tbuckley/cabot-search huggingface dataset:
Machine Learning Analysis of Whole‐Blood Transcriptomics Data in Rheumatoid Arthritis Patients Treated with Adalimumab Identifies Predictive Biomarkers of Response
Authors: Chuan Fu Yap, Nisha Nair, Ann W Morgan, John D Isaacs, Anthony G Wilson, Kimme Hyrich, Guillermo Barturen, María Riva‐Torrubia, Marta Gut, Ivo Gut, Marta E. Alarcón Riquelme, Anne Barton, Darren Plant
Journal: Arthritis & Rheumatology (2025)

Objectives Tumor necrosis factor inhibitors (TNFi) have significantly improved rheumatoid arthritis (RA) management, yet variability in patient response remains a substantial challenge, with approximately 40% of patients discontinuing TNFi due to non‐response or adverse effects. This study aimed to identify biomarkers predictive of adalimumab treatment response using whole blood transcriptomics, leveraging machine learning models for data mining followed by targeted statistical analysis. Methods A cohort of RA patients starting TNFi therapy (n=100) was assessed for treatment response at 6 months, with RNA sequencing performed on baseline (pre‐treatment) and 3‐month follow‐up samples. Machine learning classifiers were built to identify predictive biomarkers for treatment outcomes. This was followed by a network analysis on the biomarkers to elucidate the most influential biomarker, which was subsequently confirmed through survival analysis. Results Differential gene expression analysis in 97 samples passing QC identified 84 genes associated with treatment response. Random Forest classifiers achieved high predictive accuracy with AUCs up to 0.86, identifying genes contributing to treatment outcomes. Network analysis further elucidated gene interactions, highlighting MZB1 as a novel biomarker not captured by machine learning alone. MZB1's role in B cell development and antibody production was associated with anti‐drug antibody formation, impacting treatment efficacy. Conclusion This study advances the understanding of transcriptomic alterations in RA treatment and enhancing our understanding of treatment response mechanisms. Whilst the gene signatures identified require independent replication, the study serves as a starting point to pave the way for personalized therapeutic strategies in patients commencing TNFi therapy in RA.
Anti‐<scp>KIT</scp> Barzolvolimab for Chronic Spontaneous Urticaria
Authors: Marcus Maurer, Martin Metz, John Anderson, Neetu Talreja, Diane Young, Elizabeth Crowley, Margo Heath‐Chiozzi, Rick Ma, Elsa Paradise, Thomas Hawthorne, Diego Alvarado, Jonathan A. Bernstein
Journal: Allergy (2025)

ABSTRACT Background Chronic spontaneous urticaria (CSU) is characterized by mast cell (MC)‐mediated wheals and/or angioedema without identifiable triggers and is driven by MC activation. Barzolvolimab—a monoclonal anti‐KIT antibody—depletes MCs by inhibiting activation of KIT by stem cell factor. We evaluated multiple ascending doses in patients with CSU. Methods Phase 1b double‐blind placebo‐controlled trial (NCT04538794) in adults with moderate‐to‐severe (urticaria activity score over 7 days [UAS7] ≥ 16) antihistamine–refractory CSU treated with intravenous barzolvolimab for 12 weeks with a 12‐week follow‐up in four sequentially enrolled cohorts (randomized 4:1 barzolvolimab:placebo): 0.5 mg/kg, Q4W ( n = 9); 1.5 mg/kg, Q4W ( n = 8); 3 mg/kg, Q8W ( n = 9); and 4.5 mg/kg, Q8W ( n = 9). Primary and secondary objectives were safety and disease activity (UAS7 and urticaria control test [UCT]). Pharmacokinetics and pharmacodynamics were assessed. Results Patients had high mean (range) baseline CSU activity, with UAS7 = 29.6 (16.3–42.0) for barzolvolimab‐treated, UAS7 = 35.8 (19.0–42.0) for placebo‐treated, and 44% prior omalizumab use. Multiple doses of barzolvolimab were well tolerated. Hair color change was the commonest adverse event in barzolvolimab‐treated patients. Across barzolvolimab doses, rapid symptom reduction within 1 week was observed and sustained during 12 weeks; 71% of patients achieved a well‐controlled (UAS7 ≤ 6) response and 57% a complete response (UAS7 = 0). Additionally, 77% of barzolvolimab‐treated patients achieved a well‐controlled response (UCT ≥ 12) and 43% a complete response (UCT = 16) by Week 12. The kinetics of disease activity paralleled tryptase suppression, indicative of MC inhibition. Patients with and without prior omalizumab treatment responded similarly. Conclusions This study supports barzolvolimab as a promising treatment for CSU.
Polymer-assisted PD-L1 degradation and targeted photodynamic therapy synergize to suppress immunodeficient tumors
Authors: Changyong Guo, Shipeng He, Huaxing Shen, Wei Cong, Jinqiu Li, Yajing Ji, Wenjing Huang, Fei Gao, Honggang Hu
Journal: Acta Pharmaceutica Sinica B (2025)
Reply
Authors: Maria Chiara Gelmi, Laurien E Houtzagers, Annemijn P A Wierenga, Mieke Versluis, Bastiaan T Heijmans, Gregorius P M Luyten, Peter de Knijff, Marije Te Raa, Rick H de Leeuw, Martine J Jager
Journal: Ophthalmology (2025)
Streptococcus pneumoniae serotype 38 emerges as one of the dominant serotypes causing invasive pneumococcal disease in Germany and Poland, but not in the Netherlands
Authors: K. Hajji, I. Wróbel-Pawelczyk, J. van Veldhuizen, K. Maruhn, W.R. Miellet, R. Mariman, A. Steens, N.M. van Sorge, K. Trzciński, M.P.G. van der Linden, A. Skoczyńska, L.J. Visser
Journal: Journal of Infection (2025)
Targeted Delivery of Apelin Using a Novel Extracellular Vesicle Platform for Pulmonary Arterial Hypertension Treatment
Authors: Jihong Kim, Yong-Soon Choi, Jaehyun Kim, Riajul Wahab, Yeji Lee, Hyemin Joo, Seryoung Park, Inkyu Lee, Seong A. Kim, Yeong Ha Hwang, Seongeon Cho, Jiyoong Goo, Cherlhyun Jeong, Seung-Yoon Park, Gi Beom Kim, Taslim A. Al-Hilal, Gi-Hoon Nam, In-San Kim
Journal: Biomaterials (2025)
Dual Inhibition of Oxidative Phosphorylation and Glycolysis Using a Hyaluronic Acid Nanoparticle NOX Inhibitor Enhanced Response to Radiotherapy in Colorectal Cancer
Authors: Lumeng Zhang, Tongrui Liu, Minglong Chen, Shi Gao, Charles A. Staley, Lily Yang, Lei Zhu
Journal: Biomaterials (2025)
Screening scaffold proteins for improved functional delivery of luminal proteins using engineered extracellular vesicles
Authors: Zheyu Niu, Houze Zhou, Wenyi Zheng, Oliver G Hayes, Vicky W Q Hou, André Görgens, Samantha Roudi, Guannan Zhou, Rim Jawad Wiklander, Taras Sych, Erdinc Sezgin, Joel Z Nordin, Ying Zhao, Xiuming Liang, Samir E L Andaloussi
Journal: Journal of Controlled Release (2025)
ISCL/EORTC-CLTG/USCLC Recommendations for the Diagnosis, Staging and Treatment of Early-stage Paediatric Mycosis Fungoides - a Modified Delphi Consensus. Part 2: Treatment
Authors: Emmilia Hodak, Iris Amitay-Laish, Martine Bagot, Maxime Battistella, Dan Ben Amitai, Antonio Cozzio, Madeleine Duvic, Katalin Ferenczi, Francine Foss, Larisa Geskin, Emmanuella Guenova, Youn H Kim, Mark Jean-Aan Koh, Montserrat Molgó, Arti Nanda, Jan Nicolay, Tim Niehues, Pablo Ortiz-Romero, Amra Osmancevic, Evangelia Papadavid, Jong Bin Park, Pietro Quaglino, José A Sanches, Julia Scarisbrick, Maria Luisa Sulis, Rudolf Stadler, Franz Trautinger, Maarten Vermeer, Iris Wohlmuth, John A Zic, Chalid Assaf
Journal: British Journal of Dermatology (2025)

Abstract Background Paediatric mycosis fungoides (MF) is characterized by early-stage disease, a strikingly indolent course and high rates of unusual variants. Despite these clinical pecularities and the special treatment-related safety considerations in children and adolescents, detailed published data on treatments of paediatric MF are scarce, and management is currently based primarily on standard practice in adults. Objectives To develop therapeutic recommendations on behalf of the 3 largest societies for cutaneous lymphoma societies, ISCL, EORTC, and USCLC, specifically designed for MF in children and adolescents. Methods The guideline was developed through an international expert consensus process and in accordance with the EQUATOR Network’s recommendations for guideline development. A modified Delphi process was conducted, using questionnaires covering treatment modalities that are recommended by international guidelines for adult MF. Two rounds of expert feedback were conducted, with an additional one hybrid consensus meeting. Results Therapeutic recommendations were formulated focusing mainly on early-stage disease. These recommendations take into account disease-specific parameters with therapeutic implications, including the specific stage of the disease, the type of the lesion, and the presence of the folliculotropic variant, which is commonly observed in the paediatric age group. Patient-related factors, including safety concerns specific to this young age group, were also addressed. Conclusion This ISCL/EORTC/USCLC guideline provides up-to-date age-specific practical recommendations for the treatment of MF in children and adolescents
Postoperative radiotherapy in subtotally-resected recurrent WHO grade 1 meningiomas with intermediate-/high-risk molecular profiles
Authors: Maximilian Y Deng, Sybren L N Maas, Günes Anil, Philipp Sievers, Jonathan Lischalk, Eric Zhao, Sophie Rauh, Inga Jessen, Tanja Eichkorn, Sebastian Regnery, Lukas Bauer, Thomas Held, Philipp Hoegen-Sassmannshausen, Katharina Seidensaal, Juliane Hörner-Rieber, Stefan M Pfister, Antje Wick, Wolfgang Wick, Andreas von Deimling, Klaus Herfarth, Christine Jungk, Sandro M Krieg, Jürgen Debus, Felix Sahm, Laila König
Journal: Neuro-Oncology (2025)

Abstract Background Meningiomas represent the most common primary intracranial tumors in adults, with WHO grade 1 typically associated with favorable outcomes following gross total resection (GTR). Methods This retrospective study included patients with CNS WHO grade 1 meningioma and available DNA methylation profiles (n=210). Clinical tumor characteristics and treatment course (e.g., surgical resection, extent of resection, radiotherapy) were evaluated. Integrated Scores (InS) were calculated based on methylation family using the DKFZ brain tumor classifier, CNS WHO grading, and chromosomal losses, categorized as low, intermediate, or high. Survival analyses employed Kaplan-Meier and Cox regression methods, with local progression-free survival defined as primary endpoint. Results In newly diagnosed cases, GTR was associated with a 93.0% 3-year progression-free survival (PFS), compared to 69.3% following subtotal resection (STR). Stratification by IntS showed that patients in the IntS-low group had superior outcomes: 3-y PFS of 93.4 after GTR and 77.4% after STR. In contrast, patients with IntS-intermediate/high profiles showed significantly worse outcomes, with PFS of 85.9% after GTR and 40.0% after STR. Following tumor recurrence, particularly those with IntS-intermediate/high, postoperative radiotherapy (RT) after STR may improve 3-year PFS to 88.9%, compared to much lower PFS rates in newly diagnosed cases managed without adjuvant RT after STR (3-year PFS: 40.0%). Conclusion Our findings highlight the combined impact of both the extent of resection (EoR) and molecular risk profile on prognosis in newly diagnosed cases. While conservative management is feasible in lower-risk primary cases, recurrent or higher-risk patients may benefit from early postoperative RT.
Polyamine acetylation mediates crosstalk between cancer cells and myeloid cells to promote mesenchymal/plurimetabolic states in glioblastoma
Authors: Ayush B Rana, Timothy M Horton, Vijay S Thakur, Dazhi Wang, Varsha Thakur, Molly Dalzell, Juliano T Freitas, Durga Prasad Gannamedi, Ifeanyichukwu Ogobuiro, Barbara Bedogni, Sakir H Gultekin, Timothy J Garrett, Alejandro V Villarino, Jun Lu, David B Lombard, Ashish H Shah, Scott M Welford
Journal: Neuro-Oncology (2025)

Abstract Background Metabolic reprogramming in glioblastoma (GBM) is a putative determinant of GBM subtype, malignant cell state and tumor-immune crosstalk. In the present study, we investigated how polyamine metabolic rewiring contributes to the malignant cell-intrinsic and microenvironment-dependent biological processes underpinning GBM subtype classification. Methods Liquid chromatography/tandem mass spectrometry (LC-MS/MS) was used for polyamine quantification in human and murine GBM tumors and cell lines. Through single-cell RNA sequencing, metabolic profiling and additional functional experiments, we dissect the malignant cell-intrinsic and paracrine signaling processes regulated by SAT1 (spermidine/spermine-N1-acetyltransferase1) and its product, N1-acetylspermidine. Results We find that polyamine acetylation is elevated in human and murine GBM tumors and contributes to the classification of mesenchymal/plurimetabolic GBM through both regulation of tumor-cell intrinsic glucose metabolism and by facilitating metabolic crosstalk with tumor-associated macrophages/myeloid cells (TAMs). The impact of SAT1 on tumor cell metabolism is mediated, at least in part, by N1-acetylspermdine, the sole polyamine elevated in human and murine tumors. Furthermore, the relatively high levels of N1-acetylspermidine released by GBM is taken up by myeloid cells to promote intracellular polyamine flux, cellular respiration and migration. In vivo, both genetic disruption of polyamine acetylation and pharmacological inhibition of polyamine transport reduced myeloid cell infiltration and sensitized tumors to chemoradiation. Conclusions Collectively, the findings highlight a previously unidentified role for SAT1 and its product, N1-acetylspermidine, in bridging the metabolic activity of tumor cells and tumor-associated macrophages/myeloid cells (TAMs), together promoting mesenchymal/plurimetabolic states and therapeutic resistance in GBM.
First-in-man study of coronary stent 3D reconstruction in the cathlab using rotational angiography
Authors: Hakim Benamer, Liliane Ramus, Hachem-Ali Haidar, Matthieu Perier, Mehdi Saighi Bouaouina, Sophie Amelot, Régis Vaillant
Journal:  (2025)

Abstract Aims Stent under-expansion is a well-known predictor of post-PCI MACE. This article presents a new technique to image coronary stents in 3D in the cathlab utilizing only the angiographic equipment. Methods and results Thirty patients with an indication of PCI were consented and prospectively included. They underwent a 3D rotational angiography following stent deployment without contrast injection. The 3D reconstructions of the coronary stents were independently reviewed offline by three experienced interventional cardiologists. Image quality was assessed using a qualitative scale: Excellent (struts are highly contrasted and sharp), Good (struts are contrasted enough to be distinguished from the background), Fair (the overall shape of the stent can be assessed but the precise demarcation between struts and background may be ambiguous in some areas) or Limited (it is challenging to distinguish the struts from the background). The 3D stent reconstruction quality was evaluated as Excellent for 37.8% of the cases, Good for 33.3%, Fair for 22.2%, and Limited for 6.7%. Substantial to near-perfect agreement was observed among reviewers (weighted Cohen’s kappa 0.8, 0.78, 0.82 for the three pairs of reviewers respectively). The 3D quality was significantly correlated with the BMI using the Spearman rank correlation coefficient (ρ=0.74, p-value&amp;lt;0.001). Conclusions The study demonstrates that 3D rotational angiography is feasible during PCI. The 3D reconstructions were evaluated as excellent or good in most patients by three interventional cardiologists. Additional studies are necessary to validate the measurements with respect to intravascular imaging and evaluate the role of this new technique in stent optimization.
Peptide-Based Smart Nanosystem for Spatiotemporal Regulation of Bone Immunity and Cartilage Repair to Alleviate Osteoarthritis
Authors: Yang Liu, Wenwei Li, Zhichao Yang, Ming Wei, Liang Yan, Yang Lv, Zhaoyu Li, Zezhong Guo, Zheng Li, Wei Zhou, Wei Huang
Journal: Biomaterials (2025)
The epidemiology and burden of ten mental disorders in countries of the Association of Southeast Asian Nations (ASEAN), 1990–2021: findings from the Global Burden of Disease Study 2021
Authors: Anna Szücs, Stephanie C C van der Lubbe, Jorge Arias de la Torre, Jose M Valderas, Simon I Hay, Catherine Bisignano, Brooks W Morgan, Swetha Acharya, Qorinah Estiningtyas Sakilah Adnani, Geminn Louis Carace Apostol, Muhammad Shahzad Aslam, Yuni Asri, Zaw Zaw Aung, Gading Ekapuja Aurizki, Atif Amin Baig, Amiel Nazer C Bermudez, Muthia Cenderadewi, Pojsakorn Danpanichkul, Ferry Efendi, Crystal Amiel M Estrada, Nelsensius Klau Fauk, Ni Kadek Yuni Fridayani, Fernando Barroga Garcia, Faizul Hasan, Umar Idris Ibrahim, Muhana Fawwazy Ilyas, Nahlah Elkudssiah Ismail, Jazlan Jamaluddin, Roland Dominic G Jamora, Jost B Jonas, Kehinde Kazeem Kanmodi, Kashif Ullah Khan, Fireza Husnul Khotimah, Yun Jin Kim, Maria Dyah Kurniasari, Christina Yeni Kustanti, Dian Kusuma, Tri Laksono, Jerrald Lau, Arianna Maever Loreche, Zheng Feei Ma, Joemer C Maravilla, Roy Rillera Marzo, Richard James Maude, Thantrira Porntaveetus, Setyaningrum Rahmawaty, Alina Rodriguez, Bedanta Roy, Afeez Abolarinwa Salami, Yoseph Leonardo Samodra, Chandrashekhar T Sreeramareddy, Vetriselvan Subramaniyan, Thitiporn Sukaew, Desy Sulistiyorini, Lourdes Bernadette C Sumpaico-Tanchanco, Anggi Lukman Wicaksana, Yen Jun Wong, Mustafa Z Younis, Yves Miel H Zuniga, Christopher J L Murray, Damian F Santomauro, Marie Ng
Journal: The Lancet Public Health (2025)
The epidemiology and burden of cardiovascular diseases in countries of the Association of Southeast Asian Nations (ASEAN), 1990–2021: findings from the Global Burden of Disease Study 2021
Authors: Lay Hoon Goh, Bryan Chong, Stephanie C.C. van der Lubbe, Jayanth Jayabaskaran, Srinithy Nagarajan, Jobelle Chia, Catherine O Johnson, Xiaochen Dai, Jose M Valderas, Budi Aji, Kim Abbegail Tan Aldecoa, Syed Mohamed Aljunid, Roshan A Ananda, Geminn Louis Carace Apostol, Hany Ariffin, Yuni Asri, Atif Amin Baig, Amiel Nazer C Bermudez, Catherine Bisignano, Muthia Cenderadewi, Hana Chen, Mayank Dalakoti, Ferry Efendi, Emerito Jose A Aquino Faraon, Nelsensius Klau Fauk, Fernando Barroga Garcia, Arief Hargono, Eka Mishbahatul Marah Has, Faizul Hasan, Simon I Hay, Umar Idris Ibrahim, Muhammad Iqhrammullah, Benni Iskandar, Nahlah Elkudssiah Ismail, Jazlan Jamaluddin, Jost B Jonas, Sivesh Kathir Kamarajah, Yun Jin Kim, Maria Dyah Kurniasari, Asep Kusnali, Christina Yeni Yeni Kustanti, Daphne Teck Ching Lai, Graciella Angelica Lukas, Zheng Feei Ma, Santi Martini, Roy Rillera Marzo, Septi Melisa, Farizal Rizky Muharram, Christopher J L Murray, Kamarul Imran Musa, Firzan Nainu, Gustavo G Nascimento, Aqsha Nur, Sok King Ong, Veincent Christian Filipino Pepito, Thantrira Porntaveetus, Dimas Ria Angga Pribadi, Setyaningrum Rahmawaty, Kadar Ramadhan, Sheena Ramazanu, Debby Syahru Romadlon, Yoseph Leonardo Samodra, Siddharthan Selvaraj, Christianus Heru Setiawan, Shazlin Shaharudin, Vetriselvan Subramaniyan, Desy Sulistiyorini, Zhong Sun, Ingan Ukur Tarigan, Jansje Henny Vera Ticoalu, Narayanaswamy Venketasubramanian, Mugi Wahidin, Anggi Lukman Wicaksana, Matthew Aldo Wijayanto, Angga Wilandika, Yves Miel H Zuniga, Gregory A Roth, Nicholas WS Chew, Marie Ng
Journal: The Lancet Public Health (2025)
Safety, pharmacokinetics, and neutralisation activity of PGDM1400LS, a V2 specific HIV-1 broadly neutralising antibody, infused intravenously or subcutaneously in people without HIV-1 in the USA (HVTN 140/HPTN 101 part A): a first-in-human, phase 1 randomised trial
Authors: Kelly E Seaton, Carmen A Paez, Chenchen Yu, Shelly T Karuna, Theresa Gamble, Maurine D Miner, Jack Heptinstall, Lu Zhang, Fei Gao, Margaret Yacovone, Hans Spiegel, Julie B Dumond, Maija Anderson, Estelle Piwowar-Manning, Bonnie Dye, India Tindale, Lori Proulx-Burns, Meg Trahey, Simbarashe Takuva, Azwidihwi Takalani, Veronique C Bailey, Spyros A Kalams, Hyman Scott, Nonhlanhla N Mkhize, Joshua A Weiner, Margaret E Ackerman, M Juliana McElrath, Michael Pensiero, Dan H Barouch, David Montefiori, Georgia D Tomaras, Lawrence Corey, Myron S Cohen, Yunda Huang, Sharana Mahomed, Marc Siegel, Colleen F Kelley
Journal: The Lancet HIV (2025)
Imaging Proliferation of Stage IV Cutaneous Melanoma With 18F-FLT PET/CT
Authors: Bernies van der Hiel, Wouter V. Vogel, Alfons J.M. van den Eertwegh, Carmen A. Vlahu, Filip Y.F.L. de Vos, Marye J. Boers-Sonderen, Marcel P.M. Stokkel, Else A. Aalbersberg, John B.A.G. Haanen
Journal: Clinical Nuclear Medicine (2025)

Background: 18 F-FLT PET/CT visualizes cellular ﻿proliferation and may ﻿correlate more directly with tumor aggressiveness and ﻿treatment response﻿ than 18 F-﻿FDG PET/CT in melanoma patients treated with BRAF/MEK inhibitors. We aimed to assess whether 18 F-FLT PET/CT can predict early resistance to BRAF/MEK inhibitors in addition to current clinical tools in patients with BRAF-mutated metastatic melanoma. Patients and Methods: This explorative side study of the phase II multicenter REPOSIT trial included 19 patients with stage IV BRAF V600E/K-mutated cutaneous melanoma who underwent optional 18 F-FLT PET/CT. 18 F-FLT PET/CT was performed at baseline and after 2 weeks of treatment to evaluate baseline uptake and early changes in metabolic activity. 18 F-FDG PET/CT was performed at baseline for comparison. Ki67 expression was assessed in metastatic tissue samples. Analyses included: (1) visual comparison of baseline 18 F-FLT and 18 F-FDG uptake, (2) correlation of 18 F-FLT uptake with Ki-67, (3) semiquantitative analysis of baseline 18 F-FLT uptake, and (4) evaluation of percentage change in 18 F-FLT uptake after 2 weeks. Results: Patients with consistently lower 18 F-FLT than 18 F-FDG uptake in metastases had longer progression-free survival (PFS; median 9.6 months, range: 3.4 to 32.3) compared with those with equal/higher or heterogeneous 18 F-FLT uptake (3.5 to 5.3 mo). Baseline 18 F-FLT SULpeak did not correlate with Ki67 expression ( P = 0.601), nor was Ki67 associated with PFS ( P = 0.39). No significant PFS difference was observed between patients with baseline 18 F-FLT SULpeak below or above the median ( P = 0.601). However, a greater percentage decrease in 18 F-FLT uptake at 2 weeks was associated with longer PFS (median: 13.9 vs 4.3 mo, P = 0.005). Conclusions: Baseline 18 F-FLT uptake patterns relative to 18 F-FDG, and early changes in 18 F-FLT uptake, were associated with PFS in patients treated with BRAF/MEK inhibitors. These explorative findings suggest that 18 F-FLT PET/CT may have predictive value, warranting confirmation in larger prospective studies.