tbuckley/cabot-search huggingface dataset:
Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy
Authors: Michael Hallek
Journal: American Journal of Hematology (2025)

ABSTRACT Disease Overview Chronic lymphocytic leukemia (CLL) is the most frequent type of leukemia. It typically occurs in older patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that interfere with the regulation of proliferation and apoptosis in clonal B‐cells. Diagnosis The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B‐lymphocytes, which identify a clonal B‐cell population carrying the CD5 antigen as well as typical B‐cell markers. Prognosis and Staging Two clinical staging systems, Rai and Binet, provide prognostic information by using the results of physical examination and blood counts. Various biological and genetic markers provide additional prognostic information. Deletions of the short arm of chromosome 17 (del(17p)) and/or mutations of the TP53 gene predict a shorter time to progression with most targeted therapies. The CLL international prognostic index (CLL‐IPI) integrates genetic, biological, and clinical variables to identify distinct risk groups of patients with CLL. The CLL‐IPI retains its significance in the era of targeted agents, but the overall prognosis of CLL patients with high‐risk stages has improved. Therapy Only patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. When treatment is indicated, several therapeutic options exist: combinations of the BCL2 inhibitor venetoclax with obinutuzumab, or venetoclax with ibrutinib, or monotherapy with one of the inhibitors of Bruton tyrosine kinase (BTK). At relapse, the initial treatment may be repeated if the treatment‐free interval exceeds 3 years. If the leukemia relapses earlier, therapy should be changed using an alternative regimen. Future Challenges Combinations of targeted agents now provide efficient therapies with a fixed duration that generate deep and durable remissions. These fixed‐duration therapies have gained territory in the management of CLL, as they are cost‐effective, avoid the emergence of resistance, and offer treatment free time to the patient. The cure rate of these novel combination regimens is unknown. Moreover, the optimal sequencing of targeted therapies remains to be determined. A medical challenge is to treat patients who are double‐refractory to both BTK and BCL2 inhibitors. These patients need to be treated within experimental protocols using novel drugs.
A Solvatochromic and Photosensitized Lipid Droplet Probe Detects Local Polarity Heterogeneity and Labels Interacting Proteins in Human Liver Disease Tissue
Authors: Yuhui Wang, Hengke Guo, Wang Wan, Biao Jing, Yulong Bai, Jialu Sun, Xin Zhang, Zhenming Gao, Yu Liu, Xuepeng Dong
Journal: Advanced Healthcare Materials (2025)

Abstract The intricate morphology, physicochemical properties, and interacting proteins of lipid droplets (LDs) are associated with cell metabolism and related diseases. To uncover these layers of information, a solvatochromic and photosensitized LDs‐targeted probe based on the furan‐based D‐D‐π‐A scaffold is developed to offer the following integrated functions. First, the turn‐on fluorescence of the probe upon selectively binding to LDs allows for direct visualization of their location and morphology. Second, its solvatochromic fluorescence with linear correlation to polarity quantifies micro‐environmental heterogeneity among LDs. Third, the unique photosensitized properties enable photocatalytic proximity labeling and enrichment of LDs‐interacting proteins, ready for potential downstream proteomic analysis. These functions are exemplified using artificial LDs in buffer, stressed liver cell line, and diseased liver tissues biopsied from patients. While most LD sensors only offer fluorescence imaging functions, the multi‐functional LD probe reported herein integrates both singlet fluorescence and triplet photosensitization properties for LDs studies.
Mannose-modified exosomes loaded with MiR-23b-3p target alveolar macrophages to alleviate acute lung injury in Sepsis
Authors: Jiezhi Lin, Lu Yang, Tianyi Liu, Hui Zhao, Yingying Liu, Futing Shu, Hongchao Huang, Wenzhang Liu, Wei Zhang, Luofeng Jiang, Shichu Xiao, Yongjun Zheng, Zhaofan Xia
Journal: Journal of Controlled Release (2025)
Early transcriptional effects of inflammatory cytokines reveal highly redundant cytokine networks
Authors: Juliana J. Lee, Liang Yang, Jonathan J. Kotzin, Dughan Ahimovic, Michael J. Bale, Peter A. Nigrovic, Steven Z. Josefowicz, Diane Mathis, Christophe Benoist, Dughan Ahimovic, Rhys Allan, Juliana Babu, Michael Bale, Meriem Belabed, Christophe Benoist, Michelle Bessiake, Maria Brbic, Brian D. Brown, Jason Buenrostro, Odhran Casey, Marco Colonna, Myriam Croze, Fabiana Duarte, Daniel Dwyer, Andrew Earl, Jeff Ericson, Shawn Fan, Kaili Fan, Enxhi Ferraj, Michela Frascoli, Antoine Freuchet, Giovanni Galleti, Anna Globig, Ananda Goldrath, Alessandra Gurtner, Pauline Hamon, Jichang Han, Samarth Hedge, Max Heeg, Molly Henderson, Geon Ho Bae, David Hoytema van Konijnenburg, Ruaidhri Jackson, Tim Johanson, Steve Josefowicz, Harry Kane, Joonsoo Kang, Mythili Ketavarapu, Catherine Laplace, Jessica Le Berichel, Alexander Liu, Vida Luna, Ian Magill, Diane Mathis, Raphael Matthiuz, Miriam Merad, Chang Moon, Alexander Monell, Sara Mostafavi, Hadas Ner-Gaon, Trung Nguyen, Junli Nie, Rachel Niec, Peter Nigrovic, Stephen Nutt, Adriana Ortiz-Lopez, Mark Owyong, Hadas Pahima, Siba Panigrahi, Matthew Park, Quan Phan, Gwendalyn Randolph, Miguel Reina-Campos, Alexander Sasse, Maximilian Schaefer, Tal Shay, Rojesh Shrestha, Justin Shyer, Sangwan Sim, Bhavya Singh, Joseph Sun, Kennidy Takehara, Julie Tellier, Alex Tepper, Xinming Tu, Olivia Venezia, Amy Wagers, Tianze Wang, Sunny Wu, Tong Wu, Ethan Xu, Liang Yang, David Zemmour, Leon Zhou
Journal: The Journal of Experimental Medicine (2025)

Inflammatory cytokines are fundamental mediators of the organismal response to injury, infection, or other harmful stimuli. To elucidate the early and mostly direct transcriptional signatures of inflammatory cytokines, we profiled all immunologic cell types by RNAseq after systemic exposure to IL1β, IL6, and TNFα. Our results revealed a significant overlap in the responses, with broad divergence between myeloid and lymphoid cells, but with very few cell-type-specific responses. Pathway and motif analysis identified several main controllers (NF-κB, IRF8, and PU.1), but the largest portion of the response appears to be mediated by MYC, which was also implicated in the response to γc cytokines. Indeed, inflammatory and γc cytokines elicited surprisingly similar responses (∼50% overlap in NK cells). Significant overlap with interferon-induced responses was observed, paradoxically in lymphoid but not myeloid cell types. These results point to a highly redundant cytokine network, with intertwined effects between disparate cytokines and cell types.
Virological and antigenic characteristics of SARS-CoV-2 variants LF.7.2.1, NP.1, and LP.8.1
Authors: Jingyi Liu, Yuanling Yu, Sijie Yang, Fanchong Jian, Weiliang Song, Lingling Yu, Fei Shao, Yunlong Cao
Journal: The Lancet Infectious Diseases (2025)
Safety of CAR T-cell therapy for cancer in pre-existing autoimmune or inflammatory disease: a retrospective comparative cohort study
Authors: Kathleen M M Vanni, Kaitlin R McCarter, Xiaosong Wang, Caitlyn Duffy, Jamie P Dela Cruz, Holly Wobma, Sarah Nikiforow, Elena M Massarotti, Karen H Costenbader, Jessica S Little, Ellen M Gravallese, Gregory C McDermott, Caron A Jacobson, Jeffrey A Sparks
Journal: The Lancet Rheumatology (2025)
Moral Injury: An Overview of Conceptual, Definitional, Assessment, and Treatment Issues
Authors: Brett T. Litz, Hannah E. Walker
Journal: Annual Review of Clinical Psychology (2025)

Moral injury (MI) is a potential clinical problem characterized by functionally impairing moral emotions, beliefs, and behaviors as well as adverse beliefs about personal or collective humanity and life's meaning and purpose. MI can arise from personal transgressive acts or from being a victim of or bearing witness to others' inhumanity. Despite widespread interest in MI, until recently, there was no reliable measure of MI as an outcome, and prior research has revealed little about its causes, consequences, and intervention approaches. This review provides background information on the history of MI, defines key terms, and critically reviews assessment tools. Additionally, we describe a social-functional theory of the etiology of MI and a social-functional rehabilitation approach to treatment. This treatment approach, which can be used by any clinician regardless of clinical context, employs cross-cutting change agents to promote lasting corrective and humanizing prosocial experiences, enhancing belonging through valued actions and relationships.
Development and Functions of MAIT Cells
Authors: Marion Salou, Rafael A. Paiva, Olivier Lantz
Journal: Annual Review of Immunology (2025)

Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved T cells that recognize microbial metabolites. They are abundant in humans and conserved during mammalian evolution, which suggests that they have important nonredundant functions. In this article, we discuss the evolutionary conservation of MAIT cells and describe their original developmental process. MAIT cells exert a wide variety of effector functions, from killing infected cells and promoting inflammation to repairing tissues. We provide insights into these functions and discuss how they result from the context of stimulation encountered by MAIT cells in different tissues and pathological settings. We describe how MAIT cell numbers and features are modified in disease states, focusing mainly on in vivo models. Lastly, we discuss emerging strategies to manipulate MAIT cells for therapeutic purposes.
Control Principles of Neural Dynamics Revealed by the Neurobiology of Timing
Authors: Gabriel M. Stine, Mehrdad Jazayeri
Journal: Annual Review of Neuroscience (2025)

Cognition unfolds dynamically over flexible timescales. A major goal of the field is to understand the computational and neurobiological principles that enable this flexibility. Here, we argue that the neurobiology of timing provides a platform for tackling these questions. We begin with an overview of proposed coding schemes for the representation of elapsed time, highlighting their computational properties. We then leverage the one-dimensional and unidirectional nature of time to highlight common principles across these coding schemes. These principles facilitate a precise formulation of questions related to the flexible control, variability, and calibration of neural dynamics. We review recent work that demonstrates how dynamical systems analysis of thalamocortical population activity in timing tasks has provided fundamental insights into how the brain calibrates and flexibly controls neural dynamics. We conclude with speculations about the architectural biases and neural substrates that support the control and calibration of neural dynamics more generally.
Treating Opioid Use Disorder and Opioid Withdrawal in the Context of Fentanyl
Authors: Suky Martinez, Jennifer D. Ellis, Cecilia L. Bergeria, Andrew S. Huhn, Kelly E. Dunn
Journal: Annual Review of Clinical Psychology (2025)

The opioid crisis, driven by illicitly manufactured fentanyl, presents significant challenges in treating opioid use disorder (OUD) and opioid withdrawal syndrome. Fentanyl is uniquely lethal due to its rapid onset and respiratory depressant effects, driving the surge in overdose deaths. This review examines the limitations of traditional diagnostic criteria like those of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) and explores the potential of dimensional models such as the Hierarchical Taxonomy of Psychopathology (HiTOP) for a more nuanced understanding of OUD. Current treatments, including medications for OUD, are evaluated for efficacy in managing fentanyl-related OUD. Innovations in drug formulations and alternative induction methods are discussed to address the unique challenges posed by fentanyl. Psychotherapeutic and behavioral interventions, such as cognitive behavioral therapy and contingency management, are highlighted as crucial complements to pharmacotherapy. The review underscores the need for increased precision, comprehensive phenotyping, and advanced diagnostics to develop personalized treatment plans, all with the aim of improving patient outcomes and mitigating the societal impact of the opioid crisis.
First-Line Mobocertinib Versus Platinum-Based Chemotherapy in Patients With <i>EGFR</i> Exon 20 Insertion–Positive Metastatic Non–Small Cell Lung Cancer in the Phase III EXCLAIM-2 Trial
Authors: Pasi A. Jänne, Bin-Chao Wang, Byoung Chul Cho, Jun Zhao, Juan Li, Maximilian Hochmair, Solange Peters, Benjamin Besse, Nick Pavlakis, Joel W. Neal, Terufumi Kato, Yi-Long Wu, Danny Nguyen, Junjing Lin, Jianchang Lin, Florin Vranceanu, Annette Szumski, Huamao M. Lin, Robert J. Fram, Tony S.K. Mok
Journal: Journal of Clinical Oncology (2025)

Mobocertinib is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that targets EGFR exon 20 insertion (ex20ins) mutations in non-small cell lung cancer (NSCLC). This open-label, phase III trial (EXCLAIM-2: ClinicalTrials.gov identifier: NCT04129502) compared mobocertinib versus platinum-based chemotherapy as first-line treatment of EGFR ex20ins+ advanced/metastatic NSCLC. Patients with treatment-naive EGFR ex20ins+ locally advanced/metastatic NSCLC were randomly assigned 1:1 to mobocertinib 160 mg once daily or pemetrexed plus cisplatin or carboplatin every 3 weeks for four cycles followed by maintenance pemetrexed. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR), with planned interim analysis (IA) after approximately 70% of 227 expected PFS events. A total of 354 patients were randomly assigned (mobocertinib: n = 179; chemotherapy: n = 175). Baseline characteristics were balanced between arms. At IA (cutoff: April 4, 2023), the median PFS per BICR was 9.6 months in each treatment arm (hazard ratio [HR], 1.04 [95% CI, 0.77 to 1.39]; P = .803). The primary end point crossed the prespecified futility boundary (HR > 1). The confirmed objective response rate (95% CI) per BICR was 32% (26 to 40) with mobocertinib versus 30% (24 to 38) with chemotherapy; the median duration of response was 12.0 versus 8.4 months. Quality-of-life assessments indicated clinically meaningful delays in time to deterioration of lung cancer symptoms, cognitive function, and constipation with mobocertinib versus chemotherapy. Grade ≥3 adverse events in >5% of patients (mobocertinib, chemotherapy) were diarrhea (20%, 1%), anemia (6%, 10%), increased lipase (6%, 0%), and decreased neutrophil count (1%, 7%). The EXCLAIM-2 trial did not meet its primary end point. The efficacy of mobocertinib was not superior to platinum-based chemotherapy for first-line treatment of patients with EGFR ex20ins+ advanced/metastatic NSCLC.
Nanoparticle encapsulation enables systemic IGF-Trap delivery to inhibit intra-cerebral glioma growth
Authors: Yinhsuan Michely Chen, Julien Chambon, Alexandre Moquin, Masakazu Hashimoto, Stephanie Perrino, Matthew Leibovitch, Yasmine Benslimane, Orçun Haçariz, Qin Yang, Ichiro Nakano, Brian Meehan, Janusz Rak, Stéphane Gagné, Pnina Brodt
Journal: Neuro-Oncology (2025)

Abstract Background Glioblastoma is an aggressive brain cancer with a 5-year survival rate of 5-10%. Current therapeutic options are limited, due in part to drug exclusion by the blood-brain barrier, restricting access of targeted drugs to the tumor. The receptor for the type 1 insulin-like growth factor (IGF-1R) was identified as a therapeutic target in glioblastoma. We previously reported that the intracerebral growth of glioma cells with reduced IGF-1R levels was inhibited. The objectives of this study were to evaluate the sensitivity of glioma cells to a novel IGF-axis inhibitor, the IGF-Trap, and optimize its delivery to the brain. Methods We tested the effect of the IGF-Trap on the growth of the human glioma stem cells MES-1123 and U87 MG cells, and of murine GL261 cells in vivo, using subcutaneous and orthotopic implantation. Results We show that the growth of glioma cells implanted subcutaneously or orthotopically in the brain was inhibited by systemic and direct intracerebral administration of IGF-Trap, respectively, resulting in increased survival. To increase the efficiency of systemic delivery to the brain, we encapsulated the IGF-Trap in trimethyl chitosan (TRIOZAN™) nanoparticles prior to intravenous injection. We found that nanoparticle encapsulation increased the uptake and retention of the IGF-Trap in the brain and resulted in an improved therapeutic effect against intra-cerebrally growing tumors. Conclusion Our results identify the IGF-Trap as a potent inhibitor of intracerebral glioma growth and show that encapsulation in nanoparticles can improve delivery of biologics such as the IGF-Trap to the brain, thereby enhancing the therapeutic response.
Metabarcoding captures genetic diversity and links cases in outbreaks of cryptosporidiosis in New Zealand
Authors: Paul Ogbuigwe, Patrick J Biggs, Juan Carlos Garcia-Ramirez, Matthew A Knox, Anthony Pita, Niluka Velathanthir, Nigel P French, David T S Hayman
Journal: Journal of Infection (2025)

Cryptosporidiosis is a disease caused by the parasite Cryptosporidium. Globally, it is a leading cause of diarrhoea and a notifiable disease in New Zealand. Molecular analyses of Cryptosporidium isolated from notified cases do not always provide support for epidemiological links between individuals. We hypothesised this could be due to undetected diversity and the use of consensus Sanger sequence analyses. Here, we analysed 105 Cryptosporidium samples from outbreaks and sporadic cases occurring between 2010 and 2018 in New Zealand using both Next-Generation Sequencing (NGS) and Sanger sequencing of the glycoprotein 60 (gp60) locus. NGS metabarcoding at the gp60 locus uncovered significant intra- and inter-sample genotypic diversity in outbreaks and identified subtypes shared by epidemiologically linked cases, along with rare subtypes, suggesting it may be a useful tool for epidemiological investigations.
Acute encephalopathy without hyperammonemia has a different presentation than overt hepatic encephalopathy and displays similarly severe prognosis
Authors: Victor Desplats, Luc Haudebourg, Nicolas Verger, Julie Assaraf, Sarah Mouri, Charlotte Bouzbib, Dominique Bonnefont-Rousselot, Rana Alkouri, Mehdi Sakka, Philippe Sultanik, Apolline Leproux, Nicolas Weiss, Marika Rudler, Dominique Thabut
Journal: Hepatology (2025)

In cirrhosis, some patients display acute encephalopathy without hyperammonemia (NonHep E) which is not considered as overt hepatic encephalopathy (OHE). We aimed to assess the prevalence and characteristics of NonHep E and OHE in cirrhotic patients displaying acute encephalopathy, assess their respective prognosis and compare it to other causes of acute decompensation (AD) with/without hyperammonemia. We conducted a retrolective analysis from a prospective cohort of patients hospitalized for AD. Hyperammonemia was defined by NH3 >50 µmol/L. Patients were divided into 4 groups: OHE (encephalopathy and NH3 >50 µmol/L: group 1), NonHep E (encephalopathy and NH3≤50 µmol/L, group 2), and 2 control groups with AD/without encephalopathy (NH3≤50 µmol/L (group 3) or NH3>50 µmol/L (group 4)). 530 patients were included (168 group 1, 76 group 2, 125 group 3, 161 group 4). Overall, 168/244 (69%) of patients with acute encephalopathy displayed OHE and 76/244 (31%) NonHep E. NonHep E patients were significantly more exposed to medications than OHE patients. One-year transplant-free survival was of 60.4%. In multivariable analysis, compared to patients with normal ammonemia and without encephalopathy, OHE was independently associated with a lower one year transplant-free survival (1.58 (95%CI 1.14-2.18, P=0.006)). OHE patients did not display a higher risk of death or transplantation than NonHep E patients (HR 1.27, 95%CI 0.91-1.77, P=0.161). NonHep E accounts for one third of admissions for acute encephalopathy, and displays as severe prognosis as OHE. OHE is independently associated with lower transplant-free survival at one year.
Short-term starvation boosts anti-PD-L1 therapy by reshaping tumor-associated macrophages in hepatocellular carcinoma
Authors: Kun Cheng, Ning Cai, Xing Yang, Danfeng Li, Zhu Jinghan, Hui Yuan Yang, Sha Liu, Deng Ning, Huifang Liang, Jianping Zhao, Zhanguo Zhang, Wanguang Zhang
Journal: Hepatology (2025)

Immune checkpoint inhibitors (ICIs) have revolutionized systemic hepatocellular carcinoma (HCC) treatment. Nevertheless, numerous patients are refractory to ICIs therapy. It is currently unknown whether diet therapies such as short-term starvation (STS) combined with ICIs can be used to treat HCC. This study aimed to investigate whether STS could sensitize HCC tumors to immunotherapy. STS was found to attenuate tumor progression by inducing tumor-associated macrophages (TAMs) to switch to an antitumoral phenotype, enhancing phagocytosis of tumor cells, and stimulating subsequent anti-tumor immunity of CD8+ T cells as demonstrated in three HCC mouse models, NCG mice, and Rag2-KO mice. Furthermore, STS combined with anti-PD1/L1 suppressed tumor progression, while the efficacy of anti-programmed cell death 1 ligand 1 (PD-L1) was improved when combined with STS. Mechanistically, TAM-derived exosomal PD-L1 (exoPD-L1) impairs the efficacy of anti-PD-1/L1. STS attenuates exoPD-L1 secretion from TAM by regulating the fructose diphosphatase 1 (FBP1) /Akt/Rab27a axis. Modulating FBP1/Akt/Rab27a axis potentiates the anti-PD-L1 response using two liposomal delivery systems and macrophage adoptive transfer. This study describes the immunomodulatory effects of STS and provides a rationale for its application as an adjuvant in HCC immunotherapy.
Prevalence and predictors of cirrhosis and portal hypertension in the united states
Authors: Zobair M. Younossi, Leyla de Avila, Andrei Racila, Fatema Nader, James Paik, Linda Henry, Maria Stepanova
Journal: Hepatology (2025)

There is paucity of data about the prevalence of cirrhosis and portal hypertension in the US general population. We used National Health and Nutrition Examination Surveys (NHANES 2017-2020) to estimate the prevalence of cirrhosis and clinically significant (CS)-portal hypertension in alcoholic liver disease (ALD), MetALD, viral hepatitis (VH) to include chronic hepatitis B (CHB) and chronic hepatitis C (CHC), and metabolic dysfunction-associated steatotic liver disease (MASLD). Cirrhosis was evaluated using liver stiffness measurement (LSM) by transient elastography or FIB-4 score; CS-portal hypertension was defined via LSM and platelet count or the use of non-selective beta-blockers in the presence of cirrhosis. The prevalence of CLD etiologies was ALD 0.85%, MetALD 3.38%, CHB 0.23%, CHC 0.73%, ALD+VH 0.16%, MASLD 33.05%. In general population, the prevalence of ALD-cirrhosis was 0.08%, MetALD-cirrhosis 0.19%, CHB-cirrhosis 0.01%, CHC-cirrhosis 0.10%, MASLD-cirrhosis 1.27%, ALD+VH-cirrhosis 0.08%, and other cirrhosis 0.87%. The prevalence of CS-portal hypertension in CLD was: 1.31% in MetALD, 1.60% in CHB, 4.73% in CHC, 2.00% in MASLD, and 0.35% in controls, to yield the population prevalence of 0.98%. In multivariate analysis, excessive alcohol use, CHC, male sex, obesity, type 2 diabetes, and hypertension were independently associated with an increased risk of cirrhosis (all P<0.05). Predictors of having CS-portal hypertension in CLD included CHC, obesity, and type 2 diabetes (all P<0.05). The prevalence of cirrhosis in the U.S. is 2.6% while the prevalence of CS-portal hypertension is 0.98%. Individuals with MASLD comprise the majority of U.S. residents with cirrhosis.