bluuebunny/crossref_metadata_2025 huggingface dataset:
Table S5 from Clinical Importance of the lncRNA NEAT1 in Cancer Patients Treated with Immune Checkpoint Inhibitors
Authors: Toker Joseph , Iorgulescu J. Bryan , Ling Alexander L. , Villa Genaro R. , Gadet Josephina A.M.A. , Parida Laxmi , Getz Gad , Wu Catherine J. , Reardon David A. , Chiocca E. Antonio , Mineo Marco
Published: May 2023

LncRNA transcriptome analysis in glioblastoma (GSE121810)
Table S4 from Clinical Importance of the lncRNA NEAT1 in Cancer Patients Treated with Immune Checkpoint Inhibitors
Authors: Toker Joseph , Iorgulescu J. Bryan , Ling Alexander L. , Villa Genaro R. , Gadet Josephina A.M.A. , Parida Laxmi , Getz Gad , Wu Catherine J. , Reardon David A. , Chiocca E. Antonio , Mineo Marco
Published: May 2023

Glioblastoma patient characteristics (GSE121810)
Table S3 from Clinical Importance of the lncRNA NEAT1 in Cancer Patients Treated with Immune Checkpoint Inhibitors
Authors: Toker Joseph , Iorgulescu J. Bryan , Ling Alexander L. , Villa Genaro R. , Gadet Josephina A.M.A. , Parida Laxmi , Getz Gad , Wu Catherine J. , Reardon David A. , Chiocca E. Antonio , Mineo Marco
Published: May 2023

LncRNA transcriptome analysis in melanoma (GSE78220)
Supplementary Figure S3 from Proinflammatory Macrophage Activation by the Polysialic Acid-Siglec-16 Axis Is Linked to Increased Survival of Patients with Glioblastoma
Authors: Thiesler Hauke , Gretenkort Lina , Hoffmeister Leonie , Albers Iris , Ohlmeier Luisa , Röckle Iris , Verhagen Andrea , Banan Rouzbeh , Köpcke Nora , Krönke Nicole , Feuerhake Friedrich , Behling Felix , Barrantes-Freer Alonso , Mielke Dorothee , Rohde Veit , Hong Bujung , Varki Ajit , Schwabe Kerstin , Krauss Joachim K. , Stadelmann Christine , Hartmann Christian , Hildebrandt Herbert
Published: May 2023

PolySia is not associated with CD3- or CD34-positive cells
Supplementary Figure S1 from Proinflammatory Macrophage Activation by the Polysialic Acid-Siglec-16 Axis Is Linked to Increased Survival of Patients with Glioblastoma
Authors: Thiesler Hauke , Gretenkort Lina , Hoffmeister Leonie , Albers Iris , Ohlmeier Luisa , Röckle Iris , Verhagen Andrea , Banan Rouzbeh , Köpcke Nora , Krönke Nicole , Feuerhake Friedrich , Behling Felix , Barrantes-Freer Alonso , Mielke Dorothee , Rohde Veit , Hong Bujung , Varki Ajit , Schwabe Kerstin , Krauss Joachim K. , Stadelmann Christine , Hartmann Christian , Hildebrandt Herbert
Published: May 2023

PolySia is associated with GFAP-positive cells
Supplementary Fig. 6 from Clinical Importance of the lncRNA NEAT1 in Cancer Patients Treated with Immune Checkpoint Inhibitors
Authors: Toker Joseph , Iorgulescu J. Bryan , Ling Alexander L. , Villa Genaro R. , Gadet Josephina A.M.A. , Parida Laxmi , Getz Gad , Wu Catherine J. , Reardon David A. , Chiocca E. Antonio , Mineo Marco
Published: May 2023

Supplementary Fig. 6 NEAT1 expression in tumor-associated macrophages is associated with TNF-alpha signaling.
Supplementary Fig. 5 from Clinical Importance of the lncRNA NEAT1 in Cancer Patients Treated with Immune Checkpoint Inhibitors
Authors: Toker Joseph , Iorgulescu J. Bryan , Ling Alexander L. , Villa Genaro R. , Gadet Josephina A.M.A. , Parida Laxmi , Getz Gad , Wu Catherine J. , Reardon David A. , Chiocca E. Antonio , Mineo Marco
Published: May 2023

Supplementary Fig. 5 Classification of single cells.
Supplementary Fig. 4 from Clinical Importance of the lncRNA NEAT1 in Cancer Patients Treated with Immune Checkpoint Inhibitors
Authors: Toker Joseph , Iorgulescu J. Bryan , Ling Alexander L. , Villa Genaro R. , Gadet Josephina A.M.A. , Parida Laxmi , Getz Gad , Wu Catherine J. , Reardon David A. , Chiocca E. Antonio , Mineo Marco
Published: May 2023

Supplementary Fig. 4 NEAT1 counts are reduced in formalin-fixed paraffin-embedded (FFPE) tissues compared to freshfrozen tissues.
Supplementary Fig. 3 from Clinical Importance of the lncRNA NEAT1 in Cancer Patients Treated with Immune Checkpoint Inhibitors
Authors: Toker Joseph , Iorgulescu J. Bryan , Ling Alexander L. , Villa Genaro R. , Gadet Josephina A.M.A. , Parida Laxmi , Getz Gad , Wu Catherine J. , Reardon David A. , Chiocca E. Antonio , Mineo Marco
Published: May 2023

Supplementary Fig. 3 NEAT1 levels are associated with the upregulation of the interferon-gamma pathway in glioblastoma.
Data from Proinflammatory macrophage activation by the polysialic acid-Siglec-16 axis is linked to increased survival of glioblastoma patients
Authors: Thiesler Hauke , Gretenkort Lina , Hoffmeister Leonie , Albers Iris , Ohlmeier Luisa , Röckle Iris , Verhagen Andrea , Banan Rouzbeh , Köpcke Nora , Krönke Nicole , Feuerhake Friedrich , Behling Felix , Barrantes-Freer Alonso , Mielke Dorothee , Rohde Veit , Hong Bujung , Varki Ajit , Schwabe Kerstin , Krauss Joachim K. , Stadelmann Christine , Hartmann Christian , Hildebrandt Herbert
Published: May 2023

Abstract
Purpose: Interactions with tumor-associated microglia and macrophages (TAM) are critical for glioblastoma progression. Polysialic acid (polySia) is a tumor-associated glycan, but its frequency of occurrence and its prognostic value in glioblastoma are disputed. Through interactions with the opposing immune receptors Siglec-11 and Siglec-16, polySia is implicated in the regulation of microglia and macrophage activity. However, due to a nonfunctional SIGLEC16P allele, SIGLEC16 penetrance is less than 40%. Here, we explored possible consequences of SIGLEC16 status and tumor cell-associated polySia on glioblastoma outcome. Experimental Design: FFPE specimens of two independent cohorts with 70 and 100 newly diagnosed glioblastoma patients were retrospectively analyzed for SIGLEC16 and polySia status in relation to overall survival. Inflammatory TAM activation was assessed in tumors, in heterotypic tumor spheroids consisting of polySia-positive glioblastoma cells and Siglec-16-positive or –negative macrophages, and by exposing Siglec-16-positive or –negative macrophages to glioblastoma cell-derived membrane fractions. Results: Overall survival of SIGLEC16 carriers with polySia-positive tumors was increased. Consistent with proinflammatory Siglec-16 signaling, levels of TAM positive for the M2 marker CD163 were reduced, whereas the M1 marker CD74 and TNF expression were increased, and CD8+ T cells enhanced in SIGLEC16 polySia double-positive tumors. Correspondingly, TNF production was elevated in heterotypic spheroid cultures with Siglec-16-expressing macrophages. Furthermore, a higher, mainly M1-like cytokine release and activating immune signaling was observed in SIGLEC16-positive as compared to SIGLEC16-negative macrophages confronted with glioblastoma cell-derived membranes. Conclusions: Collectively, these results strongly suggest that proinflammatory TAM activation causes the better outcome in glioblastoma patients with a functional polySia-Siglec-16 axis.
Data from Clinical Importance of the lncRNA NEAT1 in Cancer Patients Treated with Immune Checkpoint Inhibitors
Authors: Toker Joseph , Iorgulescu J. Bryan , Ling Alexander L. , Villa Genaro R. , Gadet Josephina A.M.A. , Parida Laxmi , Getz Gad , Wu Catherine J. , Reardon David A. , Chiocca E. Antonio , Mineo Marco
Published: May 2023

AbstractPurpose:
mAbs targeting the PD-1/PD-L1 immune checkpoint are powerful tools to improve the survival of patients with cancer. Understanding the molecular basis of clinical response to these treatments is critical to identify patients who can benefit from this immunotherapy. In this study, we investigated long noncoding RNA (lncRNA) expression in patients with cancer treated with anti-PD-1/PD-L1 immunotherapy.
Experimental Design:
lncRNA expression profile was analyzed in one cohort of patients with melanoma and two independent cohorts of patients with glioblastoma (GBM) undergoing anti-PD-1/PD-L1 immunotherapy. Single-cell RNA-sequencing analyses were performed to evaluate lncRNA expression in tumor cells and tumor-infiltrating immune cells.
Results:
We identified the lncRNA NEAT1 as commonly upregulated between patients with melanoma with complete therapeutic response and patients with GBM with longer survival following anti-PD-1/PD-L1 treatment. Gene set enrichment analyses revealed that NEAT1 expression was strongly associated with the IFNγ pathways, along with downregulation of cell-cycle-related genes. Single-cell RNA-sequencing analyses revealed NEAT1 expression across multiple cell types within the GBM microenvironment, including tumor cells, macrophages, and T cells. High NEAT1 expression levels in tumor cells correlated with increased infiltrating macrophages and microglia. In these tumor-infiltrating myeloid cells, we found that NEAT1 expression was linked to enrichment in TNFα/NFκB signaling pathway genes. Silencing NEAT1 suppressed M1 macrophage polarization and reduced the expression of TNFα and other inflammatory cytokines.
Conclusions:
These findings suggest an association between NEAT1 expression and patient response to anti-PD-1/PD-L1 therapy in melanoma and GBM and have important implications for the role of lncRNAs in the tumor microenvironment.
Supplementary Tables and Figures from Triple-Negative Breast Cancer-Derived Extracellular Vesicles Promote a Hepatic Pre-metastatic Niche via a Cascade of Microenvironment Remodeling
Authors: Heo Woohang , Lee Woochan , Cheun Jong Ho , Lee Eun-Shin , Li Songbin , Kim Hoe suk , Son Hye-Youn , Kim Ju Hee , Woo Yeon Duk , Chung Doo Hyun , Yun Jihui , Jung Ji Gwang , Lee Han-Byoel , Han Wonshik , Kim Hong-Kyu , Kim Jong-Il , Moon Hyeong-Gon
Published: May 2023

Supplementary Table 1. Information about patients derived xenograft models and derived patient.
Supplementary Table 2. Ontology of differentially expressed genes in metastasis-harboring liver of PDX models.
Supplementary Table 3. Differentially expressed genes in liver and lung of metastasis-harboring PDX models.
Supplementary Table 4. Human ratio in lung and liver of additional PDX models identified by RNA sequencing.
Supplementary Table 5. Gene ontology of co-expressed genes with Cx3cr1 in liver of PDX models identified by RNA sequencing.
Supplementary Table 6. Top ranked genes having significant correlation with Cx3cr1 in liver of PDX models identified by RNA sequencing.
Supplementary Table 7. Demographic and clinical characteristics of all patients.
Supplementary Table 8. Information about used primer sequences for quantitative real-time PCR
Supplementary Figure 1. Liver and lung H&E staining pictures of eight nonmetastatic PDX models a. Microscopic images of non-metastasis harboring PDX mouse model's liver (left) and lung (right) taken at 400x magnification.
Supplementary Figure 2. Immunohistochemistry about CX3CR1 in liver and lung of breast cancer metastasis patients.
Supplementary Figure 3. Hepatic metastasis after four weeks after orthotopic injection of 4T1 breast cancer cells identified by H&E staining.
Supplementary Figure 4. Identification of pre-metastatic niche in liver tissues of 4T1 bearing mice a. mRNA expression of inflammation associated genes identified by real-time PCR in liver tissues of 4T1 bearing mice.
Supplementary Figure 5. Identification of CX3CR1 positive cell population.
Supplementary Figure 6. FACS analysis with anti-CX3CR1 of Raw264.7 macrophage cell lines.
Supplementary Figure 7. Trans-well migration assay of BMDM with or without CX3CL1.
Supplementary Figure 8. Mmp9 mRNA expression having significant correlation with Cx3cr1 mRNA expression in liver of PDX models.
Supplementary Figure 9. MMP9 expression of macrophages with CX3CL1 treatment.
Supplementary Figure 10. Signaling pathway of CX3CL1 treated macrophages.
Supplementary Figure 11. Splenic injection of 4T1 cells inducing hepatic metastasis within two weeks in most cases.
Supplementary Figure 12. mRNA expression about Cx3cr1 and Mmp9 in liver of vehicle or AZD8797 treated BALB/C mice identified by real-time PCR.
Supplementary Figure 13. Correlation plot of Tnfa and Cx3cr1 mRNA expression in liver and lung of PDX models.
Supplementary Figure 14. EVs isolation of CD63-mRuby-4T1.
Supplementary Table 1 from Truncation of GalNAc-type O-glycans Suppresses CD44-mediated Osteoclastogenesis and Bone Metastasis in Breast Cancer
Authors: Lin Neng-Yu , Lee Jian-Jr , Chen Syue-Ting , Lin Jung-An , Lin Chia-Hsuan , Lin Hsuan-Yu , Su Yong-Han , Chen Cheng-Chang , Lin Mei-Chun , Kuo Ching-Ying , Huang Min-Chuan
Published: May 2023

The abundance ratio of O-glycosylated proteins from mock and C1GALT1 knockdown breast cancer cells identified by mass spectrometry.
Supplementary Figure 2 from Truncation of GalNAc-type O-glycans Suppresses CD44-mediated Osteoclastogenesis and Bone Metastasis in Breast Cancer
Authors: Lin Neng-Yu , Lee Jian-Jr , Chen Syue-Ting , Lin Jung-An , Lin Chia-Hsuan , Lin Hsuan-Yu , Su Yong-Han , Chen Cheng-Chang , Lin Mei-Chun , Kuo Ching-Ying , Huang Min-Chuan
Published: May 2023

Construction of multiple mutations at O-glycosites in the stem region of CD44.
Supplementary Text and Tables from Myeloid-Derived Suppressor–Cell Dynamics Control Outcomes in the Metastatic Niche
Authors: Kreger Jesse , Roussos Torres Evanthia T. , MacLean Adam L.
Published: May 2023

Supplementary Text and Tables
Supplementary Figures from Myeloid-Derived Suppressor–Cell Dynamics Control Outcomes in the Metastatic Niche
Authors: Kreger Jesse , Roussos Torres Evanthia T. , MacLean Adam L.
Published: May 2023

Supplementary Figures
Supplementary Movie from Discovery of Podofilox as a Potent cGAMP–STING Signaling Enhancer with Antitumor Activity
Authors: Han Jing , Hu Shuiqing , Hu Yawei , Xu Yifang , Hou Yanfei , Yang Yinlong , Su Huili , Zhang Zhengyin , Liu Peng , Sun Xuxu , Zhang Conggang
Published: May 2023

Movie
Table S5 from Low TCR Binding Strength Results in Increased Progenitor-like CD8+ Tumor-Infiltrating Lymphocytes
Authors: Hay Zachary L.Z. , Knapp Jennifer R. , Magallon Roman E. , O'Connor Brian P. , Slansky Jill E.
Published: May 2023

Differential gene expression between all clusters
Table S1, S2, S3, Figure S1, S2 from Low TCR Binding Strength Results in Increased Progenitor-like CD8+ Tumor-Infiltrating Lymphocytes
Authors: Hay Zachary L.Z. , Knapp Jennifer R. , Magallon Roman E. , O'Connor Brian P. , Slansky Jill E.
Published: May 2023

Flow cytometry panels, gating strategy and comparison of TILs to other gene signatures.
Supplementary Figures S6-S10 from Microparticle-Delivered Cxcl9 Prolongs Braf Inhibitor Efficacy in Melanoma
Authors: Romano Gabriele , Paradiso Francesca , Li Peng , Shukla Pooja , Barger Lindsay N. , El Naggar Olivia , Miller John P. , Liang Roger J. , Helms Timothy L. , Lazar Alexander J. , Wargo Jennifer A. , Taraballi Francesca , Costello James C. , Kwong Lawrence N.
Published: May 2023

Supplementary Figures S6-S10
Supplementary Figures S1-S5 from Microparticle-Delivered Cxcl9 Prolongs Braf Inhibitor Efficacy in Melanoma
Authors: Romano Gabriele , Paradiso Francesca , Li Peng , Shukla Pooja , Barger Lindsay N. , El Naggar Olivia , Miller John P. , Liang Roger J. , Helms Timothy L. , Lazar Alexander J. , Wargo Jennifer A. , Taraballi Francesca , Costello James C. , Kwong Lawrence N.
Published: May 2023

Supplementary Figures S1-S5
Supplementary Data from HDAC3 Inhibition Promotes Antitumor Immunity by Enhancing CXCL10-Mediated Chemotaxis and Recruiting of Immune Cells
Authors: Li Lili , Hao Shumin , Gao Meiling , Liu Junxiao , Xu Xin , Huang Jianfei , Cheng Genhong , Yang Heng
Published: May 2023

Supplementary Fig.S1-S9Table S1-S2
Data from Reverse Translation Identifies the Synergistic Role of Immune Checkpoint Blockade and IL15 to Enhance Immunotherapy of Ovarian Cancer
Authors: Felices Martin , Wesley Erin , Bendzick Laura E. , Kodal Behiye , Hopps Rachel , Grzywacz Bartosz , Hinderlie Peter , Miller Jeffrey S. , Geller Melissa A.
Published: May 2023

Abstract
Immune checkpoint blockade (ICB) has changed the standard of care for many patients with cancer, yet no ICB is approved for ovarian cancer. We hypothesized that maintenance therapy with an IL15 “superagonist” (N-803) and ICB in combination could induce potent immune activation in ovarian cancer. Using flow cytometry, cytometry by time of flight analysis, and cytotoxicity assays, we analyzed patient samples from women with advanced epithelial ovarian cancer treated with N-803 for indications of PD-1/PD-L1 upregulation with this treatment. In addition, ICB and N-803 were evaluated in preclinical studies to determine the functional impact of combination therapy on natural killer (NK) cells in vitro and in vivo. We observed that N-803 stimulated initial NK-cell expansion in patient samples; however, proliferation was not sustained beyond 2 weeks despite continued treatment. This result was reverse translated back to the laboratory to determine the functional relevance of this finding. The addition of ICB with an antibody-dependent cellular cytotoxicity IgG1 antibody against PD-L1 (avelumab) or an IgG4 antibody against PD-1 (pembrolizumab) enhanced N-803 induced NK-cell function in vitro. Using models of human ovarian cancer and NK-cell adoptive transfer in mice, we showed enhanced antitumor control with N-803 and ICB, as well as a combination effect that enhanced NK-cell persistence and expansion in vivo. This work suggests that PD-1/PD-L1 blockade combined with IL15 signaling may overcome resistance to cytokine therapy in ovarian cancer.
Data from Low TCR Binding Strength Results in Increased Progenitor-like CD8+ Tumor-Infiltrating Lymphocytes
Authors: Hay Zachary L.Z. , Knapp Jennifer R. , Magallon Roman E. , O'Connor Brian P. , Slansky Jill E.
Published: May 2023

Abstract
T-cell receptor (TCR) binding strength to peptide-MHC antigen complex influences numerous T-cell functions. However, the vast diversity of a polyclonal T-cell repertoire for even a single antigen greatly increases the complexity of studying the impact of TCR affinity on T-cell function. Here, we determined how TCR binding strength affected the protein and transcriptional profile of an endogenous, polyclonal T-cell response to a known tumor-associated antigen (TAA) within the tumor microenvironment (TME). We confirmed that the staining intensity by flow cytometry and the counts by sequencing from MHC-tetramer labeling were reliable surrogates for the TCR-peptide-MHC steady-state binding affinity. We further demonstrated by single-cell RNA sequencing that tumor-infiltrating lymphocytes (TIL) with high and low binding affinity for a TAA can differentiate into cells with many antigen-specific transcriptional profiles within an established TME. However, more progenitor-like phenotypes were significantly biased towards lower affinity T cells, and proliferating phenotypes showed significant bias towards high-affinity TILs. In addition, we found that higher affinity T cells advanced more rapidly to terminal phases of T-cell exhaustion and exhibited better tumor control. We confirmed the polyclonal TIL results using a TCR transgenic mouse possessing a single low-affinity TCR targeting the same TAA. These T cells maintained a progenitor-exhausted phenotype and exhibited impaired tumor control. We propose that high-affinity TCR interactions drive T-cell fate decisions more rapidly than low-affinity interactions and that these cells differentiate faster. These findings illustrate divergent forms of T-cell dysfunction based on TCR affinity which may impact TIL therapies and antitumor responses.
Supplementary Methods S1 from Ultra High-plex Spatial Proteogenomic Investigation of Giant Cell Glioblastoma Multiforme Immune Infiltrates Reveals Distinct Protein and RNA Expression Profiles
Authors: Bonnett Shilah A. , Rosenbloom Alyssa B. , Ong Giang T. , Conner Mark , Rininger Aric B.E. , Newhouse Daniel , New Felicia , Phan Chi Q. , Ilcisin Saskia , Sato Hiromi , Lyssand John S. , Geiss Gary , Beechem Joseph M.
Published: May 2023

Supplementary Methods S1: Protocol for proteogenomic workflow
Supplementary Figures S16-S18 from Ultra High-plex Spatial Proteogenomic Investigation of Giant Cell Glioblastoma Multiforme Immune Infiltrates Reveals Distinct Protein and RNA Expression Profiles
Authors: Bonnett Shilah A. , Rosenbloom Alyssa B. , Ong Giang T. , Conner Mark , Rininger Aric B.E. , Newhouse Daniel , New Felicia , Phan Chi Q. , Ilcisin Saskia , Sato Hiromi , Lyssand John S. , Geiss Gary , Beechem Joseph M.
Published: May 2023

Supplementary Figure S16: Representative grey scale images of used in the assessment of spatial proteogenomic data quality across mouse tissue types. FFPE sections were stained with the GeoMx NGS Mouse Protein modules (137-plex), GeoMx Mm WTA, and antibodies against CD45 (Immune), PanCK (Tumor) and Syto13 (nuclear, DNA). Supplementary Figure S17: ROI-to-ROI comparison of the proteogenomic data to the single analyte controls. Mouse FFPE sections were stained with 137-plex GeoMx NGS Mouse Protein modules and GeoMx Mm WTA. The Pearson’s R was calculated between each ROI from the proteogenomic assay against all ROIs in the single analyte (A) RNA and (B) protein controls. Protein targets with SNR ≥ 3 and RNA targets with SNR ≥ 4 were used in the analysis. Supplementary Figure S18: Expression levels of select matching RNA and protein targets in several mouse tissue types. For protein targets with SNR ≥ 3 and the respective RNA target with SNR ≥ 4, a pairwise scatter plot was generated to visualize the concordance between respective analytes.
FIGURE 7 from Ultra High-plex Spatial Proteogenomic Investigation of Giant Cell Glioblastoma Multiforme Immune Infiltrates Reveals Distinct Protein and RNA Expression Profiles
Authors: Bonnett Shilah A. , Rosenbloom Alyssa B. , Ong Giang T. , Conner Mark , Rininger Aric B.E. , Newhouse Daniel , New Felicia , Phan Chi Q. , Ilcisin Saskia , Sato Hiromi , Lyssand John S. , Geiss Gary , Beechem Joseph M.
Published: May 2023

SPG exploration of gcGBM and GBM. A, Representative images of ROIs segmented into CD45+, GFAP+, or CD45−/GFAP−. Top differentially expressed protein targets (B) and RNA targets (C) from frontal lobe gcGBM as compared with GBM, all grade 4.
FIGURE 6 from Ultra High-plex Spatial Proteogenomic Investigation of Giant Cell Glioblastoma Multiforme Immune Infiltrates Reveals Distinct Protein and RNA Expression Profiles
Authors: Bonnett Shilah A. , Rosenbloom Alyssa B. , Ong Giang T. , Conner Mark , Rininger Aric B.E. , Newhouse Daniel , New Felicia , Phan Chi Q. , Ilcisin Saskia , Sato Hiromi , Lyssand John S. , Geiss Gary , Beechem Joseph M.
Published: May 2023

DE analysis between GFAP- and CD45-enriched segments. A, Combined volcano plot resulting from the DE analysis between GFAP- and CD45-enriched segments for RNA (●) and protein (◆) analytes. Targets with significant DE are highlighted either orange (P < 0.05), green (FDR < 0.05) or blue (FDR < 0.001); whereas targets in gray show no significant difference in expression. A subset of differentially expressed targets is labeled. Unsupervised hierarchical clustering analysis of detected RNA (B) and protein (C).
FIGURE 2 from Ultra High-plex Spatial Proteogenomic Investigation of Giant Cell Glioblastoma Multiforme Immune Infiltrates Reveals Distinct Protein and RNA Expression Profiles
Authors: Bonnett Shilah A. , Rosenbloom Alyssa B. , Ong Giang T. , Conner Mark , Rininger Aric B.E. , Newhouse Daniel , New Felicia , Phan Chi Q. , Ilcisin Saskia , Sato Hiromi , Lyssand John S. , Geiss Gary , Beechem Joseph M.
Published: May 2023

Assessment of SPG data quality versus the respective RNA and Protein control data. Assay correlation with respect to the protein analyte comparing 147-plex and 59-plex protein panel (A), protein control and proteogenomic workflows (B), and user-to-user and instrument-to-instrument reproducibility (C). D, Cell line to cell line comparison of protein control with proteogenomic protein data. For protein targets with SNR ≥ 3, the Pearson R was calculated between each cell line from the Protein Control slide against all the cell lines in the SPG slide. The max R cell line between the SPG and Protein control is labeled and highlighted green. Assay correlation of 17 phospho-specific antibodies between protein control and proteogenomic workflows (E) and user-to-user and instrument-to-instrument reproducibility (F). G, Assay correlation with respect to the RNA analyte comparing summary of Pearson R, the slope of linear regression, and change in sensitivity between workflows. The change in sensitivity corresponds to the average change in regression line slope between the SPG and the single-analyte control assay. RNA control and proteogenomic workflows (H) and user-to-user and instrument-to-instrument reproducibility (I). J, Cell line to cell line comparison of WTA control and proteogenomic WTA data to the entire CCLE RNA-seq dataset. For all overlapping targets between the CCLE and WTA data, the Pearson R in the protein control and SPG WTA data were calculated against all cell lines in the CCLE RNA-seq. Cell line labels in the plot correspond to SPG or GeoMx WTA cell lines with the highest R correlation to the CCLE data. K, Target-to-target comparison of WTA control to proteogenomic WTA data. For each RNA target with SNR ≥ 4, the Pearson R was calculated between WTA control log2 SNR transformed data and the respective proteogenomic WTA log2 SNR transformed data. Histogram shows the distribution of Pearson R.
Supplementary Table S6 from Chemokine analysis in patients with metastatic uveal melanoma suggests a role for CCL21 signaling in combined epigenetic therapy and checkpoint immunotherapy
Authors: Sah Vasu R , Jespersen Henrik , Karlsson Joakim , Nilsson Lisa M , Bergqvist Mattias , Johansson Iva , Carneiro Ana , Helgadottir Hildur , Levin Max , Ullenhag Gustav J. , Ståhlberg Anders , Olofsson Bagge Roger , Nilsson Jonas A. , Ny Lars
Published: May 2023

GSEA
Supplementary Table S5 from Chemokine analysis in patients with metastatic uveal melanoma suggests a role for CCL21 signaling in combined epigenetic therapy and checkpoint immunotherapy
Authors: Sah Vasu R , Jespersen Henrik , Karlsson Joakim , Nilsson Lisa M , Bergqvist Mattias , Johansson Iva , Carneiro Ana , Helgadottir Hildur , Levin Max , Ullenhag Gustav J. , Ståhlberg Anders , Olofsson Bagge Roger , Nilsson Jonas A. , Ny Lars
Published: May 2023

Complete differential expression results
Supplementary Table S2 from Chemokine analysis in patients with metastatic uveal melanoma suggests a role for CCL21 signaling in combined epigenetic therapy and checkpoint immunotherapy
Authors: Sah Vasu R , Jespersen Henrik , Karlsson Joakim , Nilsson Lisa M , Bergqvist Mattias , Johansson Iva , Carneiro Ana , Helgadottir Hildur , Levin Max , Ullenhag Gustav J. , Ståhlberg Anders , Olofsson Bagge Roger , Nilsson Jonas A. , Ny Lars
Published: May 2023

Baseline characteristics, patient population
Figure S5 from Chemokine analysis in patients with metastatic uveal melanoma suggests a role for CCL21 signaling in combined epigenetic therapy and checkpoint immunotherapy
Authors: Sah Vasu R , Jespersen Henrik , Karlsson Joakim , Nilsson Lisa M , Bergqvist Mattias , Johansson Iva , Carneiro Ana , Helgadottir Hildur , Levin Max , Ullenhag Gustav J. , Ståhlberg Anders , Olofsson Bagge Roger , Nilsson Jonas A. , Ny Lars
Published: May 2023

Figure S5. Immunohistochemistry magenta of a) Immunohistochemistry magenta showing
CCL21 and corresponding CCR7 expression within tumor biopsies for patient 1-013 and 3-009.
b) Patient 1-013, a lymph node biopsy showing CD20, CD3 and CCL21 staining with serial
sections. c) Patient 2-027, a liver met biopsy showing SOX10, CCR7, TK1 and PDL1 (DAB)
within the same areas as shown in Fig 6.
Figure S3 from Chemokine analysis in patients with metastatic uveal melanoma suggests a role for CCL21 signaling in combined epigenetic therapy and checkpoint immunotherapy
Authors: Sah Vasu R , Jespersen Henrik , Karlsson Joakim , Nilsson Lisa M , Bergqvist Mattias , Johansson Iva , Carneiro Ana , Helgadottir Hildur , Levin Max , Ullenhag Gustav J. , Ståhlberg Anders , Olofsson Bagge Roger , Nilsson Jonas A. , Ny Lars
Published: May 2023

Figure S3. a) Heat map showing plasma chemokine and cytokine levels pre-treatment to end
of study (EOS) in patients with progressive disease (PD) b) Heat map of plasma chemokine
levels pre-treatment to EOS in stable disease (SD) patients. c) Heat map of plasma chemokine
levels pre-treatment to EOS in partial response (PR) patients d) Levels of CXCL9 in different
response groups pretreatment and EOS. e) Levels of CXCL9 pretreatment and EOS in patients
surviving longer or shorter in the PEMDAC trail.
Data from Chemokine analysis in patients with metastatic uveal melanoma suggests a role for CCL21 signaling in combined epigenetic therapy and checkpoint immunotherapy
Authors: Sah Vasu R , Jespersen Henrik , Karlsson Joakim , Nilsson Lisa M , Bergqvist Mattias , Johansson Iva , Carneiro Ana , Helgadottir Hildur , Levin Max , Ullenhag Gustav J. , Ståhlberg Anders , Olofsson Bagge Roger , Nilsson Jonas A. , Ny Lars
Published: May 2023

Abstract
Purpose: Patients with metastatic uveal melanoma have limited therapeutic options and high mortality rate so new treatment options are needed. Patients and Methods: We previously reported that patients treated with the PD-1 inhibitor pembrolizumab and the HDAC inhibitor entinostat in the PEMDAC trial, experienced clinical benefits if their tumor originated from iris or was wildtype for BAP1 tumor suppressor gene. Here we present the two-year follow-up of the patients in the PEMDAC trial and identify additional factors that correlate with response or survival. Results: Durable responses were observed in four patients, with additional eight patients exhibiting a stable disease. The median overall survival was 13.7 months. Grade 3 adverse events were reported in 62% of the patients, but they were all manageable. No fatal toxicity was observed. Activity of thymidine kinase 1 in plasma was higher in patients with stable disease or who progressed on treatment, compared to those with partial response. Chemokines and cytokines were analyzed in plasma. Three chemokines were significantly different when comparing patients with and without response. One of the factors, CCL21, was higher in the plasma of responding patients before treatment initiation but decreased in the same patients upon treatment. In tumors, CCL21 was expressed in areas resembling tertiary lymphoid structures (TLS). High plasma levels of CCL21 and presence of TLS-like regions in the tumor correlated with longer survival. Conclusions: This study provides insight into durable responses in the PEMDAC trial, and describes dynamic changes of chemokines and cytokines in the blood of these patients.
Consumo de drogas lícitas e ilícitas entre estudantes de medicina de uma capital do Brasil
Authors: Arbigaus Cesar Alexsandro , Martini Milena Binhame Albini
Published: May 2023

Introdução: O uso de álcool, tabaco e drogas ilícitas é um problema de saúde pública mundial, trazendo sérios problemas aos indivíduos que fazem o uso e para as pessoas que estão ao seu redor. Foi observado que o uso entre estudantes do curso de medicina parece ser maior comparado com outros jovens, o que gera uma contradição, tendo em vista que esse comportamento acaba não refletindo o maior acesso e conhecimento sobre informações científicas a respeito dos problemas que esse consumo trás. Objetivo: Determinar o padrão de consumo de drogas lícitas e ilícitas entre os estudantes de medicina Metodologia: Estudo observacional transversal, incluindo estudantes de medicina da capital do Paraná. Realizou-se a coleta de dados por meio de questionário online a respeito do consumo dessas drogas e aplicação de questionários validados. Os resultados foram expressos por médias, desvios padrões, frequências e percentuais. Valores de p < 0,05 foram considerados significativos. Resultados: Evidenciou-se um maior consumo de bebidas alcoólicas entre o sexo feminino. Um maior consumo de tabaco relacionado com influência de familiares e amigos. Maior consumo de drogas ilícitas com o passar do curso, principalmente durante o internato. Conclusão: Tendo em vista os resultados obtidos, mostra-se a importância de abordar esse tema com os universitários de uma maneira a incentivar frear esse consumo, avaliar o nível do estresse que os alunos estão passando, buscando formas de fazer com que não usem as drogas como meio para se distrair, bloqueando esse ciclo vicioso.
Minority, Marginality and Modernity
Authors: Emadi Hafizullah
Published: May 2023

Ismailis are a minority community within the larger world of Sunni and Shia Muslims and were persecuted by conservative Muslim religious and political leaders. They were marginalised in the social, cultural and political arena and were forced to dissimulate their faith in order to avoid adversarial confrontation by hostile forces. Scholars and writers in the Muslim world avoided any objective and candid discussions of the community fearing that they might encounter severe reprisal by their own dogmatic and biased leaders. In Afghanistan, the Hazara Ismailis experienced discrimination, marginalisation and repression because of their ethnicity and religious beliefs. They endured years of political, social, cultural and economic deprivation. However, their situation improved after the downfall of the Taliban rule in late 2001. Although Ismailis, for the most part, were treated as footnotes in most historical literature, they became the main topic of historical and development literature after their spiritual leader, His Highness the Aga Khan iv and present Imam of the Ismailis worldwide, got involved in the reconstruction of Afghanistan’s war-torn infrastructures. Parallel to this endeavour, the Aga Khan also abolished the hereditary system of leadership in the Ismaili community, established modern institutions and appointed a new generation of leaders to guide the community.
The Ultimate Victim of Genocide and the Question of Collective Reparations
Authors: Kourtis Dimitrios A.
Published: May 2023

This article examines the options available for redressing collective victimhood, specifically in relation to genocide. First, it analyses how the question of reparations was addressed during the drafting of the Genocide Convention. Then, it focuses on the framework of the Rome Statute of the International Criminal Court and explores the types of victims the icc can acknowledge and provide remedies for under its Statute and Rules of Procedure and Evidence. Finally, the article concludes by proposing an alternative approach to secure appropriate redress for the violation of the collective right to exist belonging to the ultimate victim of genocide, the group as such.
Dialect differences and linguistic divergence
Authors: Mansfield John , Leslie-O’Neill Henry , Li Haoyi
Published: May 2023

This article presents a new type of comparative linguistic survey, analyzing (socio)linguistic variation in a database of 1,155 grammatical constructions drawn from 42 diverse languages. We focus in particular on variation in the expression of grammatical meanings, and the extent to which grammatical variation differentiates geographic dialects. This is the first study we know of to present a systematic, crosslinguistic survey of dialect differentiation. We identify three main structural types of grammatical variation—form, order, and omission—and find that in situations of close contact between dialects, where signaling of distinct group identities is more relevant, form variables are more likely to differentiate dialects than the other two types. Order and omission variables usually only differentiate dialects that have minimal contact. Our survey suggests that social signaling may have a substantial role in the divergence of grammars, and provides systematic support for previous proposals regarding convergence and divergence under contact.
Solving the taxonomic identity of Hipposideros cineraceus sensu lato (Chiroptera: Hipposideridae) in the Thai-Malay Peninsula, with the description of a new species
Authors: WONGWAIYUT PHUTITA , KARAPAN SUNATE , SAEKONG PUCHIT , FRANCIS CHARLES M. , GUILLÉN-SERVENT ANTONIO , SENAWI JULIANA , KHAN FAISAL ALI ANWARALI , BATES PAUL J. J. , JANTARIT SOPARK , SOISOOK PIPAT
Published: May 2023

A new species of small Hipposideros in the bicolor group is described based on specimens from Thailand and Malaysia. It can be distinguished from other small Hipposideros in Southeast Asia by a combination of external, craniodental, and bacular morphology, as well as echolocation call frequency. The new species has a distinct rounded swelling on the internarial septum of the noseleaf, with a forearm length of 35.3–42.6 mm, greatest skull length of 15.94–17.90 mm, and a call frequency of maximum energy of 132.3–144.0 kHz. Although clearly different in morphology, the new species forms a sister clade with H. kunzi and H. bicolor in the phylogenetic trees based on mitochondrial DNA. In addition, this study reports echolocation and genetic data, with a confirmed record of H. einnaythu from Thailand for the first time. The new species most closely resembles H. einnaythu. However, it differs in the details of the noseleaf and craniodental morphology, and it has a genetic distance of 9.6% and 10.4% based on mitochondrial COI and ND2, respectively. It is currently documented from five localities: two in peninsular Thailand, at Hala Forest in Yala Province, and Phru To Daeng Swamp Forest in Narathiwat Province, one from peninsular Malaysia at Krau Wildlife Reserve in Pahang, and another two in Sabah, Malaysian Borneo at Gunung Kinabalu, and near Madai Caves. However, it is likely that many previous records of “H. cineraceus” from Borneo refer to this species. Most records of the species are from lowland evergreen rainforest, though one record from Sabah was at 1800m. The roosting sites for this new species are currently unknown. Future research with a combination of data such as genetics, echolocation and morphology would be necessary to further determine the species geographic distribution in Southeast Asia.
Checklist, diversity descriptors and selected descriptions of a highly diverse intertidal sponge (Porifera) assemblage at Costa do Descobrimento (Bahia, Brazil)
Authors: BETTCHER LARISSA , FERNANDEZ JULIO C.C. , GASTALDI MARIANELA , BISPO ANDRÉ , LEAL CAMILLE V. , LEITE DORA , AVELINO-ALVES DHARA , CLERIER PEDRO H.B. , REZENDE DAFINNY , GULART CLARA M.R. , PINHEIRO ULISSES , HAJDU EDUARDO
Published: May 2023

Costa do Descobrimento is located in southern Bahia, Brazil, and only 22 species of sponges (Porifera) were known from the area until now, despite its important reef formations. In the present study, we report a checklist of the sponges of Costa do Descobrimento and their distribution in the studied reefs, with several species illustrated in life. We also describe nine new sponge records for this region, some of which are new records for Brazil, or new records of species previously only poorly known. We present alpha and beta diversity indices and compare the sponge assemblage of the sampled locations. Four reefs were considered: two fringing reefs (Arraial D’Ajuda—AA and Coroa Vermelha / Mutá—CVM) and two offshore Municipal Marine Park “Parque Municipal Marinho— (P.M.M. Coroa Alta—CA and P.M.M. Recife de Fora—RF). A total of 229 specimens were collected (224 Demospongiae, 2 Homoscleromorpha and 3 Calcarea). These were classified in 101 morphotypes. Studied materials included representatives of 15 orders, 34 families and 48 genera. The richest orders are Haplosclerida (29 spp.), Poecilosclerida (15 spp.) and Tetractinellida (11 spp.). The richest families were Chalinidae (24 spp.), Clionaidae (7 spp.) and Mycalidae and Suberitidae (6 spp. each). The richest genus is, by far, Haliclona (20 spp.). Only 13 species were shared among all four reefs surveyed, namely Amphimedon viridis, Cinachyrella alloclada, C. apion, Cladocroce caelum, Cliona varians, Dysidea robusta, Mycale (Naviculina) diversisigmata, Niphates erecta, Spirastrella hartmani, Tedania (Tedania) ignis, Terpios fugax, Tethya bitylastra and T. maza. The reefs with the highest richness were CA and CVM, and the lowest richness was observed in RF. The most similar reefs in terms of species composition were CA and CVM, while AA and RF were more dissimilar to the previous reefs, but also from each other. While the difference among CA, CVM and AA was mainly explained by species turnover, RF differed from the previous based on its lower richness (nestedness component). Even though CA and CVM were the richest reefs, AA presented the highest number of exclusive species, highlighting the uniqueness of this reef, and urging the inclusion of local beachrock fringing reefs in a more holistic conservation strategy at Costa do Descobrimento.
Okamejei picta sp. nov., a new rajid skate from the South China Sea (Rajiformes: Rajidae)
Authors: NG SHING-LAI , HO HSUAN-CHING , JOUNG SHOOU-JENG , LIU KWANG-MING
Published: May 2023

A new species of Okamejei is described based on two adult males collected from deep waters in the South China Sea. The new species, Okamejei picta sp. nov., is readily distinguished from most other congeners in having densely scattered black spots on dorsal disc. Okamejei hollandi and O. mengae is quite similar to the new species by their spot patterns on dorsal disc, but the new species differs from the former by a combination of characters: a yellowish brown dorsal surface densely covered with small, circular to irregular-shaped black spots; blotches on dorsal disc indistinct; posterior ocellus absent; ventral disc white; disc length 45.0–47.7% TL; distance between cloaca to caudal-fin tip 53.6–55.1% TL; trunk centra 31; total basal radials 73–76, morphology of clasper terminal skeleton, and lacking component funnel at the clasper end.
Propofol Affects H/R Induced Alveolar Macrophage Death via TLR4/NF-κB/NLRP3 Signaling Pathway
Authors: Shen Qiqi , Zhou Wugang , Wang Fanlin , Zhang Zhiling , Xu Bing
Published: May 2023

Acute lung injury (ALI) is one of the most common acute and critical diseases in clinic. The main pathological features of ALI are increase of pulmonary Vascular permeability, accumulation of inflammatory cells and pulmonary dysfunction due to diffuse pulmonary edema. At present, it
is generally believed that the main pathogenesis of ALI is the uncontrolled inflammatory response in the lung. It has been found that cell death plays an important role in the regulation of inflammatory reaction in acute lung injury. Propofol, a new fast-acting, short-acting intravenous anesthetic,
it is known that ALI can be alleviated by inhibiting the release of inflammatory factors and inhibiting the anoxia/reoxygenation-induced autophagy, chemotaxis and oxidative stress in macrophages, however, the mechanism of its role in the death of alveolar macrophage remains unknown. Therefore,
the aim of this study was to investigate the role of propofol in alveolar macrophage death and its mechanism through anoxia-reoxygenation induced ALI. NR8383 was alveolar macrophage as anoxia-reoxygenation model. LDH release, CCK-8, Elisa and Western Blot were used to investigate the pathway
of propofol through TLR4/NF-κB/NLRP3 signaling pathway, mechanism of inhibition of hypoxia-reoxygenation induced alveolar macrophage death of NR8383. The results showed that propofol decreased the release of LDH and the content of IL-1β and IL-18. In addition, propofol
pretreatment reduced the protein expression levels of TLR4 downstream pathways (p65 phosphorylation, NLRP3, cleaved-caspase-1, and GSDMD-N), all of which could be reversed by TLR4 receptor antagonist and NLRP3 receptor inhibitors, it’s causing a decrease in alveolar macrophage activity.
The results showed that propofol could significantly reduce anoxia-reoxygenation-induced alveolar macrophage death. Propofol may modulate alveolar macrophage death through TLR4/NF-κB/NLRP3 inflammatory signaling pathway, thereby alleviating anoxia-reoxygenation induced Ali, suggesting
that propofol may be a potential drug for the treatment of Ali.
miR-137 Regulates Proliferation, Migration, Invasion and EMT of Nasopharyngeal Carcinoma Cells by Targeting TWIST1
Authors: Fan Kaimei , Zhu Huicheng , Qi Lingqiang , Huang Yingliang , Xia Xiaoping , Wu Kai
Published: May 2023

To investigate the effects of miR-137 on biological cell function of nasopharyngeal carcinoma (NPC) cells. Totally, 31 pairs of NPC tissues and para-cancer tissues were collected. Meanwhile, human immortalized nasopharyngeal epithelial cell lines (NP69) and human NPC cell lines (6-10B) were cultured. The abilities of cell proliferation, invasion and migration were detected by CCK-8 and Transwell assay, respectively. The relative protein and mRNA expression level was detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. In quantitative real-time polymerase chain reaction (qRT-PCR) experiment, miR-137 was found widely low-expressed in clinical samples and cell lines of nasopharyngeal carcinoma (NPC). On-line target gene prediction software was applied to screen potential downstream target of miR-137 in NPC. Then, Twist Family BHLH Transcription Factor 1 (TWIST1) was verified by luciferase reporter assay and Western blot experiments as a target for negative regulation of miR-137 in NPC cells. We up-regulated the expression of miR-137 and/or TWIST1 in 6-10Bin vitro, and then examined the effects of cell function after by CCK8, Transwell, scratch-wound and Western blot experiments. The results showed that decreased expression of TWIST1 resulting from up-regulation of miR-137 in 6-10B cells could inhibit the biological functions of cells including proliferation, invasion, migration and process of epithelial-mesenchymal transition (EMT). Our research discovered the suppressor function of miR-137 on NPC cells by targeting TWIST1, suggesting that miR-137 could be used as a potential therapeutic target for NPC.
Inhibitory Effect of Tanshinone IIA Nanomicelles on Tumor Growth and Angiogenesis in Mice with Cervical Carcinoma Transplantation
Authors: Hu Ruihua , Chen Aimin
Published: May 2023

In recent years, traditional Chinese medicine (TCM), represented by tanshinone (Tas) and ganoderan polysaccharides, has attracted the attention of many scientists due to its mild effect of inhibiting tumors. In this research, poly-gamma-glutamic acid (γ-PGA) was degraded
into small molecule γ-PGA fragments by high-temperature acidolysis, and L-phenylalanine ethylester (L-PAE) was combined with small molecule γ-PGA fragments to generate γ-PGA-LA by dehydration condensation. The material was mixed with fat-soluble Tas IIA
to form PL-Tas IIA nanomicelles (NMs). In addition to physical characterization, the in vitro biological activity of the material was detected to establish a tumor-bearing nude mouse model, which was inoculated with cervical cancer HeLa cells. The nude mouse models were grouped, and
the effect of NMs on the growth of transplanted tumors was observed by intraperitoneal injection. The results revealed that the nanoparticle size was approximately 139.6±3.8 nm, and it had a good EPR effect, which was conducive to passive targeted therapy of tumors. The polydispersity
coefficient and zeta potential were 0.138±0.005 and 33.6±1.6 mV, respectively. The NM was cocultured with the cells under various concentration conditions, and the cell survival rate was more than 85%. The tumor cell uptake performance of the NM was ideal, and the cell uptake
ratio reached 71.62% at 60 min, as determined by flow cytometry. An in vivo tumor test demonstrated that PL-Tas IIA had a favorite tumor inhibition effect. The tumor-bearing nude mouse model showed that the prepared NMs can inhibit tumor growth, induce angiogenesis of xenografts, and
further induce tumor cell apoptosis, further verifying that the prepared NMs can inhibit cervical cancer tumor growth.