tbuckley/cabot-search huggingface dataset:
Autologous Transplant or <scp>CAR</scp>‐T as Consolidation Options in <scp>MYC</scp> Rearranged Large B‐Cell Lymphoma Patients in Remission After Salvage Treatments
Authors: Fateeha Furqan, Kwang W. Ahn, Manmeet Kaur, Jinalben Patel, Stephen Ansell, Farrukh T. Awan, John Baird, Evandro Bezerra, Umar Farooq, Henry Fung, Arushi Khurana, Lazaros Lekakis, Forat Lutfi, John McCarty, Akash Mukherjee, Rajneesh Nath, Jason Romancik, Stephen J. Schuster, Melody Smith, Allison Winter, Cameron Turtle, Craig Sauter, Mazyar Shadman, Alex Herrara, Mehdi Hamadani
Journal: American Journal of Hematology (2025)

ABSTRACT Although recent studies have demonstrated the efficacy of chimeric antigen receptor T‐cell (CAR‐T) therapy in relapsed large B‐cell lymphoma (LBCL) with MYC rearrangement (R‐MYC), the data comparing CAR‐T to autologous hematopoietic cell transplant (auto‐HCT) in such patients who achieve a complete or partial response (CR/PR) after salvage therapies are limited. We compared the clinical outcomes of patients with R‐MYC LBCL (including double and triple hit lymphomas) who underwent CAR‐T or auto‐HCT after achieving a CR/PR with salvage therapies using the Center for International Blood &amp; Marrow Transplant Research registry. Among the 252 patients (auto‐HCT = 98, CAR‐T = 154), relative to auto‐HCT, CAR‐T was associated with significantly lower overall survival (OS) (Hazard Ratio [HR] 2.09, 95% CI 1.38–3.15, p &lt; 0.001) on multivariate analysis. There were no differences in progression‐free survival (PFS) (HR 1.21, 95% CI 0.81–1.8 p = 0.36), risk of relapse (HR 1.1, 95% CI 0.71–1.69 p = 0.68), nonrelapse mortality (NRM) (HR 1.74, 95% CI 0.64–4.7 p = 0.28) while the post‐relapse survival was longer in auto‐HCT relative to CAR‐T (HR 1.93, 95% CI 1.21–3.06 p = 0.01). On propensity score matched analysis accounting for differences in characteristics across the two cohorts, we detected no significant differences in OS (HR 1.72, 95% CI 0.92–3.21 p = 0.09), PFS (HR 1.04, 95% CI 0.64–1.68 p = 0.88), NRM (HR 1.22, 95% CI 0.35–4.2 p = 0.76), relapse (HR = 0.93, 95% CI 0.54–1.6 p = 0.8) and post‐relapse survival (HR 2.25, 95% CI 0.98–5.17, p = 0.06). These data, although retrospective, support consideration for auto‐HCT in patients with R‐MYC LBCL who achieve a CR/PR after salvage therapies, particularly in regions with no or limited access to CAR‐T.
Membrane Encapsulated Fe<sub>3</sub>O<sub>4</sub>@MnO@cGAMP Nanocatalyst for Cancer Therapy: cGAS‐STING Immune Pathway Activation
Authors: Hua Chai, Renpeng Xia, Nan Ouyang, Jingyu Yao, Jiukun Hu, Minxuan Sun, Peng Miao
Journal: Advanced Healthcare Materials (2025)

Abstract Reactive oxygen species (ROS) mediated cell damage is one of the most popular and effective ways for cancer therapy. However, overexpressed antioxidant of reduced glutathione (GSH) is always activated in tumor cells, which maintains redox equilibrium. Attempts to deplete GSH and elevate ROS levels can be potent therapeutic strategies. Herein, tumor cell membrane‐encapsulated Fe 3 O 4 @MnO and 2′,3′‐cyclic GMP‐AMP (cGAMP) are prepared as the nanocatalyst for cancer therapy. The ionized Fe 3+ /Fe 2+ redox couple is utilized to initiate the Fenton reaction. Intracellular GSH level can thus be efficaciously controlled, and peroxide oxidation is catalyzed to produce excessive ROS. Meanwhile, cGAMP is released to trigger the cyclic GMP‐AMP synthase (cGAS)‐stimulator of interferon genes (STING) signaling axis. This targeted activation enhances the recruitment of macrophages, stimulates the secretion of critical pro‐inflammatory cytokines, and consequently bolsters the efficacy of innate immune responses within the tumor microenvironment.
Urease in acetogenic <i>Lachnospiraceae</i> drives urea carbon salvage in SCFA pools
Authors: Isaac J. Firth, Marissa A.R. Sim, Bradley G. Fitzgerald, Ailish E. Moore, Christian R. Pittao, Connor Gianetto-Hill, Samantha Hess, Autumn R. Sweeney, Emma Allen-Vercoe, Matthew T. Sorbara
Journal: Gut Microbes (2025)

The gut microbiota produces short-chain fatty acids (SCFA) and acidifies the proximal colon which inhibits enteric pathogens. However, for many microbiota constituents, how they themselves resist these stresses is unknown. The anaerobic Lachnospiraceae family, which includes the acetogenic genus Blautia, produce SCFA, are genomically diverse, and vary in their capacity to acidify culture media. Here, we investigated how Lachnospiraceae tolerate pH stress and found that subunits of urease were associated with acidification in a random forest model. Urease cleaves urea into ammonia and carbon dioxide, however the role of urease in the physiology of Lachnospiraceae is unknown. We demonstrate that urease-encoding Blautia show urea-dependent changes in SCFA production, acidification, growth, and, strikingly, urease encoding Blautia directly incorporate the carbon from urea into SCFAs. In contrast, ureolytic Klebsiella pneumoniae or Proteus mirabilis do not show the same urea-dependency or carbon salvage. In agreement, the combination of urease and acetogenesis functions is rare in gut taxa. We find that Lachnospiraceae urease and acetogenesis genes can be co-expressed in healthy individuals and colonization of mice with a ureolytic Blautia reduces urea availability in colon contents demonstrating Blautia urease activity in vivo. In human and mouse microbial communities, the acetogenic recycling of urea carbon into acetate by Blautia leads to the incorporation of urea carbon into butyrate indicating carbon salvage into broader metabolite pools. Altogether, this shows that urea plays a central role in the physiology of health-associated Lachnospiraceae which use urea in a distinct manner that is different from that of ureolytic pathogens.
Remission induction in refractory, drug resistant pediatric PICALM::MLLT10+ B-cell acute lymphoblastic leukemia by venetoclax
Authors: Alexandra Niedermayer, Jana Stursberg, Anke Katharina Bergmann, Martin Zimmermann, Gunnar Cario, Monika Brüggemann, Rolf Köhler, Daniel Steinbach, Christian Reimann, Felix Seyfried, Lüder Hinrich Meyer, Klaus-Michael Debatin
Journal: Leukemia (2025)
Prognostic scoring systems in chronic myeloid leukaemia
Authors: Michael Lauseker, Verena S Hoffmann, Markus Pfirrmann
Journal: Leukemia (2025)

Abstract Prognostic scores are an important tool in medical statistics. In chronic myeloid leukaemia (CML), prognostic models have existed for many years, enabling the classification of patients into groups that can be clearly differentiated in terms of their prognosis. However, over time, the focus of these models has shifted from solely survival outcomes to a broader range of diverse endpoints. This review explores the development and applications of these scores, offering recommendations for their use, and looks ahead to potential future advancements in the field. As the landscape of CML treatment evolves with newer therapeutic options, it is crucial to adapt prognostic models to reflect not only survival rates but also other important clinical milestones such as molecular remission, progression-free survival, and CML-related survival. The continued refinement of these tools, alongside international validation efforts, will be essential in providing clinicians with more accurate and individualized patient prognostication, ultimately improving therapeutic decision-making and patient outcomes.
Identifying genetic errors of immunity due to mosaicism
Authors: Elizabeth G. Schmitz, Malachi Griffith, Obi L. Griffith, Megan A. Cooper
Journal: The Journal of Experimental Medicine (2025)

Inborn errors of immunity are monogenic disorders of the immune system that lead to immune deficiency and/or dysregulation in patients. Identification of precise genetic causes of disease aids diagnosis and advances our understanding of the human immune system; however, a significant portion of patients lack a molecular diagnosis. Somatic mosaicism, genetic changes in a subset of cells, is emerging as an important mechanism of immune disease in both young and older patients. Here, we review the current landscape of somatic genetic errors of immunity and methods for the detection and validation of somatic variants.
A sensory-motor-sensory circuit underlies antinociception ignited by primary motor cortex in mice
Authors: Fei Wang, Zhi-Cheng Tian, Hui Ding, Xin-Jiang Yang, Fu-Dong Wang, Ruo-Xin Ji, Lei Xu, Zi-Xuan Cao, Sui-Bin Ma, Ming Zhang, Ya-Ting Cui, Xiang-Yu Cong, Wen-Guang Chu, Zhen-Zhen Li, Wen-Juan Han, Yong-Heng Gao, Yuan-Wang Yu, Xiang-Hui Zhao, Wen-Ting Wang, Rou-Gang Xie, Sheng-Xi Wu, Ceng Luo
Journal: Neuron (2025)
Evolution of the tumor immune landscape during treatment with tebentafusp, a T cell receptor-CD3 bispecific
Authors: Joseph J Sacco, Peter Kirk, Emma Leach, Alexander N Shoushtari, Richard D Carvajal, Camille Britton-Rivet, Sophie Khakoo, Laura Collins, Luis de la Cruz-Merino, Zeynep Eroglu, Alexandra P Ikeguchi, Paul Nathan, Omid Hamid, Marcus O Butler, Sarah Stanhope, Koustubh Ranade, Takami Sato
Journal: Cell Reports Medicine (2025)
Dual STAT3/STAT5 inhibition as a novel treatment strategy in T-prolymphocytic leukemia
Authors: Annika Dechow, Sanna Timonen, Aleksandr Ianevski, Qu Jiang, Linus Wahnschaffe, Yayi Peng, Dennis Jungherz, Kerstin Becker, Heidi A Neubauer, Susann Schönefeldt, Elvin de Araujo, Patrick Gunning, Roman Fleck, Alexandra Schrader, Michael Hallek, Natali Pflug, Richard Moriggl, Tero Aittokallio, Satu Mustjoki, Till Braun, Marco Herling
Journal: Leukemia (2025)
A structural haplotype in the 17q21.31 MAPT region is associated with increased risk for chronic traumatic encephalopathy endophenotypes
Authors: Xudong Han, Yichi Zhang, Jillian N Petrosky, Sarah Bald, Richard M Sherva, Adam Labadorf, Jonathan D Cherry, Jaeyoon Chung, Kurt Farrell, Bobak Abdolmohammadi, Shruti Durape, Brett M Martin, Joseph N Palmisano, John J Farrell, Victor E Alvarez, Bertrand R Huber, Brigid Dwyer, Daniel H Daneshvar, Kristen Dams-O'Connor, Gyungah R Jun, Kathryn L Lunetta, Lee E Goldstein, Douglas I Katz, Robert C Cantu, Martha E Shenton, Jeffrey L Cummings, Eric M Reiman, Robert A Stern, Michael L Alosco, Yorghos Tripodis, Lindsay A Farrer, Thor D Stein, John F Crary, Ann C McKee, Jesse Mez
Journal: Cell Reports Medicine (2025)
Targeting melanocortin 4 receptor to treat sleep disordered breathing in mice
Authors: Mateus R Amorim, Noah R Williams, O Aung, Melanie Alexis Ruiz, Frederick Anokye-Danso, Junia Lara de Deus, Jiali Xiong, Olga Dergacheva, Shannon Bevans-Fonti, Sean M Lee, Jeffrey S Berger, Mark N Wu, Rexford S Ahima, David Mendelowitz, Vsevolod Y Polotsky
Journal: Journal of Clinical Investigation (2025)

Weight loss medications are emerging candidates for pharmacotherapy of sleep disordered breathing (SDB). A melanocortin receptor 4 (MC4R) agonist, setmelanotide (SET), is used to treat obesity caused by abnormal melanocortin and leptin signaling. We hypothesized that SET can treat SDB in diet induced obese mice. We performed a proof-of-concept randomized crossover trial of a single dose of SET vs vehicle and a two-week daily SET vs vehicle trial, examined co-localization of Mc4r mRNAs with markers of CO2 sensing neurons Phox2b and neuromedin-B in the brainstem, and expressed Cre-dependent designer receptors exclusively activated by designer drugs or caspase in obese Mc4r-Cre mice. SET increased minute ventilation across sleep/wake states, enhanced the hypercapnic ventilatory response (HCVR) and abolished apneas during sleep. Phox2b+ neurons in the nucleus of the solitary tract (NTS) and the parafacial region expressed Mc4r. Chemogenetic stimulation of the MC4R+ neurons in the parafacial region, but not in the NTS, augmented HCVR without any changes in metabolism. Caspase elimination of the parafacial MC4R+ neurons abolished effects of SET on HCVR. Parafacial MC4R+ neurons projected to the respiratory pre-motor neurons retrogradely labeled from C3-C4. In conclusion, MC4R agonists enhance the HCVR and treat SDB by acting on the parafacial MC4R+ neurons.
Exploring [11C]CPPC as a CSF1R-targeted PET imaging marker for early Parkinson’s disease severity
Authors: Kelly A Mills, Yong Du, Jennifer M Coughlin, Catherine A Foss, Andrew G Horti, Katelyn R Jenkins, Yana Skorobogatova, Ergi Spiro, Chelsie S Motley, Robert F Dannals, Wojciech G Lesniak, Jae-Jin Song, Yu Ree Choi, Javier Redding-Ochoa, Juan C Troncoso, Valina L Dawson, Tae-In Kam, Martin G Pomper, Ted M Dawson
Journal: Journal of Clinical Investigation (2025)

Microglia-mediated brain immune changes play a role in the pathogenesis of Parkinson's disease (PD) but imaging microglia in living people with PD has relied on positron emission tomography (PET) ligands that lack specificity in labeling immune cells in the nervous system. We aimed to develop imaging of colony stimulating factor 1 receptor (CSF1R) as a microglial-sensitive marker of innate immunity. Immunohistochemistry using a CSF1R antibody evaluated colocalization with Iba-1 in PD (n = 4) and control (n = 4) human brain samples. Autoradiography using a CSF1R tritiated ligand in PD (n = 5) and controls (n = 4) human brain samples was performed to obtain Bmax. PET imaging using a CSF1R radioligand was performed in 10 controls and 12 people with PD and VT was compared between groups and correlated with disease severity. Immunohistochemistry of CSF1R in human brain shows colocalization with Iba-1 and is significantly increased in PD compared to controls. Autoradiography revealed significantly increased CSF1R ligand binding in the inferior parietal cortex of PD patients. [11C]CPPC PET showed higher binding in people with moderate PD compared to controls and correlated with more severe motor disability and poorer verbal fluency. This study underscores the significance of CSF1R imaging as a promising biomarker for brain immune function in Parkinson's disease, which may be associated with cognitive and motor disease severityFUNDING. PET imaging: the Michael J. Fox Foundation and the RMS Family Foundation. Radiotracer development: NIH (R01AG066464 and P41 EB024495). Postmortem brain tissues: NIH P30 AG066507 and BIOCARD study NIH U19 AG033655.
Precision screening facilitates clinical classification of BRCA2-PALB2 binding variants with benign and pathogenic functional effects
Authors: Muthiah Bose, Manika Indrajit Singh, Morten Frödin, Bent Ejlertsen, Claus S Sørensen, Maria Rossing
Journal: Journal of Clinical Investigation (2025)

Decoding the clinical impact of genetic variants is particularly important for precision medicine in cancer. Genetic screening of mainly breast and ovarian cancer patients has identified numerous BRCA1/BRCA2 'variants of uncertain significance' (VUS) that remain unclassified due to a lack of pedigrees and functional data. Here, we used CRISPR-Select - a technology that exploits unique inbuilt controls at the endogenous locus - to assess 54 rare ClinVar VUS located in the PALB2-binding domain (PBD) of BRCA2. Variant deleteriousness was examined in the absence and presence of PARPi, Cisplatin, or Mitomycin C. Marked functional deficiency was observed for variants in the exon 2-donor splice region (A22 = (c.66A>C), A22 = (c.66A>G), A22 = (c.66A>T), and D23H) and Trp31 amino acid (W31G, W31L, and W31C), both critical for BRCA2 function. Moreover, T10K and G25R resulted in an intermediate phenotype, suggesting these variants are hypomorphic in nature. Combining our functional results with the latest ClinGen BRCA1/2 Variant Curation Expert Panel recommendations, we could classify 49 of the 54 VUS as either likely benign (n = 45) or likely pathogenic (n = 4). Hence, CRISPR-Select is an important tool for efficient variant clinical classification. Application of this technology in the future will ultimately improve patient care. Danish Cancer Society, Novo Nordisk Foundation, Sygeforsikring Danmark, Børnecancerfonden, Neye-Fonden, Roche, Novartis, Pfizer, AstraZeneca, MSD, and Daiichi Sankyo Europe GmbH.
Genetic inactivation of FAAP100 causes Fanconi anemia due to disruption of the monoubiquitin ligase core complex
Authors: Julia Kuehl, Yutong Xue, Fenghua Yuan, Ramanagouda Ramanagoudr-Bhojappa, Simone Pickel, Reinhard Kalb, Settara C Chandrasekharappa, Weidong Wang, Yanbin Zhang, Detlev Schindler
Journal: Journal of Clinical Investigation (2025)

The Fanconi anemia (FA)/BRCA DNA repair network promotes the removal of DNA interstrand crosslinks (ICLs) to counteract their devastating consequences, including oncogenesis. Network signaling is initiated by the FA core complex, which consists of seven authentic FA proteins and an FA-associated protein, FAAP100, with incompletely characterized roles and unknown disease associations. Upon activation, the FA core complex functions as a multiprotein E3 ubiquitin ligase centered on its catalytic module, the FANCB-FANCL-FAAP100 (BLP100) subcomplex, for FANCD2 and FANCI monoubiquitylation. Here, we identified a homozygous variant in FAAP100, c.1642A>C, predicting p.(T542P), in a fetus with malformations suggestive of FA. The mutation causes sensitivity to ICL-inducing agents in cells from the affected individual and genetically engineered, FAAP100-inactivated human, avian, zebrafish, and mouse cells. All FAAP100-deficient cell types were rescued by ectopic expression of wild-type FAAP100, but not FAAP100T542P. In a confirmatory animal model, customized Faap100-/- mice exhibit embryonic lethality, microsomia, malformations, and gonadal atrophy resembling mice with established FA subtypes. Mechanistically, FAAP100T542P impairs ligase activity by preventing BLP100 subcomplex formation, resulting in defective FAAP100T542P nuclear translocation and chromatin recruitment. FAAP100 dysfunction that disrupts the FA pathway and impairs genomic maintenance, together with FAconsistent human manifestations, recommends FAAP100 as a legitimate FA gene, FANCY.
Effect of Peer Mentorship on Hospitalizations among Patients Receiving Maintenance Hemodialysis
Authors: Ladan Golestaneh, Ryung S. Kim, Christopher Roach, Keith C. Norris, Aaron D. Fox, Michal L. Melamed, Kerri L. Cavanaugh
Journal: Journal of the American Society of Nephrology (2025)

Background: Patients receiving maintenance hemodialysis are hospitalized frequently, leading to disproportionate cost of care, and contributing to high morbidity and mortality. Methods: To test the effectiveness of peer mentorship to reduce hospitalization rates among patients receiving hemodialysis we performed a multi-center, pragmatic, randomized, controlled trial. Two hundred patient participants receiving hemodialysis at high risk for hospitalization were enrolled, 140 in Bronx, NY and 60 in Nashville, TN. Of these, 101 were randomized to the peer-mentor intervention and 99 were randomized to usual care. The intervention consisted of trained mentors, patients receiving hemodialysis, placing weekly telephone calls to their assigned patient participant mentees over a 3-month period. During telephone calls, mentors listened, provided emotional and informational support, and promoted self-management. During the intervention period and up to 15 months later, patient participants were observed for incidence of the primary outcome: monthly counts of unplanned hospitalizations and emergency department (ED) visits. Results: The mean age of all patient participants was 54 (SD 13) years, 100 (50%) were female, 110 (57%) were Black and 70 (39%) were Hispanic. The adjusted incidence rate ratio (aIRR) of primary outcome was not different between intervention vs. usual care in intention to treat analysis (aIRR 0.85; 95% CI 0.64,1.15). Pre-specified as treated analyses, with as treated defined by &gt;20 minutes of telephone contact between mentor/mentee pairs, suggested effectiveness of peer mentoring (aIRR 0.60; 95% CI 0.47,0.76), and exploratory post-hoc analyses demonstrated differences in effectiveness by site and self-identified race of mentees. Conclusions: Peer mentorship did not significantly reduce the rate of hospitalization or ED visits overall, but there may have been effectiveness among the following subgroups: those enrolled in Bronx, NY and those who self-identified as Black.
Deciphering Clonal Hematopoiesis of Indeterminate Potential
Authors: Zhi Yu, Caitlyn Vlasschaert, Pradeep Natarajan
Journal: Journal of the American Society of Nephrology (2025)

Abstract Chronic kidney disease (CKD) afflicts over 10% of US adults, with its prevalence increasing sharply with age. Clonal hematopoiesis of indeterminate potential (CHIP) is a common, genetically heterogeneous blood cell disorder characterized by the age-related clonal expansion of hematopoietic cells driven by leukemogenic somatic mutations yet without hematologic malignancy or dysplasia. While CHIP is a strong risk factor for future hematologic malignancy (estimated at ∼0.5% per year, compared to &lt;0.1% for those without CHIP), it is also linked to twofold higher cardiovascular disease in epidemiologic, cell-based, and murine studies. However, more recent work has implicated CHIP with renal outcomes such as chronic kidney disease as well as acute kidney injury, independent of traditional risk factors. This review covers the observations and proposed hypotheses linking CHIP and kidney disease. The review also underscores the need for further research to elucidate the distinct pathways through which CHIP may contribute to CKD and its comorbidities, considering the heterogeneity within CKD stages and etiologies, as well as whether CHIP is a causal driver of kidney disease or a marker of aging and comorbidity. Finally, we discuss the potential of anti-inflammatory treatments to mitigate CHIP's adverse effects on kidney health, aiming to improve management strategies for patients with CHIP-associated kidney diseases.
Circulating tumour DNA and circulating tumour cells in bladder cancer — from discovery to clinical implementation
Authors: Sia V Lindskrog, Trine Strandgaard, Iver Nordentoft, Matthew D Galsky, Thomas Powles, Mads Agerbæk, Jørgen Bjerggaard Jensen, Catherine Alix-Panabières, Lars Dyrskjøt
Journal: Nature Reviews Urology (2025)
Subclassifying "Atypia of Undetermined Significance (AUS)" Category in the 2023 Bethesda System for Thyroid Cytopathology: Analyzing K-TIRADS, BRAF V600E Mutation, and Risk of Malignancy
Authors: Heejin Bang, Chulshin Cho, Mi Young Kim, Jiyeon Hyeon, Seung Eun Lee
Journal: Endocrine Pathology (2025)