tbuckley/cabot-search huggingface dataset:
Transient lymphocyte count decrease correlates with oncolytic adenovirus efficacy in humans: mechanistic and biomarker findings from TUNIMO phase I trial
Authors: Santeri A Pakola, James H A Clubb, Tatiana V Kudling, Mirte van der Heijden, Elise Jirovec, Victor Arias, Lyna Haybout, Katriina Peltola, Tuomo Alanko, Jorma Sormunen, Teijo Pellinen, Kristian Taipale, Dafne C A Quixabeira, Claudia Kistler, Riikka Havunen, Suvi Sorsa, Joao M Santos, Victor Cervera-Carrascon, Akseli Hemminki
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Oncolytic viruses (OVs) are promising immunotherapeutics to treat immunologically cold tumors. However, research on the mechanism of action of OVs in humans and clinically relevant biomarkers is still sparse. To induce strong T-cell responses against solid tumors, TILT-123 (Ad5/3-E2F-d24-hTNFa-IRES-hIL2, igrelimogene litadenorepvec) was developed. TILT-123 encodes two transgenes: tumor necrosis alpha (TNFa) and interleukin-2 (IL-2). TUNIMO ( NCT04695327 ) was a phase I clinical trial using TILT-123 in patients with advanced solid tumors aiming to assess the safety, efficacy, and immunological effects of TILT-123. Research presented in this study evaluated the immunological effects of TILT-123 in the TUNIMO trial by using biological samples collected from the patients during the study, with an objective to leverage the findings to develop possible biomarkers of response and gain insights into possible synergistic combination treatments. Methods 20 patients with advanced solid tumors were treated with TILT-123. Response to therapy was assessed with contrast-enhanced CT and fluorodeoxyglucose positron emission tomography, along with overall survival (OS) calculation. Biological samples from patients were collected in the form of blood and tumor biopsies. Collected samples were analyzed with immunohistochemistry, transcriptomics, proteomics, and flow cytometry. Results TILT-123 induced cyclical decreases in blood lymphocyte count, and more substantial blood lymphocyte count correlated with better radiographical response and longer OS. Lymphocyte count findings were confirmed with external control dataset of 96 patients. More substantial lymphocyte count change was linked to stronger immune activation in plasma proteome after intravenous TILT-123 and the presence of TILT-123 mRNA in tumors. Regarding other assays. tumor biopsies profiled showed increased amounts of CD8+ T cells, CD4+ T cells and NK cells after intravenous TILT-123, but not after intratumoral TILT-123. Transcriptional differences were seen in tumors after intravenous therapy and intratumoral therapy, with patients benefitting therapy showing stronger downregulation of immune activation at all time points. Conclusions TILT-123 therapy induced accumulation of effector lymphocytes in tumors. Peripheral lymphocyte count decrease is a promising biomarker for assessing oncolytic adenovirus therapy response.
New Oral Selective Estrogen Receptor Degraders Redefine Management of Estrogen Receptor–Positive Breast Cancer
Authors: Neha Pathak, Mafalda Oliveira
Journal: Annual Review of Medicine (2025)

Oral selective estrogen receptor degraders (SERDs) are pure estrogen receptor antagonists that have the potential to overcome common resistance mechanisms to endocrine therapy in estrogen receptor–positive breast cancer. There are currently five oral SERDs in published and ongoing clinical trials—elacestrant, camizestrant, giredestrant, imlunestrant, and amcenestrant—with more in development. They offer a reasonably well-tolerated oral therapy option with low discontinuation rates in studies. This review summarizes the currently available literature on this new class of drugs.
Hidradenitis Suppurativa
Authors: S. McCarthy
Journal: Annual Review of Medicine (2025)

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by the formation of nodules, abscesses, and fistulae at intertriginous sites. Pain, pruritus, malodor, and suppuration have a significant impact on quality of life for HS patients. Prevalence figures vary greatly in the literature from 0.05% to 4.1%, and HS is more common in females. The current understanding of the etiology and pathogenesis of HS is incomplete; numerous hypotheses concern the interplay of lifestyle factors, skin microbiota, genetics, and a dysregulated immune system. Due to its phenotypic heterogeneity and multifactorial pathogenesis, HS is a complex disease that can prove challenging to manage. Two approved biologic therapies for the management of HS have led to clinical response in approximately 50% of treated patients. New therapies targeting the interleukin (IL)-1, IL-17, IL-36, and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways are in ongoing clinical trials, and preliminary data offer hope for greater clinical efficacy in HS in the future.
Multimodal assessment predicts cognitive impairment after aneurysmal subarachnoid hemorrhage: a prospective cohort study
Authors: Peng Liu, Ruili Li, Tongyu Zhang, Yueqiao Xu, Kun Yang, Yuxia Li, Chuanliang Han, Yang Yang, Changming Wang, Jie Lu, Hongqi Zhang
Journal: International Journal of Surgery (2025)

Risk factors and mechanisms of cognitive impairment (CI) after aneurysmal subarachnoid hemorrhage (aSAH) are unclear. This study used a neuropsychological battery, MRI, ERP and CSF and plasma biomarkers to predict long-term cognitive impairment after aSAH. 214 patients hospitalized with aSAH (n = 125) or unruptured intracranial aneurysms (UIA) (n = 89) were included in this prospective cohort study. Neuropsychological tests were administered 7 to 24 months post-discharge. MRI, ERP, and CSF and plasma biomarkers were used to predict long-term CI, and area under ROC curves were calculated. Patients with aSAH CI showed significant impairment across composite scores and cognitive domains on the neuropsychological battery vs. patients with aSAH No CI. On ALFF (MRI), the right medial orbitofrontal cortex (AUC = 0.78), right inferior frontal gyrus (AUC = 0.848), and right inferior parietal lobule (AUC = 0.868) distinguished aSAH CI from aSAH No CI. For ERP, consistent changes were found across specific EEG electrodes (FP1, F3, CP1, FP2, F4, CP2), including increased PA, prolonged PL and decreased ITPC. ITPC showed the highest sensitivity for distinguishing aSAH CI from aSAH No CI, followed by PA. Channel F4 (ITPC, AUC = 0.912, PA, AUC = 0.846), corresponding to the right inferior frontal gyrus, was the most sensitive for detecting CI, followed by channel CP2 (ITPC, AUC = 0.903, PA, AUC = 0.806), corresponding to the right inferior parietal lobule. CSF (Aβ42, Aβ40, p-tau181/Aβ42, p-tau181/total-tau, total-tau) and plasma biomarkers (Aβ-40, p-tau181) were significantly associated with long-term CI. ALFF, ERP, and CSF and plasma Aβ and tau levels and ratios have clinical utility for evaluating and predicting long-term cognitive impairment following aSAH. MRI may reveal the pathogenesis of cognitive impairment following aSAH. ERP can be administered at the bedside offering sensitive, non-invasive, repeatable, and sustainable monitoring, which is particularly suitable for immobile coma patients. ERP may represent a promising method to monitor neural function and its outcomes.
Exploring the landscape of exosomes in heart failure: a bibliometric analysis
Authors: Hui Li, Zhitao Li, Qinghui Fu, Shuiqiao Fu, Tao Xiang
Journal: International Journal of Surgery (2025)

Background: Exosomes, which carry bioactive RNAs, proteins, lipids, and metabolites, have emerged as novel diagnostic markers and therapeutic agents for heart failure (HF). This study aims to elucidate the trends, key contributors, and research hotspots of exosomes in HF. Methods: We collected publications related to exosomes in HF from the Web of Science Core Collection. Using VOSviewer, CiteSpace, Excel, and SRplot software, we performed a visualization analysis of authors, countries, institutions, keywords, and references. Results: The publications on exosomes in the field of HF ( N = 2127) has grown rapidly. China ( N = 245, 42.683%) and the United States ( N = 170, 29.617%) are the leading contributors in this area. Wang L ( N = 14, 2.443%) is the most prolific author in the field. Key areas of exosome research in HF include mesenchymal stem cells (MSCs), angiogenesis, and microRNAs. Additionally, keywords and references analysis reveal that exosome research in HF is primarily focused on the role of exosomes in intercellular communication in HF, the value of miRNAs in exosomes as diagnostic markers, and the therapeutic mechanisms of MSC-derived exosomes. Conclusion: Exosomes are receiving increasing attention in the field of HF. Mapping the development landscape of exosomes in HF will help researchers accelerate progress in this area.
Multifunctional nanozymes for sonodynamic-enhanced immune checkpoint blockade therapy by inactivating PI3K/AKT signal pathway
Authors: Mei Wen, Pu Qiu, Jialan Meng, Wenjing Zhao, Xiao Wang, Shining Niu, Cheng Tao, Nuo Yu, Zhigang Chen, Dong Xie
Journal: Biomaterials (2025)
Comparison of short-and long-term outcomes between endovascular and open repair for descending thoracic aortic aneurysm: a systematic review and meta-analysis
Authors: Junning Liu, Dan Gou, Kanglin Xu, Ziao Lu, Peidong Li, Yong Lei, Yongjie Wang, Yuting Yang, Shiqiang Liu, Guiying Zhu
Journal: International Journal of Surgery (2025)

Objective: This systematic review and meta-analysis aimed to evaluate and compare the efficacy of endovascular versus open repair for the treatment of patients with descending thoracic aortic aneurysm (DTAA). Methods: A systematic search of the PubMed, Embase, and Cochrane Library databases for relevant studies was performed. Outcome data, including postoperative mortality and morbidity, operative details, all-cause survival, freedom from aortic-related survival and freedom from aortic-related re-intervention, were independently extracted by two authors in a standardized way. Results: Twenty-nine studies comprising 49 972 patients (22 049 endovascular repair; 27 923 open repair) were included. Endovascular repair was associated with a significantly lower postoperative mortality rate [odd ratio (OR): 0.57, 95% confidence interval (CI): 0.45-0.72; I 2 = 72.58%] and morbidity. In terms of long-term survival, endovascular repair yielded better freedom from aortic-related survival [hazard ratio (HR): 0.71, 95% CI: 0.54-0.93, P = 0.012] but inferior freedom from aortic-related reintervention (HR: 2.10, 95% CI: 1.45-3.04, P &lt; 0.001). Landmark analysis revealed that the open repair group experienced better all-cause survival beyond 16 months (HR: 1.64, 95% CI: 1.53-1.75, P &lt; 0.001). In addition, in the subgroup of patients with intact DTAA, those who underwent open repair exhibited a higher rate of postoperative mortality (OR: 0.58, 95% CI: 0.38-0.88; I 2 = 83.34%) but had better all-cause survival beyond 7 months (HR: 1.72, 95% CI: 1.61-1.84, P &lt; 0.001) than those who underwent endovascular repair. Conclusion: Among patients treated for DTAA, endovascular repair was associated with better freedom from aortic-related survival, a lower risk for postoperative mortality and morbidity, and shorter lengths of intervention, intensive care unit stay, and hospital stay than those who underwent open repair. Open repair yielded significantly better long-term all-cause survival and freedom from aortic-related re-intervention than endovascular repair.
Characterization changes and research waste in randomized controlled trials of global gastroesophageal reflux disease and hiatus hernia over the past 20 years
Authors: Bin Lin, Xiao-Jing Guo, Yi-Ming Jiang, Zhi-Xin Shang-Guan, Qing Zhong, Qi-Yue Chen, Jian-Wei Xie, Ping Li, Chao-Hui Zheng, Chang-Ming Huang, Jian-Xian Lin
Journal: International Journal of Surgery (2025)

Background: The results of many large randomized clinical trials (RCTs) have transformed clinical practice in gastroesophageal reflux disease (GERD) and esophageal hiatal hernia (HH). However, research waste (i.e., unpublished data, inadequate reporting, or avoidable design limitations) remains a major challenge to evidence-based medicine. To explore the characteristics of GERD and HH RCTs over the past 20 years and whether there is research waste, and to explore potential targets for improvement. Method: A cross-sectional analysis was conducted to comprehensively review and evaluate RCTs related to GERD and esophageal HH, registered in the ClinicalTrials.gov database between 2003 and 2023. A sample of eligible RCTs was identified by excluding early-stage trials, pediatric studies, and duplicate studies. Publication status was tracked using PubMed and Scopus databases, reporting adequacy was assessed according to the CONSORT guidelines, and design flaws were checked with the help of Cochrane tools. Shortcomings of RCT studies in different regions and intervention types were identified by quantifying RCT conduct, recruitment, reporting adequacy, risk of bias, and guideline citations. Results: From 2003 to 2023, a total of 182 RCTs were included in the analysis, of which 69.8% (127 trials) were drug-related, and 71.4% of the principal investigators were located in North America and Asia (65 trials [35.7%] in both). Among them, the country with the most RCTs is the United States. RCTs in Asia were under-conducted in “procedure” and “other” types and fewer RCTs were conducted in Europe in “drug” type. RCTs in Oceania and South America were relatively under-conducted in the device and “other.” The study revealed that more than 86.7% of RCTs were characterized by at least one type of research waste. Research waste was associated with the size of the RCT, blinded design, and regional healthcare access and quality index. Conclusions: This study describes for the first time the characteristics of RCTs for GERD and esophageal HH over the past 20 years and the conduct of various types of RCTs at the continental level. It identifies the burden of research waste and shortcomings in the conduct of RCT programs on each continent, which may provide evidence for the development of rational RCTs and the reduction of waste in the future.
Prevention strategies of esophageal stenosis after endoscopic resection for superficial esophageal cancer: a Bayesian network meta-analysis
Authors: Yongqi Dong, Hongyan Xu, Wanli Yu, Zijing Liu, Gang Zhao, Zhihuan Zhang, Yuan Xia, Shiyong Xiao, Qianzhang Yi, Zebin Lin
Journal: International Journal of Surgery (2025)

Introduction: What interventions effectively prevent postoperative stenosis following endoscopic resection (ER) of superficial esophageal cancer? This study aimed to identify effective interventions or combinations through a systematic review and network meta-analysis. Methods: Six databases were systematically searched for eligible studies up to 30 April 2023, on interventions to prevent esophageal stenosis post-ER. Odds ratios (ORs) evaluated stenosis rate (primary outcome) and complications (secondary outcome), while mean differences (MD) evaluated endoscopic balloon dilatation (EBD) sessions post-stenosis. Results: Twenty-three studies involving 1271 patients and 11 different interventions were included. Eight interventions were effective in preventing post-ER stenosis: oral hydrocortisone sodium succinate and aluminum phosphate gel (OHA) (OR: 0.02, 95% credible interval [CrI]: 0.00–0.11), polyglycolic acid (PGA) + ST (OR: 0.02, 95% CrI: 0.00–0.23), oral tranilast (OT) + preemptive endoscopic balloon dilatation (PEBD) (OR: 0.08, 95% CrI: 0.01–0.77), botulinum toxin (BT) (OR: 0.10, 95% CrI: 0.03–0.32), ST (OR: 0.08, 95% CrI: 0.01–0.67), oral steroid (OS) (OR: 0.11, 95% CrI: 0.05–0.28), endoscopic triamcinolone injection (ETI) + OS (OR: 0.17, 95% CrI: 0.07–0.42), and ETI (OR: 0.18, 95% CrI: 0.11–0.30). Five interventions significantly reduced EBD sessions: PGA + ST (MD: −5.78, 95% CrI: −11.04 to −1.21), ETI + OS (MD: −3.27, 95% CrI: −5.37 to −0.72), OS (MD: −6.18, 95% CrI: −9.43 to −3.38), ETI (MD: −3.81, 95% CrI: −5.74 to −1.99), and BT (MD: −2.16, 95% CrI: −4.12 to −0.40). None of the interventions significantly increased complications. Conclusions: This study confirmed the efficacy of OS, ETI, and ETI + OS and verified five other interventions (OHA, PGA + ST, OT + PEBD, BT, and ST) in preventing stenosis. Notably, PGA + ST and BT also reduced the number of EBD sessions.
Virtual 3D models, augmented reality systems and virtual laparoscopic simulations in complicated pancreatic surgeries: state of art, future perspectives, and challenges
Authors: Imán Laga Boul-Atarass, Carmen Cepeda Franco, José Domingo Sanmartín Sierra, Javier Castell Monsalve, Javier Padillo Ruiz
Journal: International Journal of Surgery (2025)

Pancreatic surgery is considered one of the most challenging interventions by many surgeons, mainly due to retroperitoneal location and proximity to key and delicate vascular structures. These factors make pancreatic resection a demanding procedure, with successful rates far from optimal and frequent postoperative complications. Surgical planning is essential to improve patient outcomes, and in this regard, many technological advances made in the last few years have proven to be extremely useful in medical fields. This review aims to outline the potential and limitations of 3D digital and 3D printed models in pancreatic surgical planning, as well as the impact and challenges of novel technologies such as augmented/virtual reality systems or artificial intelligence to improve medical training and surgical outcomes.
Induction of M1 polarization in BV2 cells by propofol intervention promotes perioperative neurocognitive disorders through the NGF/CREB signaling pathway: an experimental research
Authors: Ting Ye, Yiwei Fan, Xiangye Zeng, Xiaojing Wang, Huaping Xiao
Journal: International Journal of Surgery (2025)

Nerve growth factor (NGF) is critical in regulating the homeostasis of microglial cells. It activates various signaling pathways that mediate the phosphorylation of cAMP response element-binding protein (CREB) at key regulatory sites. The decrease in phosphorylated CREB (p-CREB) expression is linked to neuroinflammatory responses. The exact molecular mechanism by which propofol regulates microglial polarization and induces neuroinflammation via the NGF/CREB signaling axis remains unclear. This study aims to investigate the specific mechanisms by which propofol induces perioperative neurocognitive disorders through microglial M1 polarization and neuroinflammation via the NGF/CREB signaling pathway. We demonstrated that propofol impairs neurocognitive function in mice, as evidenced by behavioral deficits. It reduces NGF expression in hippocampal microglia and BV2 cells, where protein-protein interactions between NGF and CREB suggest that NGF primarily regulates neurocognitive function by modulating p-CREB. Propofol intervention and inhibition of the NGF/CREB pathway promote M1 polarization in hippocampal microglia and BV2 cells, leading to reduced cell proliferation, increased apoptosis, elevated oxidative stress, and higher levels of the inflammatory marker TNF-α. Exogenous NGF does not alter the expression of NGF or total CREB but significantly upregulates p-CREB, indicating its regulatory role in signaling pathways associated with microglial activation. Moreover, exogenous NGF mitigates propofol-induced cognitive impairments and M1 polarization, reducing apoptosis and oxidative stress levels. Our findings suggest that propofol downregulates the expression of NGF and CREB, subsequently reducing p-CREB levels. This downregulation induces M1 polarization of microglia, promoting the progression of neuroinflammation and contributing to the development of perioperative neurocognitive disorders.
Deciphering the impact of dietary habits and behavioral patterns on colorectal cancer
Authors: Qihang Yuan, Jiahua Liu, Xinyu Wang, Chunchun Du, Yao Zhang, Lin Lin, Chengfang Wang, Zhijun Hong
Journal: International Journal of Surgery (2025)

Colorectal cancer (CRC) is a malignant tumor that originates from the epithelial cells of the colon and rectum. Global epidemiological data shows that in 2020, the incidence and mortality rate of CRC ranked third and second, respectively, posing a serious threat to people’s health and lives. The factors influencing CRC are numerous and can be broadly categorized as modifiable and non-modifiable based on whether they can be managed or intervened upon. Non-modifiable factors include age, gender, family history, among others. Among the modifiable factors, dietary habits and behavioral practices are the main intervention measures that people can take to prevent CRC. Numerous studies indicate that a high intake of red and processed meats, fats, as well as habits such as smoking, alcohol consumption, and prolonged sitting, increase the risk of developing CRC. Conversely, consuming ample vegetables, fruits, high dietary fiber, and engaging in moderate regular exercise may reduce the risk of CRC. This article primarily discusses the impact of dietary habits and behavioral practices on the occurrence and development of CRC, along with possible mechanisms, laying the foundation and providing direction for the prevention and control of CRC occurrence and development.
Combined PARP14 inhibition and PD-1 blockade promotes cytotoxic T cell quiescence and modulates macrophage polarization in relapsed melanoma
Authors: Rotem Leshem, Kieran Neil Sefton, Chun Wai Wong, I-Hsuan Lin, Dervla Tamara Isaac, Mario Niepel, Adam Hurlstone
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Programmed cell death 1 (PD-1) signaling blockade by immune checkpoint inhibitors (ICI) effectively restores immune surveillance to treat melanoma. However, chronic interferon-gamma (IFNγ)-induced immune homeostatic responses in melanoma cells contribute to immune evasion and acquired resistance to ICI. Poly ADP ribosyl polymerase 14 (PARP14), an IFNγ-responsive gene product, partially mediates IFNγ-driven resistance. PARP14 inhibition prolongs PD-1 blockade responses in preclinical models, but fails to achieve full tumor clearance, suggesting the involvement of additional resistance mechanisms. Methods We identified a robust PARP14 catalytic inhibitor gene signature and evaluated its association with patient survival. Using preclinical models and single-cell RNA sequencing, we investigated immune and tumor cell adaptations to PARP14 inhibition combined with PD-1 blockade. Results Combining PARP14 inhibition and PD-1 blockade suppressed tumor-associated macrophages while increasing proinflammatory memory macrophages. Moreover, this combination mitigated the terminal exhaustion of cytotoxic T cells by inducing a quiescent state, thereby preserving functionality. Despite the enhanced immune responses, tumor cells developed adaptive resistance by engaging alternative immune evasion pathways. Conclusions Although adaptive resistance mechanisms re-emerge, PARP14 inhibition combined with PD-1 blockade offers a promising strategy to enhance treatment outcomes and overcome ICI resistance in melanoma, as immune cells are primed for further therapeutic interventions that leverage the quiescent state.