan Topinka, Mary C White, Lamia Benbrahim-Tallaa, Caterina Facchin, Andrew Kunzmann, Federica Madia, Elisa Pasqual, Roland Wedekind, Xiaobei Deng, Eero Suonio, Susana Viegas, Abdoulaye Barry, Roya Dolatkhah, Rachmad A Dongoran, Esther M Gonzalez-Gil, Felix M Onyije, Heidi Mattock, Aline de Conti, Mary K Schubauer-Berigan
Journal: The Lancet Oncology (2025)
ORCHESTRA Delphi Consensus: Clinical Management of SARS-CoV-2 Infection in People with HIV
Authors: Alessandro Tavelli, Alessandra Vergori, Antonella Cingolani, Francesca Bai, Anna Maria Azzini, Gabriel Levy Hara, Maria Giulia Caponcello, Matteo Rinaldi, Zaira R Palacios-Baena, Milo Gatti, Gaia Maccarrone, Evelina Tacconelli, Andrea Antinori, Antonella d'Arminio Monforte
Journal: Clinical Microbiology and Infection (2025)
NAT10 inhibition alleviates astrocyte autophagy by impeding ac4C acetylation of Timp1 mRNA in ischemic stroke
Authors: Li Yang, Xiaotong Li, Yaxuan Zhao, Hao Chen, Can Wang, Angrong Wu, Xintong Guo, Yue Huang, Qihui Wang, Lingyun Hao, Xiaowen Li, Ying Ji, Jin Ban, Guangtian Wang, Junli Cao, Zhiqiang Pan
Journal: Acta Pharmaceutica Sinica B (2025)
Prenatal exposure to synthetic phenols assessed in multiple urine samples and dysregulation of steroid hormone homeostasis in two European cohorts
Authors: Paulina Jedynak, Mariona Bustamante, Matthieu Rolland, Vicente Mustieles, Cathrine Thomsen, Amrit K. Sakhi, Azemira Sabaredzovic, Maria Foraster, Mireia Gascon, Maria Dolores Gómez-Roig, Elisa Llurba, Ioar Rivas, Isabelle Ouellet-Morin, Sam Bayat, Sarah Lyon-Caen, Oscar J. Pozo, Martine Vrijheid, Jordi Sunyer, Rémy Slama, Payam Dadvand, Claire Philippat
Journal: Environmental Health Perspectives (2025)

Some synthetic phenols alter hormonal pathways involved in successful pregnancy and fetal development. Despite high within-subject temporal variability of phenols, previous studies mostly utilized spot urine samples to assess pregnancy exposure. Herein we investigated associations between pregnancy exposure to eight phenols assessed in multiple pooled urine samples and steroid hormones assessed in maternal hair reflecting cumulative hormone levels over the previous weeks to months.