tbuckley/cabot-search huggingface dataset:
Detecting Suicide Risk Among Pediatric Patients: Screening, Clinical Pathways, and Care
Authors: Lisa M. Horowitz, Nathan J. Lowry, Tesia Shi, Ritika Merai, Maryland Pao, Jeffrey A. Bridge
Journal: Annual Review of Clinical Psychology (2025)

Youth suicide remains a leading cause of death in the United States and is especially pronounced in populations that have been historically underserved. Multipronged public health strategies aimed at addressing suicide may be particularly effective in pediatric medical settings, as most youth who die by suicide have visited a health care provider prior to their death. The finding that most youth suicide decedents have no mental illness diagnosis further underscores the importance of screening. This review highlights universal screening as a strategy to improve detection and management of at-risk youth. We present current research on evidence-based screening tools, clinical pathways to support the feasibility and fidelity of screening, brief interventions for managing positive screens, issues regarding screening and health equity, considerations for diverse populations, current innovations, and future directions for research and clinical practice. Evidence supports universal suicide risk screening through feasible clinical pathways that leverage pediatric health care providers as partners in suicide prevention.
Updated European Association of Urology Guidelines on the Use of Adjuvant Immune Checkpoint Inhibitors and Subsequent Therapy for Renal Cell Carcinoma
Authors: Jens Bedke, Yasmin Abu Ghanem, Laurence Albiges, Stephanie Bonn, Riccardo Campi, Umberto Capitanio, Saeed Dabestani, Milan Hora, Tobias Klatte, Teele Kuusk, Lars Lund, Lorenzo Marconi, Carlotta Palumbo, Geraldine Pignot, Thomas Powles, Maxine Tran, Alessandro Volpe, Axel Bex
Journal: European Urology (2025)
Trends in Fills, Spending, and Prices of Doxepin for Insomnia
Authors: Christopher L. Cai, Aaron S. Kesselheim, Benjamin N. Rome
Journal: JAMA (2025)

This cross-sectional study explores US prescription fills, retail spending, and prices of low-dose doxepin for insomnia and the possible cost savings to patients had they used liquid doxepin, a less expensive formulation.
Is It Really Itching?
Authors: William G. Ondo
Journal: JAMA Neurology (2025)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2025 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Long COVID Prevalence and Associated Activity Limitation in US Children
Authors: Nicole D. Ford, Anjel Vahratian, Caroline Q. Pratt, Anna R. Yousaf, Cria O. Gregory, Sharon Saydah
Journal: JAMA Pediatrics (2025)

This cross-sectional study estimates ever and current experiences of lasting COVID-19 symptoms among children and adolescents by sociodemographic characteristics.
Breaking barriers: Smart vaccine platforms for cancer immunomodulation
Authors: Mohammad Mahmoudi Gomari, Taha Ghantabpour, Nima Pourgholam, Neda Rostami, Stephen M. Hatfield, Farzaneh Namazifar, Shadi Abkhiz, Seyed Sadegh Eslami, Mahsa Ramezanpour, Mahsa Darestanifarahani, Igor Astsaturov, Sidi A. Bencherif
Journal: Cancer Communications (2025)

Abstract Despite significant advancements in cancer treatment, current therapies often fail to completely eradicate malignant cells. This shortfall underscores the urgent need to explore alternative approaches such as cancer vaccines. Leveraging the immune system's natural ability to target and kill cancer cells holds great therapeutic potential. However, the development of cancer vaccines is hindered by several challenges, including low stability, inadequate immune response activation, and the immunosuppressive tumor microenvironment, which limit their efficacy. Recent progress in various fields, such as click chemistry, nanotechnology, exosome engineering, and neoantigen design, offer innovative solutions to these challenges. These achievements have led to the emergence of smart vaccine platforms (SVPs), which integrate protective carriers for messenger ribonucleic acid (mRNA) with functionalization strategies to optimize targeted delivery. Click chemistry further enhances SVP performance by improving the encapsulation of mRNA antigens and facilitating their precise delivery to target cells. This review highlights the latest developments in SVP technologies for cancer therapy, exploring both their opportunities and challenges in advancing these transformative approaches.
Same-Day HPV Vaccination Improves Vaccine Uptake in a Dermatology STI Clinic: A Quality Improvement-Based Model for Improving Vaccination Rates
Authors: Jaclyn Rosenthal Himeles, Costner McKenzie, Sophia Manduca, Katharina S Shaw, Zina Jones, Arielle Nagler, Miriam Keltz Pomeranz, Daniel Gutierrez, John G Zampella
Journal: Journal of the American Academy of Dermatology (2025)
Improvements in moderate-to-severe hidradenitis suppurativa with upadacitinib: Results from a phase 2, randomized, placebo-controlled study
Authors: Lindsay S Ackerman, Bethanee J Schlosser, Tianyu Zhan, Vimal H Prajapati, Scott Fretzin, Hidetoshi Takahashi, Xiaohong Huang, Heidi S Camp, Alexa B Kimball
Journal: Journal of the American Academy of Dermatology (2025)
Number of people treated for hepatitis C virus infection in 2014-2023 and applicable lessons for new HBV and HDV therapies
Authors: Homie A Razavi, Imam Waked, Huma Qureshi, Loreta A Kondili, Ann-Sofi Duberg, Soo Aleman, Junko Tanaka, Jeffrey V Lazarus, Daniel Low-Beer, Zaigham Abbas, Antoine Abou Rached, Alessio Aghemo, Inka Aho, Ulus S Akarca, Said A Al-Busafi, Waleed K Al-Hamoudi, Khalid Al-Naamani, Ahmed Sabry Alaama, Manahil M Aldar, Mohammed Alghamdi, Monica Alonso Gonzalez, Haleema Alserehi, Anil C Anand, Tarik Asselah, Abdullah M Assiri, Kostas Athanasakis, Rita Atugonza, Ziv Ben-Ari, Thomas Berg, Carlos E Brandão-Mello, Ashley S M Brown, Kimberly A Brown, Robert S Brown, Philip Bruggmann, Maurizia R Brunetto, Maria Buti, Hugo Cheinquer, Peer Brehm Christensen, Vladimir Chulanov, Laura E Cisneros Garza, Carla S Coffin, Nicola Coppola, Antonio Craxi, Javier Crespo, Fuqiang Cui, Olav Dalgard, Alethse De La Torre, Victor De Ledinghen, Douglas Dieterich, Sylvia Drazilova, Jean-François Dufour, Mohamed El-Kassas, Mohammed Elbadri, Gamal Esmat, Rafael Esteban Mur, Brandon Eurich, Diana Faini, Paulo R A Ferreira, Robert Flisiak, Sona Frankova, Giovanni B Gaeta, Ivane Gamkrelidze, Edward J Gane, Virginia Garcia, Javier García-Samaniego, Manik Gemilyan, Magnus Gottfredsson, Michael Gschwantler, Ana P M Gurski, Behzad Hajarizadeh, Saeed S Hamid, Angelos Hatzakis, Julian Hercun, Ivana Hockicková, Jee-Fu Huang, Bela Hunyady, Sharon J Hutchinson, Naoko Ishikawa, Kiyohiko Izumi, Antonio Izzi, Martin Janicko, Peter Jarcuska, Agita Jeruma, Asgeir Johannessen, Kulpash S Kaliaskarova, Jia-Horng Kao, Knut B Kielland, Nicolas Kodjoh, Shyamasundaran Kottilil, Pavol Kristian, Paul Y Kwo, Martin Lagging, Hilton Lam, Pablo Lázaro, Mei-Hsuan Lee, Sabela Lens, Valentina Liakina, Young-Suk Lim, Michael Makara, Michael Manns, Casimir Mingiedi Manzengo, Sadik Memon, Maria Cássia Mendes-Correa, Vincenzo Messina, Håvard Midgard, Niamh Murphy, Erkin Musabaev, Marcelo C M Naveira, Helen Nde, Francesco Negro, Nirada Nim, Ponsiano Ocama, Sigurdur Olafsson, Casimir E Omuemu, Javier J Pamplona, Calvin Q Pan, George V Papatheodoridis, Nikolay Pimenov, Hossein Poustchi, Maria Giovanna Quaranta, Alnoor Ramji, Henna Rautiainen, Devin M Razavi-Shearer, Kathryn Razavi-Shearer, Ezequiel Ridruejo, Cielo Y Ríos-Hincapié, Shakhlo Sadirova, Faisal M Sanai, Christoph Sarrazin, Gulya Sarybayeva, Ivan Schréter, Carole Seguin-Devaux, Leandro S Sereno, Gamal Shiha, Josie Smith, Riham Soliman, Mark W Sonderup, C Wendy Spearman, Rudolf E Stauber, Catherine A M Stedman, Vana Sypsa, Frank Tacke, Norah A Terrault, Ieva Tolmane, Berend Van Welzen, Alexis S Voeller, Yasir Waheed, Carolyn Wallace, Robert N Whittaker, Vincent W-S Wong, Magdalena Ydreborg, Kakharman Yesmembetov, Ming-Lung Yu, Stefan Zeuzem, Eli Zuckerman
Journal: Journal of Hepatology (2025)
Stromal cell-derived factor-encapsulated nanoparticles target ischemic myocardium and attenuate myocardial injury via proangiogenic effects
Authors: Shin Yajima, Seung Hyun Lee, Junkai Yang, Matthew D Vergel, Manoj K Manna, Sho Kusadokoro, Yuanjia Zhu, Stefan Elde, Danielle M Mullis, Akshay Venkatesh, Sidarth Ethiraj, Tsuyoshi Ueyama, Hiroyuki Takashima, Samuel E Oh, Chris Huynh, Hanjay Wang, Yasuhiro Shudo, Shigeru Miyagawa, Yoshiki Sawa, Jayakumar Rajadas, Y Joseph Woo
Journal: Biomaterials (2025)
CircRNAs increase during vascular cell differentiation and are biomarkers for vascular disease
Authors: Bernd H Northoff, Andreas Herbst, Catharina Wenk, Lena Weindl, Gabor Gäbel, Andre Brezski, Kathi Zarnack, Alina Küpper, Stefanie Dimmeler, Alessandra Moretti, Karl-Ludwig Laugwitz, Stefan Engelhardt, Lars Maegdefessel, Reinier Boon, Stefanie Doppler, Martina Dreßen, Harald Lahm, Rüdiger Lange, Markus Krane, Knut Krohn, Alexander Kohlmaier, Lesca M Holdt, Daniel Teupser
Journal: Cardiovascular Research (2025)

Abstract Aims The role of circular RNAs (circRNAs) and their regulation in health and disease are poorly understood. Here, we systematically investigated the temporally resolved transcriptomic expression of circRNAs during differentiation of human induced pluripotent stem cells (iPSC) into vascular endothelial cells (EC) and smooth muscle cells (SMC) and explored their potential as biomarkers for human vascular disease. Methods and Results Using high-throughput RNA sequencing and a de novo circRNA detection pipeline, we quantified the daily levels of 31,369 circRNAs in a two-week differentiation trajectory from human stem cells to proliferating mesoderm progenitors to quiescent, differentiated EC and SMC. We detected a significant global increase in RNA circularization, with 397 and 214 circRNAs upregulated &amp;gt; 2 fold (adjusted P &amp;lt; 0.05) in mature EC and SMC, compared with undifferentiated progenitor cells. This global increase in circRNAs was associated with upregulation of host genes and their promoters and a parallel downregulation of splicing factors. Underlying this switch, the proliferation-regulating transcription factor MYC decreased as vascular cells matured, and inhibition of MYC led to downregulation of splicing factors such as SRSF1 and SRSF2 and changes in vascular circRNA levels. Examining the identified circRNAs in arterial tissue samples and in peripheral blood mononuclear cells (PBMC) from patients, we found that circRNA levels decreased in atherosclerotic disease, in contrast to their increase during iPSC maturation into EC and SMC. Using machine learning, we determined that a set of circRNAs derived from COL4A1, COL4A2, HSPG2, and YPEL2 discriminated atherosclerotic from healthy tissue with an AUC of 0.79. CircRNAs from HSPG2 and YPEL2 in blood PBMC samples detected atherosclerosis with an AUC of 0.73. Conclusions Time-resolved transcriptional profiling of linear and circular RNA species revealed that circRNAs provide granular molecular information for disease profiling. The identified circRNAs may serve as blood biomarkers for atherosclerotic vascular disease.
Biology and Management of Acute Myeloid Leukemia With Mutated <scp><i>NPM1</i></scp>
Authors: Evan C. Chen, Shai Shimony, Marlise R. Luskin, Richard M. Stone
Journal: American Journal of Hematology (2025)

ABSTRACT Mutations in nucleophosmin 1 ( NPM1 ) are diseased‐defining genetic alterations encountered in approximately one‐third of cases of acute myeloid leukemia (AML). A mutation in NPM1 confers a more favorable prognosis; however, clinical outcomes of NPM1 –mutated AML ( NPM1 mut AML) are diverse due to the heterogeneity of disease biology, patient characteristics, and treatment received. Research over the last two decades has dramatically expanded our understanding of the biology of NPM1 mut AML and led to the development of new therapeutic approaches and strategies for monitoring measurable residual disease (MRD). Here, we review NPM1 mut AML with a practical focus on the current treatment landscape, the role of MRD in guiding management, and emerging therapies, including menin inhibitors.
Restoring tumor antigenicity activates the “bystander” T cell immune cycle
Authors: Yifan Yang, Qiumin Yu, Haoyu Zhang, Yuchen Liu, Hexuan Wang, Ningyi Yang, Yulian Shi, Wanli Zhang, Zijie Wu, Shitong Huang, Wenbin Xie, Ran Duan, Qiuli Mao, Xupeiyao Shi, Zheng Gao, Xiaoning Wang, Hanlin Guo, Lingxiao Chen, Yi Han, Ximing Li, Liyuan Chen, Siqi Tang, Ying Fan, Wenbing Yao, Hong Tian, Xiangdong Gao
Journal: Journal of Controlled Release (2025)
A novel prostate cancer-specific fluorescent probe based on extracellular vesicles targeting STEAP1 applied in fluorescence guided surgery
Authors: Jian-Xuan Sun, Qi-Dong Xia, Jin-Zhou Xu, Ye An, Si-Yang Ma, Jing-Yu Xu, Jia-Cheng Xiang, Chen-Qian Liu, Meng-Yao Xu, Si-Han Zhang, Yang Luan, Ke Tang, Shao-Gang Wang
Journal: Journal of Controlled Release (2025)
Engineered Bdellovibrio bacteriovorus enhances antibiotic penetration and biofilm eradication
Authors: Ying Tang, Yang Chen, Yong-Dan Qi, Hui-Yi Yan, Wen-An Peng, Yu-Qiang Wang, Qian-Xiao Huang, Xin-Hua Liu, Jing-Jie Ye, Yun Yu, Xian-Zheng Zhang, Cui Huang
Journal: Journal of Controlled Release (2025)
Exercise-based cardiac rehabilitation for patients with coronary artery operation: a systematic review and meta-analysis based on current randomized controlled trials
Authors: Yan Shi, Huiqing Xu, Jige Dong
Journal: International Journal of Surgery (2025)

Background: Currently, exercise-based cardiac rehabilitation (CR) has been given increasing interest for its potentially beneficial effects on the health related quality of life (HRQoL) and outcomes of patients with coronary heart disease (CHD). The aim of this study was to evaluate the effect of exercise-based CR on patients after coronary artery bypass graſt (CABG) and percutaneous coronary interventions (PCI). Methods: We searched PubMed, Embase, Cochrane Library and Web of Science from inception to 1 December 2023 for relevant studies that evaluated the effect of exercise-based CR on patients after CABG and PCI. Our primary outcomes included the mortality, complications, hospital admissions and HRQoL between patients receiving exercise-based CR and usual care. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2 and Stata 12.0. Results: We finally indicated and included 25 randomized controlled trials (RCTs) with 4106 participants for the present analysis. Our pooled results indicated that, compared to usual care, exercise-based CR did not increasing the all-cause (RR 0.84; 95% CI 0.54 ‒ 1.31) and cardiovascular (RR 0.98; 95% CI 0.38 ‒ 2.54) mortality for patients after coronary artery operation. Similarly, exercise-based CR had equal effect on coronary artery complications for patients after coronary artery surgery, including CABG (RR 0.60; 95% CI 0.32 ‒ 1.15) and PCI (RR 0.92; 95% CI 0.55 ‒ 1.54). It was indicated that exercise-based CR significantly reduced the incidence of myocardial infarction (MI) by half with a RR of 0.50 (95% CI 0.28 ‒ 0.90). In addition, exercise-based CR also significantly reduced all-cause hospital admissions with a RR of 0.74 (95% CI 0.62 ‒ 0.88). Compared with usual care, exercise-based CR obviously improved HRQoL of patients after coronary artery operation evaluated with SF-36 summary scores (SMD 0.24; 95% CI 0.11 ‒ 0.38) and SF-36 8 domains (SMD 0.35; 95% CI 0.24 ‒ 0.46) respectively. Conclusions: Our analysis indicated that exercise-based CR had significant effect on the improvement of HRQoL of patients after coronary artery operation without increasing the mortality or incidence of re-intervention with operation.
Effect of parecoxib on postoperative delirium in patients with hyperlipidemia: a randomized, double-blind, single-center, superiority trial
Authors: Zeng Daojun, Tang Yuling, Xu Yingzhe, Ana Kowark, Mark Coburn, Zhao Yue, Zhang Qixin, Zhang Daiying, Peng Tao, Duan Xiaoxia
Journal: International Journal of Surgery (2025)

Background: Hyperlipidemia has been implicated in the higher risk of developing postoperative delirium. Prostaglandin endoperoxide synthase-2 mediates neuroinflammatory processes in postoperative delirium. This study aims to investigate whether preoperative administration of parecoxib is more efficient than a placebo in averting postoperative delirium in patients with hyperlipidemia. Materials and methods: In this randomized, double-blind, superiority trial, participants with hyperlipidemia were randomized in a 1:1 ratio to receive parecoxib (40 mg parecoxib administered intravenously before anesthesia induction) or placebo (normal saline). The primary outcome was postoperative delirium incidence within three days, with a 5.4% difference set as the superiority threshold. Secondary outcomes were cumulative incidences of emergence delirium and prostaglandin endoperoxide synthase-2 levels, inflammatory cell counts, and pain score on postoperative day 1 and postoperative adverse events. Results: This trial conducted between August 2023 and August 2024 at a tertiary hospital in China included 452 adults with hyperlipidemia, with 226 in the parecoxib group and 226 in the placebo group. The incidence of postoperative delirium in the parecoxib group was 13.72%, a reduction of 12.39% compared to the placebo group (hazard ratio, 0.491; 95% confidence interval: 0.318 to 0.759; P &lt; 0.001). The parecoxib group also had a lower incidence of emergence delirium, prostaglandin endoperoxide synthase-2 levels, white blood cell counts and neutrophil, and pain scores on postoperative day 1. The occurrence of adverse events was comparable between the two groups. Prostaglandin endoperoxide synthase-2 expression levels, white blood cell counts, and pain scores mediated the reduction of postoperative delirium incidence by parecoxib. Conclusion: Parecoxib may help in reducing the hyperlipidemia-related postoperative delirium incidence. The effective anti-inflammatory activity of prostaglandin endoperoxide synthase-2 inhibition by parecoxib and postoperative pain control may be important mechanisms for preventing postoperative delirium.
Daily physical activity habits influence surgeons’ stress in the operating room: a prospective cohort study
Authors: Sarah C Skinner, Jake A. Awtry, Léa Pascal, Stéphanie Polazzi, Jean-Christophe Lifante, Antoine Duclos
Journal: International Journal of Surgery (2025)

Background: Exercise training improves heart rate variability, and evidence suggests it can mitigate the detrimental effects of stress. This study aims to evaluate the relationship between surgeons’ physical activity habits and their stress, assessed as heart rate variability, at the start of surgery. Materials and methods: This multispecialty prospective cohort study included surgeons from fourteen cardiac, endocrine, digestive, gynecologic, orthopedic, thoracic, and urologic surgical departments of four university hospitals. Surgeons wore accelerometers 24/7 from 1 November 2020 to 31 December 2021 to quantify the mean daily step counts and daily sedentary time for 7 days prior to each operation. RMSSD, the root mean square of successive differences between normal heart beats, is a heart rate variability (HRV) metric that reflects cardiac vagal tone. We evaluated RMSSD during the first 5 minutes of surgeries performed over five 15-day periods. Data were analyzed using a multivariable linear mixed model with a random effect for surgeons. Results: We analyzed 722 surgeries performed by 37 surgeons (median age = 47 (IQR 42–55); 29 (78.4%) male). On average (SD), surgeons walked 9762 (2447) steps and were sedentary 391 (102) minutes daily. The model showed a positive relationship between steps and cardiac vagal tone, with an increase in lnRMSSD (0.028, 95% CI 0.003 to 0.053, P = 0.026) for every 1000 more steps per day, but not for sedentary behavior. Senior surgeons presented lower lnRMSSD (−0.437, −0.749 to −0.126, P = 0.006), as did surgeons who spent less total time operating over the study period (−0.337, −0.646 to −0.027, P = 0.033), compared to their counterparts. Conclusions: Higher daily step counts the week before surgery were associated with increased cardiac vagal tone, indicating lower stress levels at the beginning of surgery. This relationship highlights the influence of physical activity on surgeons’ stress in the operating room.
Glioma-induced neural functional remodeling in the hand motor cortex: precise mapping with ECoG grids during awake craniotomy—experimental research
Authors: Tao Chang, Yihan Wu, Yuxin Quan, Siliang Chen, Jiawei Liao, Wenyu Zhao, Yu Li, Yuan Fang, Yixuan Zong, Yanhui Liu, Ning Jiang, Qing Mao, Jiayuan He, Yuan Yang
Journal: International Journal of Surgery (2025)

The dilemma of achieving 'onco-functional balance' in gliomas affecting the motor cortex highlights the importance of functionally-guided resection strategies. While accurate mapping of eloquent areas often requires frequent electrical stimulation, this practice can lead to side effects like seizures and postoperative deficits. To enhance safety in functional mapping, we studied how gliomas impact hand movement areas and assessed the effectiveness of cortical electrical activity for functional mapping in this setting. We recruited patients with gliomas affecting the motor cortex and individuals with an unaffected motor cortex for awake craniotomy. During the procedures, electrocorticography (ECoG) grids were employed to record signals under three conditions: resting state, finger movements, and wrist movements. We then quantified the distances from the positively stimulated sites to the specific anatomical landmarks. Additionally, we analyzed the relationship between the ECoG power features and the stimulation responses. The cortical layout for finger activity in the MCG group was more dispersed and overlapped, typically clustering near the central sulcus and Sylvian fissure. The predictive performance of ECoG mapping exhibited significant variability across different frequency bands and clinical scenarios. Specifically, the area under the curve (AUC) for the Non-MCG group during the resting state reached its peak, with a value of 0.802 for Gamma3 (95% CI = 0.729-0.875) and 0.865 for broadband (95% CI = 0.804-0.926). In contrast, the MCG group achieved the highest AUC during wrist movements, with Gamma3 at 0.785 (95% CI = 0.719-0.849) and broadband at 0.824 (95% CI = 0.753-0.890). Gliomas in the motor cortex disrupt the distribution of hand activity, complicating intraoperative functional mapping. As a novel and reliable approach, ECoG technique can complement and guide direct cortical stimulation for precise mapping, potentially reducing its frequency, minimizing the risk of functional deficits, and achieving a balance between maximal tumor resection and neurological preservation.