tbuckley/cabot-search huggingface dataset:
Multiomic analyses uncover immunological signatures in acute and chronic coronary syndromes
Authors: Kami Pekayvaz, Corinna Losert, Viktoria Knottenberg, Christoph Gold, Irene V. van Blokland, Roy Oelen, Hilde E. Groot, Jan Walter Benjamins, Sophia Brambs, Rainer Kaiser, Adrian Gottschlich, Gordon Victor Hoffmann, Luke Eivers, Alejandro Martinez-Navarro, Nils Bruns, Susanne Stiller, Sezer Akgöl, Keyang Yue, Vivien Polewka, Raphael Escaig, Markus Joppich, Aleksandar Janjic, Oliver Popp, Sebastian Kobold, Tobias Petzold, Ralf Zimmer, Wolfgang Enard, Kathrin Saar, Philipp Mertins, Norbert Huebner, Pim van der Harst, Lude H. Franke, Monique G. P. van der Wijst, Steffen Massberg, Matthias Heinig, Leo Nicolai, Konstantin Stark
Journal: Nature Medicine (2024)

Abstract Acute and chronic coronary syndromes (ACS and CCS) are leading causes of mortality. Inflammation is considered a key pathogenic driver of these diseases, but the underlying immune states and their clinical implications remain poorly understood. Multiomic factor analysis (MOFA) allows unsupervised data exploration across multiple data types, identifying major axes of variation and associating these with underlying molecular processes. We hypothesized that applying MOFA to multiomic data obtained from blood might uncover hidden sources of variance and provide pathophysiological insights linked to clinical needs. Here we compile a longitudinal multiomic dataset of the systemic immune landscape in both ACS and CCS ( n = 62 patients in total, n = 15 women and n = 47 men) and validate this in an external cohort ( n = 55 patients in total, n = 11 women and n = 44 men). MOFA reveals multicellular immune signatures characterized by distinct monocyte, natural killer and T cell substates and immune-communication pathways that explain a large proportion of inter-patient variance. We also identify specific factors that reflect disease state or associate with treatment outcome in ACS as measured using left ventricular ejection fraction. Hence, this study provides proof-of-concept evidence for the ability of MOFA to uncover multicellular immune programs in cardiovascular disease, opening new directions for mechanistic, biomarker and therapeutic studies.
Evaluating Debio 1347 in Patients with <i>FGFR</i> Fusion-Positive Advanced Solid Tumors from the FUZE Multicenter, Open-Label, Phase II Basket Trial
Authors: Petros Grivas, Elena Garralda, Funda Meric-Bernstam, Ingo K. Mellinghoff, Lipika Goyal, James J. Harding, E. Claire Dees, Rastislav Bahleda, Nilofer S. Azad, Asha Karippot, Razelle Kurzrock, Josep Tabernero, Juha Kononen, Matthew C.H. Ng, Rutika Mehta, Nataliya V. Uboha, Frédéric Bigot, Valentina Boni, Samantha E. Bowyer, Valeriy Breder, Andrés Cervantes, Nancy Chan, James M. Cleary, Mallika Dhawan, Rikke L. Eefsen, James Ewing, Donna M. Graham, Tormod K. Guren, Jin Won Kim, Krassimir Koynov, Do-Youn Oh, Rebecca Redman, Chia-Jui Yen, David Spetzler, Marie-Claude Roubaudi-Fraschini, Valerie Nicolas-Metral, Rafik Ait-Sarkouh, Claudio Zanna, Abdallah Ennaji, Anna Pokorska-Bocci, Keith T. Flaherty
Journal: Clinical Cancer Research (2024)

This multicenter phase II basket trial investigated the efficacy, safety, and pharmacokinetics of Debio 1347, an investigational, oral, highly selective, ATP-competitive, small molecule inhibitor of FGFR1-3, in patients with solid tumors harboring a functional FGFR1-3 fusion.
Facile One-Pot Synthesis of Ir(III) Bodipy Polymeric Gemini Nanoparticles for Tumor Selective NIR Photoactivated Anticancer Therapy
Authors: Ganghao Liang, Nicolás Montesdeoca, Dongsheng Tang, Bin Wang, Haihua Xiao, Johannes Karges, Kun Shang
Journal: Biomaterials (2024)
Novel approaches in IBD therapy: targeting the gut microbiota-bile acid axis
Authors: Yinping Pan, Haojie Zhang, Minghui Li, Tingjing He, Sihao Guo, Liancai Zhu, Jun Tan, Bochu Wang
Journal: Gut Microbes (2024)

Inflammatory bowel disease (IBD) is a chronic and recurrent condition affecting the gastrointestinal tract. Disturbed gut microbiota and abnormal bile acid (BA) metabolism are notable in IBD, suggesting a bidirectional relationship. Specifically, the diversity of the gut microbiota influences BA composition, whereas altered BA profiles can disrupt the microbiota. IBD patients often exhibit increased primary bile acid and reduced secondary bile acid concentrations due to a diminished bacteria population essential for BA metabolism. This imbalance activates BA receptors, undermining intestinal integrity and immune function. Consequently, targeting the microbiota-BA axis may rectify these disturbances, offering symptomatic relief in IBD. Here, the interplay between gut microbiota and bile acids (BAs) is reviewed, with a particular focus on the role of gut microbiota in mediating bile acid biotransformation, and contributions of the gut microbiota-BA axis to IBD pathology to unveil potential novel therapeutic avenues for IBD.
Telehealth and Telemedicine
Authors: Gina M. Bonica, Richard W. Johns, Hossein Jadvar
Journal: Clinical Nuclear Medicine (2024)

Telehealth and telemedicine experienced remarkable growth during and after the recent COVID-19 pandemic. Telehealth is generally defined as nonclinical services that employ telecommunication technology. Telemedicine refers more specifically to remote clinical services including diagnosis, monitoring, and treatment. Nuclear medicine is no exception in employing telemedicine increasingly in clinical practice for image interpretation and treatment consultation and care delivery supervision. There is no doubt that soon, the use of tele-nuclear medicine will increase, comparable to the employment of telecommunication in other fields of medicine. We review the medicolegal and regulatory aspects of the evolution in the clinical practice of medicine through telehealth and telemedicine.
Myelodysplastic Syndrome Related to Successful Treatment With177Lu-PSMA for Metastatic Castration–Refractory Prostate Cancer
Authors: Lavinia Vija Racaru, Mehdi Krim, Valérian Rivet, Loic Mourey, Pr Frederic Courbon
Journal: Clinical Nuclear Medicine (2024)

177 Lu-vipivotide tetraxetan ( 177 Lu-PSMA-617/LuPSMA) received recent EMA approval for metastatic castration-resistant prostate cancer, with promising data for earlier stages. Secondary myeloid neoplasm following exposure to DNA-damaging therapy (therapy-related myelodysplastic syndrome [MDS]) is a rare severe complication of 177 Lu-oxodotreotide. We present a 77-year-old man, with synchronous liver, bone, and lymph node metastatic prostate cancer, having developed a low-risk MDS with SF3B1 mutation, 1 month after the sixth administration of LuPSMA. Although on partial metabolic and biological response with PSA nadir at 7 months after therapy, life quality was significantly altered by MDS.
BET bromodomain inhibition potentiates radiosensitivity in models of H3K27-altered diffuse midline glioma
Authors: Jun Watanabe, Matthew R. Clutter, Michael J. Gullette, Takahiro Sasaki, Eita Uchida, Savneet Kaur, Yan Mo, Kouki Abe, Yukitomo Ishi, Nozomu Takata, Manabu Natsumeda, Samantha Gadd, Zhiguo Zhang, Oren J. Becher, Rintaro Hashizume
Journal: Journal of Clinical Investigation (2024)

Diffuse midline glioma (DMG) H3K27-altered is one of the devastating childhood cancers. Radiation therapy remains the only effective treatment yet provides a 5-year survival rate of only 1%. Several clinical trials have attempted to enhance radiation anti-tumor activity using radiosensitizing agents, although none have been successful. Given this, there is a critical need for identifying effective therapeutics to enhance radiation sensitivity for the treatment of DMG. Using high-throughput radiosensitivity screening, we identified bromo- and extra-terminal domain (BET) protein inhibitors as potent radiosensitizers in DMG cells. Genetic and pharmacologic inhibition of BET bromodomain activity reduced DMG cell proliferation and enhanced radiation-induced DNA damage by inhibiting DNA repair pathways. RNA-seq and CUT & RUN showed that BET bromodomain inhibitors regulate the expression of DNA repair genes mediated by H3K27 acetylation at enhancers. BET bromodomain inhibitors enhanced DMG radiation-response in patient-derived xenografts as well as genetically engineered mouse models. Together, our results highlight BET bromodomain inhibitors as radiosensitizer and provide a rationale for developing combination therapy with radiation for the treatment of DMG.
A platinum(IV)–artesunate complex triggers ferroptosis by boosting cytoplasmic and mitochondrial lipid peroxidation to enhance tumor immunotherapy
Authors: Renming Fan, Aohua Deng, Ruizhuo Lin, Shuo Zhang, Caiyan Cheng, Junyan Zhuang, Yongrui Hai, Minggao Zhao, Le Yang, Gaofei Wei
Journal: MedComm (2024)

Abstract Ferroptosis is an iron‐dependent cell death form that initiates lipid peroxidation (LPO) in tumors. In recent years, there has been growing interest on ferroptosis, but how to propel it forward translational medicine remains in mist. Although experimental ferroptosis inducers such as RSL3 and erastin have demonstrated bioactivity in vitro, the poor antitumor outcome in animal model limits their development. In this study, we reveal a novel ferroptosis inducer, oxaliplatin–artesunate (OART), which exhibits substantial bioactivity in vitro and vivo, and we verify its feasibility in cancer immunotherapy. For mechanism, OART induces cytoplasmic and mitochondrial LPO to promote tumor ferroptosis, via inhibiting glutathione‐mediated ferroptosis defense system, enhancing iron‐dependent Fenton reaction, and initiating mitochondrial LPO. The destroyed mitochondrial membrane potential, disturbed mitochondrial fusion and fission, as well as downregulation of dihydroorotate dehydrogenase mutually contribute to mitochondrial LPO. Consequently, OART enhances tumor immunogenicity by releasing damage associated molecular patterns and promoting antigen presenting cells maturation, thereby transforming tumor environment from immunosuppressive to immunosensitive. By establishing in vivo model of tumorigenesis and lung metastasis, we verified that OART improves the systematic immune response. In summary, OART has enormous clinical potential for ferroptosis‐based cancer therapy in translational medicine.
Two-component system RstAB promotes the pathogenicity of adherent-invasive <i>Escherichia coli</i> in response to acidic conditions within macrophages
Authors: Ting Yao, Xingmei Liu, Dan Li, Yu Huang, Wen Yang, Ruiying Liu, Qian Wang, Xueping Li, Jiarui Zhou, Chen Jin, Yutao Liu, Bin Yang, Yu Pang
Journal: Gut Microbes (2024)

Adherent-invasive
225Ac-PSMA-617 Augmentation in High-Risk mCRPC Undergoing 177Lu-PSMA-617 Radioligand Therapy
Authors: Florian Rosar, Caroline Burgard, Luna Vanessa Rohloff, Arne Blickle, Mark Bartholomä, Stephan Maus, Sven Petto, Andrea Schaefer-Schuler, Samer Ezziddin
Journal: Clinical Nuclear Medicine (2024)

This pilot study investigates the efficacy and safety profile as well as predictive biomarkers of 225 Ac-PSMA-617-augmented 177 Lu-PSMA-617 radioligand therapy (RLT) in a cohort of high-risk patients with metastatic castration-resistant prostate cancer (mCRPC), enrolled in a prospective registry (NCT04833517).
Considerations for biomarker strategies in clinical trials investigating tau-targeting therapeutics for Alzheimer’s disease
Authors: Lewis K Penny, Richard Lofthouse, Mohammad Arastoo, Andy Porter, Soumya Palliyil, Charles R Harrington, Claude M Wischik
Journal: Translational Neurodegeneration (2024)

Abstract The use of biomarker-led clinical trial designs has been transformative for investigating amyloid-targeting therapies for Alzheimer’s disease (AD). The designs have ensured the correct selection of patients on these trials, supported target engagement and have been used to support claims of disease modification and clinical efficacy. Ultimately, this has recently led to approval of disease-modifying, amyloid-targeting therapies for AD; something that should be noted for clinical trials investigating tau-targeting therapies for AD. There is a clear overlap of the purpose of biomarker use at each stage of clinical development between amyloid-targeting and tau-targeting clinical trials. However, there are differences within the potential context of use and interpretation for some biomarkers in particular measurements of amyloid and utility of soluble, phosphorylated tau biomarkers. Given the complexities of tau in health and disease, it is paramount that therapies target disease-relevant tau and, in parallel, appropriate assays of target engagement are developed. Tau positron emission tomography, fluid biomarkers reflecting tau pathology and downstream measures of neurodegeneration will be important both for participant recruitment and for monitoring disease-modification in tau-targeting clinical trials. Bespoke design of biomarker strategies and interpretations for different modalities and tau-based targets should also be considered.
Rethinking therapeutic strategies of dual‐target drugs: An update on pharmacological small‐molecule compounds in cancer
Authors: Yiren Yang, Yi Mou, Lin‐Xi Wan, Shiou Zhu, Guan Wang, Huiyuan Gao, Bo Liu
Journal: Medicinal Research Reviews (2024)

Oncogenes and tumor suppressors are well-known to orchestrate several signaling cascades, regulate extracellular and intracellular stimuli, and ultimately control the fate of cancer cells. Accumulating evidence has recently revealed that perturbation of these key modulators by mutations or abnormal protein expressions are closely associated with drug resistance in cancer therapy; however, the inherent drug resistance or compensatory mechanism remains to be clarified for targeted drug discovery. Thus, dual-target drug development has been widely reported to be a promising therapeutic strategy for improving drug efficiency or overcoming resistance mechanisms. In this review, we provide an overview of the therapeutic strategies of dual-target drugs, especially focusing on pharmacological small-molecule compounds in cancer, including small molecules targeting mutation resistance, compensatory mechanisms, synthetic lethality, synergistic effects, and other new emerging strategies. Together, these therapeutic strategies of dual-target drugs would shed light on discovering more novel candidate small-molecule drugs for the future cancer treatment.
Chimeric antigen receptor T‐cell therapy in secondary central nervous system lymphoma: A multicenter analysis
Authors: Aseel Alsouqi, Gulrayz Ahmed, Juntian Wang, Giulio Cassanello, Aniko Szabo, Alexandra E. Rojek, Peter A. Riedell, Farrukh Awan, Laura Samples, Mazyar Shadman, Marie Hu, Veronika Bachanova, William Wesson, Nausheen Ahmed, Madiha Iqbal, Mohamed A. Kharfan‐Dabaja, Michael Scordo, P. Connor Johnson, Yi‐Bin Chen, Sawa Ito, Mehdi Hamadani, Matthew Frigault
Journal: American Journal of Hematology (2024)
Potent human monoclonal antibodies targeting Epstein-Barr virus gp42 reveal vulnerable sites for virus infection
Authors: Ge-Xin Zhao, Xin-Yan Fang, Guo-Long Bu, Shuai-Jia-Bin Chen, Cong Sun, Ting Li, Chu Xie, Yu Wang, Shu-Xin Li, Ning Meng, Guo-Kai Feng, Qian Zhong, Xiang-Wei Kong, Zheng Liu, Mu-Sheng Zeng
Journal: Cell Reports Medicine (2024)

Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1. These antibodies effectively neutralize EBV infection in vitro and in vivo while preserving gp42's interaction with the human leukocyte antigen class II (HLA-II) receptor. Structural analysis unveils their distinct binding epitopes on gp42, different from the HLA-II binding site. Furthermore, both 2B7 and 2C1 demonstrate potent neutralization of EBV infection in HLA-II-positive epithelial cells, expanding our understanding of gp42's role. Overall, this study introduces two human anti-gp42 antibodies with potential implications for developing EBV vaccines targeting gp42 epitopes, addressing a critical gap in EBV research.
A global initiative for ecological and evolutionary hologenomics
Authors: Aoife Leonard, Javier Abalos, Titus Adhola, Windsor Aguirre, Ostaizka Aizpurua, Shahzad Ali, Franco Andreone, Fabien Aubret, Hefer D. Ávila-Palma, Lizbeth Fabiola Bautista Alcantara, Juan F. Beltrán, Rachel Berg, Thomas Bjørneboe Berg, Sandro Bertolino, Daniel T. Blumstein, Bazartseren Boldgiv, Zbigniew Borowski, Jean Philippe Boubli, Sven Büchner, Carlos Cabido, Carlos Camacho, Juan C. Chaparro, Anne Charmantier, Guillermo D'Elía, Luis P. da Silva, Bo Dalsgaard, Christophe de Franceschi, Ferran de la Cruz, Noé U. de la Sancha, Mathieu Denoël, Raphael Eisenhofer, Nathalie Feiner, Joana M. Fernandes, Jordi Figuerola, Leonida Fusani, Laura Gangoso, Roberto García-Roa, Stefania Gasperini, Nanna Gaun, M. Thomas, P. Gilbert, Ivan Gomez-Mestre, Gary R. Graves, Jim Groombridge, Emilie A. Hardouin, Mauricio Hernández, L. Gerardo Herrera M., Kathy Hodder, Peter A. Hosner, Natali Hurtado, Javier Juste, Sarah C.L. Knowles, Kevin D. Kohl, Carmi Korine, Yurii V. Kornilev, Stephanie Kramer-Schadt, Xavier Lambin, Ella Z. Lattenkamp, Jonas Lauritsen, Guoliang Li, Celeste María López, Adrià López Baucells, Tali Magory Cohen, Emiliano Manzo, Mélanie Marteau, Lynn B. Martin, Garazi Martin Bideguren, Maria Vittoria Mazzamuto, Ara Monadjem, Pirmin Nietlisbach, Daniel Bilyeli Øksnebjerg, Jasmin G. Packer, Michael L. Pepke, Juan M. Peralta-Sánchez, Adrián Perdomo, Guillem Pérez i de Lanuza, Carlotta Pietroni, Mathilde Poyet, Carsten Rahbek, Thiruvarangan Ramaraj, Yuliaxis Ramayo Caldas, Orly Razgour, Hugo Rebelo, Jiří Reif, Rebecca Rimbach, Ricardo Rocha, Rita G. Rocha, Carlos Rodríguez Fernandes, Claudia Romeo, Suvi Ruuskanen, Scott K. Sakaluk, Francesca Santicchia, Tom Sarraude, Rune Sørås, Martina Spada, Michael A. Steele, Mason R. Stothart, Emina Sunje, Alex O. Sutton, Marta Szulkin, Yu Takahata, Charles F. Thompson, Kasper Thorup, Geizecler Tomazetto, Laura Torrent, Nia Toshkova, Claudia Tranquillo, Manfredo Alejandro Turcios-Casco, Tobias Uller, Isolde van Riemsdijk, Guillermo Velo-Antón, Goedele Verbeylen, Elin Videvall, Christian C. Voigt, Lucas A. Wauters, Maren Wellenreuther, Alexey Yanchukov, Antton Alberdi
Journal: Trends in Ecology & Evolution (2024)
Operationalizing patient-centered cancer care in low- and middle-income countries
Authors: Nirmala Bhoo-Pathy, Carolyn Taylor, Karla Unger-Saldaña
Journal: Cell Reports Medicine (2024)

Rising cancer survival rates in low- and middle-income countries (LMICs) necessitate a paradigm shift to holistic, patient-driven care, focusing on meaningful outcomes aligned with individual values. Data, co-creation, continuous improvement, and collaboration are key. By prioritizing patient-defined metrics and patient empowerment, LMICs can transform cancer care, fostering sustained well-being beyond disease control. Rising cancer survival rates in low- and middle-income countries (LMICs) necessitate a paradigm shift to holistic, patient-driven care, focusing on meaningful outcomes aligned with individual values. Data, co-creation, continuous improvement, and collaboration are key. By prioritizing patient-defined metrics and patient empowerment, LMICs can transform cancer care, fostering sustained well-being beyond disease control.
A Primary Care–Based Weight Navigation Program
Authors: Dina H. Griauzde, Cassie D. Turner, Amal Othman, Lauren Oshman, Jonathan Gabison, Patricia K. Arizaca-Dileo, Eric Walford, James Henderson, Deena Beckius, Joyce M. Lee, Eli W. Carter, Chris Dallas, Kathyrn Herrera-Theut, Caroline R. Richardson, Jeffrey T. Kullgren, Gretchen Piatt, Michele Heisler, Andrew Kraftson
Journal: JAMA Network Open (2024)

Evidence-based weight management treatments (WMTs) are underused; strategies are needed to increase WMT use and patients' weight loss. To evaluate the association of a primary care-based weight navigation program (WNP) with WMT use and weight loss. This cohort study comprised a retrospective evaluation of a quality improvement program conducted from October 1, 2020, to September 30, 2021. Data analysis was performed from August 2, 2022, to March 7, 2024. Adults with obesity and 1 or more weight-related condition from intervention and control sites in a large academic health system in the Midwestern US were propensity matched on sociodemographic and clinical factors. WNP, in which American Board of Obesity Medicine-certified primary care physicians offered weight-focused visits and guided patients' selection of preference-sensitive WMTs. Primary outcomes were feasibility measures, including rates of referral to and engagement in the WNP. Secondary outcomes were mean weight loss, percentage of patients achieving 5% or more and 10% or more weight loss, referral to WMTs, and number of antiobesity medication prescriptions at 12 months. Of 264 patients, 181 (68.6%) were female and mean (SD) age was 49.5 (13.0) years; there were no significant differences in demographic characteristics between WNP patients (n = 132) and matched controls (n = 132). Of 1159 WNP-eligible patients, 219 (18.9%) were referred to the WNP and 132 (11.4%) completed a visit. In a difference-in-differences analysis, WNP patients lost 4.9 kg more than matched controls (95% CI, 2.11-7.76; P < .001), had 4.4% greater weight loss (95% CI, 2.2%-6.4%; P < .001), and were more likely to achieve 5% or more weight loss (odds ratio [OR], 2.90; 95% CI, 1.54-5.58); average marginal effects, 21.2%; 95% CI, 8.8%-33.6%) and 10% or more weight loss (OR, 7.19; 95% CI, 2.55-25.9; average marginal effects, 17.4%; 95% CI, 8.7%-26.2%). Patients in the WNP group were referred at higher rates to WMTs, including bariatric surgery (18.9% vs 9.1%; P = .02), a low-calorie meal replacement program (16.7% vs 3.8%; P < .001), and a Mediterranean-style diet and activity program (10.6% vs 1.5%; P = .002). There were no between-group differences in antiobesity medication prescribing. The findings of this cohort study suggest that WNP is feasible and associated with greater WMT use and weight loss than matched controls. The WNP warrants evaluation in a large-scale trial.
Hospitalizations for Chronic Obstructive Pulmonary Disease Exacerbation During COVID-19
Authors: Arnaud Bourdin, Engi Ahmed, Isabelle Vachier, Nicolas Roche, Joana Pissarra, Nicolas Malafaye, Nicolas Molinari
Journal: JAMA Network Open (2024)

This cross-sectional study investigates changes in the number of chronic obstructive pulmonary disease (COPD)–related admissions before, during, and after the COVID-19 pandemic in France.
β-Blocker Use and Clinical Outcomes in Patients With COPD Following Acute Myocardial Infarction
Authors: David C. LaFon, Erika S. Helgeson, Sarah Lindberg, Helen Voelker, Surya P. Bhatt, Richard Casaburi, Steven J. Cassady, John Connett, Gerard J. Criner, Umur Hatipoglu, David A. Kaminsky, Ken M. Kunisaki, Stephen C. Lazarus, Charlene E. McEvoy, Robert M. Reed, Frank C. Sciurba, William Stringer, Mark T. Dransfield
Journal: JAMA Network Open (2024)

While β-blockers are associated with decreased mortality in cardiovascular disease (CVD), exacerbation-prone patients with chronic obstructive pulmonary disease (COPD) who received metoprolol in the Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (BLOCK-COPD) trial experienced increased risk of exacerbations requiring hospitalization. However, the study excluded individuals with established indications for the drug, raising questions about the overall risk and benefit in patients with COPD following acute myocardial infarction (AMI).