bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Stimulating Soluble Guanylyl Cyclase with the Clinical Agonist Riociguat Restrains the Development and Progression of Castration-Resistant Prostate Cancer
Authors: Zhang Ling , Troccoli Clara I. , Mateo-Victoriano Beatriz , Misiara Lincheta Laura , Jackson Erin , Shu Ping , Plastini Trisha , Tao Wensi , Kwon Deukwoo , Chen Xi Steven , Sharma Janaki , Jorda Merce , Kumar Surinder , Lombard David B. , Gulley James L. , Bilusic Marijo , Lockhart Albert C. , Beuve Annie , Rai Priyamvada
Published: January 2025

Abstract
Castration-resistant prostate cancer (CRPC) is incurable and fatal, making prostate cancer the second leading cancer-related cause of death for American men. CRPC results from therapeutic resistance to standard-of-care androgen deprivation (AD) treatments, through incompletely understood molecular mechanisms, and lacks durable therapeutic options. In this study, we identified enhanced soluble guanylyl cyclase (sGC) signaling as a mechanism that restrains CRPC initiation and growth. Patients with aggressive, fatal CRPC exhibited significantly lower serum levels of the sGC catalytic product cyclic GMP (cGMP) compared with the castration-sensitive stage. In emergent castration-resistant cells isolated from castration-sensitive prostate cancer populations, the obligate sGC heterodimer was repressed via methylation of its β subunit. Genetically abrogating sGC complex formation in castration-sensitive prostate cancer cells promoted evasion of AD-induced senescence and concomitant castration-resistant tumor growth. In established castration-resistant cells, the sGC complex was present but in a reversibly oxidized and inactive state. Subjecting CRPC cells to AD regenerated the functional complex, and cotreatment with riociguat, an FDA-approved sGC agonist, evoked redox stress-induced apoptosis. Riociguat decreased castration-resistant tumor growth and increased apoptotic markers, with elevated cGMP levels correlating significantly with lower tumor burden. Riociguat treatment reorganized the tumor vasculature and eliminated hypoxic tumor niches, decreasing CD44+ tumor progenitor cells and increasing the radiosensitivity of castration-resistant tumors. Thus, this study showed that enhancing sGC activity can inhibit CRPC emergence and progression through tumor cell–intrinsic and extrinsic effects. Riociguat can be repurposed to overcome CRPC, with noninvasive monitoring of cGMP levels as a marker for on-target efficacy.

Significance: Soluble guanylyl cyclase signaling inhibits castration-resistant prostate cancer emergence and can be stimulated with FDA-approved riociguat to resensitize resistant tumors to androgen deprivation, providing a strategy to prevent and treat castration resistance.
Data from SpatialDeX Is a Reference-Free Method for Cell-Type Deconvolution of Spatial Transcriptomics Data in Solid Tumors
Authors: Liu Xinyi , Tang Gongyu , Chen Yuhao , Li Yuanxiang , Li Hua , Wang Xiaowei
Published: January 2025

Abstract
The rapid development of spatial transcriptomics (ST) technologies has enabled transcriptome-wide profiling of gene expression in tissue sections. Despite the emergence of single-cell resolution platforms, most ST sequencing studies still operate at a multicell resolution. Consequently, deconvolution of cell identities within the spatial spots has become imperative for characterizing cell-type–specific spatial organization. To this end, we developed Spatial Deconvolution Explorer (SpatialDeX), a regression model–based method for estimating cell-type proportions in tumor ST spots. SpatialDeX exhibited comparable performance to reference-based methods and outperformed other reference-free methods with simulated ST data. Using experimental ST data, SpatialDeX demonstrated superior performance compared with both reference-based and reference-free approaches. Additionally, a pan-cancer clustering analysis on tumor spots identified by SpatialDeX unveiled distinct tumor progression mechanisms both within and across diverse cancer types. Overall, SpatialDeX is a valuable tool for unraveling the spatial cellular organization of tissues from ST data without requiring single-cell RNA-seq references.

Significance: The development of a reference-free method for deconvolving the identity of cells in spatial transcriptomics datasets enables exploration of tumor architecture to gain deeper insights into the dynamics of the tumor microenvironment.
Data from Distant Metastases of Breast Cancer Resemble Primary Tumors in Cancer Cell Composition but Differ in Immune Cell Phenotypes
Authors: Kuett Laura , Bollhagen Alina , Tietscher Sandra , Sobottka Bettina , Eling Nils , Varga Zsuzsanna , Moch Holger , de Souza Natalie , Bodenmiller Bernd
Published: January 2025

Abstract
Breast cancer is the most commonly diagnosed cancer in women, with distant metastasis being the main cause of breast cancer–related deaths. Elucidating the changes in the tumor and immune ecosystems that are associated with metastatic disease is essential to improve understanding and ultimately treatment of metastasis. Here, we developed an in-depth, spatially resolved single-cell atlas of the phenotypic diversity of tumor and immune cells in primary human breast tumors and matched distant metastases, using imaging mass cytometry to analyze a total of 75 unique antibody targets. Although the same tumor cell phenotypes were typically present in primary tumors and metastatic sites, suggesting a strong founder effect of the primary tumor, their proportions varied between matched samples. Notably, the metastatic site did not influence tumor phenotype composition, except for the brain. Metastatic sites exhibited a lower number of immune cells overall but had a higher proportion of myeloid cells as well as exhausted and cytotoxic T cells. Myeloid cells showed distinct tissue-specific compositional signatures and increased presence of potentially matrix remodeling phenotypes in metastatic sites. This analysis of tumor and immune cell phenotypic composition of metastatic breast cancer highlights the heterogeneity of the disease within patients and across distant metastatic sites, indicating myeloid cells as the predominant immune modulators that could potentially be targeted at these sites.

Significance: Multiplex imaging analysis of matched primary and metastatic breast tumors provides a phenotypic and spatial map of tumor microenvironments, revealing similar compositions of cancer cells and divergent immunologic features between matched samples.
Persistence and/or Senescence: Not So Lasting at Last?
Authors: Schmitt Clemens A.
Published: January 2025

Therapy-exposed surviving cancer cells may have encountered profound epigenetic remodeling that renders these drug-tolerant persisters candidate drivers of particularly aggressive relapses. Typically presenting as slow-to-nongrowing cells, persisters are senescent or senescence-like cells. In this issue of Cancer Research, Ramponi and colleagues study mTOR/PI3K inhibitor–induced embryonic diapause–like arrest (DLA) as a model of persistence in lung cancer and melanoma cells and compare this persister condition with therapy-induced senescence in the same cells. The DLA phenotype recapitulated some but not all features attributed to senescent cells, lacking, for instance, an inflammatory secretome otherwise known as the senescence-associated secretory phenotype. A CRISPR dropout screen pointed to methyl group–providing one-carbon metabolism and further to H4K20me3-mediated repression of senescence-associated secretory phenotype–related IFN response genes selectively in DLA-like persister cells. Conversely, inhibition of H4K20-active KMT5B/C methyltransferases derepressed inflammatory programs and was toxic in DLA cells. These findings not only suggest exploitable vulnerabilities of DLA-like persister cells but also unveil general technical and conceptual challenges of cultured multipassage cell line–based persister studies. Collectively, the approach chosen and insights obtained will stimulate a productive scientific debate on senescence-like features and their reversibility across drug-tolerant persister cells.

See related article by Ramponi et al., p. 32
Figure S3 from A Novel Lipid Nanoparticle NBF-006 Encapsulating Glutathione S-Transferase P siRNA for the Treatment of KRAS-Driven Non–small Cell Lung Cancer
Authors: Cina Cima , Majeti Bharat , O’Brien Zhihong , Wang Li , Clamme Jean Pierre , Adami Roger , Tsang Kwok Yin , Harborth Jens , Ying Wenbin , Zabludoff Sonya
Published: January 2025

NSCLC xenograft models
Supplementary Table 3 from PARP7 Inhibitors and AHR Agonists Act Synergistically across a Wide Range of Cancer Models
Authors: Chen Huadong , Gou Xuxu , Mao Ying , O’Leary Patrick C. , Diolaiti Morgan E. , Ashworth Alan
Published: January 2025

Supplementary Table 3. Primers used for Real-time quantitative PCR.
Figure S5 from A Small-Molecule BCL6 Inhibitor as an Anti-Proliferative Agent for Diffuse Large B-Cell Lymphoma
Authors: Xing Yajing , Guo Weikai , Wu Min , Xie Jiuqing , Huang Dongxia , Hu Pan , Zhou Miaoran , Zhang Lin , Zhong Yadong , Liu Mingyao , Chen Yihua , Yi Zhengfang
Published: January 2025

Figure S5. Viability of SUDHL4 and Farage cells transduced with shBCL6 or shScr was measured by CCK8 assay.
Supplemental Figure 3 from Tumor-Specific Antigen Delivery for T-cell Therapy via a pH-Sensitive Peptide Conjugate
Authors: Yurkevicz Annali M. , Liu Yanfeng , Katz Samuel G. , Glazer Peter M.
Published: January 2025

B16 OVA tumor growth in C57BL/6 mice versus OT1 mice. A, Tumor growth curves of B16 OVA melanoma tumors in C57BL/6 mice or OT1 mice, as indicated. Statistical comparisons by two-way RM-ANOVA. B, Survival curves from (A). Statistical comparisons by Log-rank (Mantel–Cox) test, n=4 mice per group.
Supplemental Figure 2 from Tumor-Specific Antigen Delivery for T-cell Therapy via a pH-Sensitive Peptide Conjugate
Authors: Yurkevicz Annali M. , Liu Yanfeng , Katz Samuel G. , Glazer Peter M.
Published: January 2025

Knockdown of β2m abrogates OT1 T cell engagement with pHLIP-SIINFEKL-treated B16-F10 cells. A, Western blot showing siRNA knockdown of β2m or GAPDH (control) in B16-F10 cells with Vinculin loading control. B, B16-F10 cells were treated with siRNA to β2m or to GAPDH followed by treatment with pHLIP-SIINFEKL or pHLIP-NULL (1uM) for 2 hours. The cells were then co-cultured with fluorescently labeled OT1 T cells for an additional two hours. Cell cultures were washed to remove unbound OT1 T cells that had not engaged with the B16-F10 cells, followed by fluorescence microscopy. C, Quantification of OT1 T cell/total cell number showing a significant reduction in OT1 engagement in the pHLIP-SIINFEKL + OT1 treatment group when the B16-F10 cells were pre-treated with β2m siRNA compared to GAPDH siRNA control. Statistical analyses by unpaired two-tailed T-test, with p-value shown.
Figure S6 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Authors: Gamma Jay M. , Liu Qiang , Beauchamp Erwan , Iyer Aishwarya , Yap Megan C. , Zak Zoulika , Ekstrom Cassidy , Pain Rony , Kostiuk Morris A. , Mackey John R. , Brandwein Joseph , Wang Jean C.Y. , Berthiaume Luc G.
Published: January 2025

Supplementary Figure S6: Zelenirstat causes manageable weight loss in mice. Body weight of mice in xenograft experiments fig3C (A) and fig3D (B). High-dose zelenirstat caused weight loss that was rapidly recovered after cessation of treatment.
Figure S3 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Authors: Gamma Jay M. , Liu Qiang , Beauchamp Erwan , Iyer Aishwarya , Yap Megan C. , Zak Zoulika , Ekstrom Cassidy , Pain Rony , Kostiuk Morris A. , Mackey John R. , Brandwein Joseph , Wang Jean C.Y. , Berthiaume Luc G.
Published: January 2025

Supplementary Figure S3: NMT2 is associated with overall survival in the GSE37642 dataset: Patients in the GSE37642 dataset were separated into quartiles based on NMT2 expression, and overall survival analyzed via Kaplan-Meier plots. Curves were compared by log-rank test.
Figure S12 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Authors: Gamma Jay M. , Liu Qiang , Beauchamp Erwan , Iyer Aishwarya , Yap Megan C. , Zak Zoulika , Ekstrom Cassidy , Pain Rony , Kostiuk Morris A. , Mackey John R. , Brandwein Joseph , Wang Jean C.Y. , Berthiaume Luc G.
Published: January 2025

Supplementary Figure S12: Matched viability assay for Resipher assays Cells were plated under identical conditions to Resipher assays in fig6D and viability measured by CellTitre BlueTM at 24 hours intervals (n = 2). No significant loss of viability was observed in 72 hours (zelenirstat added at 24 hours).
Figure S11 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Authors: Gamma Jay M. , Liu Qiang , Beauchamp Erwan , Iyer Aishwarya , Yap Megan C. , Zak Zoulika , Ekstrom Cassidy , Pain Rony , Kostiuk Morris A. , Mackey John R. , Brandwein Joseph , Wang Jean C.Y. , Berthiaume Luc G.
Published: January 2025

Supplementary Figure S11: Zelenirstat reduces glycolytic rate in AML cells. MV-4-11 (A-B) and U937 (C-D) cells were incubated with zelenirstat for 48 hours, then extracellular acidification assessed using an Aglient Seahorse and Glycolytic Rate Assay kit.
Figure S10 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Authors: Gamma Jay M. , Liu Qiang , Beauchamp Erwan , Iyer Aishwarya , Yap Megan C. , Zak Zoulika , Ekstrom Cassidy , Pain Rony , Kostiuk Morris A. , Mackey John R. , Brandwein Joseph , Wang Jean C.Y. , Berthiaume Luc G.
Published: January 2025

Supplementary Figure S10: Zelenirstat reduces OCR in U937 cells U937 cells were incubated with zelenirstat for 48 hours then analyzed using an Agilent Seahorse and Glycolytic Rate Assay kit (n = 5).
Supplementary Figure 4 from Riluzole Enhancing Anti-PD-1 Efficacy by Activating cGAS/STING Signaling in Colorectal Cancer
Authors: Liang Beiyuan , Khan Misbah , Storts Hayden , Zhang Evan H. , Zheng Xinru , Xing Xuanxuan , Claybon Hazel , Wilson Jenna , Li Chunjie , Jin Ning , Fishel Richard , Miles Wayne O. , Wang Jing J.
Published: January 2025

Supplemental figure 4 and legend
Table S3 from Advances and Challenges in RAS Signaling Targeted Therapy in Leukemia
Authors: Chen Yu , Yin Zhenghao , Westover Kenneth D. , Zhou Zhiwei , Shu Liping
Published: January 2025

Table S3. HRAS mutations in leukemia
Table S2 from Advances and Challenges in RAS Signaling Targeted Therapy in Leukemia
Authors: Chen Yu , Yin Zhenghao , Westover Kenneth D. , Zhou Zhiwei , Shu Liping
Published: January 2025

Table S2. KRAS mutations in leukemia
Supplementary Table S8 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Table S8. Organ biodistribution analysis data in %ID/g tissue for 89Zr labeled nanocarriers at 96 h in mice model bearing CT26 subcutaneous tumors. (n = 5)
Supplementary Table S7 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Table S7. Organ biodistribution analysis data in %ID/Organ tissue for 89Zr labeled nanocarriers at 96 h in mice model bearing 22rv1 subcutaneous tumors. (n = 4)
Supplementary Table S4 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Table S4. Region of interest analysis data reported as %ID/cc of the [89Zr]PEG-DFB4 on different subcutaneous tumors from Day 1-4 post injection. (n = 4)
Supplementary Table S16 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Table S16. Organ biodistribution analysis data in %ID/Organ tissue for 89Zr labeled nanocarriers at 96 h in metastatic mice model with 22rv1 cell inoculated in kidney capsule tumors. (n = 4)
Supplementary Table S15 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Table S15. Organ biodistribution analysis data in %ID/g tissue for 89Zr labeled nanocarriers at 96 h in metastatic mice model with 22rv1 cell inoculated in kidney capsule tumors. (n = 4)
Supplementary Table S13 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Table S13. Organ biodistribution analysis data in %ID/Organ tissue for 89Zr labeled nanocarriers at 96 h in mice model bearing LTL-610 subcutaneous tumors. (n = 4)
Supplementary Figure S9 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Figure S9. Organ biodistribution presented in (left) %ID/g, and (right) %ID/organ for 89Zr labeled nanocarriers in nude mice bearing CT26 subcutaneous tumors at 96 h postinjection. (n = 5, mean ± SD)
Supplementary Figure S7 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Figure S7. Coronal μPET/CT fusion and MIP images obtained at 24 h, 48 h, 72 h, and 96 h following administration of 150-170 μCi of 89Zr labeled nanocarriers in nude mice bearing LTL-610 patient derived xenograft (PDX) of tumors over left flanks.
Supplementary Figure S6 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Figure S6. Coronal μPET/CT fusion and MIP images obtained at 24 h, 48 h, 72 h, and 96 h following administration of 150-170 μCi of 89Zr labeled nanocarriers in nude mice bearing LTL-545 patient derived xenograft (PDX) of tumors over left flanks.
Supplementary Figure S4 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Figure S4. Coronal μPET/CT fusion and MIP images obtained at 18 h, 48 h, 72 h, and 96 h following administration of 150-170 μCi of 89Zr labeled nanocarriers in nude mice bearing 22rv1 subcutaneous tumors over left flanks.
Supplementary Figure S23 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Figure S23. Organ biodistribution presented in (left) %ID/g, and (right) %ID/organ of 89Zr labeled nanocarriers in nude mice inoculated with 22rv1 cells via intracardiac injection at 72 h postinjection. (n = 4, mean ± SD)
Supplementary Figure S19 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Figure S19. Coronal μPET/CT fusion and MIP images obtained at 24 h, 48 h, 72 h, and 96 h following administration of 150-170 μCi of [89Zr]PEG-DFB1-TLZ3 in nude mice inoculated with 22rv1 cells in the left kidney capsule (red arrow). Yellow arrows indicate metastatic tumor.
Supplementary Figure S18 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Figure S18. BLI of all mice in the cohort inoculated with 22rv1-Luc cells in the left kidney capsule that demonstrate prominent signal of metastatic tumors at the neck and thigh region on the day of [89Zr]PEG-DFB1-TLZ3 injection. Black arrows indicate the presence of metastatic tumors.
Supplementary Figure S17 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Figure S17. Immunofluorescence CD31 staining of the respective tumor tissue sections using rat anti-mouse CD31 antibody indicating the vascular development in different tumor phenotypes.
Supplementary Figure S12 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Figure S12. Autoradiographic images and H&E staining images of subcutaneous 22rv1 tumor sections from day 1 to day 4 post injection of 89Zr labeled nanocarriers. *Indicate the presence of necrosis.
Figure S8 from Tumor Integrin-Targeted Glucose Oxidase Enzyme Promotes ROS-Mediated Cell Death that Combines with Interferon Alpha Therapy for Tumor Control
Authors: Stinson Jordan A. , Sheen Allison , Lax Brianna M. , Yang Grace N. , Duhamel Lauren , Santollani Luciano , Fink Elizabeth , Palmeri Joseph R. , Wittrup Karl Dane
Published: January 2025

2.5F-GOX and MSA-IFNa do not cause toxicity in mice but fail to generate anti-tumor memory
Figure S7 from Tumor Integrin-Targeted Glucose Oxidase Enzyme Promotes ROS-Mediated Cell Death that Combines with Interferon Alpha Therapy for Tumor Control
Authors: Stinson Jordan A. , Sheen Allison , Lax Brianna M. , Yang Grace N. , Duhamel Lauren , Santollani Luciano , Fink Elizabeth , Palmeri Joseph R. , Wittrup Karl Dane
Published: January 2025

Fluorescence intensities of OT-I phenotypic markers from the cross-presentation assay with IFNa
Figure S4 from Tumor Integrin-Targeted Glucose Oxidase Enzyme Promotes ROS-Mediated Cell Death that Combines with Interferon Alpha Therapy for Tumor Control
Authors: Stinson Jordan A. , Sheen Allison , Lax Brianna M. , Yang Grace N. , Duhamel Lauren , Santollani Luciano , Fink Elizabeth , Palmeri Joseph R. , Wittrup Karl Dane
Published: January 2025

Comparison of OT-I phenotypes in cross-presentation assay after treatment with immunogenic cell stress-inducing chemotherapy
Data from PARP7 Inhibitors and AHR Agonists Act Synergistically across a Wide Range of Cancer Models
Authors: Chen Huadong , Gou Xuxu , Mao Ying , O’Leary Patrick C. , Diolaiti Morgan E. , Ashworth Alan
Published: January 2025

Abstract
Small-molecule inhibitors of the mono (ADP) ribosyl transferase PARP7 are being evaluated asmonotherapy for tumors overexpressing PARP7 and in combination with immune checkpoint blockade. We previously showed that sensitivity to the PARP7 inhibitor (PARP7i) RBN-2397 could be enhanced by cotreatment with agonists of the aryl hydrocarbon receptor (AHRa) in cell lines that show strong intrinsic sensitivity to RBN-2397. In this study, we demonstrated that a range of tumor cell lines that are relatively insensitive to PARP7i or AHRa as individual agents are unexpectedly profoundly sensitive to their combination. Our data show that this synergistic response is dependent on the AHR/AHR nuclear translocator and is associated with increased levels of nuclear AHR and increased transcription of AHR target genes. In some hormone receptor–positive cell lines, we find that combination treatment is associated with proteasomal turnover of the steroid hormone receptors, androgen receptor and estrogen receptor. Both wild-type and hormone-resistant mutant forms of these receptors are degraded upon treatment with AHRa and PARP7i in breast and prostate cancer models. These results suggest that combining PARP7i with AHRa may extend the utility of these drugs to a wider range of tumors, including those that are refractory to hormone therapy.
Data from A Small-Molecule BCL6 Inhibitor as an Anti-Proliferative Agent for Diffuse Large B-Cell Lymphoma
Authors: Xing Yajing , Guo Weikai , Wu Min , Xie Jiuqing , Huang Dongxia , Hu Pan , Zhou Miaoran , Zhang Lin , Zhong Yadong , Liu Mingyao , Chen Yihua , Yi Zhengfang
Published: January 2025

Abstract
The B-cell lymphoma 6 (BCL6) transcription factor plays a key role in the establishment of germinal center (GC) formation. Diffuse large B-cell lymphoma (DLBCL) originates from the GC reaction due to dysregulation of BCL6. Disrupting BCL6 and its corepressors’ interaction has become the foundation for rationally designing lymphoma therapies. However, BCL6 inhibitors with good activities in vitro and in vivo are rare, and there are no clinically approved BCL6 inhibitors. In this study, we discovered and developed a novel range of [1,2,4] triazolo[1,5-a] pyrimidine derivatives targeting BCL6/SMRT interaction. The lead compound WK692 directly bound BCL6BTB, disrupted BCL6BTB/SMRT interaction and activated the expression of BCL6 downstream genes inside cells, inhibited DLBCL growth and induced apoptosis in vitro, inhibited GC formation, decreased the proportion of follicular helper T cells, and impaired Ig affinity maturation. Further studies showed that WK692 inhibits DLBCL growth without toxic effects in vivo and synergizes with the EZH2 and PRMT5 inhibitors. Our results demonstrated that WK692 as a BCL6 inhibitor may be developed as a novel potential anticancer agent against DLBCL.
Data from Riluzole Enhancing Anti-PD-1 Efficacy by Activating cGAS/STING Signaling in Colorectal Cancer
Authors: Liang Beiyuan , Khan Misbah , Storts Hayden , Zhang Evan H. , Zheng Xinru , Xing Xuanxuan , Claybon Hazel , Wilson Jenna , Li Chunjie , Jin Ning , Fishel Richard , Miles Wayne O. , Wang Jing J.
Published: January 2025

Abstract
Colorectal cancer is the second leading cause of cancer mortality in the United States. Although immune checkpoint blockade therapies including anti-PD-1/PD-L1 have been successful in treating a subset of patients with colorectal cancer, the response rates remain low. We have found that riluzole, a well-tolerated FDA-approved oral medicine for treating amyotrophic lateral sclerosis, increased intratumoral CD8+ T cells and suppressed tumor growth of colon cancer cells in syngeneic immune–competent mice. Riluzole-mediated tumor suppression was dependent on the presence of CD8+ T cells. Riluzole activates the cytosolic DNA sensing cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway in colon cancer cells, resulting in increased expression of IFNβ and IFNβ-regulated genes including CXCL10. Inhibition of ataxia telangiectasia mutated (ATM), but not ATM-related, resulted in a synergistic increase in IFNβ expression, suggesting that riluzole induces ATM-mediated damage response that contributes to cGAS/STING activation. Depletion of cGAS or STING significantly attenuated riluzole-induced expression of IFNβ and CXCL10 as well as increase of intratumoral CD8+ T cells and suppression of tumor growth. These results indicate that riluzole-mediated tumor infiltration of CD8+ T cells and attenuation of tumor growth is dependent on tumor cell–intrinsic STING activation. To determine whether riluzole treatment primes the tumor microenvironment for immune checkpoint modulation, riluzole was combined with anti-PD-1 treatment. This combination showed greater efficacy than either single agent and strongly suppressed tumor growth in vivo. Taken together, our studies indicate that riluzole activates cGAS/STING-mediated innate immune responses, which might be exploited to sensitize colorectal tumors to anti-PD-1/PD-L1 therapies.
Data from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Abstract
The enhanced permeability and retention (EPR) effect controls passive nanodrug uptake in tumors and may provide a high tumor payload with prolonged retention for cancer treatment. However, EPR-mediated tumor uptake and distribution vary by cancer phenotype. Thus, we hypothesized that a companion PET imaging surrogate may benefit EPR-mediated therapeutic drug delivery. We developed two 89Zr-radiolabeled nanocarriers based on 4-armed starPEG40kDa with or without talazoparib (TLZ), a potent PARP inhibitor, as surrogates for the PEG-TLZ4 therapeutic scaffold. For PET imaging, PEG-DFB4 and PEG-DFB1-TLZ3 were radiolabeled with 89Zr by replacing one or all four copis of TLZ on PEG-TLZ4 with deferoxamine B (DFB). The radiolabeled nanodrugs [89Zr]PEG-DFB4 and [89Zr]PEG-DFB1-TLZ3 were tested in vivo in prostate cancer subcutaneous (s.c.) xenografts (22Rv1, LTL-545, and LTL-610) and 22Rv1 metastatic models. Their EPR-mediated tumoral uptake and penetration was compared with CT26, a known EPR-high cell line. MicroPET/CT images, organ biodistribution, and calculated kinetic parameters showed high uptake in CT26 and LTL-545 and moderate to low uptake in LTL-610 and 22Rv1. MicroPET/CT and high-resolution autoradiographic images showed nanocarrier penetration into highly permeable CT26, but heterogeneous peripheral accumulation was observed in LTL-545, LTL-610, and 22Rv1 s.c. xenografts and metastatic tumors. CD31 staining of tumor sections showed homogenous vascular development in CT26 tumors and heterogeneity in other xenografts. Both [89Zr]PEG-DFB4 and [89Zr]PEG-DFB1-TLZ3 showed similar accumulation and distribution in s.c. and metastatic tumor models. Both nanocarriers can measure tumor model passive uptake heterogeneity. Although heterogeneous, prostate cancer xenografts had low EPR. These starPEG nanocarriers could be used as PET imaging surrogates to predict drug delivery and efficacy.
Data from Targeting Tumor Antigen 5T4 Using CAR T Cells for the Treatment of Acute Myeloid Leukemia
Authors: Harrop Richard , Blount Daniel G. , Khan Naeem , Soyombo Mayowa , Moyce Laura , Drayson Mark T. , Down Jenny , Lawson Michelle A. , O’Connor Deirdre , Nimmo Rachael , Lad Yatish , Souberbielle Bernard , Mitrophanous Kyriacos , Ettorre Anna
Published: January 2025

Abstract
Chimeric antigen receptor (CAR) T cells represent a novel targeted approach to overcome deficits in the ability of the host immune system to detect and subsequently eradicate tumors. The identification of antigens expressed specifically on the surface of tumor cells is a critical first step for a targeted therapy that selectively targets cancer cells without affecting normal tissues. 5T4 is a tumor-associated antigen expressed on the cell surface of most solid tumors. However, very little is known about its expression in hematologic malignancies. In this study, we assess the expression of 5T4 in different types of leukemias, specifically acute myeloid leukemia (AML), and normal hematopoietic stem cells (HSC). We also provide an in vitro assessment of safety and efficacy of 5T4-targeting CAR T cells against HSCs and AML tumor cell lines. 5T4 expression was seen in about 50% of AML cases; AML with mutated nucleophosmin 1, AML–myelodysplasia-related, and AML not otherwise specified showed the highest percentage of 5T4+ cases. 5T4 CAR T cells efficiently and specifically killed AML tumor cell lines, including leukemic stem cells. Coculture of 5T4 CAR T cells with HSCs from healthy donors showed no impact on subsequent colony formation, thus confirming the safety profile of 5T4. A proof-of-concept study using a murine model for AML demonstrated that CAR T cells recognize 5T4 expressed on cells and can kill tumor cells both in vitro and in vivo. These results highlight 5T4 as a promising target for immune intervention in AML and that CAR T cells can be considered a powerful personalized therapeutic approach to treat AML.
Data from Tumor Integrin-Targeted Glucose Oxidase Enzyme Promotes ROS-Mediated Cell Death that Combines with Interferon Alpha Therapy for Tumor Control
Authors: Stinson Jordan A. , Sheen Allison , Lax Brianna M. , Yang Grace N. , Duhamel Lauren , Santollani Luciano , Fink Elizabeth , Palmeri Joseph R. , Wittrup Karl Dane
Published: January 2025

Abstract
Although heightened intratumoral levels of reactive oxygen species (ROS) are typically associated with a suppressive tumor microenvironment, under certain conditions ROS contribute to tumor elimination. Treatment approaches, including some chemotherapy and radiation protocols, increase cancer cell ROS levels that influence their mechanism of cell death and subsequent recognition by the immune system. Furthermore, activated myeloid cells rapidly generate ROS upon encounter with pathogens or infected cells to eliminate disease, and recently, this effector function has been noted in cancer contexts as well. Collectively, ROS-induced cancer cell death may help initiate adaptive antitumor immune responses that could synergize with current approved immunotherapies, for improved control of solid tumors. In this work, we explore the use of glucose oxidase, an enzyme which produces hydrogen peroxide, a type of ROS, to therapeutically mimic the endogenous oxidative burst from myeloid cells to promote antigen generation within the tumor microenvironment. We engineer the enzyme to target pan-tumor-expressed integrins both as a tumor-agnostic therapeutic approach and as a strategy to prolong local enzyme activity following intratumoral administration. We found the targeted enzyme potently induced cancer cell death and enhanced cross-presentation by dendritic cells in vitro and further combined with interferon alpha for long-term tumor control in murine MC38 tumors in vivo. Optimizing the single-dose administration of this enzyme overcomes limitations with immunogenicity noted for other prooxidant enzyme approaches. Overall, our results suggest ROS-induced cell death can be harnessed for tumor control and highlight the potential use of designed enzyme therapies alongside immunotherapy against cancer.
Figure S1 from Depletion of Adipose Stroma-Like Cancer-Associated Fibroblasts Potentiates Pancreatic Cancer Immunotherapy
Authors: Rupert Joseph , Daquinag Alexes , Yu Yongmei , Dai Yulin , Zhao Zhongming , Kolonin Mikhail G.
Published: January 2025

A, Fig. 1 schematic of testing the effect of Pdgfrb+ CAF depletion on PDAC progression. B, initial body weight in experiment A. C, experiment A tumor section H&E staining showing inflammation (i), necrosis (n), and well-differentiated tumor cells (arrows). D, schematic of testing the effect of Pdgfrb + CAF pre-depletion on PDAC progression. E, initial body weight in experiment D. F, tumor weights in experiment D. G, Fig. 2 schematic testing the effect of ASC-like CAF depletion on PDAC progression. H, initial body weight in experiment G. I, experiment G tumor section H&E staining indicating necrosis (n) and well-differentiated tumor cells (arrows). Scale Bars = 500μm. *=p<0.05.
Figure 1 from Depletion of Adipose Stroma-Like Cancer-Associated Fibroblasts Potentiates Pancreatic Cancer Immunotherapy
Authors: Rupert Joseph , Daquinag Alexes , Yu Yongmei , Dai Yulin , Zhao Zhongming , Kolonin Mikhail G.
Published: January 2025

The effect of Pdgfrb+ CAF depletion on orthotopic PDAC progression. Tissues resected from Pdgfrb-TK male mice after 25 days of GCV (N = 3) or control PBS (N = 4) treatment were analyzed. A, KPC tumor size upon resection. B, Representative resected KPC tumors. C, Paraffin sections of tumors in B stained with hematoxylin/eosin, trichrome blue, or subjected to αSMA and endomucin (endothelial marker) immunofluorescence. Arrows indicate examples of well-differentiated KPC cells forming cancerous ducts. Scale bar, 50 μm. D, Quantification of KPC cells in livers based on colony counts. Images: representative wells. *, P < 0.05; **, P < 0.01; ***, P < 0.005; Student t test. H&E, hematoxylin and eosin.
Association Between Enteral Protein Intake and Fat-Free Mass Accretion in Very Preterm Infants
Authors: Jerome Maggie , Gunawan Emily , Aristizabal Natalia , Chandler-Laney Paula , Salas Ariel A.
Published: January 2025

Introduction: For preterm infants, the first two weeks after birth are a time when nutrition and protein intake is variable and often falls below recommended intakes. Our objective was to investigate the relationship between protein intake, including source of protein, during the first two weeks after birth and fat-free mass (FFM) accretion in a group of very preterm infants.
Methods: In this observational cohort study, body composition was assessed using air displacement plethysmography in eligible infants <32 weeks gestational age at two weeks after birth and prior to discharge. FFM accretion was calculated as difference between the two measurements. We collected daily nutrition data for the first two weeks. Multivariable linear regression was used to assess the relationship between protein intake and body composition and weight gain.
Results: Seventy-eight infants were included (mean birthweight: 1408 ± 278 grams). Mean cumulative protein intake of this cohort in the first two weeks was 2.4±0.8 g/kg/day of which 74±19% was enteral (1.7±0.6 g/kg/day). Enteral protein intake was associated with higher FFM while parenteral protein was associated with lower FFM. Total protein intake from both sources during the first two weeks after birth was positively associated with greater weight gain.
Conclusion: Enteral protein intake during the first two weeks after birth is associated with higher FFM and weight in preterm infants. Future interventional studies should investigate the effects of higher enteral protein intake during the first two weeks after birth on growth and body composition.
Cerebral Microbleeds and Their Association With Inflammation and Blood-Brain Barrier Leakage in Small Vessel Disease
Authors: Cai Lupei , Tozer Daniel J. , Markus Hugh S.
Published: January 2025

BACKGROUND:

How cerebral microbleeds (CMBs) are formed, and how they cause tissue damage is not fully understood, but it has been suggested they are associated with inflammation, and they could also be related to increased blood-brain barrier (BBB) leakage. We investigated the relationship of CMBs with inflammation and BBB leakage in cerebral small vessel disease, and in particular, whether these 2 processes were increased in the vicinity of CMBs.

METHODS:

In 54 patients with sporadic cerebral small vessel disease presenting with lacunar stroke, we simultaneously assessed microglial activation using the positron emission tomography ligand [11C]PK11195 and BBB leakage using dynamic contrast enhanced magnetic resonance imaging, on a positron emission tomography–magnetic resonance imaging system. To assess local inflammation and BBB leakage, 3 one-voxel concentric shells were generated around each CMB on susceptibility-weighted imaging and resampled to positron emission tomography and T1 mapping images, respectively. In these 3 shells, we calculated the mean of PK11195 nondisplaceable binding potential (BPND) as a marker of microglial activation, as well as the mean influx rate as a marker of BBB leakage. In addition, 93 blood biomarkers related to cardiovascular disease, inflammation, and endothelial activation were measured to quantify systemic inflammation.

RESULTS:

No significant associations were found between the number of CMBs and the measures for microglial activation (
β
=2.6×10
−5
,
P
=0.050) and BBB leakage (
β
=−0.0001,
P
=0.400) in the white matter. There was no difference in measures of microglial activation (
P
=0.403) or BBB leakage (
P
=0.423) across the 3 shells surrounding the CMBs. Furthermore, after correcting for multiple comparisons, no associations were observed between systemic inflammation biomarkers and the number of CMBs.

CONCLUSIONS:

We found no evidence that CMBs are associated with either microglial activation assessed by [11]CPK11195 positron emission tomography or BBB leakage assessed by dynamic contrast enhanced magnetic resonance imaging, either globally or locally, in sporadic cerebral small vessel disease. There was also no association with markers of systemic inflammation.
Cryptocellus armasi, a new troglomorphic hooded tick-spider from Venezuela (Arachnida, Ricinulei)
Authors: BOTERO-TRUJILLO RICARDO , PRENDINI LORENZO
Published: January 2025

Ricinulei Thorell, 1876, or hooded tick-spiders, are among the least known arachnid orders. Represented by 88 species in the New World and 33 species in South America, only two ricinuleid species have been recorded from Venezuela, one of the Neotropical countries with the least known Ricinulei fauna. In the present contribution, Cryptocellus armasi sp. nov. is described and illustrated from male and female specimens collected inside Cueva de Toromo, a cave in the foothills of the Sierra de Perijá, in the state of Zulia, northwestern Venezuela. The new species, which belongs to the magnus species group, exhibits pronounced attenuation of the appendages. Based on this troglomorphism and hypogean habitat, the new species appears to be a troglobite, the first of its kind in Cryptocellus Westwood, 1874 and the first troglobitic ricinuleid from South America. This new species raises the number of extant ricinuleid species to 103 and the species of Cryptocellus, to 46. Thirty-four of these occur in South America and three in Venezuela. A map plotting the known distributions of the three Venezuelan species of Ricinulei is presented.