tbuckley/cabot-search huggingface dataset:
Early health economic analysis of virtual reality therapy for pain management after surgery
Authors: Tjitske D. Groenveld, Pim van Dorst, Richard P.G. ten Broek, Rianne L.M. van Boekel, Roderick F. van Beek, Simon van der Pol, Harry van Goor
Journal: International Journal of Surgery (2025)

Introduction: Virtual reality (VR) therapy is increasingly used to mitigate pain and anxiety in inpatient settings, with varying effectiveness in postoperative settings. The costs of VR therapy also differ among suppliers. This health-economic analysis aims to inform policy- and decision-makers on the potential impact of VR therapy from a societal perspective based on pain management at discharge and the development of chronic postsurgical pain (CPSP). Methods: A Markov model was developed to simulate 1-year postoperative costs and effects. Using a threshold and headroom analysis, the Incremental Cost-effectiveness Ratio (ICER) was calculated for various VR effectiveness estimates and costs when VR therapy demonstrated cost-effectiveness or cost-savings for postoperative pain management. VR effectiveness was based on opioid use at discharge, affecting the Markov model’s initial distribution and CPSP development. The ICER was calculated from quality-adjusted life-years (QALYs) and costs associated with CPSP. A univariate sensitivity analysis was used to assess parameter uncertainty by varying each parameter by ±20% from the base-case value. Results: VR therapy needs to reduce opioid use at discharge by at least 2.8% to be cost-effective at a willingness-to-pay threshold of €20 000 per QALY and VR costs of €47.48 per patient. To be cost-saving, a reduction of at least 6.5% is needed. The sensitivity analysis indicated that the transition probability from “pain with opioid” to “pain free” in month 2 had the most impact on the ICER. Other significant variables included VR effectiveness and costs, each influencing the ICER by over €5000. Conclusion: The needed 2.8% reduction in opioid use at discharge seems plausible based on literature. However, knowledge gaps regarding the effectiveness of VR, the incidence of chronic postoperative pain, and societal costs of chronic pain need to be addressed, to better understand VR therapy’s role in optimizing postoperative pain management.
Group-based trajectory analysis of postoperative quality of recovery and outcomes after esophagectomy
Authors: Feng Yin, Lan-Tao Li, Xie Wang, Hong-Wei Zhang, Hai Yu
Journal: International Journal of Surgery (2025)

Background: Numerous guidelines for perioperative care in esophagectomy have been developed to promote postoperative quality of recovery (QoR). However, the trajectories and predictors of QoR based on patient-reported outcome after esophagectomy have not been characterized. Methods: This multi-center, prospective, observational study enrolled 206 patients undergoing esophagectomy. Primary analysis was to estimate the trajectories of QoR using group-based trajectory modeling. Results: Four distinct QoR trajectories were identified: poor QoR (38, 18.4%), poor to moderate QoR (83, 40.3%), moderate to good QoR (51, 24.8%), and good QoR (34, 16.5%). Secondary analysis revealed that preoperative nutritional risk (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.03 to 1.23), lower preoperative QoR-15 score (OR, 0.75; 95% CI, 0.61 to 0.91), longer duration of surgery (OR, 1.02; 95% CI, 1.01 to 1.04), and higher area under the curve of postoperative pain scores during coughing (OR, 1.22; 95% CI, 1.09 to 1.36) were significantly associated with the poor QoR trajectory. Conclusions: Notably, four postoperative QoR trajectories were identified and the predictors for poor QoR trajectory included preoperative nutritional risks, lower preoperative QoR-15 scores, longer surgical duration, and higher postoperative pain scores during coughing.
Single-cell and spatial transcriptome analysis revealed cellular heterogeneity of glycosyltransferases in cervical cancer, and identified GALNT3-negative epithelial cells as a protective factor: a retrospective cohort study based on public database
Authors: Junbo Xiao, Ren Niu, Fangchao Zhao
Journal: International Journal of Surgery (2025)

Abstract Cervical cancer (CC) is a common and deadly malignancy among women worldwide, characterized by high mortality and poor prognosis. Glycosyltransferases (GTs) are enzymes that catalyze glycosyl transfer reactions and play significant roles in cancer development and progression. However, their role in cervical cancer remains unclear. Methods: This study combined single-cell RNA sequencing (scRNA-seq) data and spatial transcriptomics (stRNA-seq) to explore the role of GTs in cervical cancer. We utilized comprehensive scoring algorithms to evaluate GT expression, conducted cell communication analysis, and identified differentially expressed GT-related genes in tumor-associated epithelial cells. Functional assays were performed to assess the impact of GALNT3 expression on cervical cancer cell proliferation and invasiveness. Results: Our analysis revealed that GT-related genes are highly enriched in cervical cancer epithelial cells. We identified 11 differentially expressed GT-related genes, including GALNT3, which showed distinct characteristics in epithelial cells. GALNT3-negative epithelial cells were found to be a protective factor for cervical cancer patients, showing a significant negative correlation with tumor-associated macrophages and myeloid-derived suppressor cells. Knockdown or overexpression of GALNT3 significantly affected cell proliferation and invasiveness in C-33A and Caski cell lines. Conclusion: This study highlights the critical role of GTs, particularly GALNT3, in the progression and prognosis of cervical cancer. GALNT3-negative epithelial cell infiltration could be a favorable factor for cervical cancer prognosis, providing new insights for therapeutic strategies targeting GTs in cervical cancer.
Transcutaneous auricular vaguas nerve stimulation promotes adipose tissue browning and mitochondrial integrity by regulating BCAA metabolism in obese rats: an experimental study
Authors: Chen Xin, Shaoyuan Li, Bowen Feng, Lan Sun, Yifei Wang, Jinling Zhang, Yuzhengheng Zhang, Ningyi Zou, Qing Zhou, Peijing Rong
Journal: International Journal of Surgery (2025)

Abstract Transcutaneous auricular vagus nerve stimulation (taVNS) may exert its anti-obesity effects by promoting the browning of adipose tissue with unclear mechanisms. Modulation of branched-chain amino acid (BCAA) metabolism in adipose tissue may play a key role in this process. In this study, six weeks of taVNS significantly reduced body weight gain, body mass index, and the accumulation of inguinal and epididymal white adipose tissue in high-fat diet (HFD)-induced obese rats, with effects comparable to those of orlistat. Notably, taVNS increased both the content and thermogenic activity of interscapular brown adipose tissue (BAT) in obese rats. Infrared thermal imaging confirmed increased BAT thermogenesis, while transmission electron microscopy indicated improved mitochondrial morphology and function. Molecular analysis revealed that taVNS upregulated uncoupling protein 1 (UCP1), the transporter protein solute carrier family 25 member 44 (SLC25A44), and protein phosphatase Mg 2 + /Mn 2 + dependent 1 K (PPM1K) expression while downregulating branched-chain α-ketoacid dehydrogenase kinase (BCKDK), thereby promoting BCAA metabolism and adipose tissue browning. We conclude that the anti-obesity effects of taVNS are closely related to BCAA metabolism in BAT. These findings highlight taVNS as a promising approach for obesity management, though further studies are needed to clarify the neurobiological pathways involved and advance taVNS technology.
Ex vivo lung perfusion with GLP-1R agonist mitigates ischemia/reperfusion injury through pyroptosis modulation in lung transplantation– an experimental study
Authors: Yufei Zhang, Tao Liu, Huaizu Guo, Jianxin Shi, Jun Yang, Shijie Fu, Xufeng Pan, Feng Li, Hai Zhang, Dawei Zhang, Hong Yang, Lulu Zheng, Meng Shi, Wenyong Zhou
Journal: International Journal of Surgery (2025)

Background: Ischemia/reperfusion injury (IRI) presents a significant hurdle in lung transplantation. Our previous research showed that the glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide (Lir) improves lipopolysaccharide-induced acute lung injury in murine models. This study aims to further investigate the lung-protective mechanisms of GLP-1R agonist. Methods: An in vitro hypoxia/reoxygenation (H/R) model with BEAS-2B cells and an in vivo donation after cardiac death (DCD) rat lung transplant model were utilized. Lir was administered using an ex vivo lung perfusion (EVLP) system. Lung function, injury, and pyroptosis mechanisms were assessed. Validation experiments included quantitative reverse transcription PCR, immunoblot analysis, activity assays and proteomic analysis, among others, to evaluate how GLP-1R agonist protect lungs from IRI by modulating pyroptosis, thereby improving lung function and reducing injury. Results: Perfusion of the donor lung with Lir using EVLP improved the function of DCD lungs and mitigated IRI. Bioinformatics analysis and validation experiments provided evidence of increased expression of NOD-like receptors signals and pyroptosis in lung transplantation IRI, which was suppressed by Lir treatment. Further investigations revealed that the thioredoxin-binding protein (TXNIP) played a crucial regulatory role in the pyroptosis of IRI, with the NOD-like receptor family pyrin domain-containing 3 (NLRP3) emerging as a key target. In addition, this study found that Lir promotes GLP-1R-dependent TXNIP ubiquitination and modulates TXNIP mRNA stability via the GLP-1R/miR-17 axis. Conclusion: This study demonstrates, for the first time, that a novel EVLP-based drug delivery approach using GLP-1R agonist can protect lungs from IRI by modulating pyroptosis, thereby improving lung function and reducing injury. The research uncovers a previously unknown mechanism where GLP-1R agonist modulates the protein TXNIP through GLP-1R/miR-17 signaling. These insights underscore the potential of GLP-1R agonists as targeted therapies for primary graft dysfunction in lung transplant recipients, opening new avenues for clinical interventions to improve transplant outcomes.
Traffic Light Labels and Dietary Behavior Change
Authors: Hongwei Liu, Zihan Hu, Qi Song, Jinji Xu, Shupeng Mai, Zhenni Zhu
Journal: JAMA Network Open (2025)

Importance Evidence from everyday dining situations regarding the effects of traffic light labels (TLLs) on dietary improvement remains inconsistent. Objective To evaluate the effects of TLLs on dietary consumption and choices in cafeteria settings. Design, Setting, and Participants This 2-arm, parallel randomized clinical trial was conducted at a company staff cafeteria in Shanghai, China, from September to December 2022. Of 153 adult participants, 76 were randomly assigned to the intervention group and 77 to the control group. Data analysis was conducted from July to October 2024. Intervention The intervention group gained access to TLLs offering a comprehensive rating of added sugar, fat, and sodium for each dish on the lunch menu, while the control group did not. Main Outcomes and Measures Primary outcomes were lunch intake of added sugar, fat, and sodium. Secondary outcomes included the mean traffic light score (calculated based on the number of dishes consumed, with higher scores indicating worse overall dietary choices) and number of green-coded (reaching dietary recommendations), yellow-coded (between the recommendation and mean intake of the Chinese population), and red-coded (above the upper limit of intake) dishes. The primary and secondary outcomes were automatically calculated based on the precollected recipe dataset of the cafeteria and the Chinese food composition database when participants ordered meals using an applet during weekday lunchtime. Weekly median values of these outcomes were used for analyses, which were conducted for the intention-to-treat population. Results Among 153 participants, the mean (SD) age was 32.7 (7.5) years, and 97 (63.4%) were female. At week 12, compared with the control group, the intervention group demonstrated no statistically significant decrease in dietary consumption of added sugar (mean difference, −0.15 [95% CI, −0.75 to 0.46] g), fat (mean difference, −1.54 [95% CI, −6.13 to 3.05] g), or sodium (mean difference, −116.12 [95% CI, −454.78 to 222.54] mg). Similarly, no statistically significant differences were observed in dietary choices based on the mean traffic light score (mean difference, −0.05 [95% CI, −0.12 to 0.03]) or the number of green-coded (odds ratio [OR], 1.15 [95% CI, 0.99-1.32]), yellow-coded (OR, 1.04 [95% CI, 0.90-1.20]), and red-coded (OR, 0.84 [95% CI, 0.57-1.23]) dishes. Conclusions and Relevance In this randomized clinical trial, TLLs indicating added sugar, fat, and sodium ratings on menus failed to improve dietary consumption and choices in a company cafeteria setting. This finding suggests that TLLs on menus may not effectively promote dietary improvement in this setting. Trial Registration Chinese Clinical Trial Registry Identifier: ChiCTR2100051771
Personalized Visual Perceptual Learning Digital Therapy for Visual Field Defects Following Stroke
Authors: Eun Namgung, Bum Joon Kim, Jee Hyun Kwon, Moon-Ku Han, Hahn Young Kim, Jin-Man Jung, Jae Guk Kim, Kwang-Yeol Park, Jaseong Koo, Keun-Sik Hong, Kyung-Ho Yu, A-Hyun Cho, Jun Young Chang, Sun U. Kwon, Byung Joo Lee, Ha-Gyun Choi, Moonju Cho, Gyeong-Moon Kim, Dong-Wha Kang
Journal: JAMA Network Open (2025)

Importance Effective treatments for restoring visual field defects (VFDs) in patients with stroke necessitate validation through randomized clinical trials. Objective To evaluate the efficacy and safety of a personalized digital therapeutic based on visual perceptual learning for treating poststroke VFDs. Design, Setting, and Participants A multicenter randomized clinical trial was conducted from October 19, 2022, to November 8, 2023, at 12 hospitals in South Korea. The study included poststroke outpatients 19 years or older with persistent VFDs (&amp;amp;gt;3 months after stroke) and neuroimaging-confirmed stroke lesions in the visual pathway. Intervention The training group underwent personalized visual discrimination tasks (orientation and rotation) using a mobile virtual reality headset 5 days a week for 12 weeks, with 360 trials per day. The control group received no intervention. Main Outcome and Measures The primary outcome was improved visual areas (defined as sensitivity increased by ≥6 decibels [dB] during 12 weeks) assessed using Humphrey visual field tests at baseline and 12 weeks. Results Of 93 enrolled stroke outpatients with VFDs, 82 were included in the final analysis (41 in the intervention group and 41 in the control group; median [IQR] age, 52 [42-65] years; 57 male [69.5%]). As primary measures, the training group, with a high adherence rate, showed significantly greater improvement (sensitivity increased by ≥6 dB) in the whole field (median difference, 72 [95% CI, 36-108] degrees squared; P = .003; mean [SD], 194.1 [197.3] vs 82.5 [95.0] degrees squared) and defective hemifield (median difference, 72 [95% CI, 36-108] degrees squared; P = .002; mean [SD], 158.9 [159.0] vs 72.0 [91.4] degrees squared) compared with the control group. As secondary measures, mean (SD) Humphrey visual field test scores improved after 12 weeks in the training group (whole field: 0.72 [1.55] dB; P = .005; defective hemifield: 1.20 [2.08] dB; P &amp;amp;lt; .001) but not in the control group (whole field: 0.03 [1.30] dB; P = .88; defective hemifield: 0.06 [1.85] dB; P = .84). Conclusions and Relevance In this randomized clinical trial of a digital therapeutic for chronic poststroke VFDs, the visual perceptual learning–based training demonstrated significant improvements in the whole field and defective hemifield. Trial Registration ClinicalTrials.gov Identifier: NCT05525949
Endothelia-targeting eye drops deliver a STING inhibitor to effectively reduce retinal neovascularization in ischemic retinopathy
Authors: Siying Wen, Xuemin He, Jiachen Wang, Zheyao Wen, Heying Ai, Mengyin Cai, Yi Yang, Hejun Li, Shasha Li, Guojun Shi, Aimin Xu, Zecong Xiao, Xintao Shuai, Yanming Chen
Journal: Biomaterials (2025)
Safety Planning Interventions for Suicide Prevention in Children and Adolescents
Authors: Carly Albaum, Samantha H. Irwin, Jessica Muha, Anett Schumacher, Sherinne Clarissa, Yaron Finkelstein, Jeffrey A. Bridge, Daphne J. Korczak
Journal: JAMA Pediatrics (2025)

Importance Suicide ideation and suicide-related behavior (eg, suicide attempts) are increasingly prevalent among adolescents. Evidence supports safety planning interventions for adults at risk for suicide; the effectiveness for adolescents is unknown. Objective To evaluate the effectiveness of safety planning as a standalone intervention for adolescents with suicide ideation and/or suicide-related behavior. Data Sources Ovid MEDLINE, OVID PsycINFO, EBSCO CINAHL, and Scopus (Elsevier) from January 1, 2008, to March 26, 2024. Study Selection Included were all studies that examined safety planning as a standalone treatment for adolescents and assessed suicide ideation, suicide-related behavior including suicide attempts, and/or re-presentations to health care settings. Included were peer-reviewed studies evaluating intervention effectiveness or efficacy, with or without a control condition. Nonempirical studies, gray literature, and studies not available in English were excluded. Data Extraction and Synthesis Two reviewers performed data extraction and quality assessment independently. Meta-analytic random-effects models were used to calculate effect size estimates. Risk of bias was assessed using Joanna Briggs Institute Critical Appraisal tools. Main Outcomes and Measures The outcomes planned for extraction were suicide ideation, suicide-related behavior (eg, attempts; planning with intent to act), and re-presentation to health care settings (ie, emergency department visit; inpatient admission) during the follow-up period. Results Ten studies including 1002 adolescents (mean [SD] age, 15.0 [0.4] years; 76.0% female) met inclusion criteria; 5 were included (n = 619) in the meta-analysis. There was no significant association between safety planning interventions and suicide ideation (Hedges g = 0.11; 95% CI, 0.01-0.21), behavior (Hedges g = −0.09; 95% CI, −0.20 to 0.02), attempts (risk ratio [RR], 1.03; 95% CI, 0.12-8.88) or suicide-related re-presentation (RR, 0.99; 95% CI, 0.29-3.35) at follow-up. Risk of bias for the majority of studies was moderate to high. Conclusions and Relevance This systematic review and meta-analysis found limited research evaluating safety planning with adolescents. Although available data do not support safety planning as a standalone treatment for reducing suicide-related outcomes among children and adolescents, well-powered studies are needed to address this common intervention for suicide prevention in adolescents.
The CD70-CD27 axis in cancer immunotherapy: Predictive biomarker and therapeutic target
Authors: Ikuan Sam, Nadine Ben Hamouda, Marina Alkatrib, Cecile Gonnin, Peter J. Siska, Stephane Oudard, Céleste Lebbé, Eric Tartour
Journal: Clinical Cancer Research (2025)

Abstract The CD27-CD70 interaction is recognized as a positive costimulatory pathway for T cell priming and expansion. However, recent studies showed that chronic CD27-CD70 interaction in cancer can lead to apoptosis of T cells, rendering them dysfunctional. CD70 is expressed not only by hematological tumors but also by solid tumor cells. This expression is regulated by hypoxia-induced factor (HIF), Epstein-Barr virus (EBV) infection, and epithelial-mesenchymal transition. CD27 expression on intratumoral T cells identifies exhausted and dysfunctional T cells, as well as regulatory T cells with enhanced immunosuppressive activity. Given the preferential expression of CD70 on certain tumor cells, several therapeutic approaches including antibody-drug conjugate, anti-CD70 CAR T cells, and anti-CD70 monoclonal antibodies (mAb), have been investigated in various preclinical models and clinical trials. To date, the most significant clinical results are observed in hematological malignancies. However, no therapeutic tools specifically targeting the deleterious CD27-CD70 interaction have been developed. Most CD70-targeting mAb also deplete other CD70-expressing cells, such as activated T cells. Interestingly, chronic CD27-CD70 interaction results in the release of detectable soluble CD27 in patient plasma. The presence of high levels of soluble CD27 in plasma correlates with resistance to anti-PD-(L)1 in renal cancer, melanoma, and non-small cell lung cancer. Conversely, the absence of a predictive impact soluble CD27 in melanoma patients treated with the more toxic combination of anti-PD-1 and anti-CTLA-4 may justify therapeutic escalation with this regimen. Thus, the CD27-CD70 axis may serve as both a potential biomarker to guide the choice of immunotherapy and a novel clinical target.
Tiotropium Initiation and Dementia Risk in Chronic Obstructive Pulmonary Disease
Authors: Che-Yuan Wu, Tetyana Kendzerska, Christa Wang, Lisa Y. Xiong, Jodi D. Edwards, Peter P. Liu, Refik Saskin, Walter Swardfager
Journal: JAMA Internal Medicine (2025)

Importance Long-acting muscarinic antagonists (LAMAs), such as tiotropium, are inhaled anticholinergic bronchodilators. However, there is limited clinical evidence examining whether LAMAs may have clinically meaningful central anticholinergic effects, such as increased dementia risk. Objective To determine the association between tiotropium initiation and dementia risk in older adults with chronic obstructive pulmonary disease (COPD). Design, Setting, and Participants This population-based, active-comparator, new-user cohort study used linkable administrative databases from Ontario, Canada, with a target trial emulation framework. The cohort included new users of tiotropium monotherapy or a long-acting β 2 -agonist plus inhaled corticosteroid (LABA-ICS) who were 66 years or older with COPD and without dementia, from September 4, 2004, to February 29, 2012. The follow-up period was up to 10 years from treatment initiation. Analyses were conducted from May 13, 2024, to March 6, 2025. Exposures Tiotropium monotherapy initiators were compared with LABA-ICS initiators. The primary analysis used an intention-to-treat exposure definition. Main Outcomes and Measures Incident dementia was determined using a validated algorithm. A 1-year lag time was implemented to mitigate reverse causality and to account for disease latency. Cause-specific hazard ratios (HRs) with death as a competing risk were obtained from Cox models with propensity score fine stratification weights. Weighted incidence rate differences (IRDs) per 1000 person-years were calculated. Results Among 30 960 tiotropium monotherapy initiators and 19 530 LABA-ICS initiators, the mean (SD) age was 75.1 (6.7) years and 46.7% were female. Over a median (IQR) follow-up period of 7.59 (3.91-10.0) years from treatment initiation, tiotropium monotherapy vs LABA-ICS initiation was associated with a small increase in dementia risk per 1000 person-years (incidence rates, 29.6 [95% CI, 28.8-30.4] vs 27.4 [95% CI, 26.4-28.3]; IRD, 2.3 [95% CI, 1.0-3.5]; HR, 1.09 [95% CI, 1.04-1.14]). The secondary as-treated analysis showed no significant association per 1000 person-years (incidence rates, 24.1 [95% CI, 22.2-26.0] vs 21.4 [95% CI, 18.5-24.3]; IRD, 2.7 [95% CI, −0.8 to 6.1]; HR, 1.11 [95% CI, 0.93-1.32]). Conclusions and Relevance In this cohort study, among older adults with COPD, the small absolute rate increase in incident dementia associated with tiotropium monotherapy vs LABA-ICS was of questionable clinical importance, particularly when weighed against the established clinical benefits of tiotropium.