tbuckley/cabot-search huggingface dataset:
Commentary on “Epigenome-wide analysis across the development span of pediatric acute lymphoblastic leukemia: backtracking to birth”
Authors: Emma Raitoharju, Saara Marttila
Journal: Molecular Cancer (2025)

Abstract VTRNA2-1 is a polymorphically imprinted locus. The proportion of individuals with a maternally imprinted VTRNA2-1 locus is consistently approximately 75% in populations of European origin, with the remaining circa 25% having a non-methylated VTRNA2-1 locus. Recently, VTRNA2-1 hypermethylation at birth was suggested to be a precursor of paediatric acute lymphoblastic leukaemia with biomarker potential. The results presented by Ghantous et al. [1] allow for an alternative interpretation to what the authors discussed, and we argue that the observed methylation difference at birth is due to an uneven distribution of imprinted and non-methylated individuals among the cases and controls, with all individuals presenting normative physiological VTRNA2-1 methylation levels. In addition, the notable interindividual variation arising from the polymorphic imprinting in VTRNA2-1 methylation levels calls into question the validity of VTRNA2-1 methylation as a biomarker.
Time to nursing home admission and death in people with dementia: systematic review and meta-analysis
Authors: Chiara C Brück, Sanne S Mooldijk, Lieke M Kuiper, Muhammed L Sambou, Silvan Licher, Francesco Mattace-Raso, Frank J Wolters
Journal: BMJ (2025)

Abstract Objective To summarise available evidence on time to nursing home admission and death among people with dementia, and to explore prognostic indicators. Design Systematic review and meta-analysis. Data sources Medline, Embase, Web of Science, Cochrane, and Google Scholar from inception to 4 July 2024. Eligibility criteria for selecting studies Longitudinal studies on survival or nursing home admission in people with dementia. Studies with fewer than 150 participants, recruitment during acute hospital admission, or less than one year of follow-up were excluded. Results 19 307 articles were identified and 261 eligible studies included. 235 reported on survival among 5 553 960 participants and 79 reported on nursing home admission among 352 990 participants. Median survival from diagnosis appeared to be strongly dependent on age, ranging from 8.9 years at mean age 60 for women to 2.2 years at mean age 85 for men. Women overall had shorter survival than men (mean difference 4.1 years (95% confidence interval 2.1 to 6.1)), which was attributable to later age at diagnosis in women. Median survival was 1.2 to 1.4 years longer in Asia than in the US and Europe, and 1.4 years longer for Alzheimer’s disease compared with other types of dementia. Compared with studies before 2000, survival was longer in contemporary clinic based studies (P trend =0.02), but not in community based studies. Taken together, variation in reported clinical characteristics and study methodology explained 51% of heterogeneity in survival. Median time to nursing home admission was 3.3 years (interquartile range 1.9 to 4.0). 13% of people were admitted in the first year after diagnosis, increasing to 57% at five years, but few studies appropriately accounted for competing mortality risk when assessing admission rates. Conclusions The average life expectancy of people with dementia at time of diagnosis ranged from 5.7 years at age 65 to 2.2 at age 85 in men and from 8.0 to 4.5, respectively, in women. About one third of remaining life expectancy was lived in nursing homes, with more than half of people moving to a nursing home within five years after a dementia diagnosis. Prognosis after a dementia diagnosis is highly dependent on personal and clinical characteristics, offering potential for individualised prognostic information and care planning. Systematic review registration PROSPERO CRD42022341507.
Recent Advances in Zeolitic Imidazolate Frameworks as Drug Delivery Systems for Cancer Therapy
Authors: Yuhan Wang, Yixin Tang, Lei Guo, Xi Yang, Shanli Wu, Ying Yue, Caina Xu
Journal: Asian Journal of Pharmaceutical Sciences (2025)

Biological nanotechnologies based on functional nanoplatforms have synergistically catalyzed the emergence of cancer therapies. As a subtype of metal-organic frameworks (MOFs), zeolitic imidazolate frameworks (ZIFs) have exploded in popularity in the field of biomaterials as excellent protective materials with the advantages of conformational flexibility, thermal and chemical stability, and functional controllability. With these superior properties, the applications of ZIF-based materials in combination with various therapies for cancer treatment have grown rapidly in recent years, showing remarkable achievements and great potential. This review elucidates the recent advancements in the use of ZIFs as drug delivery agents for cancer therapy. The structures, synthesis methods, properties, and various modifiers of ZIFs used in oncotherapy are presented. Recent advances in the application of ZIF-based nanoparticles as single or combination tumor treatments are reviewed. Furthermore, the future prospects, potential limitations, and challenges of the application of ZIF-based nanomaterials in cancer treatment are discussed. We except to fully explore the potential of ZIF-based materials to present a clear outline for their application as an effective cancer treatment to help them achieve early clinical application.
ctDNA: A Gateway for Personalized Risk Stratification in Surgically Resectable Hepatocellular Cancer
Authors: David J. Pinato, Pasquale Lombardi, Antonio D'Alessio, Aria Torkpour, Claudia Angela Maria. Fulgenzi, Leonardo Brunetti
Journal: Clinical Cancer Research (2025)

While deemed potentially curative, surgical resection of hepatocellular carcinoma (HCC) is associated with >70% risk of post-operative relapse. Recurrence is uniquely multifactorial in HCC, potentially stemming from metachronous re-occurrence of the original tumor or de novo cancerization. Circulating tumor DNA may improve personalized risk stratification post-resection, a setting where adjuvant immunotherapy has failed to provide survival benefits.
Comprehensive transthoracic echocardiographic evaluation of doxorubicin-induced cardiotoxicity: a multimodal imaging approach in an animal model
Authors: Sibren Haesen, Lisa Steegen, Dorien Deluyker, Virginie Bito
Journal:  (2025)

Abstract Aims Anthracycline-induced cardiotoxicity has high incidence rates and causes significant mortality among cancer survivors. Damage to myocardial tissue leads to left ventricular (LV) dilation with systolic dysfunction, typically assessed through echocardiographic measurement of LV ejection fraction (LVEF) and volumes. Early detection is crucial for improving patient outcomes. We aimed to evaluate cardiotoxicity progression and diagnostic performance of different echocardiographic modalities in an animal model. Methods and results Female Sprague Dawley rats received either intravenous doxorubicin (DOX) injections weekly for 8 weeks (2 mg/kg/week) or saline (control). Transthoracic LV echocardiography was performed before treatment and at 4, 6, and 8 weeks in the treatment course. Two researchers performed and evaluated M-mode, B-mode, and four-dimensional (4D) echocardiography. Bland–Altman plots were created to show the bias and limits of agreement when comparing echocardiographic modalities. Simple linear regression and Pearson correlation were applied to evaluate interobserver variability. Six weeks after the first DOX injection, LVEF, radial LV fractional shortening, LV end-systolic volume, and LV end-diastolic volume were significantly reduced compared with baseline. LV dysfunction and dilation became more pronounced after 8 weeks of DOX treatment. For all parameters, 4D- and M-mode showed the lowest bias and narrowest limits of agreement. The correlation between the researchers’ measurements was strong for most parameters. Conclusion Our rat model of DOX-induced cardiotoxicity demonstrates that volumetric changes are more pronounced. Both 4D- and M-mode imaging techniques proved effective and reliable compared with the standard B-mode approach, with minimal interobserver variability, indicating strong reproducibility.
Gut microbiota in Alzheimer’s disease: Understanding molecular pathways and potential therapeutic perspectives
Authors: Simone Lista, Antonio Munafò, Filippo Caraci, Camillo Imbimbo, Enzo Emanuele, Piercarlo Minoretti, José Pinto-Fraga, María Merino-País, Paula Crespo-Escobar, Susana López-Ortiz, Giovanni Monteleone, Bruno P Imbimbo, Alejandro Santos-Lozano
Journal: Ageing Research Reviews (2025)
Exploring Kidney Oxygenation Responses to Dapagliflozin, Exenatide, and Their Combination in Patients With Type 2 Diabetes and Chronic Kidney Disease: Observations From a Prespecified Pilot Study of a Randomized Crossover Trial
Authors: Ellen M. Apperloo, Hiddo J.L. Heerspink, Annemarie B. van der Aart, Dennis Rouw, Daniël H. van Raalte, Klaas Hoogenberg, Niels Jongs, Marcel H.A. Muskiet
Journal: Diabetes Care (2025)
Monocytic reactive oxygen species-induced T cell apoptosis impairs cellular immune response to SARS-CoV-2 mRNA vaccine
Authors: Sandrine Gimenez, Emna Hamrouni, Sonia André, Morgane Picard, Calayselvy Soundaramourty, Claire Lozano, Thierry Vincent, Tu-Anh Tran, Lucy Kundura, Jérôme Estaquier, Pierre Corbeau
Journal: Journal of Allergy and Clinical Immunology (2025)
Active Components in Internet-Based Cognitive-Behavioral Therapy for Social Anxiety Disorder: A Randomized Full Factorial Trial
Authors: Dajana Šipka, Rodrigo Lopes, Tobias Krieger, Jan Philipp Klein, Thomas Berger
Journal: Psychotherapy and Psychosomatics (2025)

Introduction: Many studies have demonstrated that social anxiety disorder (SAD) can be effectively treated with psychotherapy, particularly cognitive-behavioral therapy (CBT), including internet-based CBT (ICBT). Despite evidence-based treatments, many individuals do not sufficiently benefit from them. Identifying the active components could help improve the effectiveness of SAD treatment. This study tested the effects of four treatment components (psychoeducation, cognitive restructuring, attention training, and exposure) within ICBT for SAD to investigate its active components. Methods: This randomized full factorial trial consisted of four factors (i.e., treatment components) and 16 conditions. A total of 464 adults with a diagnosed SAD were recruited from the community. The primary outcome was SAD symptoms at 8 weeks (post-assessment). Secondary outcomes included SAD diagnosis, SAD symptoms at follow-up (4 months after post), depression and anxiety symptoms, quality of life, client satisfaction, and adverse effects. Results: Conditions including psychoeducation and exposure were significantly more effective in reducing SAD symptoms at post compared to conditions without these components. Conditions including cognitive restructuring and attention training did not show superiority over conditions without them at post. However, all treatment conditions significantly reduced symptoms compared to the condition without a treatment component. At follow-up, the superiority of psychoeducation and exposure was not significant anymore due to the version without the respective components catching up. Conclusion: The findings suggest that while all treatment components of ICBT for SAD are beneficial compared to no treatment, psychoeducation and exposure include specific active components that significantly improve treatment outcomes more quickly in ICBT for SAD.
Phase 1 Trial of TTI-101, a First-in-Class Oral Inhibitor of STAT3 in Patients with Advanced Solid Tumors
Authors: Apostolia M. Tsimberidou, David J. Vining, Sukeshi P. Arora, Sofia de Achaval, Jeffrey Larson, John Kauh, Carrie Cartwright, Rony Avritscher, Imran Alibhai, David J. Tweardy, Ahmed O. Kaseb
Journal: Clinical Cancer Research (2025)

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is essential for the survival and immune sequestration of cancer cells. We conducted a phase 1 study of TTI‑101, a first-in-class, selective small-molecule inhibitor of STAT3, in patients with advanced metastatic cancer. Patients were treated with TTI-101 orally twice daily in 28-day cycles at 4 dose levels (DLs): 3.2 (DL1), 6.4 (DL2), 12.8 (DL3), and 25.6 (DL4) mg/kg/d ("3+3" design). Three TTI-101 formulations were used in a stepwise manner (NCT03195699). Sixty-four patients were treated (median age, 63 years; male sex, 52%; median number of prior therapies, 3). No dose-limiting toxicities or fatal treatment-related adverse events (TRAEs) were observed. Diarrhea (mostly grade 1/2) was the only TRAE observed in ≥30% of subjects. Five patients had grade 3 TRAEs that resolved. TTI-101 showed linear pharmacokinetics from DL1 to DL3, with plateauing at DL3. The recommended phase 2 dose is 12.8 mg/kg/d (DL3). Of the 41 patients who were evaluable for response, 5 (12%) had confirmed partial responses (cPRs) and 17 (41%) had stable disease. Three (18%) of the 17 patients with HCC had a cPR (median time to treatment failure, 10.6 months). Two other cPRs were noted in one patient with ovarian cancer and one with gastric cancer. TTI-101 was well-tolerated. cPRs were observed across tumor types. The anti-tumor activity of TTI-101 monotherapy in patients with advanced, metastatic solid tumors is promising. A phase 2 study of TTI-101 in HCC is currently underway.
<scp>Cardiovascular magnetic resonance</scp>‐estimated pulmonary capillary wedge pressure, congestion markers, and effect of empagliflozin in patients with heart failure with reduced ejection fraction and dysglycaemia (<scp>SUGAR</scp>‐<scp>DM</scp>‐<scp>HF</scp>)
Authors: Joanna Osmanska, Kieran F. Docherty, Colin Berry, Pardeep S. Jhund, Kenneth Mangion, Patrick B. Mark, John J.V. McMurray, Giles Roditi, Naveed Sattar, Mark C. Petrie, Ross T. Campbell, Matthew M.Y. Lee
Journal: European Journal of Heart Failure (2025)

Abstract Aims A cardiovascular magnetic resonance (CMR) approach to non‐invasively estimate left ventricular (LV) filling pressure was recently developed and shown to correlate with invasively measured pulmonary capillary wedge pressure (PCWP). We examined the association between CMR‐estimated PCWP (CMR‐PCWP) and other imaging and biomarker measures of congestion, and the effect of empagliflozin on these, in the SUGAR‐DM‐HF trial (NCT03485092). Methods and results SUGAR‐DM‐HF enrolled 105 patients with heart failure with reduced ejection fraction (HFrEF) and pre‐diabetes or type 2 diabetes who were randomly assigned to empagliflozin 10 mg or placebo once daily for 36 weeks. Transthoracic echocardiography (TTE) was performed at screening and physical examination, lung ultrasound (LUS), CMR, and blood sample collection at baseline and 36 weeks. The mean age of participants was 69 years, mean LV ejection fraction was 33%, and mean CMR‐PCWP was 15.1 mmHg (standard deviation 2.5 mmHg). CMR‐PCWP correlated with log N‐terminal pro‐B‐type natriuretic peptide (Pearson's r = 0.31, p = 0.0012), total number of B‐lines on LUS (Spearman's rho = 0.34, p &lt; 0.001), TTE average E/e' ( r = 0.22, p = 0.03) and CMR ventricular volumes (LV end‐systolic volume: r = 0.51, p &lt; 0.001; right ventricular end‐systolic volume: r = 0.55, p &lt; 0.001). Mean CMR‐PCWP decreased from baseline to 36 weeks by −0.37 (95% confidence interval −0.78 to 0.05) mmHg and −0.17 (−0.69 to 0.36) mmHg in the empagliflozin and placebo groups, respectively; placebo‐corrected difference −0.43 mmHg (−1.09 to 0.23, p = 0.20). Conclusion Cardiovascular magnetic resonance‐estimated PCWP correlates with clinical and ultrasound markers of congestion in HFrEF. CMR not only enables assessment of cardiac structure and function but also provides a non‐invasive assessment of LV filling pressure.
Sacubitril/valsartan versus valsartan initiation in patients naïve to renin–angiotensin system inhibitors: Insights from <scp>PARAGLIDE</scp>‐<scp>HF</scp>
Authors: Nina Nouhravesh, Alexander H. Gunn, Derek Cyr, Adrian F. Hernandez, David A. Morrow, Eric J. Velazquez, Jonathan H. Ward, Samiha Sarwat, Kavita Sharma, Kristin M. Williamson, Randall C. Starling, Serge Lepage, Shelley Zieroth, Scott D. Solomon, Robert J. Mentz
Journal: European Journal of Heart Failure (2025)

Abstract Aims Whether prior treatment with angiotensin‐converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) modifies efficacy and safety of sacubitril/valsartan (Sac/Val) in patients with heart failure (HF) and ejection fraction (EF) &gt;40% is unclear, thus Sac/Val according to ACEi/ARB status at baseline was assessed. Methods and results This was a pre‐specified analysis of Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF (PARAGLIDE‐HF), a double‐blind, randomized controlled trial of Sac/Val versus valsartan, categorizing patients according to baseline ACEi/ARB status. The primary endpoint was time‐averaged proportional change in N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) from baseline through weeks 4 and 8. Secondary analyses included a win‐ratio analysis of the hierarchical outcome of (i) cardiovascular death; (ii) HF hospitalizations; (iii) urgent HF visits; and (iv) time‐averaged proportional change in NT‐proBNP from baseline to weeks 4 and 8, in addition to safety outcomes. Among 466 patients, 107 (23%) were ACEi/ARB naïve at the time of randomization. NT‐proBNP favoured Sac/Val irrespective of ACEi/ARB status (naïve: 0.76, 95% confidence interval [CI] 0.51–1.13; users: 0.88, 95% CI 0.74–1.05; p interaction = 0.52). The win ratio of the hierarchical outcome was 1.13 (95% CI 0.86–1.49) for ACEi/ARB users and 1.38 (95% CI 0.81–2.37) for ACEi/ARB naïve ( p interaction = 0.51). Safety endpoints showed non‐significant interactions by ACEi/ARB status, with odds ratio of 1.79 (95% CI 0.68–4.72) and 0.71 (95% CI 0.29–1.78) for symptomatic hypotension and worsening renal function, respectively for ACEi/ARB naïve. Conclusion In HF with EF &gt;40% stabilized after worsening HF, safety and efficacy were similar irrespective of ACEi/ARB status at baseline, supporting early initiation irrespective of prior ACEi/ARB use.
Targeting KRAS: from metabolic regulation to cancer treatment
Authors: Yanyan Shi, Huiling Zheng, Tianzhen Wang, Shengpu Zhou, Shiqing Zhao, Mo Li, Baoshan Cao
Journal: Molecular Cancer (2025)

The Kirsten rat sarcoma viral oncogene homolog (KRAS) protein plays a key pathogenic role in oncogenesis, cancer progression, and metastasis. Numerous studies have explored the role of metabolic alterations in KRAS-driven cancers, providing a scientific rationale for targeting metabolism in cancer treatment. The development of KRAS-specific inhibitors has also garnered considerable attention, partly due to the challenge of acquired treatment resistance. Here, we review the metabolic reprogramming of glucose, glutamine, and lipids regulated by oncogenic KRAS, with an emphasis on recent insights into the relationship between changes in metabolic mechanisms driven by KRAS mutant and related advances in targeted therapy. We also focus on advances in KRAS inhibitor discovery and related treatment strategies in colorectal, pancreatic, and non-small cell lung cancer, including current clinical trials. Therefore, this review provides an overview of the current understanding of metabolic mechanisms associated with KRAS mutation and related therapeutic strategies, aiming to facilitate the understanding of current challenges in KRAS-driven cancer and to support the investigation of therapeutic strategies.
WS<sub>2</sub>/MHS PdTe<sub>2</sub>/Si Mixed‐Dimensional Heterojunction as Ultra‐Broadband Photodetector for Health and Safety Monitoring
Authors: Cuicui Ling, Chen Rong, Boxuan Men, Jingyao Wang, Jiayi Sun, Tuo Zhang, Lingtan Zhang, Tianchao Guo, Peiheng Zhou, Wenpeng Liu
Journal: Advanced Healthcare Materials (2025)

Abstract Ultra‐broadband photodetectors (UB‐PDs) are essential in medical applications, public safety monitoring, and various other fields. However, developing UB‐PDs covering multiple bands from ultraviolet to medium infrared remains a challenge due to material limitations. Here, a mixed‐dimensional heterojunction composed of 2D WS 2 /monodisperse hexagonal stacking (MHS) 3D PdTe 2 particles on 3D Si is proposed, capable of detecting light from 365 to 9600 nm. The exceptional performance of this photodetector is attributed to MHS PdTe₂ particles, which increase the specific surface area and enhance UV‐to‐NIR absorption of the 2D WS₂ nanofilm. At 980 nm (0 V), the device achieves a responsivity of 7.8 × 10 2 mA W −1 , a detectivity of 2.5 × 10 13 Jones, and a sensitivity of 2.6 × 10 8 cm 2 W −1 . The MHS PdTe₂ layer amplifies the built‐in electric field and enhances heterojunction self‐powered capability. This photodetector exhibits a high switching ratio (10 4 ), a rapid response time (24.14 µs), and a significant photocurrent gain at zero bias. Its application in blood oxygen saturation analysis is demonstrated based on dual‐wavelength photoplethysmography (PPG) at 650 and 905 nm, and infrared perspective imaging at 808 nm. Additionally, the device can differentiate materials based on their transmittance at 9600 nm. This research opens new avenues for the multifunctional use of UB‐PDs.
Transferrin‐Based Bismuth Nanoparticles for Radiotherapy with Immunomodulation Against Orthotopic Glioma
Authors: Xiaoyu Huang, Wei Ge, Shuxian Li, Ruofan Huang, Fu Wang
Journal: Advanced Healthcare Materials (2025)

Abstract Modern radiotherapy frequently employs radiosensitizers for radiation dose deposition and triggers an immunomodulatory effect to enhance tumor destruction. However, developing glioma‐targeted sensitizers remains challenging due to the blood–brain barrier (BBB) and multicomponent instability. This study aims to green‐synthesize transferrin–bismuth nanoparticles (TBNPs) as biosafe radiosensitizers to enhance X‐ray absorption by tumors and stimulate the immune response for glioma therapy. The proposed protein‐based strategy provides TBNPs with BBB‐crossing ability and prevents off‐target toxicity. Cellular experiments following 4 Gy of X‐ray irradiation reveal that TBNPs increase DNA damage in glioma cells and trigger immunomodulation, thereby inducing immunogenic cell death. Furthermore, TBNPs effectively inhibit tumor growth through synergistic radiotherapy and immunotherapy in an orthotopic glioma mouse model. The findings highlight TBNPs as promising radiosensitizers for effective and biosafe radiotherapy with immunomodulation.