tbuckley/cabot-search huggingface dataset:
Spatial heterogeneity of immune regulators drives dynamic changes of local immune responses, affecting disease outcomes in pancreatic cancer
Authors: Eva Karamitopoulou, Anna Silvia Wenning, Animesh Acharjee, Pauline Aeschbacher, Ilaria Marinoni, Inti Zlobec, Beat Gloor, Aurel Perren
Journal: Clinical Cancer Research (2024)

Pancreatic ductal adenocarcinoma (PDAC) is considered a low-immunogenic (LI) tumor with a "cold" tumor microenvironment and is mostly unresponsive to immune checkpoint blockade therapies. In this study, we decipher the impact of intratumoral heterogeneity of immune determinants on antitumor responses.
Hope for Motherhood: Pregnancy After Allogeneic Hematopoietic Cell Transplantation - a National Multicenter Study
Authors: Katja Sockel, Annika Neu, Maren Goeckenjan, Markus Ditschkowski, Inken Hilgendorf, Nicolaus Kroeger, Francis Ayuketang Ayuk, Friedrich Stölzel, Jan M Middeke, Matthias Eder, Wolfgang Andreas Bethge, Jürgen Finke, Hartmut Bertz, Guido Kobbe, Martin Kaufmann, Uwe Platzbecker, David Beverungen, Christoph Schmid, Malte von Bonin, Katharina Egger-Heidrich, Lisa Heberling, Karolin Trautmann-Grill, Raphael Teipel, Gesine Bug, Johanna Tischer, Alessia Fraccaroli, Matthias Alexander Fante, Daniel Wolff, Thomas Luft, Julia Winkler, Kerstin Schäfer-Eckart, Christof Scheid, Udo Holtick, Stefan Klein, Igor Blau, Andreas Burchert, Gerald Georg Wulf, Justin Hasenkamp, Rainer Schwerdtfeger, Stephan Kaun, Christian Junghanss, Friederike Wortmann, Susann Winter, Helga Neidlinger, Catrin Theuser, Jan Beyersmann, Martin Bornhäuser, Sandra Schmeller, Johannes Schetelig
Journal: Blood (2024)

Abstract Improved long-term survival rates after allogeneic hematopoietic cell transplantation (alloHCT) make family planning for young adult cancer survivors an important topic. However, treatment-related infertility risk poses challenges. To assess pregnancy and birth rates in a contemporary cohort, we conducted a national multicenter study using data from the German Transplant Registry, focusing on adult women aged 18 to 40 years who underwent alloHCT between 2003 and 2018. Of 2654 women who underwent transplantation, 50 women experienced 74 pregnancies, occurring at a median of 4.7 years after transplant. Fifty-seven of these resulted in live births (77%). The annual first birth rate among HCT recipients was 0.45%, which is &amp;gt;6 times lower than in the general population. The probability of a live birth 10 years after HCT was 3.4%. Factors associated with an increased likelihood of pregnancy were younger age at alloHCT, nonmalignant transplant indications, no total body irradiation or a cumulative dose of &amp;lt;8 Gy, and nonmyeloablative/reduced-intensity conditioning. Notably, 72% of pregnancies occurred spontaneously, with assisted reproductive technologies used in the remaining cases. Preterm delivery and low birth weight were more common than in the general population. This study represents the largest data set reporting pregnancies in a cohort of adult female alloHCT recipients. Our findings underscore a meaningful chance of pregnancy in alloHCT recipients. Assisted reproductive technologies techniques are important and funding should be made available. However, the potential for spontaneous pregnancies should not be underestimated, and patients should be informed of the possibility of unexpected pregnancy despite reduced fertility. Further research is warranted to understand the impact of conditioning decisions on fertility preservation.
Sutureless Valves, a “Wireless” Option for Patients With Aortic Valve Disease
Authors: Cristiano Spadaccio, Antonio Nenna, Angelo Pisani, Grzegorz Laskawski, Francesco Nappi, Marc R Moon, Fausto Biancari, Arminder S Jassar, Kevin L Greason, Malakh L Shrestha, Nikolaos Bonaros, David Rose
Journal: Journal of the American College of Cardiology (2024)
Effects of Rapid Uptitration of Neurohormonal Blockade on Effective, Sustainable Decongestion and Outcomes in STRONG-HF
Authors: Jan Biegus, Alexandre Mebazaa, Beth Davison, Gad Cotter, Christopher Edwards, Jelena Čelutkienė, Ovidiu Chioncel, Alain Cohen-Solal, Gerasimos Filippatos, Maria Novosadova, Karen Sliwa, Marianna Adamo, Mattia Arrigo, Carolyn S P Lam, Jozine M Ter Maaten, Benjamin Deniau, Marianela Barros, Kamilė Čerlinskaitė-Bajorė, Albertino Damasceno, Rafael Diaz, Etienne Gayat, Antoine Kimmoun, Peter S Pang, Matteo Pagnesi, Hadiza Saidu, Koji Takagi, Daniela Tomasoni, Adriaan A Voors, Marco Metra, Piotr Ponikowski
Journal: Journal of the American College of Cardiology (2024)
NETosis Impact on Tumor Biology, Radiation, and Systemic Therapy Resistance
Authors: Yvonne M. Mowery, Jason J. Luke
Journal: Clinical Cancer Research (2024)

Neutrophil extracellular trap (NET)osis via lytic neutrophil death or neutrophil activation is associated with standard cancer therapies, notably including radiotherapy; is immunosuppressive; and may enhance metastasis and treatment resistance. This emerging area of research should be prioritized in drug development and standard of care treatment paradigms including radiation therapy, chemotherapy, and immunotherapy. See related article by Teijeira et al., p. 4131.
Vaccine-based immunotherapy and related preclinical models for glioma
Authors: Binghao Zhao, Longping Yao, Maryam Hatami, Wenbin Ma, Thomas Skutella
Journal: Trends in Molecular Medicine (2024)

Glioma, the most common primary malignant tumor in the central nervous system (CNS), lacks effective treatments, and >60% of cases are glioblastoma (GBM), the most aggressive form. Despite advances in immunotherapy, GBM remains highly resistant. Approaches that target tumor antigens expedite the development of immunotherapies, including personalized tumor-specific vaccines, patient-specific target selection, dendritic cell (DC) vaccines, and chimeric antigen receptor (CAR) and T cell receptor (TCR) T cells. Recent studies show promising results in treating GBM and lower-grade glioma (LGG), fostering hope for future immunotherapy. This review discusses tumor vaccines against glioma, preclinical models in immunological research, and the role of CD4
Author Correction: A spatial architecture-embedding HLA signature to predict clinical response to immunotherapy in renal cell carcinoma
Authors: Lisa Kinget, Stefan Naulaerts, Jannes Govaerts, Isaure Vanmeerbeek, Jenny Sprooten, Raquel S Laureano, Nikolina Dubroja, Gautam Shankar, Francesca M Bosisio, Eduard Roussel, Annelies Verbiest, Francesca Finotello, Markus Ausserhofer, Diether Lambrechts, Bram Boeckx, Agnieszka Wozniak, Louis Boon, Johan Kerkhofs, Jessica Zucman-Rossi, Maarten Albersen, Marcella Baldewijns, Benoit Beuselinck, Abhishek D Garg
Journal: Nature Medicine (2024)
Allergenic potency of various foods of mammalian origin in patients with α‐Gal syndrome
Authors: Marija Perusko, Jeanette Grundström, Maria Eldh, Annika Reinhardt, Verena Fuhrmann, Meltem Düzakin, Carl Hamsten, Maria Starkhammar, Danijela Apostolovic, Marianne van Hage
Journal: Allergy (2024)

Abstract Background The α‐Gal syndrome (AGS) is an emerging allergy to mammalian food caused by IgE‐mediated reactions to the carbohydrate galactose‐α‐1,3‐galactose (α‐Gal). Mammalian food sources contain α‐Gal, but the amount differs. The objective of this study was to investigate the allergenic potency of various foods of mammalian origin among AGS patients. Methods Twenty‐six AGS patients were included. Food extracts from innards, lean meats, processed meat products, milk, and whey were analyzed. Immunoblot, ELISA, immunofluorescence, and basophil activation test were used to determine the α‐Gal content, characterize IgE binding, and assess foods' allergenicity. Results The determined amount of α‐Gal, IgE reactivity to food extracts, and food extract potencies to activate patients' basophils correlated well with each other. Pork and beef kidney showed the highest allergenicity. Beef liver and bacon showed allergenicity comparable to that of lean meats. Game meat seemed to have a higher allergenic potency than meats from farm‐raised animals. The processed meat products liver pâté and black pudding, despite lower α‐Gal content, demonstrated moderate allergenicity. Milk showed the lowest allergenicity. IgE reactivity to food extracts was highly similar for all patients and strongly dominated by the α‐Gal epitope. Conclusions The allergenic potency of mammalian meat depends on the origin of the meat, the different cuts, and type of processing, with innards posing the greatest risk to AGS patients. Even processed mammalian meat constitutes a risk. Dairy products show the lowest risk. This study highlights the importance of analyzing even more foods to improve the management of AGS.
Improved prevention and treatment strategies for differentiation syndrome contribute to reducing early mortality in patients with acute promyelocytic leukemia
Authors: Qian Wu, Xiaofei Yang, Jingren Zhang, Mengxing Xue, Xueqing Dou, Zheng Ge, Yifei Chen, Weiying Gu, Weimin Dong, Hongying Cao, Naike Jiang, Xuemei Sun, Zefa Liu, Jinning Shi, Hui Chen, Cixian Zhang, Fengling Min, Hongli Sun, Xiaoli Qian, Hongjian Yuan, Yuan Feng, De-Pei Wu, Suning Chen
Journal: Blood Cancer Journal (2024)
Unlocking opioid neuropeptide dynamics with genetically encoded biosensors
Authors: Chunyang Dong, Raajaram Gowrishankar, Yihan Jin, Xinyi Jenny He, Achla Gupta, Huikun Wang, Nilüfer Sayar-Atasoy, Rodolfo J. Flores, Karan Mahe, Nikki Tjahjono, Ruqiang Liang, Aaron Marley, Grace Or Mizuno, Darren K. Lo, Qingtao Sun, Jennifer L. Whistler, Bo Li, Ivone Gomes, Mark Von Zastrow, Hugo A. Tejeda, Deniz Atasoy, Lakshmi A. Devi, Michael R. Bruchas, Matthew R. Banghart, Lin Tian
Journal: Nature Neuroscience (2024)

Abstract Neuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for the precise dissection of their complex and diverse dynamics in a circuit-specific manner. Opioid peptides modulate pain, reward and aversion and as such have high clinical relevance. To illuminate the spatiotemporal dynamics of endogenous opioid signaling in the brain, we developed a class of genetically encoded fluorescence sensors based on kappa, delta and mu opioid receptors: κLight, δLight and µLight, respectively. We characterized the pharmacological profiles of these sensors in mammalian cells and in dissociated neurons. We used κLight to identify electrical stimulation parameters that trigger endogenous opioid release and the spatiotemporal scale of dynorphin volume transmission in brain slices. Using in vivo fiber photometry in mice, we demonstrated the utility of these sensors in detecting optogenetically driven opioid release and observed differential opioid release dynamics in response to fearful and rewarding conditions.
A nonoscillatory, millisecond-scale embedding of brain state provides insight into behavior
Authors: David F. Parks, Aidan M. Schneider, Yifan Xu, Samuel J. Brunwasser, Samuel Funderburk, Danilo Thurber, Tim Blanche, Eva L. Dyer, David Haussler, Keith B. Hengen
Journal: Nature Neuroscience (2024)
Outpatient reception via collaboration between nurses and a large language model: a randomized controlled trial
Authors: Peixing Wan, Zigeng Huang, Wenjun Tang, Yulan Nie, Dajun Pei, Shaofen Deng, Jing Chen, Yizhi Zhou, Hongru Duan, Qingyu Chen, Erping Long
Journal: Nature Medicine (2024)
BACH2 regulates diversification of regulatory and proinflammatory chromatin states in TH17 cells
Authors: Pratiksha I. Thakore, Alexandra Schnell, Linglin Huang, Maryann Zhao, Yu Hou, Elena Christian, Sarah Zaghouani, Chao Wang, Vasundhara Singh, Anvita Singaraju, Rajesh Kumar Krishnan, Deneen Kozoriz, Sai Ma, Venkat Sankar, Samuele Notarbartolo, Jason D. Buenrostro, Federica Sallusto, Nikolaos A. Patsopoulos, Orit Rozenblatt-Rosen, Vijay K. Kuchroo, Aviv Regev
Journal: Nature Immunology (2024)
Consumer wearable devices for evaluation of heart rate control using digoxin versus beta-blockers: the RATE-AF randomized trial
Authors: Simrat K Gill, Andrey Barsky, Xin Guan, Karina V Bunting, Andreas Karwath, Otilia Tica, Mary Stanbury, Sandra Haynes, Amos Folarin, Richard Dobson, Julia Kurps, Folkert W Asselbergs, Diederick E Grobbee, A John Camm, Marinus J C Eijkemans, Georgios V Gkoutos, Dipak Kotecha
Journal: Nature Medicine (2024)

Abstract Consumer-grade wearable technology has the potential to support clinical research and patient management. Here, we report results from the RATE-AF trial wearables study, which was designed to compare heart rate in older, multimorbid patients with permanent atrial fibrillation and heart failure who were randomized to treatment with either digoxin or beta-blockers. Heart rate ( n = 143,379,796) and physical activity ( n = 23,704,307) intervals were obtained from 53 participants (mean age 75.6 years (s.d. 8.4), 40% women) using a wrist-worn wearable linked to a smartphone for 20 weeks. Heart rates in participants treated with digoxin versus beta-blockers were not significantly different (regression coefficient 1.22 (95% confidence interval (CI) −2.82 to 5.27; P = 0.55); adjusted 0.66 (95% CI −3.45 to 4.77; P = 0.75)). No difference in heart rate was observed between the two groups of patients after accounting for physical activity ( P = 0.74) or patients with high activity levels (≥30,000 steps per week; P = 0.97). Using a convolutional neural network designed to account for missing data, we found that wearable device data could predict New York Heart Association functional class 5 months after baseline assessment similarly to standard clinical measures of electrocardiographic heart rate and 6-minute walk test (F1 score 0.56 (95% CI 0.41 to 0.70) versus 0.55 (95% CI 0.41 to 0.68); P = 0.88 for comparison). The results of this study indicate that digoxin and beta-blockers have equivalent effects on heart rate in atrial fibrillation at rest and on exertion, and suggest that dynamic monitoring of individuals with arrhythmia using wearable technology could be an alternative to in-person assessment. ClinicalTrials.gov identifier: NCT02391337 .
Oncogenic and immunological targets for matched therapy of pediatric blood cancer patients: Dutch iTHER study experience
Authors: Judith M. Boer, Uri Ilan, Aurélie Boeree, Karin P. S. Langenberg, Jan Koster, Marco J. Koudijs, Jayne Y. Hehir‐Kwa, Stefan Nierkens, Corinne Rossi, Jan J. Molenaar, Bianca F. Goemans, Monique L. den Boer, C. Michel Zwaan
Journal: HemaSphere (2024)

Over the past 10 years, institutional and national molecular tumor boards have been implemented for relapsed or refractory pediatric cancer to prioritize targeted drugs for individualized treatment based on actionable oncogenic lesions, including the Dutch iTHER platform. Hematological malignancies form a minority in precision medicine studies. Here, we report on 56 iTHER leukemia/lymphoma patients for which we considered cell surface markers and oncogenic aberrations as actionable events, supplemented with ex vivo drug sensitivity for six patients. Prior to iTHER registration, 34% of the patients had received allogeneic hematopoietic cell transplantation (HCT) and 18% CAR-T therapy. For 51 patients (91%), a sample with sufficient tumor percentage (≥20%) required for comprehensive diagnostic testing was obtained. Up to 10 oncogenic actionable events were prioritized in 49/51 patients, and immunotherapy targets were identified in all profiled patients. Targeted treatment(s) based on the iTHER advice was given to 24 of 51 patients (47%), including immunotherapy in 17 patients, a targeted drug matching an oncogenic aberration in 12 patients, and a drug based on ex vivo drug sensitivity in one patient, resulting in objective responses and a bridge to HCT in the majority of the patients. In conclusion, comprehensive profiling of relapsed/refractory hematological malignancies showed multiple oncogenic and immunotherapy targets for a precision medicine approach, which requires multidisciplinary expertise to prioritize the best treatment options for this rare, heavily pretreated pediatric population.
Recommendations for diagnosis, treatment, and prevention of iron deficiency and iron deficiency anemia
Authors: Achille Iolascon, Immacolata Andolfo, Roberta Russo, Mayka Sanchez, Fabiana Busti, Dorine Swinkels, Patricia Aguilar Martinez, Rayan Bou‐Fakhredin, Martina U. Muckenthaler, Sule Unal, Graça Porto, Tomas Ganz, Antonis Kattamis, Lucia De Franceschi, Maria Domenica Cappellini, Malcolm G. Munro, Ali Taher
Journal: HemaSphere (2024)

Abstract Iron is an essential nutrient and a constituent of ferroproteins and enzymes crucial for human life. Generally, nonmenstruating individuals preserve iron very efficiently, losing less than 0.1% of their body iron content each day, an amount that is replaced through dietary iron absorption. Most of the iron is in the hemoglobin (Hb) of red blood cells (RBCs); thus, blood loss is the most common cause of acute iron depletion and anemia worldwide, and reduced hemoglobin synthesis and anemia are the most common consequences of low plasma iron concentrations. The term iron deficiency (ID) refers to the reduction of total body iron stores due to impaired nutrition, reduced absorption secondary to gastrointestinal conditions, increased blood loss, and increased needs as in pregnancy. Iron deficiency anemia (IDA) is defined as low Hb or hematocrit associated with microcytic and hypochromic erythrocytes and low RBC count due to iron deficiency. IDA most commonly affects women of reproductive age, the developing fetus, children, patients with chronic and inflammatory diseases, and the elderly. IDA is the most frequent hematological disorder in children, with an incidence in industrialized countries of 20.1% between 0 and 4 years of age and 5.9% between 5 and 14 years (39% and 48.1% in developing countries). The diagnosis, management, and treatment of patients with ID and IDA change depending on age and gender and during pregnancy. We herein summarize what is known about the diagnosis, treatment, and prevention of ID and IDA and formulate a specific set of recommendations on this topic.
Reduced adipocyte glutaminase activity promotes energy expenditure and metabolic health
Authors: Simon Lecoutre, Salwan Maqdasy, David Rizo-Roca, Gianluca Renzi, Ivan Vlassakev, Lynn M. Alaeddine, Romane Higos, Jutta Jalkanen, Jiawei Zhong, Danae S. Zareifi, Scott Frendo-Cumbo, Lucas Massier, Ondrej Hodek, Marta Juvany, Thomas Moritz, Thais de Castro Barbosa, Muhmmad Omar-Hmeadi, Marta López-Yus, Fatiha Merabtene, Jimon Boniface Abatan, Geneviève Marcelin, Elie-Julien El Hachem, Christine Rouault, Martin O. Bergo, Paul Petrus, Juleen R. Zierath, Karine Clément, Anna Krook, Niklas Mejhert, Mikael Rydén
Journal: Nature Metabolism (2024)

Glutamine and glutamate are interconverted by several enzymes and alterations in this metabolic cycle are linked to cardiometabolic traits. Herein, we show that obesity-associated insulin resistance is characterized by decreased plasma and white adipose tissue glutamine-to-glutamate ratios. We couple these stoichiometric changes to perturbed fat cell glutaminase and glutamine synthase messenger RNA and protein abundance, which together promote glutaminolysis. In human white adipocytes, reductions in glutaminase activity promote aerobic glycolysis and mitochondrial oxidative capacity via increases in hypoxia-inducible factor 1α abundance, lactate levels and p38 mitogen-activated protein kinase signalling. Systemic glutaminase inhibition in male and female mice, or genetically in adipocytes of male mice, triggers the activation of thermogenic gene programs in inguinal adipocytes. Consequently, the knockout mice display higher energy expenditure and improved glucose tolerance compared to control littermates, even under high-fat diet conditions. Altogether, our findings highlight white adipocyte glutamine turnover as an important determinant of energy expenditure and metabolic health.
Building a translational cancer dependency map for The Cancer Genome Atlas
Authors: Xu Shi, Christos Gekas, Daniel Verduzco, Sakina Petiwala, Cynthia Jeffries, Charles Lu, Erin Murphy, Tifani Anton, Andy H. Vo, Zhiguang Xiao, Padmini Narayanan, Bee-Chun Sun, Aloma L. D’Souza, J. Matthew Barnes, Somdutta Roy, Cyril Ramathal, Michael J. Flister, Zoltan Dezso
Journal: Nature Cancer (2024)

Cancer dependency maps have accelerated the discovery of tumor vulnerabilities that can be exploited as drug targets when translatable to patients. The Cancer Genome Atlas (TCGA) is a compendium of 'maps' detailing the genetic, epigenetic and molecular changes that occur during the pathogenesis of cancer, yet it lacks a dependency map to translate gene essentiality in patient tumors. Here, we used machine learning to build translational dependency maps for patient tumors, which identified tumor vulnerabilities that predict drug responses and disease outcomes. A similar approach was used to map gene tolerability in healthy tissues to prioritize tumor vulnerabilities with the best therapeutic windows. A subset of patient-translatable synthetic lethalities were experimentally tested, including PAPSS1/PAPSS12 and CNOT7/CNOT78, which were validated in vitro and in vivo. Notably, PAPSS1 synthetic lethality was driven by collateral deletion of PAPSS2 with PTEN and was correlated with patient survival. Finally, the translational dependency map is provided as a web-based application for exploring tumor vulnerabilities.
Zwitterionic Poly‐Carboxybetaine Polymers Restore Lubrication of Inflamed Articular Cartilage
Authors: Patrick Weber, Maryam Asadikorayem, Marcy Zenobi‐Wong
Journal: Advanced Healthcare Materials (2024)

Osteoarthritis is a degenerative joint disease that is associated with decreased synovial fluid viscosity and increased cartilage friction. Though viscosupplements are available for decades, their clinical efficacy is limited and there is ample need for more effective joint lubricants. This study first evaluates the tribological and biochemical properties of bovine articular cartilage explants after stimulation with the inflammatory cytokine interleukin-1β. This model is then used to investigate the tribological potential of carboxybetaine (CBAA)-based zwitterionic polymers of linear and bottlebrush architecture. Due to their affinity for cartilage tissue, these polymers form a highly hydrated surface layer that decreases friction under high load in the boundary lubrication regime. For linear pCBAA, these benefits are retained over several weeks and the relaxation time of cartilage explants under compression is furthermore decreased, thereby potentially boosting the weeping lubrication mechanism. Bottlebrush bb-pCBAA shows smaller benefits under boundary lubrication but is more viscous than linear pCBAA, therefore providing better lubrication under low load in the fluid-film regime and enabling a longer residence time to bind to the cartilage surface. Showing how CBAA-based polymers restore the lost lubrication mechanisms during inflammation can inspire the next steps toward more effective joint lubricants in the future.