tbuckley/cabot-search huggingface dataset:
Erratum: First-Line Nivolumab Plus Relatlimab Versus Nivolumab Plus Ipilimumab in Advanced Melanoma: An Indirect Treatment Comparison Using RELATIVITY-047 and CheckMate 067 Trial Data
Authors: Georgina V. Long, Evan J. Lipson, F. Stephen Hodi, Paolo A. Ascierto, James Larkin, Christopher Lao, Jean-Jacques Grob, Flavia Ejzykowicz, Andriy Moshyk, Viviana Garcia-Horton, Zheng-Yi Zhou, Yiqiao Xin, Jennell Palaia, Laura McDonald, Sarah Keidel, Anthony Salvatore, Divya Patel, Leon A. Sakkal, Hussein Tawbi, Dirk Schadendorf
Journal: Journal of Clinical Oncology (2025)
Trend and Provider- and Organizational-Level Factors Associated With Early Palliative Care Billing Among Patients Diagnosed With Distant-Stage Cancers in 2010-2019 in the United States
Authors: Xin Hu, Youngmin Kwon, Changchuan Jiang, Qinjin Fan, Kewei Sylvia Shi, Zhiyuan Jason Zheng, Jingxuan Zhao, Joan L. Warren, K. Robin Yabroff, Xuesong Han
Journal: Journal of Clinical Oncology (2025)

Early integration of specialized palliative care (PC) is recommended by clinical guidelines for advanced-stage cancers, but real-world evidence of its use is limited. We examined the recent trend of early PC billing among Medicare beneficiaries with distant-stage cancers and associated provider- and organization-level factors. Using SEER-Medicare data, we identified Medicare Fee-For-Service beneficiaries 65.5 years and older diagnosed with distant-stage female breast, colorectal, non-small cell lung, small cell lung, pancreatic, or prostate cancers in 2010-2019 with a survival of ≥6 months. Early PC billing was identified by diagnosis codes or hospice and palliative medicine (HPM) specialty codes on outpatient claims within first 3 months of cancer diagnosis or up to hospice admission date, whichever came first. Annual percentages of patients receiving early PC were assessed. We attributed treating physicians and organizations to patients and identified provider- and organization-level factors associated with early PC billing and the between-provider and between-organization variation in early PC billing using multivariable regressions. Among 102,032 patients treated by 18,908 unique physicians, the percentage with early PC billing increased from 1.44% to 10.36% in 2010-2019 (P < .001). Treating physician's early PC referrals in the previous year and organizations' employment of any HPM specialist were associated with 3.01 percentage points (ppts, 95% CI, 2.50 to 3.52) and 4.54 ppts (95% CI, 3.65 to 5.42) higher likelihood of early PC billing. Between-provider variation in early PC was considerable but declined from 51.0% in 2010-2013 to 45.3% in 2017-2019. Similar patterns were found for between-organization variation. Despite growth in early PC billing among patients with distant-stage cancers in 2010-2019, its level remained low. Provider and organizational characteristics such as referral patterns and availability of HPM specialists within the organization may be important drivers for early PC utilization.
Management of Patients With <i>EGFR</i> Exon 20–Mutant Advanced Non–Small Cell Lung Cancer
Authors: Lova Sun, Melina E. Marmarelis, Charu Aggarwal
Journal: Journal of Clinical Oncology (2025)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.
Erratum: Comparison of Standard-of-Care Idecabtagene Vicleucel and Ciltacabtagene Autoleucel in Relapsed/Refractory Multiple Myeloma
Authors: Doris K. Hansen, Lauren C. Peres, Danai Dima, Alicia Richards, Leyla Shune, Aimaz Afrough, Shonali Midha, Binod Dhakal, Mehmet H. Kocoglu, Shebli Atrash, Christopher Ferreri, Omar Castaneda, James A. Davis, Evguenia Bhurtel, Joseph McGuirk, Charlotte Wagner, Radhika Bansal, Patrick Costello, Kinaya Smith, Alex Lieberman-Cribbin, Gabriel De Avila, Sneha Purvey, Hitomi Hosoya, Lekha Mikkilineni, Laura B. Oswald, Gurbakhash Kaur, Oren Pasvolsky, Mahmoud Gaballa, Megan M. Herr, Peter Forsberg, Murali Janakiram, Myo Htut, Sireesha Asoori Maringanti, Nilesh Kalariya, Hamza Hashmi, Ran Reshef, Douglas W. Sborov, Omar Nadeem, Faiz Anwer, Jack Khouri, Shahzad Raza, Djordje Atanackovic, Melissa Alsina, Ciara L. Freeman, Frederick L. Locke, Peter Voorhees, Larry D. Anderson, Shambavi Richard, Thomas Martin, Yi Lin, Krina K. Patel, Surbhi Sidana
Journal: Journal of Clinical Oncology (2025)
Letter to the editor: Comparative efficacy of pharmacologic therapies for MASH in reducing liver fat content: Systematic review and network meta-analysis
Authors: Wang Huang, Hao Sun
Journal: Hepatology (2025)

Department of Gastrointestinal Surgery, Chongqing University Cancer Hospital, Chongqing, 400030, China Correspondence Hao Sun, No. 181 Hanyu Road, Shapingba District, Chongqing 400030, P.R. China. Email: [email protected]
The relationship between mean arterial pressure and terlipressin in hepatorenal syndrome-acute kidney injury reversal: a post hoc analysis
Authors: Giuseppe Cullaro, Andrew S. Allegretti, Kavish R. Patidar, Khurram Jamil, Juan Carlos Q. Velez
Journal: Hepatology (2025)

Terlipressin reverses hepatorenal syndrome-acute kidney injury (HRS-AKI) by increasing mean arterial pressure (MAP). To further characterize the relationship between terlipressin and MAP and their impact on HRS-AKI reversal, we used patient-level data from Phase 3 clinical trials REVERSE and CONFIRM. In this post hoc analysis we employed a linear mixed-effects model to assess terlipressin's impact on MAP, exploring the relationship between MAP, treatment group, and time, incorporating a random intercept for individual patients. Time-dependent Cox models analyzed MAP's role in HRS-AKI reversal. We conducted a mediation analysis to evaluate how time-weighted MAP mediated HRS-AKI reversal. This analysis included 487 patients (60% terlipressin, 40% placebo). At baseline, there were no differences in median MAP between terlipressin and placebo (77 mmHg vs 76 mmHg, p=0.3); the terlipressin group had significantly higher MAPs after randomization (Day 1: 85 mmHg vs 75 mmHg; Day 3: 81 mmHg vs 76 mmHg; all p<0.001). In mixed-effects models, terlipressin was associated with a 6.0 mmHg increase in MAP over placebo occurring on Day 1, with no significant interaction between treatment group and time (p>0.05). In time-dependent Cox models, each 5 mmHg increase in MAP was associated with 1.17x the hazard of HRS-AKI reversal (95% CI 1.11-1.22). In mediation analysis, MAP significantly mediated HRS-AKI reversal, regardless of treatment group (average proportion mediated: 33%, 95% CI 14-76). These data highlight that terlipressin leads to an early, sustained increase in MAP, which is a key pharmacodynamic target for HRS-AKI reversal.
Safety and efficacy of a fitusiran antithrombin-based dose regimen in people with hemophilia A or B: the ATLAS-OLE study
Authors: Guy Young, Kaan Kavakli, Robert Klamroth, Tadashi Matsushita, Flora Peyvandi, Steven W. Pipe, Savita Rangarajan, Ming-Ching Shen, Alok Srivastava, Jing Sun, Huyen A Tran, Chur-Woo You, Bulent Bülent Zülfikar, Laurel A. Menapace, Chuanwu Zhang, Yuqian Shen, Marja Puurunen, Marek Demissie, Gili Kenet
Journal: Blood (2025)

Fitusiran, a subcutaneous investigational siRNA therapeutic, lowers antithrombin (AT) to increase thrombin generation and rebalance hemostasis in people with hemophilia. This phase 3 open-label extension study (ATLAS‑OLE, NCT03754790) evaluated safety and efficacy of antithrombin-based dose regimen (AT-DR) in males ≥ 12 years with severe hemophilia A/B, with/without inhibitors. The original 80 mg monthly (QM) dose regimen (ODR) was optimized to AT-DR targeting AT activity levels 15-35% to mitigate thrombotic risk (starting dose 50 mg once every 2 months [Q2M], individually adjusted to 20 mg Q2M or 20/50/80 mg QM as needed). Primary and secondary endpoints were safety and efficacy, respectively. Integrated safety analyses assessed safety of AT-DR and ODR across all fitusiran studies and integrated efficacy analyses compared efficacy of AT‑DR in ATLAS‑OLE with phase 3 parent study control groups. At interim data cut-off, 213 participants were enrolled on AT-DR (78% on Q2M regimens). Integrated safety analyses of participants receiving AT-DR (n = 286) demonstrated that AT-DR was well tolerated. In ATLAS-OLE, median (interquartile range) observed annualized bleeding rate (ABR) with AT-DR was 3.7 (0.0, 7.5). Integrated efficacy analyses demonstrated superiority of AT-DR over on-demand clotting factor concentrates (CFCs) (71% mean ABR reduction, P < 0.0001), and on-demand bypassing agents (BPAs) (73% mean ABR reduction, P = 0.0006); improvement over BPA prophylaxis (70% mean ABR reduction); and comparable ABR to CFC prophylaxis. Fitusiran AT‑DR was well tolerated and maintained bleed protection with as few as 6 injections per year. This trial was registered at www.clinicaltrials.gov as #NCT03754790.
The role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in managing metabolic dysfunction-associated steatotic liver disease
Authors: Hannes Hagström, Vincent Wai-Sun Wong
Journal: Hepatology (2025)

1Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden 2Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden 3Medical Data Analytic Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China 4State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China Correspondence Hannes Hagström, Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden; Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden. Email: [email protected]
Maintenance Chemotherapy in Patients With High-Risk Rhabdomyosarcoma: Long-Term Survival Analysis of the European <i>Paediatric</i> Soft Tissue Sarcoma Study Group RMS 2005 Trial
Authors: Gianni Bisogno, Julia Chisholm, Raquel Hladun, Gian Luca De Salvo, Florent Guerin, Michela Casanova, Henry Mandeville, Rita Alaggio, Beatrice Coppadoro, Daniel Orbach, Andrea Ferrari, Rick van Rijn, Anne-Sophie Defachelles, Myriam Ben-Arush, Heidi Glosli, Maja Cesen, Johannes H.M. Merks, Véronique Minard-Colin
Journal: Journal of Clinical Oncology (2025)

The European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 trial evaluated maintenance chemotherapy in high-risk rhabdomyosarcoma (RMS). Patients were randomly assigned to either discontinue treatment (standard arm) or receive six 28-day cycles of vinorelbine (25 mg/m2) once per day on days 1, 8, and 15, plus once daily low-dose cyclophosphamide (25 mg/m2; experimental arm). Initial results showed improved overall survival (OS), but disease-free survival (DFS) improvement was not statistically significant. This report presents mature survival outcomes after extended follow-up. Between April 2006 and December 2016, 186 patients were enrolled in the standard arm and 185 in the experimental arm. After a median follow-up of 122.1 months from diagnosis and 114 months from random assignment, recurrence, progression, or death occurred in 103 patients (61 standard arm, 42 experimental arm). The 10-year DFS was 66.5% (95% CI, 59 to 74) in the standard arm versus 77.1% (95% CI, 70.3 to 82.5) in the experimental arm (P = .025). Corresponding 10-year OS rates were 70.8% (95% CI, 63.3 to 77.0) and 82.9% (95% CI, 76.6 to 87.7; P = .0099). Long-term results of the RMS2005 trial confirm the survival benefit of maintenance chemotherapy with vinorelbine and low-dose cyclophosphamide for patients with high-risk RMS.
A synthesis of meta-analyses of immersive virtual reality interventions in pain
Authors: Tessa Rooney, Louise Sharpe, Natalie Winiarski, Jemma Todd, Ben Colagiuri, Dimitri Van Ryckeghem, Geert Crombez, Stefan C Michalski
Journal: Clinical Psychology Review (2025)

The severity and impact of pain can vary greatly, even in individuals with the same physical injury. This variation underscores the need for a variety of treatment strategies in effective pain management. Virtual reality (VR) is an emerging technology that has been used as a treatment in diverse pain populations and for diverse indications. In recent decades, many trials, systematic reviews, and meta-analyses have examined the impact of VR for pain management. While there is some evidence for efficacy in terms of distraction, pre-exposure, and physical therapy; populations, comparators and interventions differ significantly between existing meta-analyses. Thus, the present umbrella review was conducted to determine the overall strength of evidence for all identified populations, comparators, and interventions by synthesising available meta-analyses. Fifty-four meta-analyses reporting on the effect of immersive VR interventions in pain management were identified. Overall, VR interventions appeared efficacious for procedural pain conditions, where used for distraction, and when compared to standard care. While there was some evidence for efficacy in chronic pain populations, this only indicated short-term improvement in pain intensity. We also identified numerous areas for future research wherein the available results were inconclusive, such as examining long term interventions and outcomes for chronic pain populations, reporting of adverse events, and examining the efficacy of VR interventions designed for physical therapy, augmented cognitive therapies, or pre-exposure.
Systematic review and meta-analysis of artificial intelligence in classifying HER2 status in breast cancer immunohistochemistry
Authors: Daniel Arruda Navarro Albuquerque, Matheus Trotta Vianna, Luana Alencar Fernandes Sampaio, Andrei Vasiliu, Eduardo Henrique Cunha Neves Filho
Journal: npj Digital Medicine (2025)

The DESTINY-Breast04 trial has recently demonstrated survival benefits of trastuzumab-deruxtecan (T-DXd) in metastatic breast cancer patients with low Human Epidermal Growth Factor Receptor 2 (HER2) expression. Accurate differentiation of HER2 scores has now become crucial. However, visual immunohistochemistry (IHC) scoring is labour-intensive and prone to high interobserver variability, and artificial intelligence (AI) has emerged as a promising tool in diagnostic medicine. We conducted a diagnostic meta-analysis to evaluate AI's performance in classifying HER2 IHC scores, demonstrating high accuracy in predicting T-DXd eligibility, with a pooled sensitivity of 0.97 [95% CI 0.96-0.98] and specificity of 0.82 [95% CI 0.73-0.88]. Meta-regression revealed better performance with deep learning and patch-based analysis, while performance declined in externally validated and those utilising commercially available algorithms. Our findings indicate that AI holds promising potential in accurately identifying HER2-low patients and excels in distinguishing 2+ and 3+ scores.
Repeatability of fully automated, inline quantitative assessment of myocardial perfusion in patients with suspected coronary artery disease
Authors: Mohamed Elshibly, Charley Budgeon, Simran Shergill, Rachel England, Kelly Parke, Aida Moafi, Hui Xue, Peter Kellman, Gerry P McCann, Jayanth R Arnold
Journal:  (2025)

Recent developments in the field of myocardial perfusion assessment with cardiovascular magnetic resonance (CMR) enable the automated inline quantification of myocardial blood flow (MBF). Previous studies have assessed its repeatability in healthy volunteers. This study assessed the repeatability of this technique in patients with suspected stable coronary artery disease (CAD). Patients with suspected CAD were studied twice on separate days. CMR perfusion imaging was performed at rest and during adenosine stress using a dual-sequence T1-weighted saturation recovery gradient echo sequence. Inline automatic reconstruction and image post-processing were implemented within the Gadgetron software framework, calculating MBF using a blood tissue exchange model. Repeatability of global stress and rest MBF, and myocardial perfusion reserve (MPR) were evaluated using Bland-Altman plots and intraclass correlation coefficients. Fifty-four patients (mean age 67 ± 9 years, 78% male) were studied. The median interval between the two scans was 2 days (IQR 3). There was no significant interstudy difference in global stress MBF (1.46 ± 0.51 mL/min/g vs. 1.51 ± 0.59mLmin/g, P = 0.44), global rest MBF (0.54 ± 0.14 mL/min/g vs. 0.56 ± 0.16 mL/min/g, P = 0.48), or global MPR (2.72 ± 0.80 vs. 2.84 ± 1.13, P = 0.76) between the two scans. Stress MBF, rest MBF, and MPR showed intraclass correlations of 0.60 (95% CI 0.39-0.75), 0.63 (95% CI 0.36-0.77), and 0.39 (95% CI 0.09-0.62), respectively. In patients with suspected CAD, quantitative assessment of myocardial perfusion by fully automated inline myocardial mapping shows moderate repeatability for stress and rest MBF, but poorer repeatability with MPR.
Bispecific antibodies targeting the N-terminal and receptor binding domains potently neutralize SARS-CoV-2 variants of concern
Authors: Adonis A. Rubio, Viren A. Baharani, Bernadeta Dadonaite, Megan Parada, Morgan E. Abernathy, Zijun Wang, Yu E. Lee, Michael R. Eso, Jennie Phung, Israel Ramos, Teresia Chen, Gina El Nesr, Jesse D. Bloom, Paul D. Bieniasz, Michel C. Nussenzweig, Christopher O. Barnes
Journal: Science Translational Medicine (2025)

The ongoing emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that reduce the effectiveness of antibody therapeutics necessitates development of next-generation antibody modalities that are resilient to viral evolution. Here, we characterized amino-terminal domain (NTD)- and receptor binding domain (RBD)-specific monoclonal antibodies previously isolated from coronavirus disease 2019 (COVID-19) convalescent donors for their activity against emergent SARS-CoV-2 VOCs. Among these, the NTD-specific antibody C1596 displayed the greatest breadth of binding to VOCs, with cryo-electron microscopy structural analysis revealing recognition of a distinct NTD epitope outside of the site i antigenic supersite. Given C1596's favorable binding profile, we designed a series of bispecific antibodies (bsAbs), termed CoV2-biRNs, that featured both NTD and RBD specificities. Two of the C1596-inclusive bsAbs, CoV2-biRN5 and CoV2-biRN7, retained potent in vitro neutralization activity against all Omicron variants tested, including XBB.1.5, BA.2.86, and JN.1, contrasting the diminished potency of parental antibodies delivered as monotherapies or as a cocktail. Furthermore, prophylactic delivery of CoV2-biRN5 reduced the viral load within the lungs of K18-hACE2 mice after challenge with SARS-CoV-2 XBB.1.5. In conclusion, NTD-RBD bsAbs offer promising potential for the design of resilient, next-generation antibody therapeutics against SARS-CoV-2 VOCs.
Efficient Hybrid Environment Expression for Look-and-Step Behavior of Bipedal Walking
Authors: chao li, Qingqing Li, Junhang Lai, Xuechao Chen, Zhangguo Yu, Zhihong Jiang
Journal: Cyborg and Bionic Systems (2025)

The look-and-step behavior of biped robots requires quickly extracting planar regions and obstacles with limited computing resources. To this end, this paper proposes an efficient method representing the environment as a hybrid of feasible planar regions and a heightmap. The feasible planar regions are used for footstep planning, preventing the body from hitting obstacles, and the heightmap is used to calculate foot trajectory to avoid foot collision during the swing process. The planar regions are efficiently extracted by leveraging the organized structure of points for nearest neighbor searches. To ensure safe locomotion, these extracted planar regions exclude areas that could cause the robot's body to collide with the environment. The proposed method completes this perception process in 0.16 s per frame using only a central processing unit, making it suitable for look-and-step behavior of biped robots. Experiments conducted in typical artificial scenarios with BHR-7P and BHR-8P demonstrate its efficiency and safety, validating its effectiveness for the look-and-step behavior of biped robots.
Srebf2 mediates successful optic nerve axon regeneration via the mevalonate synthesis pathway
Authors: Mengming Hu, Matthew B. Veldman
Journal: Molecular Neurodegeneration (2025)

Axon regeneration within the mammalian central nervous system is extremely limited. In optic neuropathy conditions like glaucoma, the inability of retinal ganglion cell (RGC) axons to regenerate is a major impediment to functional recovery. In contrast, adult teleost fish such as zebrafish can fully regenerate RGC axons enabling visual recovery from optic nerve (ON) injury making it an ideal model to probe the mechanisms of successful axon regeneration. Laser Capture Microdissection followed by RNA-sequencing (LCM-seq) was used to identify genes and pathways differentially expressed in RGCs during ON regeneration. We validate these findings by in situ hybridization and qRT-PCR. Using loss- and gain-of-function experiments we demonstrate the necessity of srebf2 for efficient ON regeneration and recovery of visual function. Finally, we use LCM-seq coupled with experimental manipulations to identify downstream srebf2 target genes and test the role of hmgcra/b and mevalonate in this process. Statistical analysis was performed using Student's t-test, two-way ANOVA, or repeated measures with appropriate post-hoc tests where applicable. LCM-seq comparison of uninjured versus 3-day post ON injury RGCs identified significant upregulation of the cholesterol synthesis pathway during axon regeneration. The master regulator of this pathway, the transcription factor srebf2, is upregulated throughout the regeneration phase. Chemical inhibition or morpholino-based gene knockdown of srebf2 decreased axon regeneration into the ON and optic tectum and delayed recovery of visual behavior over the course of normal optic nerve regeneration without causing a significant loss of RGCs. Constitutively active srebf2 can fully rescue axon regeneration and visual behavior losses caused by inhibition of endogenous srebf2 but does not accelerate regeneration compared to the control group. LCM-seq confirms the expected regulation of predicted srebf2 target genes after loss- or gain-of-function in vivo. Downstream of srebf2, hmgcra/b knockdown or simvastatin treatment delayed axon regeneration and this effect was rescued by supplemental mevalonate. Mevalonate treatment alone was sufficient to accelerate ON regeneration. These results demonstrate that srebf2 and the downstream mevalonate synthesis pathway plays an important role in regulating efficient axon regeneration in the zebrafish visual system. Involvement of this pathway should be closely examined in failed mammalian ON regeneration.