tbuckley/cabot-search huggingface dataset:
<sup>68</sup>Ga-FAPI-46 PET/CT in the evaluation of gliomas: comparison with <sup>18</sup>F-FDG PET/CT and contrast-enhanced MRI
Authors: Dan Ruan, Jianping Sun, Chengkun Han, Jiayu Cai, Lingyu Yu, Liang Zhao, Yizhen Pang, Changjing Zuo, Long Sun, Zhanxiang Wang, Guowei Tan, Xiaobo Qu, Haojun Chen
Journal: Theranostics (2024)

Rationale: This study compared 68Ga-FAPI-46 PET/CT, 18F-fluorodeoxyglucose (FDG) PET/CT, and contrast-enhanced MRI (CE-MRI) for glioma imaging, classification, and recurrence detection and explored PET parameters and molecular pathological profiles. Methods: Between June 2020 and June 2024, we prospectively enrolled patients with space-occupying lesions in the brain or previously treated gliomas. All patients underwent sequential CE-MRI, 68Ga-FAPI-46, and 18F-FDG PET/CT. Diagnostic accuracy was assessed based on a reference standard, and PET parameters were analysed for correlations with WHO grading and molecular characteristics. Results: Forty-eight patients (median age, 51 years; 32 men) with 40 confirmed gliomas were enrolled. For primary tumour diagnosis, the sensitivity of 68Ga-FAPI-46 PET/CT was equivalent to CE-MRI (95% vs. 100%, P = 0.99) and 18F-FDG PET/CT (95% vs. 77%, P = 0.13). 68Ga-FAPI-46 uptake was higher in grade IV than in grade I-II gliomas (5.03 vs. 1.14, P = 0.02). 68Ga-FAPI-46 PET/CT showed significantly higher maximum standardized uptake value and tumour-to-background ratio (TBR) in recurrent tumours than in treatment-related changes and demonstrated favourable sensitivity and specificity for detecting recurrent gliomas, though not significantly superior to 18F-FDG PET/CT (sensitivity: 100% vs. 85%, P = 0.48; specificity: 100% vs. 80%, P = 0.99) and CE-MRI (sensitivity: 100% vs. 100%, P = NA; specificity: 100% vs. 40%, P = 0.25). Glial fibrillary acidic protein-mutant gliomas exhibited higher 68Ga-FAPI-46 uptake than wild-type gliomas. Conclusion: 68Ga-FAPI-46 PET/CT outperformed 18F-FDG and CE-MRI in diagnosing glioma recurrence, although the results were not statistically significant. For primary glioma diagnosis, 68Ga-FAPI-46 PET/CT, despite having a better TBR, did not surpass 18F-FDG PET/CT and CE-MRI in terms of sensitivity and specificity. However, 68Ga-FAPI-46 PET/CT is superior to 18F-FDG for visualizing and classifying gliomas.
Ultrafast power doppler ultrasound enables longitudinal tracking of vascular changes that correlate with immune response after radiotherapy
Authors: Shannon E Martello, Jixin Xia, Jiro Kusunose, Benjamin C Hacker, McKenzie A Mayeaux, Erica J Lin, Adrienne Hawkes, Aparna Singh, Charles F Caskey, Marjan Rafat
Journal: Theranostics (2024)

While immunotherapy shows great promise in patients with triple negative breast cancer, many will not respond to treatment. Radiotherapy has the potential to prime the tumor-immune microenvironment for immunotherapy. However, predicting response is difficult due to tumor heterogeneity across patients, which necessitates personalized medicine strategies that incorporate tumor tracking into the therapeutic approach. Here, we investigated the use of ultrasound (US) imaging of the tumor vasculature to monitor the tumor response to treatment.
Plant conservation in the age of genome editing: opportunities and challenges
Authors: Kangquan Yin, Mi Yoon Chung, Bo Lan, Fang K. Du, Myong Gi Chung
Journal: Genome biology (2024)

Abstract Numerous plant taxa are threatened by habitat destruction or overexploitation. To overcome these threats, new methods are urgently needed for rescuing threatened and endangered plant species. Here, we review the genetic consequences of threats to species populations. We highlight potential advantages of genome editing for mitigating negative effects caused by new pathogens and pests or climate change where other approaches have failed. We propose solutions to protect threatened plants using genome editing technology unless absolutely necessary. We further discuss the challenges associated with genome editing in plant conservation to mitigate the decline of plant diversity.
Validity, reliability and responsiveness of digital visual analogue scales for chronic spontaneous urticaria monitoring: A <scp>CRUSE</scp>® mobile health study
Authors: Bernardo Sousa‐Pinto, Aiste Ramanauskaite, Sophia Neisinger, Ellen Witte‐Händel, Ana M. Gimenez‐Arnau, Carole Guillet, Claudio Alberto S. Parisi, Constance H. Katelaris, Daria Fomina, Désirée Larenas‐Linnemann, Elizabeth García, Emek Kocatürk, Frank Siebenhaar, Hermenio Lima, Igor Kaidashev, Iman Nasr, Isabel Ogueta Canales, Ivan Cherrez Ojeda, Jacques Hébert, Jean Bousquet, Jonathan A. Bernstein, Jonny Peter, Jorge Sanchez, Jose Ignacio Larco Sousa, Kanokvalai Kulthanan, Karsten Weller, Kiran Godse, Krzysztof Rutkowski, Lasma Lapina, Laurence Bouillet, Leo Lianyi Han, Luis Felipe Ensina, Margarida Gonçalo, Markus Magerl, Martijn van Doorn, Martin Metz, Maryam Khoshkhui, Michihiro Hide, Murat Türk, Nataļja Kurjāne, Niall Conlon, Pascale Salameh, Pavel Kolkhir, Riccardo Asero, Roman Stepanenko, Sabine Altrichter, Sara Gil‐Mata, Simon Francis Thomsen, Torsten Zuberbier, Vladyslav Tsaryk, Young‐Min Ye, Zenon Brzoza, Zuotao Zhao, Marcus Maurer
Journal: Allergy (2024)

Abstract Background CRUSE® is an app that allows patients with chronic spontaneous urticaria (CSU) to monitor their daily disease activity through the use of visual analogue scales (VASs). We aimed to determine the concurrent validity, reliability, responsiveness and minimal important difference (MID) of CRUSE® VASs. Method s We evaluated the properties of three daily VASs: VAS for how much patients were affected by their CSU (‘VAS urticaria’), VAS for the impact of urticaria on work/school productivity (‘VAS productivity’) and the VAS of EQ‐5D. Concurrent validity was assessed by measuring the association between each VAS and the Urticaria Activity Score (UAS). Intra‐rater reliability was determined based on the data of users providing multiple daily questionnaires within the same day. Test–retest reliability and responsiveness (ability to change), respectively, were tested in clinically stable and clinically unstable users. MIDs were determined using distribution‐based methods. Results We included 5938 patients (67,380 days). Concurrent validity was high, with VAS urticaria being more strongly associated with the UAS score than the remaining VASs. Intra‐rater reliability was also high, with intraclass correlation coefficients (ICC) being above 0.950 for all VASs. Moderate‐high test–retest reliability and responsiveness were observed, with reliability ICC being highest for VAS EQ‐5D and responsiveness being highest for VAS urticaria. The MID for VAS urticaria was 17 (out of 100) units, compared to 15 units for VAS productivity and 11 units for VAS EQ‐5D. Conclusion Daily VASs for CSU available in the CRUSE® app display high concurrent validity and intra‐rater reliability and moderate‐high test–retest reliability and responsiveness.
Unlocking the dual role of LSD1 in tumor immunity: innate and adaptive pathways
Authors: Yu Zhang, Ningjie Guo, Haoyi Zhu, Mengyang Liu, Jiahui Hao, Shoukai Wang, Ting Guo, Maa Mamun, Jingru Pang, Qi Liu, Yichao Zheng, Hongmin Liu, Pilei Si, Lijuan Zhao
Journal: Theranostics (2024)

The roles of innate and adaptive immunity are crucial in both the development of cancer and its response to treatment. Numerous studies have demonstrated that histone lysine-specific demethylase 1 (LSD1) is overexpressed in various cancers. Elevated levels of LSD1 intricately modulate immune checkpoints, the function of immune cells, and the expression of immunomodulators, impacting both innate and adaptive immunity. Moreover, compelling evidence suggests that inhibiting LSD1 enhances tumor immunity, suppresses tumor growth, and improves the effectiveness of immunotherapy. However, a comprehensive classification of LSD1's role in both innate and adaptive immunity is lacking. In this review, we outline the role of LSD1 in tumor immunity in terms of both innate and adaptive immunity, summarizing the mechanisms associated with LSD1-mediated tumor immunity and its potential regulatory capacity in tumor immune escape. Finally, we summarize the research status of LSD1 inhibitors in tumor immunotherapy, which be valuable for promoting the development of effective LSD1-targeted agents used as combination immunotherapy drugs.
TRIM4 enhances small-molecule-induced neddylated-degradation of CORO1A for triple negative breast cancer therapy
Authors: Wen-Jie Gu, Xiao-Xia Liu, Yi-Wen Shen, Yi-Ting Gong, Yi-Li Chen, Jiayi Lin, Dong Lu, Li-Jun Zhang, Hong-Zhuan Chen, Yi Jin, Zha-Jun Zhan, Wei-Dong Zhang, Jin-Mei Jin, Xin Luan
Journal: Theranostics (2024)

Background: As a critical member of the Coronin family, Coronin 1A (CORO1A) plays a crucial role in the progression of triple-negative breast cancer (TNBC). However, CORO1A is typically considered "undruggable" due to its smooth surface and complex protein-protein interactions (PPIs). Molecular glues have emerged as one of the most effective strategies to rapidly degrade such "undruggable" targets. Neddylation, an emerging approach, has shown promise in targeting pathogenic proteins for degradation through the NEDD8 pathway, making the degradation of CORO1A an attractive pharmacological strategy. Methods: A phenotypic drug screening strategy coupled with multi-omics approaches was utilized to rapidly identify a molecular glue degrader for CORO1A and to uncover the associated mechanisms. The Omics and Text-based Target Enrichment and Ranking (OTTER) tools, co-immunoprecipitation (Co-IP) assay, mass spectrometry, and the separation of phases-based protein interaction reporter (SPPIER) method were employed to explore the interaction between Aurovertin B (AB) and CORO1A via TRIM4. The pharmacological effects of AB were assessed using TNBC patient-derived organoids (PDOs) and 3D bioprinting models. Results: We identified AB as a previously undisclosed molecular glue that significantly promotes the neddylation and proteasomal degradation of CORO1A via TRIM4, an atypical E3 ligase. Notably, the degradation of CORO1A markedly inhibited various cellular processes and exerted robust antitumor effects in TNBC PDOs and 3D bioprinting models. Conclusions: Our findings underscore the critical role of CORO1A in TNBC and lay a crucial foundation for the development of innovative drugs based on molecular glue technology.
Immunological facets of prostate cancer and the potential of immune checkpoint inhibition in disease management
Authors: Stian Bakke Hansen, Bilal Unal, Omer Faruk Kuzu, Fahri Saatcioglu
Journal: Theranostics (2024)

Prostate cancer (PCa) is the most common non-cutaneous cancer in men and a major cause of cancer-related deaths. Whereas localized PCa can be cured by surgery and radiotherapy, metastatic disease can be treated, but is not curable. Inhibition of androgen signaling remains the main therapeutic intervention for treatment of metastatic PCa, in addition to chemotherapy, radionuclide therapy and emerging targeted therapies. Although initial responses are favorable, resistance to these therapies invariably arise with development of castration resistant PCa (CRPC) and lethal phenotypes. Recent findings have implicated the crosstalk between PCa cells and the tumor microenvironment (TME) as a key factor for disease progression and metastasis, and the immune system is becoming an increasingly attractive target for therapy. Given the striking success of immune checkpoint inhibitors (ICIs) in various cancer types, preclinical and clinical studies have begun to explore their potential in PCa. It has become clear that the PCa TME is largely immunosuppressive, and ICI therapy does not have efficacy for PCa. Intense effort is therefore being made in the field to understand the mechanisms of suppression and to turn the immunosuppressive TME into an immune active one that would enable ICI efficacy. Herein we examine this recent body of knowledge and how the mutational landscape of PCa integrates with an immunosuppressive TME to circumvent ICI-mediated T-cell activity and tumor killing. We then review the emerging potential success of combinatorial ICI approaches, utility of careful patient selection, and potential novel strategies to improve the efficacy of ICI for PCa therapy.
Improved quality control of allergen products: Assessing the molecular allergen composition by mass spectrometry
Authors: Steffen Augustin, Thomas Eichhorn, Martin Wald, Frank Fischer, Marek Jutel, Oliver Pfaar, Christoph Willers
Journal: Allergy (2024)

Abstract Background Natural allergen sources contain a variety of allergens, against which allergic subjects have developed individual sensitization profiles. Ideal allergen products for skin prick testing (SPT) and allergen immunotherapy (AIT) should contain the complete set of allergens of the respective allergen sources to cover all sensitization profiles. However, commercially available allergen products were shown to vary regarding their allergen composition. Methods The qualitative allergen composition of different SPT and AIT products produced from pollen of grasses, birch, mugwort and from house dust mites was assessed by a consistent high‐resolution liquid chromatography‐coupled tandem mass spectrometry method (LC–MS/MS). Results All major, mid‐tier and most minor allergens were detected in each of the investigated three batches of SPT and AIT products, demonstrating the completeness of the allergen composition and a high degree of batch‐to‐batch consistency. Conclusion This is the first study using a single consistent high‐resolution LC–MS/MS method to provide solid data on the qualitative allergen composition of SPT and AIT products manufactured from various common allergen sources. The applied method showed high reliability in qualitative batch‐to‐batch consistency testing and can be performed fast and with high throughput. High‐resolution LC–MS/MS is applicable for process development and quality control to ensure market availability of allergen products corresponding to the composition of the respective natural allergen sources.
Subclassification of obesity for precision prediction of cardiometabolic diseases
Authors: Daniel E. Coral, Femke Smit, Ali Farzaneh, Alexander Gieswinkel, Juan Fernandez Tajes, Thomas Sparsø, Carl Delfin, Pierre Bauvin, Kan Wang, Marinella Temprosa, Diederik De Cock, Jordi Blanch, José Manuel Fernández-Real, Rafael Ramos, M. Kamran Ikram, Maria F. Gomez, Maryam Kavousi, Marina Panova-Noeva, Philipp S. Wild, Carla van der Kallen, Michiel Adriaens, Marleen van Greevenbroek, Ilja Arts, Carel Le Roux, Fariba Ahmadizar, Timothy M. Frayling, Giuseppe N. Giordano, Ewan R. Pearson, Paul W. Franks
Journal: Nature Medicine (2024)

Abstract Obesity and cardiometabolic disease often, but not always, coincide. Distinguishing subpopulations within which cardiometabolic risk diverges from the risk expected for a given body mass index (BMI) may facilitate precision prevention of cardiometabolic diseases. Accordingly, we performed unsupervised clustering in four European population-based cohorts ( N ≈ 173,000). We detected five discordant profiles consisting of individuals with cardiometabolic biomarkers higher or lower than expected given their BMI, which generally increases disease risk, in total representing ~20% of the total population. Persons with discordant profiles differed from concordant individuals in prevalence and future risk of major adverse cardiovascular events (MACE) and type 2 diabetes. Subtle BMI-discordances in biomarkers affected disease risk. For instance, a 10% higher probability of having a discordant lipid profile was associated with a 5% higher risk of MACE (hazard ratio in women 1.05, 95% confidence interval 1.03, 1.06, P = 4.19 × 10 −10 ; hazard ratio in men 1.05, 95% confidence interval 1.04, 1.06, P = 9.33 × 10 −14 ). Multivariate prediction models for MACE and type 2 diabetes performed better when incorporating discordant profile information (likelihood ratio test P &lt; 0.001). This enhancement represents an additional net benefit of 4−15 additional correct interventions and 37−135 additional unnecessary interventions correctly avoided for every 10,000 individuals tested.
Re: Potter et al.: Concordance between self-reported visual difficulty and objective visual impairment: The National Health and Aging Trends Study (Ophthalmology. 2024 Jun 12:S0161-6420(24)00363-4.doi: 10.1016/j.ophtha.2024.06.009. Online ahead of print.)
Authors: Yating Zhou, Fei Xue
Journal: Ophthalmology (2024)
Optimal timing of anticoagulation after acute ischaemic stroke with atrial fibrillation (OPTIMAS): a multicentre, blinded-endpoint, phase 4, randomised controlled trial
Authors: David J Werring, Hakim-Moulay Dehbi, Norin Ahmed, Liz Arram, Jonathan G Best, Maryam Balogun, Kate Bennett, Ekaterina Bordea, Emilia Caverly, Marisa Chau, Hannah Cohen, Mairead Cullen, Caroline J Doré, Stefan T Engelter, Robert Fenner, Gary A Ford, Aneet Gill, Rachael Hunter, Martin James, Archana Jayanthi, Gregory Y H Lip, Sue Massingham, Macey L Murray, Iwona Mazurczak, Philip S Nash, Amalia Ndoutoumou, Bo Norrving, Hannah Sims, Nikola Sprigg, Tishok Vanniyasingam, Nick Freemantle
Journal: The Lancet (2024)

The optimal timing of anticoagulation for patients with acute ischaemic stoke with atrial fibrillation is uncertain. We investigated the efficacy and safety of early compared with delayed initiation of direct oral anticoagulants (DOACs) in patients with acute ischaemic stroke associated with atrial fibrillation.
Effects of atrial fibrillation ablation on arrhythmia burden and ventricular function in end‐stage heart failure: Lessons from CASTLE‐HTx
Authors: Vanessa Sciacca, Christian Sohns, Harry J.G.M. Crijns, Nassir F. Marrouche, Rene Schramm, Maximilian Moersdorf, Thomas Fink, Leonard Bergau, Gerhard Hindricks, Nikolaos Dagres, Samuel Sossalla, Angelika Costard‐Jaeckle, Henrik Fox, Mustapha El Hamriti, Frank Konietschke, Volker Rudolph, Jan Gummert, Jan G.P. Tijssen, Philipp Sommer
Journal: European Journal of Heart Failure (2024)

Abstract Aims The CASTLE‐HTx trial showed the benefit of atrial fibrillation (AF) ablation compared to medical therapy in decreasing mortality, need for left ventricular assist device implantation or heart transplantation (HTx) in patients with end‐stage heart failure (HF). Herein we describe the effects of catheter ablation on AF burden, arrhythmia recurrences, and ventricular function in end‐stage HF. Methods and results The CASTLE‐HTx protocol randomized 194 patients in end‐stage HF with AF to catheter ablation and medical therapy or medical therapy alone. AF burden, left ventricular ejection fraction (LVEF), and type of AF were assessed at baseline and at each follow‐up visit. Overall, 97 patients received ablation; 66 patients (68%) underwent pulmonary vein isolation (PVI) and 31 patients (32%) were treated with PVI and additional ablation. Electroanatomic mapping showed the extent of left atrial low voltage (cardiomyopathy) &gt;10% in 31 (31.9%) patients. At 12 months post‐ablation, persistent AF was present in 31/89 patients (34.8%), which was significantly less frequent compared to baseline ( p = 0.0001). Median AF burden reduction was 36.3 (interquartile range 13.6–63.3) percentage points at 12 months and LVEF improved from 29.2 ± 6.2% to 39.1 ± 8.3% ( p &lt; 0.001) following ablation. AF burden reduction &lt;50% was significantly associated with LVEF improvement ≥5% at 12 months after ablation ( p = 0.017). Conclusion Atrial fibrillation ablation in end‐stage HF leads to a substantial decrease in AF burden, a regression from persistent to paroxysmal AF and notably improved LVEF. Favourable ablation outcomes were observed in patients regardless of the presence or absence of signs indicating left atrial cardiomyopathy.
Timing of veno‐arterial extracorporeal membrane oxygenation support in patients with cardiogenic shock
Authors: Jonas Sundermeyer, Caroline Kellner, Benedikt N. Beer, Angela Dettling, Lisa Besch, Stefan Blankenberg, Ingo Eitel, Derk Frank, Norbert Frey, Tobias Graf, Paulus Kirchhof, Jannis Krais, Dirk von Lewinski, Norman Mangner, Sven Möbius‐Winkler, Peter Nordbeck, Martin Orban, Matthias Pauschinger, Can Martin Sag, Clemens Scherer, Carsten Skurk, Holger Thiele, Dirk Westermann, Benedikt Schrage
Journal: European Journal of Heart Failure (2024)

Abstract Aims The optimal timing for implementing mechanical circulatory support (MCS) in cardiogenic shock (CS) remains indeterminate. This study aims to evaluate patient characteristics and outcome associated with the time interval between CS onset and veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) implementation. Methods and results In this study, patients with CS treated with MCS at 15 tertiary care centres in three countries were enrolled. Patients treated with MCS were stratified into early (&lt;2 h), intermediate (2–12 h) and delayed (≥12–24 h) MCS implantation by using the time interval between CS onset and MCS device implementation. Adjusted logistic and Cox regression models were fitted to assess the association between timing of MCS implementation, patient characteristics and 30‐day mortality. A total of 330 patients with CS treated with VA‐ECMO and/or microaxial flow pump were included in this study; 20.9% received early, 55.8% intermediate, and 23.3% delayed MCS. Although crude 30‐day mortality was slightly lower in patients with early MCS (58.1% vs. 64.7% vs. 64.3%), adjusted analyses showed no significant association between timing of MCS implantation and 30‐day all‐cause mortality (hazard ratio [HR] for early vs. intermediate MCS: 0.93, 95% confidence interval [CI] 0.59–1.46, p = 0.74; HR for early vs. delayed MCS: 1.29, 95% CI 0.78–2.13, p = 0.33). Moreover, the incidence of complications, related and unrelated to MCS, did not differ significantly among groups. Conclusion In this exploratory study of patients with CS treated with MCS, the timing of device implantation within 24 h after CS onset was not associated with mortality. This supports a restrictive MCS approach, reserving its application for patients experiencing CS deterioration despite conventional therapy.
Letter regarding the article ‘Heart failure with improved versus persistently reduced left ventricular ejection fraction: A comparison of the <scp>BIOSTAT</scp>‐<scp>CHF</scp> (European) study with the <scp>ASIAN</scp>‐<scp>HF</scp> registry’
Authors: Juan Manuel Salvador‐Casabón, Isaac Lacambra‐Blasco, Juan Ignacio Pérez‐Calvo
Journal: European Journal of Heart Failure (2024)
Reply to Letter to Editor re: Kamboj, A.K., D.A. Patel, and R. Yadlapati, Long-Term Proton Pump Inhibitor Use: Review of Indications and Special Considerations. Clin Gastroenterol Hepatol, 2024. 22(7): p. 1373-1376.
Authors: Amrit K Kamboj, Dhyanesh A Patel, Rena Yadlapati
Journal: Clinical Gastroenterology and Hepatology (2024)
mGluR7: the new player protecting the central nervous system
Authors: Pan Li, Wangrui Lei, Yushu Dong, Xiaowu Wang, Xingyan Ye, Ye Tian, Yaru Yang, Jie Liu, Ning Li, Xiaochen Niu, Xin Wang, Yifan Tian, Lu Xu, Yang Yang, Jincheng Liu
Journal: Ageing Research Reviews (2024)
Single-Cell Sequencing Insights into the Transcriptional Landscape of Parkinson's Disease
Authors: Yun Su, Huimin Zheng, Xin Cui, Shuyu Zhang, Shuo Zhang, Zhengwei Hu, Xiaoyan Hao, Mengjie Li, Guangyu Guo, Zongping Xia, Changhe Shi, Chengyuan Mao, Yuming Xu
Journal: Ageing Research Reviews (2024)