tbuckley/cabot-search huggingface dataset:
Evaluation and Management of Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2024 Clinical Practice Guideline
Authors: Magdalena Madero, Adeera Levin, Sofia B. Ahmed, Juan Jesus Carrero, Bethany Foster, Anna Francis, Rasheeda K. Hall, William G. Herrington, Guy Hill, Lesley A. Inker, Rümeyza Kazancıoğlu, Edmund Lamb, Peter Lin, Natasha McIntyre, Kelly Morrow, Glenda Roberts, Dharshana Sabanayagam, Michael Shlipak, Rukshana Shroff, Navdeep Tangri, Teerawat Thanachayanont, Ifeoma Ulasi, Germaine Wong, Chih-Wei Yang, Luxia Zhang, Karen A. Robinson, Lisa M. Wilson, Renee F. Wilson, Bertram L. Kasiske, Michael Cheung, Amy Earley, Paul E. Stevens, Elke Schaeffner
Journal: Annals of Internal Medicine (2025)

The Kidney Disease: Improving Global Outcomes (KDIGO) organization updated its existing clinical practice guideline in 2024 to provide guidance on the evaluation, management, and treatment of chronic kidney disease (CKD) in adults and children who are not receiving kidney replacement therapy.
DLK1 distinguishes subsets of NF1-associated malignant peripheral nerve sheath tumors with divergent molecular signatures
Authors: Dana K. Mitchell, Kylee Brewster, Stavriani C. Makri, Jaffar Khan, Eric A. Albright, Andrew Horvai, Henry Mang, Qingbo Lu, Shelley A. H. Dixon, Emily White, M. Reza Saadatzadeh, Khadijeh Bijangi-Vishehsaraei, Silpa Gampala, Brooke E. Hickey, Hannah Leffew, Xiaohong Li, Li Jiang, Marisa D. Ciesielski, Waylan K. Bessler, Christopher D. Collier, Aaron Cohen-Gadol, Melissa L. Fishel, Christine A. Pratilas, Karen E. Pollok, Steven P. Angus, Steven Rhodes, D. Wade. Clapp
Journal: Clinical Cancer Research (2025)

Abstract Purpose: MPNST is the leading cause of premature death among individuals with NF1 and the transcriptional aberrations that precede malignant transformation and contribute to MPNST tumorigenesis remain poorly defined. Alterations involving CDKN2A and components of PRC2 have been implicated as early drivers of PNST evolution, but these events do not occur in all MPNST. Accordingly, emerging data has begun to highlight the importance of molecular-based stratification to improve outcomes in patients with NF1-PNST. Experimental design: Here we perform an integrated analysis of multiple, independent datasets obtained from human NF1 patients to gain critical insight into PNST evolution and MPNST heterogeneity. Results: We show that DLK1 is significantly increased in MPNST and provide evidence that DLK1 overexpression may precede histological changes consistent with malignancy. In complementary analyses, we find that serum levels of DLK1 are significantly higher in both mice and humans harboring MPNST compared to those without malignancy. Importantly, while DLK1 expression is increased in MPNST overall, through the integration of multiple, independent datasets we demonstrate that divergent levels of DLK1 expression distinguish MPNST subsets characterized by unique molecular programs and potential therapeutic vulnerabilities. Specifically, we show that overexpression of DLK1 is associated with the reactivation of embryonic signatures, an immunosuppressive microenvironment and a worse overall survival in patients with NF1-MPNST. Conclusions: Collectively, our findings provide critical insight into MPNST tumorigenesis and support prospective studies evaluating the utility of DLK1 tissue and serum levels in augmenting diagnosis, risk assessment and therapeutic stratification in the setting of NF1-PNST.
Emerin Dysregulation Drives the Very-Small-Nuclear Phenotype and Lineage Plasticity that Associates with a Clinically Aggressive Subtype of Prostate Cancer
Authors: Le Zhang, Pai-Chi Teng, Karen A. Cavassani, Jasmine Wang, Catherine Grasso, Joshua Watson, Zijing Chen, Kai-Han Tu, Brenda Salumbides, Krizia Rohena-Rivera, Lilit Gevorkian, Minhyung Kim, Sungyong You, Dolores Di Vizio, Howard M. Sandler, Timothy Daskivich, Neil A. Bhowmick, Michael R. Freeman, Hsian-Rong Tseng, Jie-Fu Chen, Edwin M. Posadas
Journal: Clinical Cancer Research (2025)

Abstract Background: Circulating tumor cells (CTCs) with a very-small-nuclear phenotype (vsnCTCs) in prostate cancer (PCa) are characterized by nuclei smaller than 8.5 μm. Our previous studies established an association between vsnCTCs and visceral metastasis. Reduction of emerin (EMD), a nuclear envelope protein, contributes to PCa metastasis and nuclear shape instability. Here we investigated the correlation between EMD expression and the vsnCTC phenotype and its clinical impact. Methods: We analyzed CTCs from 93 mCRPC patients and categorized them as either vsnCTC+ or vsnCTC- and compared overall survival (OS) and progression-free survival (PFS). C4-2B, 22Rv1, and DU145 with EMD knockdown were developed and characterized by nuclear size and gene expression by GSEA analysis. Abiraterone- and enzalutamide-resistant (Abi-R/Enza-R) C4-2B cells were also characterized by nuclear size and EMD expression. Results: vsnCTC+ patients had significantly worse OS and PFS compared to vsnCTC- patients. EMD expression was markedly reduced in CTCs from vsnCTC+ patients compared to vsnCTC- patients, with a significant positive correlation between EMD expression and CTC nuclear size. EMD knockdown in PCa cells resulted in smaller nuclei, enhanced invasion, and the upregulation of genes associated with lineage plasticity. Additionally, C4-2B Abi-R/Enza-R cells had smaller nuclei and lower EMD expression. vsnCTC+ cells also showed enhanced platinum sensitivity. Conclusions: The presence of vsnCTCs represents a novel hallmark of an aggressive subtype of mCRPC, closely linked to EMD loss and lineage plasticity. These findings highlight the importance of EMD dysregulation in the vsn phenotype, disease progression, and therapeutic resistance in patients with PCa.
Thrombosis‐Driven Disease Progression in <i>JAK2</i>‐Mutant Polycythemia Vera and Essential Thrombocythemia: Reassessing Risk‐Based Management
Authors: Tiziano Barbui, Valerio De Stefano, Elena Rossi, Arianna Ghirardi, Alessandra Carobbio, Giuseppe Gaetano Loscocco, Annalisa Condorelli, Paola Guglielmelli
Journal: American Journal of Hematology (2025)

ABSTRACT This paper explores emerging therapies in polycythemia vera and essential thrombocythemia, focusing on thrombosis as a driver of disease progression leading to myelofibrosis, blast phase, second cancers, and mortality. While the thrombosis rate in high‐risk patients has declined, it remains persistently high in low‐risk individuals, with most events being arterial. Inflammation driven by JAK2 V617F mutation plays a primary role in pathogenesis, and mounting evidence suggests arterial thrombosis itself can fuel a self‐sustaining cycle of inflammation, thereby accelerating hematologic and systemic complications. Early intervention with cytoreductive and anti‐inflammatory drugs may not only prevent incidental thrombosis but also disrupt this inflammatory circuit.
The spectrum of IDH- and H3-wildtype high-grade glioma subgroups occurring across teenage and young adult patient populations
Authors: Rita Pereira, Alan Mackay, Yura Grabovska, Amelia Bradley, Tabitha Bloom, James Nicoll, Delphine Boche, John Procter, Mellissa Maybury, Johanna Schagen, Liam Walker, Federico Roncaroli, Konstantina Karabatsou, Olumide Ogunbiyi, Thijs van Dalen, Jai Sidpra, Sabrina Rossi, Evelina Miele, David S. Ziegler, Zhifeng Shi, Thomas S. Jacques, Darren Hargrave, Bassel Zebian, Cristina Bleil, Joseph Yates, Emma Norton, Henry Mandeville, Antonia Creak, Liam Welsh, Lynley Marshall, Fernando Carceller, Sucheta J. Vaidya, Zita Reisz, Safa Al-Sarraj, Angela Mastronuzzi, Andrea Carai, Maria Vinci, Kathreena M. Kurian, Ho-keung Ng, Sebastian Brandner, Chris Jones, Matthew Clarke
Journal: Clinical Cancer Research (2025)

Abstract Background: High-grade gliomas (HGG) occur in any central nervous system (CNS) location and any age. HGGs in teenagers/young adults (TYA) are understudied. This project aimed to characterise these tumours to support accurate patient stratification. Methods: 207 histone/IDH-wildtype tumours from patients aged 13–30 years were collected. DNA methylation profiling (Illumina EPIC BeadArrays, brain tumour classifier (MNPv12.6 R package)) classified cases against reference cohorts. Calibrated scores guided characterisation workflows (RNA-based ArcherDx fusion panel (n=92), whole exome sequencing (WES) (n=107), histological review). Results: 53.4% (n=86) matched paediatric-type subgroups (pedHGG_RTK1A/B/C (31.7%, n=51 PDGFRA, CDKN2A/B, SETD2, NF1 alterations), pedHGG_MYCN (8.1%, n=13, MYCN/ID2 amplifications), and pedHGG_RTK2A/B (7.5%, n=12, TP53, BCOR, ATRX, EGFR alterations)). 18.0% (n=29) classified as adult-type subgroups (GBM_MES (15.5%, n=25, RB1, PTEN, NF1 alterations) and GBM_RTK1/2 (2.5%, n=4, CDK4 amplifications)). 23 cases (14.7%) classified as novel, poorly-characterised subgroups with distinct methylation profiles and molecular features (pedHGG_A/B (n=10 6.2%), HGG_E (n=6 3.7%), HGG_B (n=2 1.0%), GBM_CBM (n=5 3.1%)) with variable histological morphology. 8 cases (5.1%) showed hypermutator phenotypes, enriched in HGG_E, including siblings with constitutional mismatch repair deficiency (CMMRD). TYA HGGs also develop on a background of childhood cancer treatments. Age-distribution comparisons using publicly available methylation/sequencing data (HGG_B (n=19), GBM_CBM (n=35), GBM_MES_ATYP (n=102)), irrespective of age, show HGG_B is TYA-specific (median 29 years) and GBM_CBM and GBM_MES_ATYP show TYA distribution peaks, with GBM_MES_ATYP showing copy number differences and worse survival compared with adult-specific GBM_MES_TYP. Conclusion: TYA HGGs comprise novel methylation subgroups with distinct molecular profiles. Accurate stratification will open opportunities to utilise more effective treatments.
Subgrouping germinal center-derived B-cell lymphomas based on machine learning-deduced DNA methylation modules
Authors: Selina Glaser, Anja Fischer, Juan Emilio Martínez-Manjón, Cristina López, Helene Kretzmer, Birgit Burkhardt, Daniel Hübschmann, Michael Hummel, Wolfram Klapper, Julia Kolarova, Markus Kreuz, German Ott, Bernhard Radlwimmer, Maciej Rosolowski, Matthias Schlesner, Andreas Rosenwald, Stephan Stilgenbauer, Rabea Wagener, Igor Zwir, Lorenz Trümper, Ralf Küppers, Peter Lichter, Ole Ammerpohl, Coral del Val, Reiner Siebert
Journal: Leukemia (2025)
Classification of Myelodysplastic, Myeloproliferative, and Myelodysplastic/Myeloproliferative Neoplasms: The Past, Present, and Future
Authors: Daniel A. Arber, Attilio Orazi
Journal: American Journal of Hematology (2025)

ABSTRACT With the recent publication of new classification systems of hematopoietic neoplasms, understanding how recognition of disease entities has occurred over time and the subsequent development of formal disease classifications is of importance. This review focuses on the early recognition of myeloid disorders, especially chronic myeloid disorders, and how clinical observations became associated with specific cytologic, histologic, immunophenotypic, and eventually genetic features. This combined approach to disease classification is of particular importance in the evaluation of chronic myeloid neoplasms and has resulted in the definition of clinicopathologic disease entities that allow for more customized treatment approaches. The constant incorporation of ever‐increasing information related to these disorders illustrates that disease classification is a constantly evolving process that requires constant updates as we strive to better understand the disorders we diagnose and treat.
Supramolecular Additive Screening to Engineer Microfibrous Rafts for Expansion of Pluripotent Stem Cells in Dynamic Suspension
Authors: Johnick F. van Sprang, Jasper G. M. Aarts, Boris Arts, Joyce E. P. Brouns, Muhabbat I. Komil, Paul A. A. Bartels, Patricia Y. W. Dankers
Journal: Advanced Healthcare Materials (2025)

Abstract Human induced pluripotent stem cells (hiPSCs) hold the potential to generate any human tissue for transplantation in regenerative therapies. These complex cell therapies require billions of cells, which is challenging to acquire in planar adherent cultures. Transitioning hiPSCs to 3D suspension culture on microcarrier materials, often bead‐shaped, improves the total surface area accessible to cells, thereby enabling culture scale‐up. However, bead‐shaped microcarriers do not have the optimal shape configuration, because it is the lowest surface‐to‐volume ratio of all geometrical shapes, and it also induces uncontrolled cell clumping. Application of synthetic, microfibrous rafts as a replacement for bead‐shaped microcarriers potentially solves these issues. Here, microfibrous rafts are engineered by first screening a supramolecular biomaterial library composed of bisurea (BU)‐peptide conjugate additives for its ability to induce hiPSC adhesion and maintenance of its pluripotent state, followed by electrospinning the screening‐hit into raft‐like structures. The resulting rafts contain cylinder‐like microfibers, which have a higher surface‐to‐volume ratio compared to conventional bead‐shaped microcarriers, and the flat configuration of the rafts prevents clumping.
A Mannosylated peptidyl lipid CManDA doped into cytidinyl/cationic lipids efficiently delivers siG12Ss to lung cancer in vivo
Authors: Hua Guo, Jiamei Hong, Yuejie Zhu, Hongzhe Gui, Hongyi Liu, Runan Ren, Yi Li, Saijun Shan, Zhu Guan, Mingzhe Liu, Zhenjun Yang
Journal: Journal of Controlled Release (2025)

Gene therapy has attracted widespread attention in recent years, and one of the important delivery systems is the LNP. However, many LNPs have potential toxicity and accumulate in the liver. Here, we designed and synthesized a Gemini-type mannosylated peptidyl lipid called CManDA(M), which, in combination with the cytidinyl lipid DNCA(D) and the peptidyl lipid CLD(C) (D/50C/50 M), could transfect siRNA (siG12S) into A549 cells to target and silence the KRASG12S gene. The fluorescence intensity in the tumor area of the D/50C/50 M/Cy5.5-siG12S group increased by approximately 2.5 times. Furthermore, full 2'-F/2'-OMe-modified siG12Ss could also be transfected by D/50C/50 M into cells, resulting in target gene silencing. The tumor weight in the D/50C/50 M/M3 group (1.5 mg/kg, i.v.) was reduced by 50 % after administration in a mouse axillary tumor (A549) model, whereas the tumor bioluminescence intensity was only approximately 30 % of that in the blank group in a mouse orthotopic lung cancer model and showed no significant toxicity. Further studies revealed that the mannose groups of CManDA can be exposed on the nanoparticle surface to bind lectins, and CManDA can also shield the formation of a protein corona and alter the composition of the protein corona, which aids in the enhancement of its active targeting function. CManDA is expected to be a safe and effective helper lipid for tumor-targeted delivery of siRNA in vivo.
Integrating multi-omics data to reveal the host-microbiota interactome in inflammatory bowel disease
Authors: Fengyuan Su, Meng Su, Wenting Wei, Jiayun Wu, Leyan Chen, Xiqiao Sun, Moyan Liu, Shiqiang Sun, Ren Mao, Arno R. Bourgonje, Shixian Hu
Journal: Gut Microbes (2025)

Numerous studies have accelerated the knowledge expansion on the role of gut microbiota in inflammatory bowel disease (IBD). However, the precise mechanisms behind host-microbe cross-talk remain largely undefined, due to the complexity of the human intestinal ecosystem and multiple external factors. In this review, we introduce the interactome concept to systematically summarize how intestinal dysbiosis is involved in IBD pathogenesis in terms of microbial composition, functionality, genomic structure, transcriptional activity, and downstream proteins and metabolites. Meanwhile, this review also aims to present an updated overview of the relevant mechanisms, high-throughput multi-omics methodologies, different types of multi-omics cohort resources, and computational methods used to understand host-microbiota interactions in the context of IBD. Finally, we discuss the challenges pertaining to the integration of multi-omics data in order to reveal host-microbiota cross-talk and offer insights into relevant future research directions.
Worsening disease severity as measured by I-SEE associates with decreased treatment response to topical steroids in eosinophilic esophagitis patients
Authors: Craig C. Reed, Sean S. LaFata, Timothy S. Gee, Hannah L. Thel, Brenderia A. Cameron, Angela Z. Xue, Akshatha Kiran, Adolfo A. Ocampo, Justin McCallen, Christopher J. Lee, Stephanie A. Borinsky, Walker D. Redd, Trevor S. Barlowe, Rayan N. Kaakati, Cary C. Cotton, Swathi Eluri, Evan S. Dellon
Journal: Clinical Gastroenterology and Hepatology (2025)
Association of Daily Steps Over Time with Adult Asthma Incidence
Authors: Joshua C Halevi, Jeffrey Annis, Hiral Master, Basil M Kahwash, Evan L Brittain, Katherine N Cahill
Journal: Journal of Allergy and Clinical Immunology (2025)

Higher daily step counts is associated with reduced risk of many chronic diseases. Increased physical activity improves asthma outcomes. There are no known prevention strategies for adult incident asthma. To determine whether objective physical activity impacts adult asthma incidence. Participants in the All of Us Research Program retrospective cohort aged ≥ 18 years with linked personal activity tracker and electronic health record data met inclusion. Asthma was defined as two ICD-9/10 codes and ≥ 1 medication. Participants with an asthma diagnosis date before/within six months of activity monitor initiation were assigned prevalent asthma; participants diagnosed after six months of activity monitoring were assigned incident asthma. 8,360 participants met inclusion. Median average steps/day were higher among asthma-free participants [7,795 (5,879-9,921, 95% CI), n = 7,700] than participants with prevalent [6,968 (5,036-9,014, 95% CI), n = 450] or incident asthma [6,953 (5,215-8,261), n = 210] (p < 0.0001). Significant time by incident asthma interaction was observed with a greater decline in steps/day over time in the incident asthma cohort (p = 0.018). An inverse relationship was observed between average steps/day and asthma incidence after adjusting for age, sex, race, body mass index, major depressive disorder, sleep apnea, and chronic obstructive lung disease [adjusted hazard ratio 0.93 (0.88-0.98, 95% CI) per 1,000 average daily step increase]. Objectively measured daily steps are lower in adults who develop incident asthma and may represent a modifiable risk factor to reduce asthma incidence. Future studies should objectively monitor physical activity among adults at risk for and with asthma.
An injectable hydrogel loaded with miRNA nanocarriers promotes vessel-associated osteoclast (VAO)-mediated angiogenesis and bone regeneration in osteonecrosis of the rat femoral head
Authors: Hongyu Quan, Chencan Ren, Hongkun Xie, Zibo He, Haibin Ding, Jinbao Li, Taiyang Li, Fuyou Wang, Shiwu Dong, Hong Jiang
Journal: Biomaterials (2025)
Effective transcatheter intracoronary delivery of mRNA-lipid nanoparticles targeting the heart
Authors: Kazuma Handa, Masashi Kawamura, Masao Sasai, Takashi Matsuzaki, Akima Harada, Lisa Fujimura, Julia Whitehouse, Shunsuke Saito, Sho Komukai, Tetsuhisa Kitamura, Anri Fujishiro, Kunio Hirano, Kenji Miki, Shigeru Miyagawa
Journal: Journal of Controlled Release (2025)

Messenger RNA (mRNA) has great potential to provide innovative medical solutions in the treatment of heart failure. Although lipid nanoparticles (LNPs) are an established mRNA delivery system, effectively delivering LNPs to the heart remains a significant challenge. Here, we evaluated the efficacy of transcatheter intracoronary (IC) administration compared to intravenous (IV) and intramyocardial (IM) administration in normal and ischemia-reperfusion (I/R) model rabbit hearts using LNPs encapsulating Firefly Luciferase (FLuc) mRNA. In the normal model, IVIS spectrum data showed that FLuc expression was widespread throughout the heart in the IC group and was significantly higher than in the IV group, and comparable to the IM group, where it was highly expressed only at the injection sites. Histological analysis revealed that FLuc-expressing cells were observed in cardiomyocytes, endothelial cells, smooth muscle cells, and fibroblasts. In the I/R model, FLuc expression was also significantly higher in the IC group than the IV group, and comparable to the IM group. Although FLuc expression was strongly observed in the infarcted area in all three delivery groups, the IC group demonstrated the most widespread FLuc expression in the remote area. Histological analysis revealed significantly higher FLuc-expressing cells in the remote area in the IC group than in all other groups. IC administration effectively delivered mRNA-LNPs not only to the damaged area but also to the remote area (non-damaged area) in the diseased heart. Moreover, VEGF mRNA-LNP administration via the IC method to I/R model rabbit hearts significantly reduced the infarct area and attenuated the impairment of cardiac function caused by I/R injury compared to other methods. Considering the invasiveness and clinically limited applications of IM administration, our study suggests that less invasive IC administration is a clinically safe and useful method for delivery to a wider range of myocardial tissue in the heart.
Metabolic Improvements With Tirzepatide in Lipodystrophy: A Novel Option?
Authors: Rasimcan Meral, Merve Celik Guler, Diarratou Kaba, Jeevitha Prativadi, Eric D. Frontera, Maria Cristina Foss-Freitas, Noura Nachawi, David T. Broome, Marissa Lightbourne, Rebecca J. Brown, Simeon I. Taylor, Elif A. Oral
Journal: Diabetes Care (2025)

OBJECTIVE Lipodystrophy encompasses a group of rare disorders associated with severe metabolic disease. These disorders are defined by abnormal fat distribution, with near-total (generalized lipodystrophy [GL]) or partial (partial lipodystrophy [PL]; e.g. familial partial lipodystrophy [FPLD]) absence of adipocyte mass, leading to a decreased ability to store lipids safely. Excess lipids are more likely to be stored in nonadipose tissues, which leads to the metabolic manifestations. We have recently shown that glucagon-like peptide-1 agonists are associated with metabolic improvements in FPLD. Here, we hypothesize that tirzepatide, a dual incretin, may also lead to metabolic improvement in patients with lipodystrophy. RESEARCH DESIGN AND METHODS An observational cohort of patients with lipodystrophy who received tirzepatide clinically were tracked in the context of ongoing natural history studies. RESULTS Seventeen patients received tirzepatide, 14 who had FPLD (aged 30–74 years; n = 12 female and 2 male). After a median 8.7 months of follow-up, the following were significantly reduced: BMI (median difference, −1.7; range, −5.9 to 0.9 kg/m2; P = 0.008), HbA1c (median difference, −1.1%; range −6.3% to −0.1%; P &amp;lt; 0.001), triglycerides (median difference, −65 mg/dL [−0.73 mmol/L]; range, −3,820 to 43 mg/dL [−43.2 to 0.49 mmol/L]; P = 0.003), and total daily insulin requirements (median difference, −109; range, −315 to 0 units/day; P = 0.002). Three additional patients with rarer forms of lipodystrophy, also with robust response to tirzepatide, are also discussed (atypical PL, n = 1; acquired GL; n = 2; aged 35–64 years; all female). Side effects were limited to benign gastrointestinal symptoms. CONCLUSIONS Tirzepatide may be an effective treatment for patients with lipodystrophy.