tbuckley/cabot-search huggingface dataset:
Enhanced therapeutic efficacy of anti-PD-1 blockade by targeting LAMP2A inhibits lysosomal degradation of STING and TBK1
Authors: Xueying Wang, Diekuo Zhang, Jiaqing Xiao, Lei Wang, Junrong Wang, Xiaoqiao Cui, Jiaqi Tan, Yong Liu, Susheng Miao
Journal: Theranostics (2025)

Rationale: LAMP2A is a key translocase in chaperone-mediated autophagy (CMA), and the STING/TBK1 axis is crucial in antitumor immunity. This study explored the complex mechanisms by which CMA regulates the STING/TBK1 degradation and whether targeting LAMP2A could enhance the efficacy of PD-1 monoclonal antibodies. Methods: The expression of STING and TBK1 was detected after treatment with various inhibitors of protein degradation pathways. Confocal microscopy was used to detect the localization of STING and TBK1 in lysosomes. R software was used to analyze LAMP2A expression and prognosis. The biological function of LAMP2A was examined by in vitro and in vivo experiments. Results: Through in vitro and in vivo experiments and a review of clinical specimens, we identified STING/TBK1 as a novel substrate of CMA. Downregulation of LAMP2A enhanced IFNβ production and cellular antiviral response by inhibiting CMA-mediated degradation of STING and TBK1. Based on these observations, further in vivo experiments confirmed that the LAMP2A loss combined with PD-1 monoclonal antibodies significantly stimulated the activation of infiltrating CD8+ T cells, thereby inhibiting tumor growth. Also, non-responder head and neck squamous cell carcinoma (HNSCC) patients undergoing neoadjuvant immuno-chemotherapy had higher levels of LAMP2A and lower levels of PD-L1 expression in their tumor tissues. Conclusions: Our study has revealed a prospective combination therapy, in which diclofenac functioning as a LAMP2A inhibitor, enhances the anti-tumor efficacy of PD-1 monoclonal antibody by inhibiting the degradation of STING and TBK1.
Nanovaccines empowering CD8<sup>+</sup> T cells: a precision strategy to enhance cancer immunotherapy
Authors: Yunfan Lin, Pei Lin, Rongwei Xu, Xu Chen, Ye Lu, Jiarong Zheng, Yucheng Zheng, Zihao Zhou, Zizhao Mai, Xinyuan Zhao, Li Cui
Journal: Theranostics (2025)

Cancer immunotherapy leveraging nanovaccines represents a cutting-edge frontier in precision medicine, specifically designed to potentiate CD8+ T cell-based immunotherapy. This review thoroughly delineates the evolving landscape of cancer nanovaccine development, emphasizing their advantageous role in modulating the immunosuppressive tumor microenvironment (TME) to enhance CD8+ T cell efficacy. We critically analyze current innovations in nanovaccine design, focusing on their capacity to deliver tumor antigens and immunostimulatory adjuvants effectively. These nanovaccines are engineered to overcome the physical and immunological barriers of the TME, facilitating the robust activation and proliferation of CD8+ T cells. Challenges such as delivery efficacy, safety, and scalable manufacturing are discussed, alongside future prospects which include the potential of developing specific biomaterial approaches to provide durable antitumor immunity. This comprehensive analysis not only underscores the transformative potential of cancer nanovaccines in enhancing CD8+ T cell responses but also highlights the critical need for advanced solutions to overcome the complex interplay of factors that limit the efficacy of current immunotherapies.
3D bioprinting of prefabricated artificial skin with multicomponent hydrogel for skin and hair follicle regeneration
Authors: Xiaoxiao Ma, Xiaohui Zhu, Sheng Lv, Chunyan Yang, Zihao Wang, Meilan Liao, Bohao Zhou, Yiming Zhang, Shiyu Sun, Ping Chen, Zhonghua Liu, Haiyan Chen
Journal: Theranostics (2025)

Background: The timely management of large-scale wounds and the regeneration of skin appendages constitute major clinical issues. The production of high-precision and customizable artificial skin via 3D bioprinting offers a feasible means to surmount the predicament, within which the selection of bioactive materials and seed cells is critical. This study is aimed at employing skin stem cells and multicomponent hydrogels to prefabricate artificial skin through 3D bioprinting, which enables the regeneration of skin and its appendages. Methods and Results: We employed gelatin methacrylate (GelMA) and hyaluronic acid methacrylate (HAMA) as bioactive materials, in conjunction with epidermal stem cells (Epi-SCs) and skin-derived precursors (SKPs), to fabricate artificial skin utilizing 3D bioprinting. The photosensitive multicomponent hydrogel, comprising 5% GelMA and 0.5% HAMA, demonstrated excellent printability, suitable solubility and swelling rates, as well as stable mechanical properties. Moreover, this hydrogel exhibited exceptional biocompatibility, effectively facilitating the proliferation of SKPs while maintaining the cellular characteristics of both SKPs and Epi-SCs. The transplantation of this artificial skin into cutaneous wounds in nude mice led to complete wound healing and functional tissue regeneration. The regenerated tissue comprised epidermis, dermis, hair follicles, blood vessels, and sebaceous glands, closely resembling native skin. Remarkably, the artificial skin demonstrated sustained tissue regeneration capacity even after 12 h of in vitro culture, facilitating comprehensive functional skin regeneration. Conclusions: Our research presented a skin repair strategy for prefabricated cell-loaded artificial skin, thereby successfully facilitating the regeneration of the epidermis, dermis, hair follicles, blood vessels, and sebaceous glands within the wound.
Spatial Metabolomics and Transcriptomics Reveal Metabolic Reprogramming and Cellular Interactions in Nasopharyngeal Carcinoma with High PD-1 Expression and Therapeutic Response
Authors: Lili Ji, Dujuan Wang, Guangzheng Zhuo, Zhe Chen, Liping Wang, Qian Zhang, Yuhang Wan, Guohong Liu, Yunbao Pan
Journal: Theranostics (2025)

Nasopharyngeal carcinoma (NPC) is a heterogeneous cancer with variable therapeutic responses, highlighting the need to better understand the molecular factors influencing treatment outcomes. This study aims to explore spatially metabolic and gene expression alterations in NPC patients with different therapeutic responses and PD-1 expression levels. Methods: This study employs spatial metabolomics (SM) and spatial transcriptomics (ST) to investigate significant alterations in metabolic pathways and metabolites in NPC patients exhibiting therapeutic sensitivity or elevated programmed death 1 (PD-1) expression. The spatial distribution of various cell types within the TME and their complex interactions were also investigated. Identified prognostic targets were validated using public datasets from TCGA, and further substantiated by in vitro functional analyses. Results: SM analysis revealed substantial reprogramming in lipid metabolism, branched-chain amino acid (BCAA) metabolism, and glutamine metabolism, which were closely associated with therapeutic response and PD-1 expression. ST analysis highlighted the critical role of interactions between precursor T cells and malignant epithelial cells in modulating therapeutic response in NPC. Notably, six key genes involved in BCAA metabolism (IL4I1, OXCT1, BCAT2, DLD, ALDH1B1, HADH) were identified in distinguishing patients with therapeutic sensitivity from those with therapeutic resistance. Functional validation of DLD and IL4I1 revealed that gene silencing significantly inhibited NPC cell proliferation, colony formation, wound healing, and invasion. Silencing DLD or IL4I1 induced cell cycle arrest. Reduction in α-Ketomethylvaleric acid (KMV) levels was demonstrated upon IL4I1 silencing. Immunohistochemical analysis further confirmed that high expression of these six genes was significantly associated with poor prognosis in NPC patients, a trend corroborated by data from the TCGA head and neck cancer cohort. Conclusions: This study highlights the pivotal roles of key molecular players in therapeutic response in NPC, providing compelling evidence for their potential application as prognostic biomarkers and therapeutic targets, thereby contributing to precision oncology strategies aimed at improving patient outcomes.
Biliary drainage prior to pancreatoduodenectomy with Endoscopic Ultrasound-guided choledochoduodenostomy vs conventional Endoscopic Retrograde Cholangiopancreatography: a propensity score matched study and surgeon-survey
Authors: Jeska A. Fritzsche, Mike J.P. de Jong, Bert A. Bonsing, Olivier Busch, Freek Daams, Wouter J.M. Derksen, Lydi van Driel, Sebastiaan Festen, Erwin-Jan M. van Geenen, Frederik J H Hoogwater, Akin Inderson, Sjoerd D. Kuiken, Mike S.L. Liem, Daan J. Lips, Maarten W. Nijkamp, Hjalmar Van Santvoort, Peter D. Siersema, Martijn W.J. Stommel, Niels G Venneman, Robert C Verdonk, Frank P. Vleggaar, Roeland F. de Wilde, Marc. G. Besselink, Roy L.J. van Wanrooij, Rogier P. Voermans
Journal: Endoscopy (2025)

Background Preoperative endoscopic biliary drainage may lead to complications (16%-24%), potentially hampering surgical exploration. Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) may reduce drainage-related complications, however it is unknown whether EUS-CDS could in itself hamper surgical exploration as series with surgeon reported outcomes are lacking. Aim is to assess the impact of preoperative EUS-CDS on pancreatoduodenectomy. Method Consecutive patients who underwent pancreatoduodenectomy after preoperative biliary drainage were included in all eight centers that performed EUS-CDS in the mandatory Dutch Pancreatic Cancer Audit (Jan 2020-Dec 2022). Primary outcome was major postoperative complications. Secondary outcomes included bile leak grade B/C, postoperative pancreatic fistula (POPF) grade B/C, and overall postoperative complications. A propensity score matching (1:3) analysis was performed. Surgeons who performed a pancreatoduodenectomy after EUS-CDS were asked to complete a survey. Results Overall, 937 patients with pancreatoduodenectomy after preoperative biliary drainage were included (42 EUS-CDS, 895 ERCP). Major postoperative complications occurred in eight patients (19%) in the EUS-CDS group and 292 patients (33%) in the ERCP group (RR 0.50; 95%CI, 0.23-1.07). No significant differences were observed in overall complications (RR 0.95; 95%CI, 0.51-1.76), bile leak (RR 1.25; 95%CI, 0.31-4.98) or POPF (RR 0.62; 95%CI, 0.25-1.56). Results were similar after matching. The survey was completed for 29 pancreatoduodenectomies; surgery was not (n=13, 45%), 'slightly' (n=8, 28%), 'clearly' (n=5, 17%) or 'severely' (n=2, 7%) more complex because of the EUS-CDS. Conclusion This early experience suggests that preoperative biliary drainage with EUS-CDS does not increase the rate of complications after pancreatoduodenectomy and only infrequently hampers surgical exploration.
Future treatment paradigms in pulmonary arterial hypertension: a personal view from physicians, health authorities, and patients
Authors: Franck F Rahaghi, Marc Humbert, Marius M Hoeper, R James White, Robert P Frantz, Paul M Hassoun, Anna R Hemnes, Steven M Kawut, Vallerie V McLaughlin, Gergely Meszaros, Peter G M Mol, Steven D Nathan, Mitchel A Psotka, Farbod N Rahaghi, Olivier Sitbon, Norman Stockbridge, Jason Weatherald, Faiez Zannad, Sandeep Sahay
Journal: The Lancet Respiratory Medicine (2025)
Prevalence, clinical management, and outcomes of adults hospitalised with endemic arbovirus illness in southeast Europe (MERMAIDS-ARBO): a prospective observational study
Authors: Louise Sigfrid, Xin Hui S Chan, Louella M R Kasbergen, Lauren Hookham, Jia Wei, Siyu Chen, James L Lee, Reina S Sikkema, Erwin de Bruin, Victor M Corman, Chantal Reusken, Katherine Loens, Corneliu Petru Popescu, Mihaela Lupse, Violeta Briciu, Pellumb Pipero, Arjan Harxhi, Edmond Puca, Albina Ponosheci Biçaku, Maja Travar, Maja Ostojic, Rusmir Baljic, Jurica Arapović, Dragan Ledina, Đurđica Cekinović Grbeša, Ivica Čabraja, Anca Meda Văsieşiu, Ivan-Christian Kurolt, Stela Halichidis, Victoria Birlutiu, Zeljana Sulaver, Irina M Dumitru, Ruxandra Moroti, Aleksandra Barac, Goran Stevanovic, Athina Pyrpasopoulou, Metaxia N Papanikolaou, Vasilios Koulouras, Ljiljana Betica Radić, Emmanuel Roilides, Alemka Markotić, Ushma Galal, Emmanuelle Denis, Lynsey Goodwin, Lance Turtle, Iosif Marincu, Simin Aysel Florescu, Hamdi Ramadani, Remi N Charrel, Herman Goossens, Margareta Ieven, Christian Drosten, Peter W Horby, Marion P G Koopmans
Journal: The Lancet Infectious Diseases (2025)
Multi-antigen serology and a diagnostic algorithm for the detection of arbovirus infections as novel tools for arbovirus preparedness in southeast Europe (MERMAIDS-ARBO): a prospective observational study
Authors: Louella M R Kasbergen, Erwin de Bruin, Felicity Chandler, Louise Sigfrid, Xin Hui S Chan, Lauren Hookham, Jia Wei, Siyu Chen, Corine H GeurtsvanKessel, Sandra Scherbeijn, Remi N Charrel, Nazli Ayhan, James L Lee, Victor M Corman, Chantal Reusken, Katherine Loens, Corneliu Petru Popescu, Mihaela Lupse, Violeta Briciu, Anca Meda Văsieşiu, Pellumb Pipero, Arjan Harxhi, Edmond Puca, Albina Ponosheci Biçaku, Maja Travar, Maja Ostojić, Rusmir Baljic, Jurica Arapović, Dragan Ledina, Đurđica Cekinović Grbeša, Ivica Čabraja, Ivan-Christian Kurolt, Stela Halichidis, Victoria Birlutiu, Irina M Dumitru, Ruxandra Moroti, Aleksandra Barac, Goran Stevanovic, Athina Pyrpasopoulou, Vasilios Koulouras, Ljiljana Betica Radić, Metaxia N Papanikolaou, Emmanuel Roilides, Alemka Markotić, Ushma Galal, Emmanuelle Denis, Lynsey Goodwin, Lance Turtle, Simin Aysel Florescu, Hamdi Ramadani, Herman Goossens, Margareta Ieven, Christian Drosten, Peter W Horby, Reina S Sikkema, Marion P G Koopmans
Journal: The Lancet Infectious Diseases (2025)
Traction-assisted and saline immersion endoscopic submucosal dissection for complete resection of peri-appendiceal large nonpedunculated colorectal polyps
Authors: Michele Montori, Maria E. Argenziano, Pieter J. Poortmans, Sander Smeets, Andrea Sorge, Luca Maroni, David J. Tate
Journal: Endoscopy (2025)

Endoscopic resection can be challenging for large nonpedunculated colorectal polyps (LNPCPs) around the appendiceal orifice. Factors predicting failure of endoscopic mucosal resection (EMR) include deep invasion of the appendiceal orifice and >50% involvement of the appendiceal orifice. In contrast, patients with a previous appendectomy are often able to undergo complete resection using EMR for LNPCPs that completely cover the prior appendiceal orifice [1]. Unfortunately, it is often difficult to tell upfront which of these factors is present in a given LNPCP.
Contrast-enhanced endoscopic ultrasonography for diagnosis of leiomyosarcoma of the inferior vena cava
Authors: Wen Zhang, Ming-Yan Cai
Journal: Endoscopy (2025)

Endoscopic ultrasound (EUS) has become an important diagnostic tool for various diseases [1]. Contrast-enhanced (CE)-EUS has emerged as an effective technique that is complementary to conventional EUS and allows visualization of microvessels and parenchymal perfusion, and more accurate characterization of the lesion [2].
Cold snaring vs. standard forceps biopsy in sampling colorectal cancer: a comparative case report
Authors: Simona Agazzi, Eukene Rojo, Elena De Cristofaro, Jérôme Rivory, Thomas Walter, Tanguy Fenouil, Mathieu Pioche
Journal: Endoscopy (2025)

An accurate histological diagnosis of colorectal cancer is essential for promptly establishing appropriate therapeutic management. Furthermore, nowadays larger samples are needed to evaluate immunological and genetic panels. For malignant lesions that cannot be removed endoscopically, the European Guidelines recommend taking six carefully targeted biopsies from the suspected cancer focus [1]. Despite advancements in endoscopic imaging, a retrospective study of 962 patients undergoing colorectal adenocarcinoma resection found that 29% (62/217) required repeat endoscopy due to sampling errors [2], leading to a 1.36-fold increase in time to surgery (95% CI 1.20–1.54, p<0.001) and higher healthcare costs. Choi et al. found that positive diagnosis rates for the first, second, and third biopsy specimens of advanced colorectal cancer were 78.1%, 87.5%, and 93.8%, respectively, with no significant increase from additional biopsies [3]. Reducing biopsy numbers by increasing targeted tissue sample size through cold snaring could enhance diagnostic sensitivity, minimize repeat procedures, and reduce pathologist workload.
Reintervention for recurrent biliary obstruction after stent-in-stent deployment of multi-hole self-expandable metal stents
Authors: Takeshi Ogura, Yuki Uba, Takafumi Kanadani, Nobuhiro Hattori, Hiroki Nishikawa
Journal: Endoscopy (2025)

Malignant hilar biliary obstruction (MHBO) can be treated by bilateral deployment of uncovered self-expandable metal stents (SEMSs) using a stent-in-stent (SIS) technique [1]. If an uncovered SEMS becomes obstructed due to tumor ingrowth, several steps, such as guidewire insertion, stricture dilation, or stent deployment, are needed. In addition, stent obstruction is sometimes observed, and because of technical complexity, some authors perform endoscopic ultrasound-guided biliary drainage; however, it is well known that critical adverse events such as stent migration into the abdominal cavity can occur with this approach. Recently, a fully covered SEMS with multiple side holes (MHSEMS; HANAROSTENT Biliary Multi-hole NEO; M.I. Tech Co., Ltd, Pyeongtaek, South Korea) has become available ([Fig. 1]). This stent was designed to prevent stent migration by allowing small tissue ingrowths to form in the multiple small (1.8 mm) side holes along the covering membrane [2] [3]. The primary indication for this stent is distal biliary obstruction, but biliary stenting for MHBO using an SIS technique has also been reported [4]. However, a reintervention technique for MHSEMS obstruction after SIS deployment has not been reported. Here, we describe technical tips for reintervention using the SIS technique for an occluded MHSEMS.
<i>Roseburia hominis</i> improves host metabolism in diet-induced obesity
Authors: Wenli Huang, Wenyi Zhu, Yu Lin, Francis K. L. Chan, Zhilu Xu, Siew C. Ng
Journal: Gut Microbes (2025)

Next-generation live biotherapeutics are promising to aid the treatment of obesity and metabolic diseases. Here, we reported a novel anti-obesity probiotic candidate, Roseburia hominis, that was depleted in stool samples of obese subjects compared with lean controls, and its abundance was negatively correlated with body mass index and serum triglycerides. Supplementation of R. hominis prevented body weight gain and disorders of glucose and lipid metabolism, prevented fatty liver, inhibited white adipose tissue expansion and brown adipose tissue whitening in mice fed with high-fat diet, and boosted the abundance of lean-related species. The effects of R. hominis could be partially attributed to the production of nicotinamide riboside and upregulation of the Sirtuin1/mTOR signaling pathway. These results indicated that R. hominis is a promising candidate for the development of next-generation live biotherapeutics for the prevention of obesity and metabolic diseases.
Endoscopic ultrasound-guided hepaticogastrostomy without tract dilation using a novel 0.035-inch guidewire
Authors: Ritsuko Oishi, Haruo Miwa, Kazuki Endo, Hiromi Tsuchiya, Yuichi Suzuki, Kazushi Numata, Shin Maeda
Journal: Endoscopy (2025)

Biliary peritonitis is one of the complications of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS), and it is mostly caused by tract dilation [1] [2] [3]. In patients with acute cholangitis, bile leakage may cause refractory infection in the abdominal cavity. Therefore, omitting tract dilation is expected to reduce the risk of bile peritonitis; however, plastic stent placement without tract dilation has been reported as challenging [4]. A novel 0.035-inch guidewire (CAPELLA 0.035; Japan Lifeline Co., Ltd., Tokyo, Japan) has a stiff shaft that facilitates stent deployment in EUS-HGS ([Fig. 1]), which is also compatible with most devices designed for 0.025-inch guidewires. Herein, we present two cases in which a plastic stent was successfully placed without tract dilation using a CAPELLA 0.035 during EUS-HGS ([Video 1]).
Novel use of superb microvascular imaging in endoscopic ultrasound-guided tissue acquisition for pancreatic mass
Authors: Akashi Fujita, Masafumi Mizuide, Shomei Ryozawa, Yuki Tanisaka, Ryuhei Jinushi, Ryuichi Watanabe, Ryo Sato
Journal: Endoscopy (2025)

Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is a crucial method for diagnosing pancreatic lesions [1] [2] [3] [4] [5]. The Aplio i800 ultrasound device (Canon Medical Systems, Tochigi, Japan) features superb microvascular imaging (SMI), which provides highly sensitive and high-resolution imaging of microvascular flow without contrast agents. SMI has two modes – monochrome SMI (mSMI), which isolates microvascular signals, and color-coded SMI (cSMI), which enhances the visibility of pulsatile flow. These modes complement each other, enabling precise assessment of tumor vascularity and aiding in biopsy site selection, even in challenging cases with heterogeneous or necrotic lesions. This noncontrast imaging technology offers significant advantages in evaluating pancreatic tumors, where accurate visualization of vascularity is critical for diagnosis and treatment planning.
Gene therapy in children with AIPL1-associated severe retinal dystrophy: an open-label, first-in-human interventional study
Authors: Michel Michaelides, Yannik Laich, Sui Chien Wong, Ngozi Oluonye, Serena Zaman, Neruban Kumaran, Angelos Kalitzeos, Harry Petrushkin, Michalis Georgiou, Vijay Tailor, Marc Pabst, Kim Staeubli, Roni O Maimon-Mor, Peter R Jones, Steven H Scholte, Anastasios Georgiadis, Jacqueline van der Spuy, Stuart Naylor, Alexandria Forbes, Tessa M Dekker, Eugene R Arulmuthu, Alexander J Smith, Robin R Ali, James W B Bainbridge
Journal: The Lancet (2025)
[18F]fluorodeoxyglucose and [18F]fluorocholine PET-CT for staging optimisation and treatment modification in hepatocellular carcinoma (PET-HCC01): a prospective multicentre study
Authors: Jean-Charles Nault, Marouane Boubaya, Myriam Wartski, Anthony Dohan, Stanislas Pol, Gabriel Pop, Michael Soussan, Olivier Sutter, Charlotte Costentin, Julie Roux, Christian Sengel, Marie Lequoy, Françoise Montravers, Yves Menu, Georges-Philippe Pageaux, Denis Mariano Goulart, Boris Guiu, Alain Luciani, Pierre Nahon, Marco Dioguardi Burgio, Mathilde Wagner, Philippe Maksud, Sebastien Mulé, Manon Allaire, Sabrina Sidali, Audrey Coilly, Florent L Besson, Maïté Lewin, Hélène Regnault, Clémence Hollande, Giuliana Amaddeo, Maxime Ronot, Nathalie Ganne-Carrié, Emmanuel Itti, Coralie Bloch-Queyrat, Vincent Levy, Rachida Lebtahi, Julia Chalaye, Mohamed Bouattour
Journal: The Lancet. Gastroenterology & hepatology (2025)