tbuckley/cabot-search huggingface dataset:
Unveiling adipose populations linked to metabolic health in obesity
Authors: Isabel Reinisch, Adhideb Ghosh, Falko Noé, Wenfei Sun, Hua Dong, Peter Leary, Arne Dietrich, Anne Hoffmann, Matthias Blüher, Christian Wolfrum
Journal: Cell Metabolism (2024)

Precision medicine is still not considered as a standard of care in obesity treatment, despite a large heterogeneity in the metabolic phenotype of individuals with obesity. One of the strongest factors influencing the variability in metabolic disease risk is adipose tissue (AT) dysfunction; however, there is little understanding of the link between distinct cell populations, cell-type-specific transcriptional programs, and disease severity. Here, we generated a comprehensive cellular map of subcutaneous and visceral AT of individuals with metabolically healthy and unhealthy obesity. By combining single-nucleus RNA-sequencing data with bulk transcriptomics and clinical parameters, we identified that mesothelial cells, adipocytes, and adipocyte-progenitor cells exhibit the strongest correlation with metabolic disease. Furthermore, we uncovered cell-specific transcriptional programs, such as the transitioning of mesothelial cells to a mesenchymal phenotype, that are involved in uncoupling obesity from metabolic disease. Together, these findings provide valuable insights by revealing biological drivers of clinical endpoints.
Early downmodulation of tumor glycolysis predicts response to fasting-mimicking diet in triple-negative breast cancer patients
Authors: Francesca Ligorio, Andrea Vingiani, Tommaso Torelli, Caterina Sposetti, Lorenzo Drufuca, Fabio Iannelli, Lucrezia Zanenga, Catherine Depretto, Secondo Folli, Gianfranco Scaperrotta, Giuseppe Capri, Giulia V Bianchi, Cristina Ferraris, Gabriele Martelli, Ilaria Maugeri, Leonardo Provenzano, Federico Nichetti, Luca Agnelli, Riccardo Lobefaro, Giovanni Fucà, Giuseppe Fotia, Luigi Mariani, Daniele Morelli, Vito Ladisa, Maria Carmen De Santis, Laura Lozza, Giovanna Trecate, Antonino Belfiore, Silvia Brich, Alessia Bertolotti, Daniele Lorenzini, Angela Ficchì, Antonia Martinetti, Elisa Sottotetti, Alessio Arata, Paola Corsetto, Luca Sorrentino, Mattia Rediti, Giulia Salvadori, Saverio Minucci, Marco Foiani, Giovanni Apolone, Massimiliano Pagani, Giancarlo Pruneri, Filippo de Braud, Claudio Vernieri
Journal: Cell Metabolism (2024)
Foundation model of ECG diagnosis: Diagnostics and explanations of any form and rhythm on ECG
Authors: Yuanyuan Tian, Zhiyuan Li, Yanrui Jin, Mengxiao Wang, Xiaoyang Wei, Liqun Zhao, Yunqing Liu, Jinlei Liu, Chengliang Liu
Journal: Cell Reports Medicine (2024)

We propose a knowledge-enhanced electrocardiogram (ECG) diagnosis foundation model (KED) that utilizes large language models to incorporate domain-specific knowledge of ECG signals. This model is trained on 800,000 ECGs from nearly 160,000 unique patients. Despite being trained on single-center data, KED demonstrates exceptional zero-shot diagnosis performance across various regions, including different locales in China, the United States, and other regions. This performance spans across all age groups for various conditions such as morphological abnormalities, rhythm abnormalities, conduction blocks, hypertrophy, myocardial ischemia, and infarction. Moreover, KED exhibits robust performance on diseases it has not encountered during its training. When compared to three experienced cardiologists on real clinical datasets, the model achieves comparable performance in zero-shot diagnosis of seven common clinical ECG types. We concentrate on the zero-shot diagnostic capability and the generalization performance of the proposed ECG foundation model, particularly in the context of external multi-center data and previously unseen disease.
Definitions matter: Multicenter investigation of incidence and outcome of poor graft function after hematopoietic cell transplantation
Authors: Konradin F. Müskens, Winny N. R. Collot‐d'Escury, Rana Dandis, Saskia Haitjema, Jürgen Kuball, Moniek A. de Witte, Marc Bierings, Caroline A. Lindemans, Stefan Nierkens, Mirjam E. Belderbos
Journal: HemaSphere (2024)

Abstract Despite advances in allogeneic hematopoietic cell transplantation (HCT), poor graft function (PGF) remains an important complication with substantial morbidity and mortality. The investigation of preventive and therapeutic PGF treatments is hindered by inconsistencies in reported incidence and outcomes across studies, which may be explained by heterogeneity in PGF definition. To assess the impact of definition heterogeneity, we conducted a multicenter study, analyzing over 35.000 longitudinal blood counts from 427 pediatric and 405 adult HCT recipients. We compared the incidence, risk factors, and outcome of PGF, based on the three most common definitions. We identified 97 pediatric and 75 adult HCT recipients fulfilling at least one PGF definition. The 2‐year cumulative incidence of PGF varied significantly depending on the definition used, ranging from 6.8% to 20% in children and 4.9% to 18% in adults. Two‐year mortality for PGF patients ranged from 33% to 40% in children and 46% to 65% in adults. Notably, PGF patients identified solely by lenient definitions had similar mortality to HCT recipients with good graft function. Risk factors for PGF also varied by definition in both cohorts, and included older recipient age and cord blood transplantation. In conclusion, our study demonstrates that differences in PGF definition significantly impact the reported incidence, risk factors, and outcome. This underscores the need to harmonize PGF definitions across scientific studies, clinical practice, and transplant registries. Future studies, using standardized, quantitative thresholds for PGF, are required to determine optimal treatment strategies for both mild and severe forms of PGF.
Proliferating CLL cells express high levels of CXCR4 and CD5
Authors: Daniel Friedman, Drshika P. Mehtani, Jennifer B. Vidler, Piers E. M. Patten, Robbert Hoogeboom
Journal: HemaSphere (2024)

Abstract Chronic lymphocytic leukemia (CLL) is an incurable progressive malignancy of CD5 + B cells with a birth rate between 0.1% and 1% of the entire clone per day. However, the phenotype and functional characteristics of proliferating CLL cells remain incompletely understood. Here, we stained peripheral blood CLL cells for ki67 and DNA content and found that CLL cells in G1‐phase have a CXCR4 lo CD5 hi phenotype, while CLL cells in S/G2/M‐phase express high levels of both CXCR4 and CD5. Induction of proliferation in vitro using CD40L stimulation results in high ki67 levels in CXCR4 lo CD5 hi cells with CXCR4 expression increasing as CLL cells progress through S and G2/M‐phases, while CXCR4 hi CD5 lo CLL cells remained quiescent. Dye dilution experiments revealed an accumulation of Ki67 hi ‐divided cells in the CXCR4 hi CD5 hi fraction. In Eµ‐TCL1 transgenic mice, the CXCR4 hi CD5 hi fraction expressed high levels of ki67 and was expanded in enlarged spleens of diseased animals. Human peripheral blood CXCR4 hi CD5 hi CLL cells express increased levels of IgM and the chemokine receptors CCR7 and CXCR5 and migrate efficiently toward CCL21. We found higher levels of CXCR4 in patients with progressive disease and the CXCR4 hi CD5 hi fraction was expanded upon clinical relapse. Thus, this study defines the phenotype and functional characteristics of dividing CLL cells identifying a novel subclonal population that underlies CLL pathogenesis and may drive clinical outcomes.
Inequality in accessing sexual and reproductive health for transgender people in South Asia through an intersectional lens: a scoping review
Authors: Sadaf Murad-Kassam, Salima Siraj, Shrinithi Subramanian
Journal: International Journal of Transgender Health (2024)

Background Transgender individuals face significant barriers to accessing sexual and reproductive health (SRH) services globally. These challenges are exacerbated in South Asian countries, where stigma, discrimination, and a lack of specialized healthcare support prevail. Countries such as India, Nepal, Bangladesh, and Pakistan fall behind in ensuring equal healthcare rights and access for the transgender community.
Inter-organ communication is a critical machinery to regulate metabolism and aging
Authors: Kyohei Tokizane, Shin-Ichiro Imai
Journal: Trends in Endocrinology and Metabolism (2024)

Inter-organ communication (IOC) is a complex mechanism involved in maintaining metabolic homeostasis and healthy aging. Dysregulation of distinct forms of IOC is linked to metabolic derangements and age-related pathologies, implicating these processes as a potential target for therapeutic intervention to promote healthy aging. In this review, we delve into IOC mediated by hormonal signaling, circulating factors, organelle signaling, and neuronal networks and examine their roles in regulating metabolism and aging. Given the role of the hypothalamus as a high-order control center for aging and longevity, we particularly emphasize the importance of its communication with peripheral organs and pave the way for a better understanding of this critical machinery in metabolism and aging.
Skeletal muscle adaptations and post-exertional malaise in long COVID
Authors: Braeden T Charlton, Richie P Goulding, Richard T Jaspers, Brent Appelman, Michèle van Vugt, Rob C I Wüst
Journal: Trends in Endocrinology and Metabolism (2024)

When acute SARS-CoV-2 infections cause symptoms that persist longer than 3 months, this condition is termed long COVID. Symptoms experienced by patients often include myalgia, fatigue, brain fog, cognitive impairments, and post-exertional malaise (PEM), which is the worsening of symptoms following mental or physical exertion. There is little consensus on the pathophysiology of exercise-induced PEM and skeletal-muscle-related symptoms. In this opinion article we highlight intrinsic mitochondrial dysfunction, endothelial abnormalities, and a muscle fiber type shift towards a more glycolytic phenotype as main contributors to the reduced exercise capacity in long COVID. The mechanistic trigger for physical exercise to induce PEM is unknown, but rapid skeletal muscle tissue damage and intramuscular infiltration of immune cells contribute to PEM-related symptoms.
Whole Body Synergy-Based Balance Control for Quadruped Robot with Manipulator on Sloped Terrain
Authors: Ru Kang, Huifeng Ning, Fei Meng, Zewen He
Journal: Cyborg and Bionic Systems (2024)

A quadruped robot with a manipulator that combines dynamic motion and manipulation capabilities will greatly expand its application scenarios. However, the addition of the manipulator raises the center of mass of the quadruped robot, increasing complexity in motion control and posing new challenges for maintaining balance on sloped terrains. To address this, a balance control method based on whole-body synergy is proposed in this study, emphasizing adaptive adjustment of the robot system's overall balance through effective utilization of the manipulator's active motion. By establishing a mapping relationship between the manipulator and the robot's attitude angle under system equilibrium, the desired manipulator motion is guided by real-time estimates of terrain angles during motion, enhancing motion efficiency while ensuring robot balance. Furthermore, to enhance motion tracking accuracy, the optimization of system angular momentum and manipulator manipulability is incorporated into hierarchical optimization tasks, improving manipulator controllability and overall system performance. Simulation and experimental results demonstrate that the quadruped robot with a manipulator exhibits reduced velocity and attitude angle fluctuations, as well as smoother foot-end force dynamics during climbing motions with the addition of manipulator adaptive adjustment. These results validate the effectiveness and superiority of the manipulator-based adaptive adjustment strategy proposed in this paper.
Comparison of Radionuclide Drug Conjugates With Boron Neutron Capture Therapy: An Overview of Targeted Charged Particle Radiation Therapy
Authors: Yingjun Zhang, Paolo Coghi, Zimo Ren, Narayan S. Hosmane, Yinghuai Zhu
Journal: Medicinal Research Reviews (2024)

ABSTRACT Targeted charged alpha‐ and beta‐particle therapies are currently being used in clinical radiation treatments as newly developed methods for either killing or controlling tumor cell growth. The alpha particles can be generated either through a nuclear decay reaction or in situ by a nuclear fission reaction such as the boron neutron capture reaction. Different strategies have been employed to improve the selectivity and delivery of radiation dose to tumor cells based on the source of the clinically used alpha particles. As a result, the side effects of the treatment can be minimized. The increasing attention and research efforts on targeted alpha‐particle therapy have been fueled by exciting results of both academic research and clinical trials. It is highly anticipated that alpha‐particle therapy will improve the efficacy of treating malignant tumors. In this overview, we compare radionuclide drug conjugates (RDC) with boron neutron capture therapy (BNCT) to present recent developments in targeted alpha‐particle therapy.
Subacute Infarction of Recurrent Artery of Heubner Mimicking CNS Tumor With Correlative Brain MRI and 18F-FDG PET/CT Findings
Authors: Elif Aslı Özer, MD, Can Özütemiz, Anton Nosov, Gaurav Saigal, Ahmet Turan Ilica
Journal: Clinical Nuclear Medicine (2024)

Abstract A 62-year-old man, previously treated for oral cavity carcinoma, presented with new-onset cognitive-motor symptoms. Brain MRI revealed a periventricular, avidly enhancing lesion in the right anterior basal ganglia and hypothalamus suspicious for a brain tumor, particularly CNS lymphoma. 18 F-FDG brain PET/CT showed corresponding uptake suggestive of primary brain tumor, lymphoma, or metastasis. Follow-up MRI showed resolution of enhancement and mass effect favoring an evolving subacute infarct. The diagnosis of an infarct in the recurrent artery of Heubner territory was facilitated by MRI, and recurrent artery of Heubner infarction was noted as a potential cause for false-positive 18 F-FDG uptake on PET/CT, mimicking intracranial tumor.
Cognitive Impairment and Brain Metabolic Changes in Post-Acute Sequelae of COVID-19
Authors: Laura Rozenblum, Thomas Debroucker, Marie-Odile Habert, Marine Soret, Serge Desarnaud, Valérie Causse Lemercier, Eric Guedj, Esaie Marshall, Dominique Salmon, Aurélie Kas
Journal: Clinical Nuclear Medicine (2024)

Purpose Neurological symptoms often prominent in post-acute sequelae of COVID-19 (PASC) necessitate deeper understanding. Our objective was to investigate brain metabolism in PASC and examine correlations with neurological symptoms during both the acute and chronic stages. Methods Eighty-seven adults experiencing PASC with neurocognitive symptoms were recruited in the PERSICOR prospective study and examined using brain [ 18 F]FDG PET/CT. Comprehensive clinical variables including neurocognitive symptoms were evaluated. PET images were compared voxel-wise with SPM12 software ( P &lt; 0.05, false discovery rate corrected) and volume-of-interest basis (BrainVisa software) with those of 55 healthy controls recruited before COVID-19 pandemic. We also investigated differences in brain metabolism according to the time interval after acute COVID-19. The correlation between brain metabolism and neurocognitive symptoms was assessed. Results Frequently reported neurological symptoms included concentration difficulties (79%) and immediate/working memory impairments (66%). Significant hypometabolism was identified in regions previously identified in PASC: left fusiform gyrus (33% of patients), amygdala (23% on left, 28% on right), parahippocampal area (25% left, 24% right), and vermis (22%). The most substantial metabolism decreases were observed in the pons (5.5% decrease in the whole patient group vs controls) and right amygdala (−4.2%). Concentration and memory impairments correlated with decreased metabolism in prefrontal and mesial/inferior temporal areas, respectively ( P &lt; 0.01 for both). A shorter interval between PET imaging and the acute phase of COVID-19 correlated with reduced glucose metabolism in the brainstem, thalamus, mesiotemporal lobe, frontobasal cortex, and olfactory bulb ( P &lt; 10 −3 ). Conclusion This study underscores the links between neurological symptoms and cerebral hypometabolism in specific regions in PASC. These findings illuminate the complex neuropathophysiological mechanisms of PASC and pave the way for potential therapeutic interventions.
Granulocyte Colony-Stimulating Factor–Associated Aortitis Unveiled by 18F-FDG PET/CT
Authors: Hélène Artigou, Hervé Foka Tichoue, Cindy Marques, Frédéric Charlotte, PA Vion, Aurélie Kas, Laura Rozenblum
Journal: Clinical Nuclear Medicine (2024)

Abstract In oncology, G-CSF (granulocyte colony-stimulating factor) is often administered to counteract chemotherapy-induced neutropenia. Recent studies have highlighted a significant side effect, G-CSF–associated aortitis, with an incidence of ~0.4%. Identification of this condition’s imaging characteristics is crucial for nuclear medicine specialists, given its substantial impact on clinical decision-making. It is notably prevalent in the follow-up of gynecologic malignancies and lymphoma. We detail a case of G-CSF–related aortitis in a metastatic ovarian cancer patient, diagnosed by increased 18 F-FDG uptake in the aortic arch on PET/CT, confirmed by contrast-enhanced CT and biopsy, which regressed spontaneously in under 5 weeks without corticosteroid treatment.
Tocilizumab and immune signatures for targeted management of cytokine release syndrome in immune checkpoint therapy
Authors: D Daoudlarian, A Segot, S Latifyan, R Bartolini, V Joo, N Mederos, H Bouchaab, R Demicheli, K Abdelhamid, N Ferahta, J Doms, G Stalder, A Noto, L Mencarelli, V Mosimann, D Berthold, A Stravodimou, C Sartori, K Shabafrouz, J A Thompson, Y Wang, S Peters, G Pantaleo, M Obeid
Journal: Annals of Oncology (2024)
Prognostic value of residual disease (RD) biology and gene expression changes during the neoadjuvant treatment in patients with HER2+ early breast cancer (EBC)
Authors: Aranzazu Fernandez-Martinez, Maki Tanioka, Sung Gwe Ahn, Paola Zagami, Tomás Pascual, Mattia Rediti, Gong Tang, Katherine A Hoadley, David Venet, Naim U Rashid, Patricia A Spears, Serena Di Cosimo, Evandro de Azambuja, Anup Choudhury, Priya Rastogi, Md N Islam, Javier Cortes, Antonio Llombart-Cussac, Sandra M Swain, Christos Sotiriou, Aleix Prat, Charles M Perou, Lisa A Carey
Journal: Annals of Oncology (2024)
Avelumab + axitinib vs sunitinib as first-line treatment for patients with advanced renal cell carcinoma: final analysis of the phase 3 JAVELIN Renal 101 trial
Authors: T K Choueiri, K Penkov, H Uemura, M T Campbell, S Pal, C Kollmannsberger, J L Lee, B Venugopal, A J M van den Eertwegh, S Negrier, H Gurney, L Albiges, R Berger, J B A G Haanen, V Oyervides Juárez, B I Rini, J Larkin, F Nolè, M Schmidinger, M B Atkins, Y Tomita, B Ellers-Lenz, J Hoffman, R Sandner, J Wang, A di Pietro, R J Motzer
Journal: Annals of Oncology (2024)
Correlation Between Progression-Free and Overall Survival in Patients with Hodgkin Lymphoma: A Comprehensive Analysis of Individual Patient Data from Randomized GHSG Trials
Authors: P J Bröckelmann, H Müller, M Fuchs, S Gillessen, D A Eichenauer, S Borchmann, A S Jacob, K Behringer, J Momotow, J Ferdinandus, B Böll, X Yang, C Kobe, H-T Eich, C Baues, W Klapper, A Engert, P Borchmann, B von Tresckow
Journal: Annals of Oncology (2024)

We aimed to evaluate the correlation of progression-free (PFS) and overall survival (OS) after first-line treatment of classical Hodgkin lymphoma (HL) and the potential of PFS to serve as a surrogate parameter for OS. We analyzed individual patient data obtained during and after treatment with polychemotherapy within nine randomized phase III trials (GHSG HD7-HD15) between 01/93 - 08/18. Effects of 16 experimental treatments on PFS and OS on trial level were evaluated by estimation of the treatment effects with Cox proportional hazards (PH) regression and a linear weighted least squares regression. On the patient level, marginal Cox PH models for multiple endpoints were applied according to the Wei-Lin-Weissfeld method. At least one PFS and OS event was recorded in 1,682 and 1,064 of 10,605 patients, respectively. At trial level there was a strong correlation of treatment effects on PFS and OS (weighted Pearson r= 0.72, R2= 0.54, P< 0.001). At patient level, moderate to strong correlation of treatment effects on PFS and OS was confirmed with Pearson r ranging between 0.61 - 0.85 (each P< 0.001) and overall r= 0.74. A regression model accounting for different types of experimental treatments and historical progress over trial generations reached very strong correlation (R2= 0.93). Applying this model to data from the contemporary first-line ECHELON-1 trial allowed for prediction of OS from PFS (prognosticated ln[HR(OS)]= -0.68 as compared to observed ln[HR(0.59)]= -0.53). In first-line trials of HL, PFS and OS as well as treatment effects and prognostic effects on PFS and OS are strongly correlated. PFS thereby predicts treatment effects on OS to a high degree and many years before OS can be reliably evaluated.
Challenges and promises of big team comparative cognition
Authors: Nicolás Alessandroni, Drew Altschul, Heidi A. Baumgartner, Marina Bazhydai, Sarah F. Brosnan, Krista Byers-Heinlein, Josep Call, Lars Chittka, Mahmoud Elsherif, Julia Espinosa, Marianne S. Freeman, Biljana Gjoneska, Onur Güntürkün, Ludwig Huber, Anastasia Krasheninnikova, Valeria Mazza, Rachael Miller, David Moreau, Christian Nawroth, Ekaterina Pronizius, Susana Ruiz-Fernández, Raoul Schwing, Vedrana Šlipogor, Ingmar Visser, Jennifer Vonk, Justin Yeager, Martin Zettersten, Laurent Prétôt
Journal: Nature Human Behaviour (2024)
The impact of self-report inaccuracy in the UK Biobank and its interplay with selective participation
Authors: Tabea Schoeler, Jean-Baptiste Pingault, Zoltán Kutalik
Journal: Nature Human Behaviour (2024)

Abstract Although the use of short self-report measures is common practice in biobank initiatives, such a phenotyping strategy is inherently prone to reporting errors. To explore challenges related to self-report errors, we first derived a reporting error score in the UK Biobank (UKBB; n = 73,127), capturing inconsistent self-reporting in time-invariant phenotypes across multiple measurement occasions. We then performed genome-wide scans on the reporting error score, applied downstream analyses (linkage disequilibrium score regression and Mendelian randomization) and compared its properties to the UKBB participation propensity. Finally, we improved phenotype resolution for 24 measures and inspected the changes in genomic findings. We found that reporting error was present across all 33 assessed self-report measures, with repeatability levels as low as 47% (childhood body size). Reporting error was not independent from UKBB participation, evidenced by the negative genetic correlation between the two outcomes ( r g = −0.77), their shared causes (for example, education) and the loss in self-report accuracy following participation bias correction. Across all analyses, the impact of reporting error ranged from reduced power (for example, for gene discovery) to biased estimates (for example, if present in the exposure variable) and attenuation of genome-wide quantities (for example, 21% relative attenuation in SNP heritability for childhood height). Our findings highlight that both self-report accuracy and selective participation are competing biases and sources of poor reproducibility for biobank-scale research.
Synthetic nanoparticles functionalized with cell membrane-mimicking, bone-targeting, and ROS-controlled release agents for osteoporosis treatment
Authors: Weijun Zhang, Ye Zhang, Zhengan Hao, Pengjie Yao, Jinwu Bai, Hongyu Chen, Xiaoyong Wu, Yuliang Zhong, Deting Xue
Journal: Journal of Controlled Release (2024)