tbuckley/cabot-search huggingface dataset:
Adjuvant cytokine-induced killer cell immunotherapy in hepatocellular carcinoma: Extended follow-up of a randomized controlled trial and post-treatment immune cell profiling.
Authors: Jeong-Hoon Lee, Youngsu Park, Hyunjae Shin, Byeong Geun Song, Won-Mook Choi, Hyung Joon Han, Youngwoo Lee, Tae-Jin Song, Jong-Eun Yeon, Young-Suk Lim, Joon Hyeok Lee, Jae Woong Yoon, Yunmi Ko, Jeayeon Park, Moon Haeng Hur, Yun Bin Lee, Yoon Jun Kim, Hyejeong Lee, Joo-Young Park, Jung-Hwan Yoon
Journal: Journal of Clinical Oncology (2025)

518 Background: Notwithstanding the pressing need for adjuvant therapy for hepatocellular carcinoma (HCC), most adjuvant therapies, including atezolizumab/bevacizumab, have failed. Meanwhile, adjuvant immunotherapy utilizing autologous cytokine-induced killer (CIK) cells for HCC improved recurrence-free survival (RFS) in a previously reported randomized controlled trial (RCT) and real-world data. This study aimed to assess the longer-term outcomes of the RCT and elucidate the underlying mechanisms of sustained effects of CIK cell treatment. Methods: This study comprised two parts: a long-term follow-up of the preceding RCT and an analysis of immune cells in patients who received adjuvant CIK cell treatment. In the original RCT, 226 patients who underwent curative treatment for stage I or II HCC were randomly allocated to either the CIK (n=114, 16 injections of 6.4×10 9 CIK cells over an 11-month period) or control group (n=112). The follow-up period was extended to 9 years after the enrollment of the last patient. The primary endpoint was recurrence-free survival (RFS). The secondary endpoints included cancer-specific survival (CSS) and overall survival (OS). Parallelly, a prospective study was conducted to investigate post-treatment changes of immune cells in peripheral blood of 7 patients, who received repeated transfer of CIK cells after curative treatment for HCC, using flow cytometry. Results: In the extended follow-up of the RCT (median follow-up=115.7 months, interquartile range=74.2–130.5 months), the CIK group sustained a significantly prolonged RFS (median=43.5 vs 27.4 months; hazard ratio [HR]=0.74, 95% confidence interval [CI]=0.55–0.99, P =0.045) and CSS (median=unreached; HR=0.49, 95% CI=0.25–0.95, P=0.04) compared to the control group. Adjuvant CIK cell therapy reduced the risk of overall death by 30%, although it did not achieve statistical significance (median=unreached; HR=0.70, 95% CI=0.44–1.11, P=0.1). A preliminary analysis of peripheral blood immune cells revealed that the CIK cell treatment tended to increase the frequencies of CD8 + and CD4 + classical memory cells. Conclusions: Adjuvant CIK cell treatment demonstrated significantly enhanced RFS and CSS in the prolonged follow-up of the RCT extending to 9 years in patients who received curative treatment for HCC. The CIK group also demonstrated a consistent trend of improved OS. The increase in memory T cell populations might be linked to the sustained off-treatment anti-tumor efficacy of CIK cell treatment.
Selective internal radiation therapy with yttrium-90 resin microspheres followed by lenvatinib plus PD-1 inhibitor for large or huge advanced-stage hepatocellular carcinoma: A retrospective cohort study from China.
Authors: Jingjun Huang, Wensou Huang, Licong Liang, Yongjian Guo, Mingyue Cai, Liteng Lin, Jingwen Zhou, Kangshun Zhu
Journal: Journal of Clinical Oncology (2025)

581 Background: Yttrium-90 resin microspheres have been introduced into China in recent years, but the efficacy or safety on Chinese patients are rarely reported. This study aimed to evaluate the efficacy and safety of selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres followed by lenvatinib and PD-1 inhibitor in Chinese patients with large (5.1–10.0 cm in diameter) or huge (&gt;10.0 cm) advanced-stage hepatocellular carcinoma (HCC). Methods: Data of large or huge Barcelona Clinic Liver Cancer stage C HCC patients treated with SIRT followed by lenvatinib plus PD-1 inhibitor from November 2022 to October 2023 were prospectively collected and retrospectively analyzed. Key endpoints included overall survival (OS), progression-free survival (PFS), complete response rate (CRR), objective response rate (ORR), disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors, and adverse events (AEs) graded based on Common Terminology Criteria for Adverse Events v5.0. Risk factors affecting PFS were analyzed using univariate and multivariate Cox regression models. Results: A total of 30 patients (27 males, 3 females; mean age 54 ± 11 years) were included. The mean longest diameter of the tumor was 9.6 ± 4.2 cm (range: 5.2–17.6 cm). Nineteen (63.3%) patients had more than three intrahepatic lesions, 15 (50.0%) had vascular invasion, and 13 (43.3%) had extrahepatic metastasis. Sixteen (53.3%) patients had undergone prior anticancer therapies. Two patients received two SIRT procedures, and the rest had one. Lenvatinib and PD-1 inhibitor treatment was initiated 3–7 days after the initial SIRT procedure. CRR was 20.0%, ORR was 73.3%, and DCR was 90.0%. Median PFS was 8.0 months (95% CI, 5.6–10.4), and median OS was not reached. OS rates at 6, 12, and 18 months were 93%, 74%, and 74%, respectively. Univariate and multivariate analysis indicated that baseline alpha-fetoprotein levels, baseline eosinophil count, and neutrophil-to-lymphocyte ratio at 1 month after SIRT were independent risk factors for PFS. AEs of any grade occurred in 86.7% of patients, with grade 3 AEs in 23.3%, and no grade 4/5 AEs were recorded. Conclusions: SIRT followed by lenvatinib and PD-1 inhibitor demonstrates promising efficacy and a favorable safety profile in Chinese patients with large or huge advanced-stage HCC.
The association of antibiotic use and survival among patients receiving first line immunotherapy-based treatment for advanced gastroesophageal cancers.
Authors: Nicole Baranda Balmaceda, Junxiao Hu, Vida Alami, S. Lindsey Davis, Alexis Diane Leal, Robert William Lentz, Hannah Ruth Robinson, Emily Baiyee Toegel, Christopher Hanyoung Lieu, Wells A. Messersmith, Benjamin Edward Ueberroth, Alexander Hayden, Sunnie S. Kim
Journal: Journal of Clinical Oncology (2025)

349 Background: The advent of immune checkpoint inhibition (ICI) has improved the survival for patients with gastroesophageal cancer (GEC). It is vital to understand the relationship between the tumor microenvironment and the ability of the immune system to prevent and eliminate cancer cells. Antibiotics (abx), frequently used in patients on cancer-directed therapy, can alter gut microbiota leading to dysbiosis and altered immune responses. Some research shows its use is associated with decreased ICI efficacy in RCC, NSCLC, and melanoma. The goal of our study is to investigate the association of abx timing and survival with 1L ICI-based treatments for advanced GEC. Methods: The retrospective, multicenter analysis used the Flatiron Health deidentified electronic health record-derived database of real world (rw) patients with advanced esophageal, GEJ, and gastric cancers (EC/GEJC/GC) who received ICI +/- chemotherapy (chemo) as 1L therapy. Abx exposure was defined by antibiotic use from 42 days before to 42 days after starting ICI. The cox proportion hazards models were used to compare rw overall survival (OS) and progression-free survival (PFS) across exposure groups. Results: A total of 990 patients were included for the main group analysis with comparison of survival and abx usage and timing: 876 did not receive abx, 58 received abx within 42 days after starting ICI, and 56 received abx within 42 days prior to starting ICI. The median age was 66 with 44.4% EC, 33.5% GC, and 22% GEJC. The majority of patients had adenocarcinoma (87.9%). The unadjusted OS HR for abx (within 42 days) before ICI was 0.99 (0.68-1.46, p=0.971) and (within 42 days) after ICI was 1.56 (1.11-2.19, p=0.011), suggesting worse OS with abx use after ICI initiation. HR trended towards worse PFS for those receiving abx after 1L ICI [1.36 (0.97-1.90 p= 0.073)]. In subgroup analysis, the negative effect of starting abx after 1L ICI over abx before ICI was more prominent in those receiving ICI monotherapy compared to those receiving chemo/ICI. Conclusions: Our study identifies a poorer survival association of abx administration after 1L ICI-based therapy for advanced GEC, primarily driven by ICI monotherapy. Main group comparison between abx usage and timing: OS Abx Use/Timing n (%) HR No 876 (88.5) Yes, after 1L IO 58 (5.9) 1.56 (1.11-2.19, p=0.011) Yes, before 1L IO 56 (5.7) 0.99 (0.68-1.46, p=0.971) Subgroup comparison between abx usage and timing by treatment type Chemo + IO: OS Yes, after 1L IO 44 (6.9) 1.32 (0.88-1.98,p=0.177) Yes, before 1L IO 38 (6.0) 1.01 (0.62-1.65, p=0.964) IO monotherapy: OS Yes, after 1L IO 12 (4.9) 2.64 (1.38-5.06, p=0.003) Yes, before 1L IO 12 (4.9) 1.09 (0.53-2.23, p=0.810)
Predicting mortality in upper gastrointestinal tract cancer using long short-term memory neural networks.
Authors: Manaswitha Thota, Sidharth Mahajan, Sri Harsha Boppana, Sri Lasya Boppana, Sachin Sravan Kumar Komati, David Mintz
Journal: Journal of Clinical Oncology (2025)

340 Background: Upper gastrointestinal (GI) tract cancers represent a significant global health burden, characterized by high morbidity and mortality rates, with an increasing incidence among aging populations and varying outcomes based on gender and ethnicity. Early prediction of mortality rates in upper gastrointestinal cancer can significantly enhance treatment strategies and patient outcomes. This study describes current trends in upper gastrointestinal cancer and proposes a predictive model, developed using Long Short-Term Memory (LSTM) neural networks to project future trends using demographic data. Methods: We extracted mortality data from the Center for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiological Research (WONDER) Database spanning 1999, normalized it and encoded categorical variables such as age, sex, ethnicity, and race numerically. Using Studio R to analyze mortality trends, we developed an LSTM model known for its ability to capture and utilize long term data patterns. The model, trained with a sequence length of 20, predicted future data points based on the previous 20. We then assessed its accuracy and generalization with a test set. Ultimately, our model is able to utilize demographic variables to forecast annual mortality and survival rates. Results: The mortality rates for upper GI tract cancers are notably higher among elderly individuals, particularly those aged 80 and above, with males and certain ethnic groups, such as Hispanics. The accuracy of the trained model was evaluated by calculating the Mean Squared Error (MSE), a measure of the difference between the predicted and actual value, with zero indicating no difference between the two. Our LSTM model achieved a training MSE of 0.00085 and a validation MSE of 0.0016, indicating good reliability and accuracy. Conclusions: Our analysis highlighted clear mortality trends and demonstrated the model’s effectiveness in improving mortality predictions in upper gastrointestinal cancer. However, limitations due to the dataset’s lack of clinical variables (such as comorbidities, cancer stage, and prior treatments) and its reliance on a single dataset may affect external validity. Future research is needed to determine if the model can be applied for clinical prognosis or strategic planning. We ultimately created and validated an LSTM neural network model with the CDC WONDER dataset, showing promising results. Future development will aim to include clinical characteristics to create a more personalized predictive tool.
Lysyl oxidase nanozyme-loaded hydrogel for sustained release and promotion of diabetic bone defect regeneration
Authors: Shan Xu, Jian Zhang, Jun Che, Zhengzhou Sha, Mingtao Zhang, Zhiyan Zhang, Tangyong Xiang, Weixi Zhong, Li Wu, Gaohong Lv, Baochang Cai, Liu Xu, Cheng Xu, Zhipeng Chen
Journal: Journal of Controlled Release (2025)
Relatively Increased CO <sub>2</sub> Delivered to the Brain From the Descending Aorta Leading to an Elevated Respiratory Rate Causing Differential Hypocapnia (RIDDLER or East-West Syndrome): New Pitfalls in Awake Peripheral V-A ECMO
Authors: Alex Rosenberg, Louit Thakuria, Christophe Vandenbriele
Journal: Circulation (2025)
SLICE-CEA CardioLink-8: A Randomized Trial of Evolocumab on Carotid Artery Atherosclerotic Plaque Characteristics in Asymptomatic High-Risk Carotid Stenosis
Authors: C. David Mazer, Alan R. Moody, Hwee Teoh, Adrian Quan, Randi Elituv, Thayalasuthan Vivekanandan, Peiyu Li, Kevin E. Thorpe, Myriam Lafreniere-Roula, Raj Verma, Michael Moroney, Jack H. Casey, Navneet Singh, Aditya Bharatha, Rasha Mahmoud, Regis Manorajah, Andrew Jayarajah, Anish N. Kapadia, Andrew D. Dueck, Mohammed Al-Omran, Deepak L. Bhatt, Lawrence A. Leiter, Subodh Verma
Journal: Circulation (2025)
CircTTC13 promotes sorafenib resistance in hepatocellular carcinoma through the inhibition of ferroptosis by targeting the miR-513a-5p/SLC7A11 axis
Authors: Ying Zhang, Ruiwei Yao, Mingyi Li, Chongkai Fang, Kunliang Feng, Xiuru Chen, Jinan Wang, Rui Luo, Hanqian Shi, Xinqiu Chen, Xilin Zhao, Hanlin Huang, Shuwei Liu, Bing Yin, Chong Zhong
Journal: Molecular Cancer (2025)

The high mortality rate from hepatocellular carcinoma (HCC) is due primarily to challenges in early diagnosis and the development of drug resistance in advanced stages. Many first-line chemotherapeutic drugs induce ferroptosis, a form of programmed cell death dependent on ferrous iron-mediated oxidative stress, suggesting that drug resistance and ensuing tumor progression may in part stem from reduced ferroptosis. Since circular RNAs (circRNAs) have been shown to influence tumor development, we examined whether specific circRNAs may regulate drug-induced ferroptosis in HCC. Through circRNA sequencing, we identified a novel hsa_circ_0000195 (circTTC13) that is overexpressed in HCC tissues. This overexpression is linked to higher tumor grade, more advanced tumor stage, decreased ferroptosis, and poorer overall survival. Overexpression of CircTTC13 in HCC cell lines and explant tumors was associated with increased proliferation rates, enhanced metastatic capacity, and resistance to sorafenib, while also inhibiting ferroptosis. Conversely, circTTC13 silencing reduced malignant characteristics and promoted ferroptosis. In silico analysis, luciferase assays, and fluorescence in situ hybridization collectively demonstrated that circTTC13 directly targets and reduces miR-513a-5p expression, which in turn leads to the upregulation of the negative ferroptosis regulator SLC7A11. Moreover, the inhibition of SLC7A11 mirrored the effect of circTTC13 knockdown, whereas ferroptosis inhibition mimicked the effect of circTTC13 overexpression. Both circTTC13 and SLC7A11 were highly expressed in drug-resistant HCC cells, and circTTC13 silencing induced ferroptosis and reversed sorafenib resistance in explant tumors. These findings identify circTTC13 as a critical driver of HCC progression and resistance to drug-induced ferroptosis via upregulation of SLC7A11. The cicTTC13/miR-513a-5p/SLC7A11 axis represents a potential therapeutic target for HCC.
Extensive benchmarking of a method that estimates external model performance from limited statistical characteristics
Authors: Tal El-Hay, Jenna M. Reps, Chen Yanover
Journal: npj Digital Medicine (2025)

Predictive model performance may deteriorate when applied to data sources that were not used for training, thus, external validation is a key step in successful model deployment. As access to patient-level external data sources is typically limited, we recently proposed a method that estimates external model performance using only external summary statistics. Here, we benchmark the proposed method on multiple tasks using five large heterogeneous US data sources, where each, in turn, plays the role of an internal source and the remaining—external. Results showed accurate estimations for all metrics: 95th error percentiles for the area under the receiver operating characteristics (discrimination), calibration-in-the-large (calibration), Brier and scaled Brier scores (overall accuracy) of 0.03, 0.08, 0.0002, and 0.07, respectively. These results demonstrate the feasibility of estimating the transportability of prediction models using an internal cohort and external statistics. It may become an important accelerator of model deployment.
Risk factors for pancreatic cancer in individuals with intraductal papillary mucinous neoplasms and no high-risk stigmata during up to 5 years of surveillance: a prospective longitudinal cohort study
Authors: Tsuyoshi Hamada, Hiroki Oyama, Daniel Nevo, Shuichi Tange, Shinya Takaoka, Yoshikuni Kawaguchi, Kazunaga Ishigaki, Kensaku Noguchi, Tomotaka Saito, Tatsuya Sato, Tatsunori Suzuki, Naminatsu Takahara, Mariko Tanaka, Kiyoshi Hasegawa, Tetsuo Ushiku, Yousuke Nakai, Maxim S Petrov, Mitsuhiro Fujishiro
Journal: Gut (2025)

Background Cyst size, its growth rate, and diameter of the main pancreatic duct (MPD) are all associated with pancreatic carcinoma prevalence in intraductal papillary mucinous neoplasms (IPMNs). Objective To examine the above factors in relation to future risk of incident pancreatic carcinoma in individuals with IPMNs harbouring no high-risk stigmata. Design In a prospective longitudinal cohort, we analysed 2549 patients with IPMNs. A multivariable cause-specific Cox proportional hazards regression model was built to estimate HRs for incident pancreatic carcinoma. Results IPMN size at baseline and its annual growth rate over 2 years of follow-up were associated with incident pancreatic carcinoma (p trend &lt;0.001). The multivariable cause-specific HR per 10 mm increase in IPMN size was 1.28 (95% CI 1.10 to 1.50). The annual growth rates of 1.5–2.4 mm/year and ≥2.5 mm/year over 2 years were associated with multivariable cause-specific HRs of 1.91 (95% CI 0.78 to 4.67) and 4.52 (95% CI 2.28 to 8.98), respectively (vs &lt;1.5 mm/year). Neither IPMN size at 5 years nor its maximum growth rate during 5 years was associated with incident pancreatic carcinoma (p trend &gt;0.07). MPD diameter at 5 years was associated with incident pancreatic carcinoma (multivariable cause-specific HR per 2 mm increase, 2.12; 95% CI 1.72 to 2.63). A predictive nomogram was generated for calculating the risk of incident pancreatic carcinoma. Conclusion IPMN size and its growth rate predict future pancreatic carcinoma risk only during first 5 years of follow-up. MPD diameter at 5 years may identify patients who still harbour a high risk for pancreatic carcinoma.
Continuous risk monitoring and management of heart failure: Rationale and design of the <scp>ALLEVIATE</scp>‐<scp>HF</scp> trial
Authors: Javed Butler, Rami Kahwash, Muhammad Shahzeb Khan, Bart Gerritse, Aimee Laechelt, Jennifer Wehking, Shantanu Sarkar, Brian van Dorn, Verla Laager, Nirav Patel, Michael R. Zile
Journal: European Journal of Heart Failure (2025)

Abstract Aims Early identification and management of worsening heart failure (HF) is necessary to prevent disease progression and hospitalizations. The ALLEVIATE‐HF (Algorithm Using LINQ Sensors for Evaluation and Treatment of Heart Failure) trial is a prospective, randomized, controlled, double‐blind, multicentre trial that aims to assess the safety and efficacy of using the Reveal LINQ™ insertable cardiac monitor (ICM) in patients with HF to continuously monitor and evaluate HF risk status and guide timely interventions. Methods The ICM algorithm uses parameters derived from electrocardiogram (atrial fibrillation [AF], ventricular rate during AF, heart rate variability, and night heart rate), three‐axis accelerometer (patient activity duration), and subcutaneous bioimpedance (fluid volume, respiration rate). The trial will enroll ~760 patients with New York Heart Association class II or III HF with recent hospitalization for HF or needing intravenous diuretics in the outpatient setting or elevated natriuretic peptide levels, who do not have an implanted cardiac implantable electronic device or haemodynamic monitor. Patients are randomized to an observation or an intervention arm, where the latter will receive an intervention pathway with remote nurses implementing individualized pro re nata (PRN or ‘as needed’) 4‐day medication interventions for acute volume management upon high risk. After 13 months of randomized follow‐up, all patients enter an unblinded prolonged follow‐up phase with PRN interventions upon high risk. The primary hierarchical composite endpoint for the study includes cardiovascular death, HF events, Kansas City Cardiomyopathy Questionnaire score, and 6‐min walk test distance. Conclusion ALLEVIATE‐HF will evaluate how ICM‐based HF management can impact the outcomes of patients with HF regardless of ejection fraction.
Integrated Antigenic and Nucleic Acid Detection in Single Virions and Extracellular Vesicles with Viral Content (Adv. Healthcare Mater. 3/2025)
Authors: Kim Truc Nguyen, Xilal Y. Rima, Luong T. H. Nguyen, Xinyu Wang, Kwang Joo Kwak, Min Jin Yoon, Hong Li, Chi‐Ling Chiang, Jacob Doon‐Ralls, Kelsey Scherler, Shannon Fallen, Stephanie L. Godfrey, Julie A. Wallick, Setty M. Magaña, Andre F. Palmer, Inyoul Lee, Christopher C. Nunn, Kimberly M. Reeves, Henry G. Kaplan, Jason D. Goldman, James R. Heath, Kai Wang, Preeti Pancholi, L. James Lee, Eduardo Reátegui
Journal: Advanced Healthcare Materials (2025)
Enhancement of Bone Repair in Diabetic Rats with Metformin‐Modified Silicified Collagen Scaffolds (Adv. Healthcare Mater. 3/2025)
Authors: Yi‐Rong Wang, Xiao‐Xia Zhang, Xu‐Xu Chen, Xin‐Hua Yin, Ming Yang, Kuo Jiang, Shi‐Chang Liu
Journal: Advanced Healthcare Materials (2025)
Electrode Droplet Microarray (eDMA): An Impedance Platform for Label‐Free Parallel Monitoring of Cellular Drug Response in Nanoliter Droplets (Adv. Healthcare Mater. 3/2025)
Authors: Meijun Zhou, Joaquin E. Urrutia Gomez, Nikolaj K. Mandsberg, Sida Liu, Sabine Schmidt, Matthias Meier, Pavel A. Levkin, Heinz‐Georg Jahnke, Anna Popova
Journal: Advanced Healthcare Materials (2025)
Bilayer Scaffolds Synergize Immunomodulation and Rejuvenation via Layer‐Specific Release of CK2.1 and the “Exercise Hormone” Lac‐Phe for Enhanced Osteochondral Regeneration (Adv. Healthcare Mater. 3/2025)
Authors: Po‐Lin Liu, Shu‐Hang He, Zhi‐Han Shen, Xu‐Ran Li, Qing‐Song Deng, Zhan‐Ying Wei, Chang‐Ru Zhang, Xiao‐Qiu Dou, Tong‐He Zhu, Helen Dawes, Jian Lu, Shang‐Chun Guo, Shi‐Cong Tao
Journal: Advanced Healthcare Materials (2025)