tbuckley/cabot-search huggingface dataset:
The adverse impact of perioperative body composition abnormalities on outcomes after split liver transplantation: a multicenter retrospective cohort study
Authors: Hao Chen, Zhihang Hu, Qingguo Xu, Chiyu He, Xinyu Yang, Wei Shen, Zuyuan Lin, Huigang Li, Li Zhuang, Jinzhen Cai, Jan Lerut, Shusen Zheng, Di Lu, Xiao Xu
Journal: International Journal of Surgery (2024)

Background: Split liver transplantation increases graft availability, but its safe and effective utilization is insufficiently documented. This study aimed to investigate the association between perioperative body composition abnormalities and outcomes in adult split liver transplantation. Materials and Methods: 240 recipients who underwent split liver transplantation in three centers were enrolled in this retrospective cohort study. Body composition abnormalities including sarcopenia, myosteatosis, visceral obesity, and sarcopenic obesity were evaluated at baseline and one month after surgery using computed tomography. Their impact on outcomes including early allograft dysfunction, early complications, intensive care unit stay, graft regeneration rate and survival was analyzed. Results: Recipients with sarcopenia or myosteatosis had a higher risk of early allograft dysfunction, higher early complication rate, and longer length of intensive care unit stay (all P &lt;0.05), while there was no difference in graft regeneration rate. Recipient and graft survival were significantly worse for recipients with body composition abnormalities (all P &lt;0.05). In multivariable Cox-regression analysis, sarcopenia (hazard ratio=1.765, P =0.015), myosteatosis (hazard ratio=2.066, P =0.002), and visceral obesity (hazard ratio=1.863, P =0.008) were independently associated with shorter overall survival. Piling up of the three factors increased the mortality risk stepwise ( P &lt;0.001). Recipients experienced skeletal muscle loss and muscle fat infiltration one month after surgery. Postoperative worsening sarcopenia (hazard ratio=2.359, P =0.009) and myosteatosis (hazard ratio=1.878, P =0.026) were also identified as independent risk factors for mortality. Conclusion: Sarcopenia, myosteatosis and their progression negatively affect outcomes including early allograft dysfunction, early complications, intensive care unit stay and survival after SLT. Systemic evaluation and dynamic monitoring of body composition are valuable.
Left ventricular strain–volume loops in bicuspid aortic valve disease: new insights in cardiomechanics
Authors: Zoë A Keuning, Thijs P Kerstens, Robert R Zwaan, Daniel J Bowen, Hendrik J Vos, Arie P J van Dijk, Jolien W Roos-Hesselink, Dick H J Thijssen, Alexander Hirsch, Annemien E van den Bosch
Journal:  (2024)

Abstract Aims By combining temporal changes in left ventricular (LV) global longitudinal strain (GLS) with LV volume, LV strain–volume loops can assess cardiac function across the cardiac cycle. This study compared LV strain–volume loops between bicuspid aortic valve (BAV) patients and controls, and investigated the loop’s prognostic value for clinical events. Methods and results From a prospective cohort of congenital heart disease patients, BAV patients were selected and compared with healthy volunteers, who were matched for age and sex at group level. GLS analysis from apical views was used to construct strain–volume loops. Associations with clinical events, i.e. a composite of all-cause mortality, heart failure, arrhythmias, and aortic valve replacement, were assessed by Cox regression. A total of 113 BAV patients were included (median age 32 years, 40% female). BAV patients demonstrated lower Sslope (0.21%/mL, [Q1–Q3: 0.17–0.28] vs. 0.27%/mL [0.24–0.34], P &amp;lt; 0.001) and ESslope (0.19%/mL [0.12–0.25] vs. 0.29%/mL [0.21–0.43], P &amp;lt; 0.001) compared with controls, but also greater uncoupling during early (0.48 ± 1.29 vs. 0.05 ± 1.21, P = 0.04) and late diastole (0.66 ± 1.02 vs. −0.07 ± 1.07, P &amp;lt; 0.001). Median follow-up duration was 9.9 [9.3–10.4] years. Peak aortic jet velocity (HR 1.22, P = 0.03), enlarged left atrium (HR 3.16, P = 0.003), E/e′ ratio (HR 1.17, P = 0.002), GLS (HR 1.16, P = 0.008), and ESslope (HR 0.66, P = 0.04) were associated with the occurrence of clinical events. Conclusion Greater uncoupling and lower systolic and diastolic slopes were observed in BAV patients compared with healthy controls, suggesting presence of altered LV cardiomechanics. Moreover, lower ESslope was associated with clinical events, highlighting the strain–volume loop’s potential as prognostic marker.
Non-invasive liver disease assessment to identify portal hypertension: A systematic review supporting the AASLD Practice Guideline
Authors: Don C. Rockey, Mouaz Alsawas, Andres Duarte-Rojo, Keyur Patel, Deborah Levine, Sumeet K. Asrani, Bashar Hasan, Tarek Nayfeh, Yahya Alsawaf, Samer Saadi, Konstantinos Malandris, M. Hassan Murad, Richard K. Sterling
Journal: Hepatology (2024)

Portal hypertension is a serious complication of cirrhosis, which leads to life-threatening complications. HVPG, a surrogate of portal pressure, is the reference standard test to assess the severity of portal hypertension. However, since HVPG is limited by its invasiveness and availability, noninvasive liver disease assessments to assess portal pressure, especially clinically significant portal hypertension (CSPH), are needed.
Reply to G.B. Mann et al and S. Sorscher
Authors: Reshma Jagsi, Kent A. Griffith, Eleanor E. Harris, Jean L. Wright, Abram Recht, Alphonse G. Taghian, Lucille Lee, Meena S. Moran, William Small, Candice Johnstone, Asal Rahimi, Gary Freedman, Mahvish Muzaffar, Bruce Haffty, Kathleen Horst, Simon N. Powell, Jody Sharp, Michael Sabel, Anne Schott, Mahmoud El-Tamer
Journal: Journal of Clinical Oncology (2024)
Imaging-based non-invasive liver disease assessment for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline
Authors: Andres Duarte-Rojo, Bachir Taouli, Daniel H. Leung, Deborah Levine, Tarek Nayfeh, Bashar Hasan, Yahya Alsawaf, Samer Saadi, Abdul Mounaem Majzoub, Apostolos Manolopoulos, Samir Haffar, Ayca Dundar, M. Hassan Murad, Don C. Rockey, Mouaz Alsawas, Richard K. Sterling
Journal: Hepatology (2024)

Transient elastography (TE), shear wave elastography, and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F).
Comment on ‘Breast-conserving surgery is associated with a lower incidence of suicide among females with breast cancer in the United States: a population-based retrospective cohort study’
Authors: Yueting Li, Pengxu Shi, Tianzhi Zheng
Journal: International Journal of Surgery (2024)

aDepartment of Breast Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Dadong District bDepartment of Bone Surgery, The People's Hospital of Liaoning Province, Shenhe District, Shenyang, Liaoning Province, People's Republic of China Yueting Li and Pengxu Shi, contributed equally to this work. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article Published online ■ ■ *Corresponding author. Address: Department of Breast Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, No. 44 Xiaoheyan Road, Dadong District, Shenyang 110042, Liaoning Province, People's Republic of China. E-mail: [email protected] (Y. Li). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
AASLD Practice Guideline on blood-based non-invasive liver disease assessments of hepatic fibrosis and steatosis
Authors: Richard K. Sterling, Keyur Patel, Andres Duarte-Rojo, Sumeet K. Asrani, Mouaz Alsawas, Jonathan A. Dranoff, Maria Isabel Fiel, M. Hassan Murad, Daniel H. Leung, Deborah Levine, Tamar H. Taddei, Bachir Taouli, Don C. Rockey
Journal: Hepatology (2024)

Sterling, Richard K.; Patel, Keyur; Duarte-Rojo, Andres; Asrani, Sumeet K.; Alsawas, Mouaz; Dranoff, Jonathan A.; Fiel, Maria Isabel; Murad, M. Hassan; Leung, Daniel H.; Levine, Deborah; Taddei, Tamar H.; Taouli, Bachir; Rockey, Don C. Author Information
AASLD Practice Guideline on imaging-based non-invasive liver disease assessments of hepatic fibrosis and steatosis
Authors: Richard K. Sterling, Andres Duarte-Rojo, Keyur Patel, Sumeet K. Asrani, Mouaz Alsawas, Jonathan A. Dranoff, Maria Isabel Fiel, M. Hassan Murad, Daniel H. Leung, Deborah Levine, Tamar H. Taddei, Bachir Taouli, Don C. Rockey
Journal: Hepatology (2024)

Sterling, Richard K.; Duarte-Rojo, Andres; Patel, Keyur; Asrani, Sumeet K.; Alsawas, Mouaz; Dranoff, Jonathan A.; Fiel, Maria Isabel; Murad, M. Hassan; Leung, Daniel H.; Levine, Deborah; Taddei, Tamar H.; Taouli, Bachir; Rockey, Don C. Author Information
Gut bacteria–derived serotonin promotes immune tolerance in early life
Authors: Katherine Z. Sanidad, Stephanie L. Rager, Hannah C. Carrow, Aparna Ananthanarayanan, Ryann Callaghan, Lucy R. Hart, Tingting Li, Purnima Ravisankar, Julia A. Brown, Mohammed Amir, Jenny C. Jin, Alexandria Rose Savage, Ryan Luo, Florencia Mardorsky Rowdo, M. Laura Martin, Randi B. Silver, Chun-Jun Guo, Jan Krumsiek, Naohiro Inohara, Melody Y. Zeng
Journal: Science Immunology (2024)

The gut microbiota promotes immune system development in early life, but the interactions between the gut metabolome and immune cells in the neonatal gut remain largely undefined. Here, we demonstrate that the neonatal gut is uniquely enriched with neurotransmitters, including serotonin, and that specific gut bacteria directly produce serotonin while down-regulating monoamine oxidase A to limit serotonin breakdown. We found that serotonin directly signals to T cells to increase intracellular indole-3-acetaldehdye and inhibit mTOR activation, thereby promoting the differentiation of regulatory T cells, both ex vivo and in vivo in the neonatal intestine. Oral gavage of serotonin into neonatal mice resulted in long-term T cell-mediated antigen-specific immune tolerance toward both dietary antigens and commensal bacteria. Together, our study has uncovered an important role for specific gut bacteria to increase serotonin availability in the neonatal gut and identified a function of gut serotonin in shaping T cell response to dietary antigens and commensal bacteria to promote immune tolerance in early life.
Compliance With NCCN Guidelines for Evaluation and Treatment of Anemia Among Patients With Solid Tumors
Authors: Demetra Hypatia Hufnagel, Lia Manfredi Bos, Alaina Johnson Brown, Lauren Shore Prescott
Journal: Journal of the National Comprehensive Cancer Network (2024)

NCCN Guidelines for Hematopoietic Growth Factors recommend evaluation and treatment of anemia in patients with cancer. However, a paucity of data exists regarding compliance with these recommendations.
Single-cell NAD(H) levels predict clonal lymphocyte expansion dynamics
Authors: Lucien Turner, Tran Ngoc Van Le, Eric Cross, Clemence Queriault, Montana Knight, Krittin Trihemasava, James Davis, Patrick Schaefer, Janet Nguyen, Jimmy Xu, Brian Goldspiel, Elise Hall, Kelly Rome, Michael Scaglione, Joel Eggert, Byron Au-Yeung, Douglas C. Wallace, Clementina Mesaros, Joseph A. Baur, Will Bailis
Journal: Science Immunology (2024)

Adaptive immunity requires the expansion of high-affinity lymphocytes from a heterogeneous pool. Whereas current models explain this through signal transduction, we hypothesized that antigen affinity tunes discrete metabolic pathways to license clonal lymphocyte dynamics. Here, we identify nicotinamide adenine dinucleotide (NAD) biosynthesis as a biochemical hub for the T cell receptor affinity-dependent metabolome. Through this central anabolic role, we found that NAD biosynthesis governs a quiescence exit checkpoint, thereby pacing proliferation. Normalizing cellular NAD(H) likewise normalizes proliferation across affinities, and enhancing NAD biosynthesis permits the expansion of lower affinity clones. Furthermore, single-cell differences in NAD(H) could predict division potential for both T and B cells, before the first division, unmixing proliferative heterogeneity. We believe that this supports a broader paradigm in which complex signaling networks converge on metabolic pathways to control single-cell behavior.
Serum cytokine biosignatures for identification of tuberculosis among HIV-positive inpatients
Authors: Huihua Zhang, LingHua Li, YanXia Liu, Wei Xiao, RuiYao Xu, MengRu Lu, WenBiao Hao, YuChi Gao, Xiaoping Tang, Youchao Dai
Journal: Thorax (2024)

Background Serum cytokines correlate with tuberculosis (TB) progression and are predictors of TB recurrence in people living with HIV. We investigated whether serum cytokine biosignatures could diagnose TB among HIV-positive inpatients. Methods We recruited HIV-positive inpatients with symptoms of TB and measured serum levels of inflammation biomarkers including IL-2, IL-4, IL-6, IL-10, tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). We then built and tested our TB prediction model. Results 236 HIV-positive inpatients were enrolled in the first cohort and all the inflammation biomarkers were significantly higher in participants with microbiologically confirmed TB than those without TB. A binary support vector machine (SVM) model was built, incorporating the data of four biomarkers (IL-6, IL-10, TNF-α and IFN-γ). Efficacy of the SVM model was assessed in training (n=189) and validation (n=47) sets with area under the curve (AUC) of 0.92 (95% CI 0.88 to 0.96) and 0.85 (95% CI 0.72 to 0.97), respectively. In an independent test set (n=110), the SVM model yielded an AUC of 0.85 (95% CI 0.76 to 0.94) with 78% (95% CI 68% to 87%) specificity and 85% (95% CI 66% to 96%) sensitivity. Moreover, the SVM model outperformed interferon-gamma release assay (IGRA) among advanced HIV-positive inpatients irrespective of CD4 + T-cell counts, which may be an alternative approach for identifying Mycobacterium tuberculosis infection among HIV-positive inpatients with negative IGRA. Conclusions The four-cytokine biosignature model successfully identified TB among HIV-positive inpatients. This diagnostic model may be an alternative approach to diagnose TB in advanced HIV-positive inpatients with low CD4 + T-cell counts.
CD22 CAR T cells demonstrate high response rates and safety in pediatric and adult B-ALL: Phase 1b results
Authors: Liora M. Schultz, Nikeshan Jeyakumar, Anne Marijn Kramer, Bita Sahaf, Hrishi Srinagesh, Parveen Shiraz, Neha Agarwal, Mark Hamilton, Courtney Erickson, Ashley Jacobs, Jennifer Moon, Christina Baggott, Sally Arai, Sushma Bharadwaj, Laura J. Johnston, Michaela Liedtke, Robert Lowsky, Everett Meyer, Robert Negrin, Andrew Rezvani, Judy Shizuru, Surbhi Sidana, Emily Egeler, Sharon Mavroukakis, Ramya Tunuguntla, Nikolaos Gkitsas-Long, Aidan Retherford, Annie Kathleen Brown, Anne-Louise Gramstrap-Petersen, Raquel Martin Ibañez, Steven A. Feldman, David B. Miklos, Crystal L. Mackall, Kara L. Davis, Matthew Frank, Sneha Ramakrishna, Lori Muffly
Journal: Leukemia (2024)

Chimeric antigen receptor (CAR) T cells targeting CD22 (CD22-CAR) provide a therapeutic option for patients with CD22
NFKBIE mutations are selected by the tumor microenvironment and contribute to immune escape in chronic lymphocytic leukemia
Authors: Alice Bonato, Supriya Chakraborty, Riccardo Bomben, Giulia Canarutto, Giulia Felician, Claudio Martines, Antonella Zucchetto, Federico Pozzo, Marija Vujovikj, Jerry Polesel, Annalisa Chiarenza, Maria Ilaria Del Principe, Giovanni Del Poeta, Giovanni D’Arena, Roberto Marasca, Agostino Tafuri, Luca Laurenti, Silvano Piazza, Aleksandar J. Dimovski, Valter Gattei, Dimitar G. Efremov
Journal: Leukemia (2024)

Abstract Loss-of-function mutations in NFKBIE, which encodes for the NF-κB inhibitor IκBε, are frequent in chronic lymphocytic leukemia (CLL) and certain other B-cell malignancies and have been associated with accelerated disease progression and inferior responses to chemotherapy. Using in vitro and in vivo murine models and primary patient samples, we now show that NFKBIE-mutated CLL cells are selected by microenvironmental signals that activate the NF-κB pathway and induce alterations within the tumor microenvironment that can allow for immune escape, including expansion of CD8+ T-cells with an exhausted phenotype and increased PD-L1 expression on the malignant B-cells. Consistent with the latter observations, we find increased expression of exhaustion markers on T-cells from patients with NFKBIE-mutated CLL. In addition, we show that NFKBIE-mutated murine CLL cells display selective resistance to ibrutinib and report inferior outcomes to ibrutinib treatment in NFKBIE-mutated CLL patients. These findings suggest that NFKBIE mutations can contribute to CLL progression through multiple mechanisms, including a bidirectional crosstalk with the microenvironment and reduced sensitivity to BTK inhibitor treatment.
Upadacitinib Reduces Crohn’s Disease Symptoms Within the First Week of Induction Therapy
Authors: Jean-Frédéric Colombel, Tadakazu Hisamatsu, Raja Atreya, Francesca Bresso, Lena Thin, Remo Panaccione, Rogério Serafim Parra, Sharanya Ford, Valencia P Remple, Ana Paula Lacerda, Samuel I Anyanwu, Madhuja Mallick, Andrew Garrison, Miguel Regueiro
Journal: Clinical Gastroenterology and Hepatology (2024)

Upadacitinib (UPA), an oral Janus kinase inhibitor, is approved to treat moderately to severely active Crohn's disease (CD). Because symptomatic response is an important initial treatment goal for patients, we evaluated the rapidity of symptomatic improvement in patients with CD receiving UPA 45 mg once daily (UPA45) induction therapy.
Vedolizumab and Ustekinumab Levels in Pregnant Women With Inflammatory Bowel Disease and Infants Exposed In Utero
Authors: Ralley Prentice, Emma Flanagan, Emily K. Wright, Peter R. Gibson, Sam Rosella, Ourania Rosella, Jakob Begun, Yoon-Kyo An, Ian C. Lawrance, Michael A. Kamm, Miles Sparrow, Rimma Goldberg, Lani Prideaux, Sara Vogrin, Katerina V. Kiburg, Alyson L. Ross, Megan Burns, Sally J. Bell
Journal: Clinical Gastroenterology and Hepatology (2024)
Upadacitinib Achieves Clinical and Endoscopic Outcomes in Crohn’s Disease Regardless of Prior Biologic Exposure
Authors: Laurent Peyrin-Biroulet, Remo Panaccione, Edouard Louis, Raja Atreya, David T. Rubin, James O. Lindsay, Jesse Siffledeen, Dana J. Lukin, John Wright, Kenji Watanabe, Sharanya Ford, Valencia P. Remple, Ana P. Lacerda, Elena Dubcenco, Andrew Garrison, Qian Zhou, Sofie Berg, Samuel I. Anyanwu, Stefan Schreiber
Journal: Clinical Gastroenterology and Hepatology (2024)

Upadacitinib, an oral Janus kinase inhibitor, achieved significantly higher rates of clinical remission and endoscopic response vs placebo during induction (U-EXCEL [NCT03345849], U-EXCEED [NCT03345836]) and maintenance (U-ENDURE [NCT03345823]) treatment in patients with moderate-to-severe Crohn's disease. Prior biologic failure is often associated with reduced responses to subsequent therapies. This post hoc analysis assessed upadacitinib efficacy by prior biologic failure status.
Evaluation of two commercial broth microdilution systems for dalbavancin susceptibility testing of methicillin-resistant Staphylococcus aureus and other resistant Gram-positive cocci
Authors: Ilaria Baccani, Alberto Antonelli, Sara Cuffari, Caterina Ferretti, Tommaso Giani, Gian Maria Rossolini
Journal: Clinical Microbiology and Infection (2024)
Prostate-specific Membrane Antigen Positron Emission Tomography–detected Disease Extent and Overall Survival of Patients with High-risk Nonmetastatic Castration-resistant Prostate Cancer: An International Multicenter Retrospective Study
Authors: Manuel Weber, Wolfgang P. Fendler, Aravind S. Ravi Kumar, Jeremie Calais, Johannes Czernin, Harun Ilhan, Fred Saad, Alexander Kretschmer, Turkay Hekimsoy, Sabine D. Brookman-May, Suneel D. Mundle, Eric J. Small, Matthew R. Smith, Paola M. Perez, Thomas A. Hope, Ken Herrmann, Michael S. Hofman, Matthias Eiber, Boris A. Hadaschik
Journal: European Urology (2024)

Previously, we demonstrated that prostate-specific membrane antigen positron emission tomography (PSMA-PET) revealed distant metastases in 109/200 patients (39% distant nodes, 24% bone, and 6% visceral organ) with nonmetastatic castration-resistant prostate cancer (nmCRPC) and high-risk features (International Society of Urological Pathology score ≥4 and/or prostate-specific antigen doubling time ≤10 mo) without metastases by conventional imaging. However, the impact of disease extent determined by PSMA-PET on patient outcomes is unknown. We followed these 200 patients for a median of 43 mo after PSMA-PET and retrospectively assessed the association between patient characteristics, PSMA-PET findings, treatment management, and outcomes using a Kaplan-Meier model and Cox multivariable regressions. Among assessed disease characteristics, polymetastatic disease (five or more distant lesions on PET) was independently associated with shorter overall survival (OS; median 61 mo vs not reached; hazard ratio [95% confidence interval], 1.81 [1.00–3.27]; p = 0.050) and time to new metastases (median 38 vs 60 mo; 1.80 [1.10–2.96]; p = 0.019), and initial pN1 status with shorter OS (55 mo vs not reached; 1.94 [1.12–3.37]; p = 0.019). Following PSMA-PET, locoregional salvage therapies were used most commonly in no/local disease (58%), and androgen receptor signaling inhibitors were used in distant metastatic disease (51%). PSMA-PET provides additional risk stratification for patients with nmCRPC. Polymetastatic disease (five or more distant lesions) is associated with worse outcomes. A novel sensitive imaging technology, called prostate-specific membrane antigen positron emission tomography (PSMA-PET), allows doctors to detect the spread of prostate cancer, known as distant metastases, earlier and more accurately than in the past. In our study, PSMA-PET detected none to many metastases in patients who were considered free of distant metastasis by conventional imaging. These findings predicted outcomes and were used to select appropriate treatment.
Unveiling the hidden players: exploring the role of gut mycobiome in cancer development and treatment dynamics
Authors: Lingxi Li, Xiaowen Huang, Haoyan Chen
Journal: Gut Microbes (2024)

The role of gut fungal species in tumor-related processes remains largely unexplored, with most studies still focusing on fungal infections. This review examines the accumulating evidence suggesting the involvement of commensal and pathogenic fungi in cancer biological process, including oncogenesis, progression, and treatment response. Mechanisms explored include fungal influence on host immunity, secretion of bioactive toxins/metabolites, interaction with bacterial commensals, and migration to other tissues in certain types of cancers. Attempts to utilize fungal molecular signatures for cancer diagnosis and fungal-derived products for treatment are discussed. A few studies highlight fungi's impact on the responsiveness and sensitivity to chemotherapy, radiotherapy, immunotherapy, and fecal microbiota transplant. Given the limited understanding and techniques in fungal research, the studies on gut fungi are still facing great challenges, despite having great potentials.
Dexamethasone Intracanalicular Insert for Clinically Significant Aqueous-Deficient Dry Eye
Authors: Michael X. Lin, Lee Guo, Ian J. Saldanha, Shanna VanCourt, Julia Zeng, Sezen Karakus, Michelle Hessen, Gavin Li, Esen K. Akpek
Journal: Ophthalmology (2024)