tbuckley/cabot-search huggingface dataset:
Selective Enhancer Dependencies in MYC-Intact and MYC-Rearranged Germinal Center B-cell Diffuse Large B-cell Lymphoma
Authors: Ashwin R. Iyer, Aishwarya Gurumurthy, Shih-Chun A. Chu, Rohan Kodgule, Athalee R. Aguilar, Travis Saari, Abdullah Ramzan, Jan Rosa, Juhi Gupta, Arvind Emmanuel, Cody N. Hall, John S. Runge, Anna B. Owczarczyk, Jang W. Cho, Matthew B. Weiss, Rockwell Anyoha, Kristin Sikkink, Savanna Gemus, Charles P. Fulco, Anamarija M. Perry, Anthony D. Schmitt, Jesse M. Engreitz, Noah A. Brown, Marcin P. Cieslik, Russell J. H. Ryan
Journal: Blood Cancer Discovery (2025)

Abstract High expression of MYC and its target genes identify germinal center B-cell diffuse large B-cell lymphomas (GCB-DLBCL) associated with poor outcomes. We used CRISPR-interference profiling of human lymphoma cell lines to define essential enhancers in the MYC locus and non-immunoglobulin rearrangement partner loci, including a recurrent rearrangement between MYC and the BCL6 locus control region. GCB-DLBCL cell lines without MYC rearrangement are dependent on an evolutionarily-conserved enhancer we name “germinal center MYC enhancer 1” (GME-1), which is activated by the transcription factor complex of OCT2, OCA-B, and MEF2B, shows an active chromatin state in normal human and mouse germinal center B cells, and demonstrates selective acetylation and MYC promoter topological interactions in MYC-intact GCB-DLBCL biopsies. Whole-genome sequencing identified tandem copy gains of the GME-1 enhancer as a rare but recurrent event in DLBCL. Our findings shed new light on mechanisms that dysregulate MYC, a key driver of B cell malignancy.
The Biology in the Pattern: Metastatic organotropism and clinical outcome depend on DNA damage response and immune interactions in pancreatic cancer
Authors: Aristeidis Papargyriou, Maximilian Reichert
Journal: Cancer Research (2025)

Abstract Metastatic cancer remains a leading cause of cancer-related mortality, with a 5-year survival rate of just 8% for pancreatic ductal adenocarcinoma (PDAC). Among patients with metastatic PDAC, those with liver metastases experience significantly worse outcomes compared to the rare cases of isolated lung metastases. Recent findings by Link and colleagues reveal that these distinct metastatic patterns reflect underlying biological differences beyond established molecular subtypes. Specifically, the authors curated a primary organotropism (pORG) gene signature that is enriched in the liver cohorts. In detail they found that high-pORG/liver-avid tumors are characterized by high replication stress, enriched DNA repair pathways, and an immunosuppressive microenvironment, whereas low-pORG/lung-avid tumors display stronger immune infiltration, higher T cell density and reduce the richness of TCR repertoire, and better survival outcomes. These insights suggest that the clinical pattern of metastasis provides meaningful information about tumor biology and prognosis, complementing current subtype classifications in PDAC.
In the Right Place and the Right State: Spatial Crosstalk and Immune State Dictate Leukemia Response to Immunotherapy
Authors: Giorgio Orofino, Cristina Toffalori, Luca Vago
Journal: Cancer Research (2025)

Abstract Donor Lymphocyte Infusion (DLI) is a crucial therapeutic strategy for relapsed myeloid malignancies post-allogeneic hematopoietic cell transplantation (allo-HCT), leveraging the graft-versus-leukemia (GvL) effect to restore immune control. While highly effective in chronic myeloid leukemia (CML), its efficacy in acute myeloid leukemia (AML) remains limited, with underlying mechanisms not fully understood. Recent research by Maurer and colleagues utilized cutting-edge technologies to dissect immune-leukemia interactions within the bone marrow niche, identifying a cytotoxic CD8+ T cell population as a key mediator of the anti-leukemic response. The study highlights a dynamic expansion of T and NK cells in responders, whereas non-responders display an immune suppressive bone marrow niche. TCR tracking revealed that the primary effectors of GvL in AML originate from the DLI infusion, yet their activation depends on a permissive bone marrow microenvironment. These insights emphasize that leukemia progression and immune response are shaped not only by malignant cells but also by broader niche dynamics. Further investigation is needed to define the different mechanisms that drives response or resistance to cellular therapies, but also to dissect the antigenic specificity of GvL-mediating T cells and define biomarkers predicting response to DLI.
Astrocytes as Key Regulators of Neural Signaling in Health and Disease
Authors: Woojin Won, Mridula Bhalla, Jae-Hun Lee, C. Justin Lee
Journal: Annual Review of Neuroscience (2025)

Astrocytes, traditionally viewed as supportive cells within the central nervous system (CNS), are now recognized as dynamic regulators of neural signaling and homeostasis. They actively engage in synaptic transmission and brain health by releasing gliotransmitters such as glutamate, GABA, ATP, adenosine, lactate, and d -serine. Astrocytes also play a critical role in ion homeostasis and immune response through cytokine modulation and reactive oxygen species regulation. In pathological states, astrocytes can become reactive, contributing to neurodegeneration through dysregulated gliotransmitter release and metabolic dysfunction. Recently developed molecular and pharmacological tools allow the exploration of astrocytic response to injury and its influence on neuronal function. This review explores the multifaceted roles of astrocytes in health and disease, emphasizing sensory and motor functions as well as various neurological and psychiatric disorders. Understanding astrocyte-neuron signaling in health and disease provides crucial insights into their dual roles, offering novel avenues for therapeutic interventions in CNS disorders.
Reward Processing in Mood Disorders and Schizophrenia: A Neurodevelopmental Framework
Authors: Robin Nusslock, Vijay A. Mittal, Lauren B. Alloy
Journal: Annual Review of Clinical Psychology (2025)

Major depressive disorder (MDD), bipolar disorder, and schizophrenia involve disruptions in processing rewarding stimuli. In this review, we propose that distinct mechanistic pathways underlie these disruptions in mood disorders versus schizophrenia, and we highlight the importance of understanding these differences for developing personalized treatments. We summarize evidence suggesting that reward processing abnormalities in mood disorders are driven by dysregulated motivational systems; MDD is characterized by blunted responses to reward cues, and bipolar disorder is characterized by heightened responses. In contrast, we argue that reward processing disruptions in schizophrenia do not reflect abnormalities in motivation or hedonic experience; rather, they reflect impairments in the cognitive representation of past and future rewards as well as misdirected attention to irrelevant stimuli. To integrate these findings, we present a neurodevelopmental framework for the onset of mood and psychotic disorders and explore how disruptions in normative brain development contribute to their pathophysiology, timing, and onset. Additionally, we move beyond viewing these conditions as homogeneous disorders and discuss how reward processing profiles may align with specific symptom dimensions.
The intestinal barrier: a pivotal role in health, inflammation, and cancer
Authors: Markus F Neurath, David Artis, Christoph Becker
Journal: The Lancet. Gastroenterology & hepatology (2025)

SummaryThe intestinal barrier serves as a boundary between the mucosal immune system in the lamina propria and the external environment of the intestinal lumen, which contains a diverse array of microorganisms and ingested environmental factors, including pathogens, food antigens, toxins, and other foreign substances. This barrier has a central role in regulating the controlled interaction between luminal factors and the intestinal immune system. Disruptions of intestinal epithelial cells, which serve as a physical barrier, or the antimicrobial peptides and mucins they produce, which act as a chemical barrier, can lead to a leaky gut. In this state, the intestinal wall is unable to efficiently separate the intestinal flora and luminal contents from the intestinal immune system. The subsequent activation of the immune system has an important role in the pathogenesis of inflammatory bowel disease, as well as in metabolic dysfunction-associated steatohepatitis, primary sclerosing cholangitis, and colorectal cancer. Dysregulated intestinal barrier integrity has also been described in patients with chronic inflammatory diseases outside the gastrointestinal tract, including rheumatoid arthritis and neurodegenerative disorders. Mechanistic studies of barrier dysfunction have revealed that the subsequent local activation and systemic circulation of activated immune cells and the cytokines they secrete, as well as extracellular vesicles, promote proinflammatory processes within and outside the gastrointestinal tract. In this Review, we summarise these findings and highlight several new therapeutic concepts currently being developed that attempt to control inflammatory processes via direct or indirect modulation of intestinal barrier function.
Public health priorities for mpox clade Ib in pregnant, breastfeeding, and paediatric populations in DR Congo
Authors: Susanne Krasemann, Joseph Nelson Siewe Fodjo, Osama A A Mohamed, Isaac Barhishindi, Christian Tshongo, Alfred Kesheni Bisimwa, Wyvine Ansima Bapolisi, Robert Colebunders, Esto Bahizire, Laurens Liesenborghs, Placide Mbala-Kingebeni, Patrick D M C Katoto
Journal: The Lancet Infectious Diseases (2025)
Adrenocortical carcinoma: a practical guide for clinicians
Authors: Martin Fassnacht, Soraya Puglisi, Otilia Kimpel, Massimo Terzolo
Journal: The Lancet Diabetes & Endocrinology (2025)

Adrenocortical carcinoma is a rare endocrine malignancy. The management of patients with adrenocortical carcinoma is challenging for several reasons, including its heterogeneous but frequently aggressive biological behaviour; tumour-related hormonal excess (eg, Cushing's syndrome or virilisation); the overall paucity of evidence regarding diagnostic investigation and treatment; the approval of only one drug (mitotane); and the scarcity of centres with sufficient experience. In this Review, we present 25 questions on the most important aspects of the clinical management of adult patients with adrenocortical carcinoma that we have frequently asked ourselves over the past 25 years. We offer our personal answers and perspectives, drawing upon published evidence as well as more than 60 years of collective clinical experience and insights from our management of more than 1700 patients across two centres in Germany and Italy.
Effect of digital adherence technologies on treatment outcomes in people with drug-susceptible tuberculosis: four pragmatic, cluster-randomised trials
Authors: Degu Jerene, Kristian van Kalmthout, Jens Levy, Jason Alacapa, Natasha Deyanova, Tanyaradzwa Dube, Andrew Mganga, Bianca Tasca, Alexsey Bogdanov, Egwuma Efo, Katya Gamazina, Anna Marie Celina Garfin, Volodymyr Kochanov, Adrian Leung, Norma Madden, Noriah Maraba, Christopher Finn McQuaid, Liberate Mleoh, Baraka Onjare, Rachel Powers, Yana Terleiva, Job van Rest, Agnes Gebhard, Katherine Fielding, Salome Charalambous
Journal: The Lancet (2025)
Safety and immunogenicity of a pentavalent meningococcal conjugate vaccine targeting serogroups A, C, W, Y, and X when co-administered with routine childhood vaccines at ages 9 months and 15 months in Mali: a single-centre, double-blind, randomised, controlled, phase 3, non-inferiority trial
Authors: Fatoumata Diallo, Fadima C Haidara, Milagritos D Tapia, Clara P Dominguez Islas, Mark R Alderson, William P Hausdorff, Lionel Martellet, Nancy Hosken, Dhananjay Kapse, Prasad S Kulkarni, Kelly Townsend-Payne, Francesca Vanni, Christine M Posavad, Samba O Sow, Karen L Kotloff, Wilbur H Chen
Journal: The Lancet (2025)
Africa's defining moment: the time to lead the HIV response is now
Authors: Mumbi Chola, Izukanji Sikazwe, Magda Robalo, Pokuaa Oduro-Bonsrah, Alex Coutinho, Robb Sheneberger, Jekwu Ozoemene, Pierre M'pele, Damaris Nyamweya, Sasha Stevenson, Yvette Raphael, Sesupo Makakole Nene, John Ataguba, Mohamed Chakroun, Michel Sidibe
Journal: The Lancet Global Health (2025)

For decades, external actors, such as donors, funders, and implementing partners, have shaped Africa's HIV response. Although this strategy has saved millions of lives, it entrenched dependency, leaving Africa vulnerable to global donors' shifting priorities. With declining HIV funding and competing global crises, Africa must rise to lead its response.
Cell‐free DNA for detection and monitoring of extramedullary AML relapse
Authors: Henri C. Hupe, Clara P. Wienecke, Stephan Bartels, Elisa Schipper, Jannika Leßmann, Alina Lasch, Maximilian Bader, Razif Gabdoulline, Martin Neugebohren, Elke Dammann, Hans H. Kreipe, Ulrich Lehmann, Anke K. Bergmann, Nataliya Di Donato, Michael Stadler, Matthias Eder, Arnold Ganser, Florian H. Heidel, Felicitas Thol, Michael Heuser
Journal: HemaSphere (2025)

Abstract Isolated extramedullary manifestations (IEM) of acute myeloid leukemia (AML) are recurrent events, especially following allogeneic hematopoietic cell transplantation (alloHCT). To date, measurable residual disease (MRD) assessment for this difficult‐to‐treat patient cohort has not been established. In this study, we evaluated highly sensitive next‐generation sequencing (NGS) of IEM‐AML tumor and compared it with cell‐free DNA (cfDNA) from plasma, as well as highly sensitive NGS analysis of bone marrow mononuclear cells (BMMC) and peripheral blood mononuclear cells (PBMC), in a cohort of 15 IEM‐AML patients with 19 IEM‐AML episodes. cfDNA demonstrated a superior representation of IEM‐AML tumor mutations compared to BMMC or PBMC, with a median variant allele frequency (VAF) of 0.8% and a mutation detection rate of 62% (37 of 60 mutations), compared to a median VAF of 0.05% and detection rate of 27%, respectively (16 of 60 mutations, p &lt; 0.01). Among 44 mutations identified in 14 IEM‐AML relapse tumors, 30 mutations (68%) were known from initial diagnosis. Using diagnostic mutations from initial diagnosis for MRD analysis and detection of IEM‐AML relapse, 16 of 17 IEM‐AML relapse episodes were detected via cfDNA, whereas only 7 of 17 were identified using conventional analysis of BMMC or PBMC. Our findings demonstrate that cfDNA analysis from plasma effectively captures the molecular profile of IEM‐AML. More than one‐third of clinically relevant mutations were exclusively detected through cfDNA and were missed by conventional NGS‐MRD of BMMC or PBMC. These results suggest that MRD monitoring using cfDNA offers a more comprehensive and sensitive approach to detecting IEM‐AML relapse compared to standard methods.
Lactate: A key regulator of the immune response
Authors: Alba Llibre, Salih Kucuk, Atrayee Gope, Michelangelo Certo, Claudio Mauro
Journal: Immunity (2025)

SummaryLactate, the end product of both anaerobic and aerobic glycolysis in proliferating and growing cells—with the latter process known as the Warburg effect—is historically considered a mere waste product of cell and tissue metabolism. However, research over the past ten years has unveiled multifaceted functions of lactate that critically shape and impact cellular biology. Beyond serving as a fuel source, lactate is now known to influence gene expression through histone modification and to function as a signaling molecule that impacts a wide range of cellular activities. These properties have been particularly studied in the context of both adaptive and innate immune responses. Here, we review the diverse roles of lactate in the regulation of the immune system during homeostasis and disease pathogenesis (including cancer, infection, cardiovascular diseases, and autoimmunity). Furthermore, we describe recently proposed therapeutic interventions for manipulating lactate metabolism in human diseases.
Switching TKIs during CML therapy is frequent, mostly driven by intolerance, and does not affect survival: a prospective Quebec registry study
Authors: Lambert Busque, Marc-Étienne Beaudet, Michaël Harnois, Hanane Moussa, Natasha Szuber, Luigina Mollica, Robert Delage, Harold Olney, Pierre Laneuville, Ghislain Cournoyer, Inès Chamakhi, Marc Lalancette, Danielle Talbot, Vincent Ethier, Pierre Desjardins, Sarit Assouline
Journal: Blood Cancer Journal (2025)
Hyperuricaemia and gout in the Pacific
Authors: Baptiste Gérard, Megan Leask, Tony R. Merriman, Thomas Bardin, Erwan Oehler, Aniva Lawrence, Satupaitea Viali, Samuela ‘Ofanoa, Leanne Te Karu, Lisa K. Stamp, Nicola Dalbeth, Tristan Pascart
Journal: Nature Reviews Rheumatology (2025)
Sex Differences in Peripheral Vascular Disease: A Scientific Statement From the American Heart Association
Authors: Esther S.H. Kim, Shipra Arya, Yolanda Bryce, Heather L. Gornik, Chandler A. Long, Mary M. McDermott, Amy West Pollak, Vincent Lopez Rowe, Alexander E. Sullivan, Mary O. Whipple
Journal: Circulation (2025)

Sex differences in the risk factors, diagnosis, treatment, and outcomes of patients with cardiovascular disease have been well described; however, the bulk of the literature has focused on heart disease in women. Data on sex differences in peripheral vascular disease are ill defined, and there is a need to report and understand those sex-related differences to mitigate adverse outcomes related to those disparities. Although peripheral vascular disease is a highly diverse group of disorders affecting the arteries, veins, and lymphatics, this scientific statement focuses on disorders affecting the peripheral arteries to include the aorta and its branch vessels. The purpose of this scientific statement is to report the current status of sex-based differences and disparities in peripheral vascular disease and to provide research priorities to achieve health equity for women with peripheral vascular disease.
A novel dominant-negative variant of IRF8 in a mother and son: Clinical, phenotypic and biological characteristics
Authors: Hyoungjun Ham, Crescent R Isham, Elizabeth H Ristagno, Cristina Correia, Scott M Ennis, Richard K Kandasamy, Kishore Garapati, Cheng Zhang, Mindy C Kohlhagen, Elham Sadighi Akha, Maria F Rodriguez-Quevedo, Destiny F Schultz, Baoyu Chen, Thomas G Boyce, Seth W Gregory, Mira A Kohorst, Surendra Dasari, David L Murray, Kevin C Halling, Benjamin R Kipp, Attila Kumánovics, Hu Li, Akhilesh Pandey, Daniel D Billadeau, Amir A Sadighi Akha
Journal: Journal of Allergy and Clinical Immunology (2025)
An In Situ Curing, Shear‐Responsive Biomaterial Designed for Durable Embolization of Microvasculature
Authors: Quynh P. Pham, Jeffrey V. Groom, Chander Sadasivan, David J. Fiorella, David C. Madoff, Lee‐Jae Guo, Michael Fornaciari, Courtney Guertin, Craig Wiltsey, Lee Core, Jonathan Merlo, William Wustenberg, Renu Virmani, Adam S. Arthur, Robert S. Langer, George M. Whitesides, Upma Sharma
Journal: Advanced Healthcare Materials (2025)

Abstract Endovascular embolization is a minimally‐invasive technique whereby blood vessels supplying pathological structures are selectively occluded with various embolic agents. In many scenarios, it is desirable for the embolic to distally penetrate to the level of the microvasculature, which maximizes devascularization. Existing agents exhibit inconsistent distal penetration and have other limitations including tendency for proximal reflux, patient pain during infusion, lack of fluoroscopic radiopacity, potential for catheter adhesion, susceptibility to recanalization, and other usability challenges. NeoCast is an in situ curing, solvent‐free, non‐adhesive biomaterial composed of polydimethylsiloxane, bismuth trioxide, and fumed silica that possesses shear‐responsive properties enabling manual injectability through commercially‐available microcatheters with large and small diameter lumens. Here, embolization performance with and without flow arrest, in both arterial and venous preclinical anatomies is reported. NeoCast reproducibly achieves a rate of distal penetration with microvascular occlusion that is superior to existing agents, exhibits excellent fluoroscopic visibility, and provides durable occlusion. There is mild inflammation when NeoCast is infused into blood vessels and absence of neurotoxicity when implanted directly into brain tissue. The engineered NeoCast material is poised to become a next‐generation, liquid embolic agent for applications in which distal microvascular occlusion is desired.
Determinants of late metastases in renal cell carcinoma
Authors: Payal Kapur, Hua Zhong, Alana Christie, Haitao Xu, Qi Cai, Ellen Araj, David Kim, Jeffrey Miyata, Vanina T Tcheuyap, Colleen T Ball, David D Thiel, Alexander Parker, Samuel O Antwi, Brad C Leibovich, Zora Modrusan, John C Cheville, James Brugarolas
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract The mechanisms underlying metastatic latency in renal cell carcinoma (RCC) remain poorly understood. This study evaluated two large independent cohorts for differences in tumor biology between patients who developed metastases early (≤1 year after nephrectomy) and those with late-onset (&amp;gt;3 years). In the discovery cohort (n = 161), late-metastatic RCC (late-mRCC) was associated with clear cell histology (88.9% vs 78.7%), lower pathological stage (pT1-2; 40.3% vs 18.0%), and favorable histopathological features including low grade (40.0% vs 2.3%), less sarcomatoid (5.6% vs 21.8%), and reduced necrosis (37.7% vs 78.3%; all p &amp;lt; .02). Late-mRCC tumors exhibited increased angiogenesis (63.5% vs 19.4%) and reduced inflammation (78.8% vs 50.0%; all p &amp;lt; .02) profiles. Genomic driver analyses revealed comparable rates of PBRM1 and SETD2 loss in both late- and early-mRCC, while BAP1 loss was significantly less common in late-mRCC (7.5% vs 27.1%; p &amp;lt; .02). In multivariable models, BAP1/PBRM1/SETD2 status and tumor necrosis emerged as key discriminators of late-mRCC. These findings were confirmed in the second cohort (n = 307). Late-mRCC was enriched for fatty acid oxidation and angiogenesis pathways, supporting a less aggressive phenotype. This was further evidenced by a lower engraftment rate in murine models (0% vs 36.5%; p &amp;lt; .001) and significantly longer overall survival from the time of metastasis (median survival doubled, p &amp;lt; .001). Interestingly, late-mRCC shared genomic and phenotypic features with RCC that metastasizes to the pancreas, suggesting a common underlying biology that influences both metastatic latency and pancreatic tropism. Overall, these findings advocate for recognition of late-mRCC, due to its distinct biology and improved prognosis.