bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figures S1-10 from Targeting N-linked Glycosylation for the Therapy of Aggressive Lymphomas
Authors: Scheich Sebastian , Chen Jiji , Liu Jiamin , Schnütgen Frank , Enssle Julius C. , Ceribelli Michele , Thomas Craig J. , Choi Jaewoo , Morris Vivian , Hsiao Tony , Nguyen Hang , Wang Boya , Bolomsky Arnold , Phelan James D. , Corcoran Sean , Urlaub Henning , Young Ryan M. , Häupl Björn , Wright George W. , Huang Da Wei , Ji Yanlong , Yu Xin , Xu Weihong , Yang Yandan , Zhao Hong , Muppidi Jagan , Pan Kuan-Ting , Oellerich Thomas , Staudt Louis M.
Published: July 2023

Supplemental Figure 1. IRF4-GFP knock-in reporter cell lines. Supplemental Figure 2. IRF4-GFP CRISPR screen in adult T-cell lymphoma and screen controls. Supplemental Figure 3. The OST is essential for DLBCL. Supplemental Figure 4. The role of the OST complex in radiation chimeras. Supplemental Figure 5. The B-cell receptor is glycosylated by the OST complex. Supplemental Figure 6. B-cell receptor deglycosylation leads to higher surface expression. Supplemental Figure 7. B-cell receptor deglycosylation leads to signaling changes in proximal BCR signaling components. Supplemental Figure 8. BCR deglycosylation leads to recruitment of CD22 on the cell surface to the BCR and signaling alterations in GCB DLBCL. Supplemental Figure 9. BCR internalization and My-T-BCR formation in glycosylation deficient cells. Supplemental Figure 10. NGI-1 synergizes with BTK and PI3K inhibitors.
Data from The DNA Damage Response and Inflammation in Cancer
Authors: Klapp Vanessa , Álvarez-Abril Beatriz , Leuzzi Giuseppe , Kroemer Guido , Ciccia Alberto , Galluzzi Lorenzo
Published: July 2023

Abstract
Genomic stability in normal cells is crucial to avoid oncogenesis. Accordingly, multiple components of the DNA damage response (DDR) operate as bona fide tumor suppressor proteins by preserving genomic stability, eliciting the demise of cells with unrepairable DNA lesions, and engaging cell-extrinsic oncosuppression via immunosurveillance. That said, DDR sig­naling can also favor tumor progression and resistance to therapy. Indeed, DDR signaling in cancer cells has been consistently linked to the inhibition of tumor-targeting immune responses. Here, we discuss the complex interactions between the DDR and inflammation in the context of oncogenesis, tumor progression, and response to therapy.
Significance:
Accumulating preclinical and clinical evidence indicates that DDR is intimately connected to the emission of immunomodulatory signals by normal and malignant cells, as part of a cell-extrinsic program to preserve organismal homeostasis. DDR-driven inflammation, however, can have diametrically opposed effects on tumor-targeting immunity. Understanding the links between the DDR and inflammation in normal and malignant cells may unlock novel immunotherapeutic paradigms to treat cancer.
Data from Mitophagy Promotes Resistance to BH3 Mimetics in Acute Myeloid Leukemia
Authors: Glytsou Christina , Chen Xufeng , Zacharioudakis Emmanouil , Al-Santli Wafa , Zhou Hua , Nadorp Bettina , Lee Soobeom , Lasry Audrey , Sun Zhengxi , Papaioannou Dimitrios , Cammer Michael , Wang Kun , Zal Tomasz , Zal Malgorzata Anna , Carter Bing Z. , Ishizawa Jo , Tibes Raoul , Tsirigos Aristotelis , Andreeff Michael , Gavathiotis Evripidis , Aifantis Iannis
Published: July 2023

Abstract
BH3 mimetics are used as an efficient strategy to induce cell death in several blood malignancies, including acute myeloid leukemia (AML). Venetoclax, a potent BCL-2 antagonist, is used clinically in combination with hypomethylating agents for the treatment of AML. Moreover, MCL1 or dual BCL-2/BCL-xL antagonists are under investigation. Yet, resistance to single or combinatorial BH3-mimetic therapies eventually ensues. Integration of multiple genome-wide CRISPR/Cas9 screens revealed that loss of mitophagy modulators sensitizes AML cells to various BH3 mimetics targeting different BCL-2 family members. One such regulator is MFN2, whose protein levels positively correlate with drug resistance in patients with AML. MFN2 overexpression is sufficient to drive resistance to BH3 mimetics in AML. Insensitivity to BH3 mimetics is accompanied by enhanced mitochondria–endoplasmic reticulum interactions and augmented mitophagy flux, which acts as a prosurvival mechanism to eliminate mitochondrial damage. Genetic or pharmacologic MFN2 targeting synergizes with BH3 mimetics by impairing mitochondrial clearance and enhancing apoptosis in AML.
Significance:
AML remains one of the most difficult-to-treat blood cancers. BH3 mimetics represent a promising therapeutic approach to eliminate AML blasts by activating the apoptotic pathway. Enhanced mitochondrial clearance drives resistance to BH3 mimetics and predicts poor prognosis. Reverting excessive mitophagy can halt BH3-mimetic resistance in AML.

This article is highlighted in the In This Issue feature, p. 1501
Data from An African-Specific Variant of TP53 Reveals PADI4 as a Regulator of p53-Mediated Tumor Suppression
Authors: Indeglia Alexandra , Leung Jessica C. , Miller Sven A. , Leu Julia I-Ju , Dougherty James F. , Clarke Nicole L. , Kirven Nicole A. , Shao Chunlei , Ke Lei , Lovell Scott , Barnoud Thibaut , Lu David Y. , Lin Cindy , Kannan Toshitha , Battaile Kevin P. , Yang Tyler Hong Loong , Batista Oliva Isabela , Claiborne Daniel T. , Vogel Peter , Liu Lijun , Liu Qin , Nefedova Yulia , Cassel Joel , Auslander Noam , Kossenkov Andrew V. , Karanicolas John , Murphy Maureen E.
Published: July 2023

Abstract
TP53 is the most frequently mutated gene in cancer, yet key target genes for p53-mediated tumor suppression remain unidentified. Here, we characterize a rare, African-specific germline variant of TP53 in the DNA-binding domain Tyr107His (Y107H). Nuclear magnetic resonance and crystal structures reveal that Y107H is structurally similar to wild-type p53. Consistent with this, we find that Y107H can suppress tumor colony formation and is impaired for the transactivation of only a small subset of p53 target genes; this includes the epigenetic modifier PADI4, which deiminates arginine to the nonnatural amino acid citrulline. Surprisingly, we show that Y107H mice develop spontaneous cancers and metastases and that Y107H shows impaired tumor suppression in two other models. We show that PADI4 is itself tumor suppressive and that it requires an intact immune system for tumor suppression. We identify a p53–PADI4 gene signature that is predictive of survival and the efficacy of immune-checkpoint inhibitors.
Significance:
We analyze the African-centric Y107H hypomorphic variant and show that it confers increased cancer risk; we use Y107H in order to identify PADI4 as a key tumor-suppressive p53 target gene that contributes to an immune modulation signature and that is predictive of cancer survival and the success of immunotherapy.

See related commentary by Bhatta and Cooks, p. 1518.

This article is highlighted in the In This Issue feature, p. 1501
Data from C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in FLT3-Mutant Leukemia
Authors: Sabatier Marie , Birsen Rudy , Lauture Laura , Mouche Sarah , Angelino Paolo , Dehairs Jonas , Goupille Léa , Boussaid Ismael , Heiblig Maël , Boet Emeline , Sahal Ambrine , Saland Estelle , Santos Juliana C. , Armengol Marc , Fernández-Serrano Miranda , Farge Thomas , Cognet Guillaume , Simonetta Federico , Pignon Corentin , Graffeuil Antoine , Mazzotti Céline , Avet-Loiseau Hervé , Delos Océane , Bertrand-Michel Justine , Chedru Amélie , Dembitz Vilma , Gallipoli Paolo , Anstee Natasha S. , Loo Sun , Wei Andrew H. , Carroll Martin , Goubard Armelle , Castellano Rémy , Collette Yves , Vergez François , Mansat-De Mas Véronique , Bertoli Sarah , Tavitian Suzanne , Picard Muriel , Récher Christian , Bourges-Abella Nathalie , Granat Fanny , Kosmider Olivier , Sujobert Pierre , Colsch Benoit , Joffre Carine , Stuani Lucille , Swinnen Johannes V. , Guillou Hervé , Roué Gael , Hakim Nawad , Dejean Anne S. , Tsantoulis Petros , Larrue Clément , Bouscary Didier , Tamburini Jerome , Sarry Jean-Emmanuel
Published: July 2023

Abstract
Although transcription factor CCAAT-enhancer binding protein α (C/EBPα) is critical for normal and leukemic differentiation, its role in cell and metabolic homeostasis is largely unknown in cancer. Here, multiomics analyses uncovered a coordinated activation of C/EBPα and Fms-like tyrosine kinase 3 (FLT3) that increased lipid anabolism in vivo and in patients with FLT3-mutant acute myeloid leukemia (AML). Mechanistically, C/EBPα regulated the fatty acid synthase (FASN)–stearoyl-CoA desaturase (SCD) axis to promote fatty acid (FA) biosynthesis and desaturation. We further demonstrated that FLT3 or C/EBPα inactivation decreased monounsaturated FA incorporation to membrane phospholipids through SCD downregulation. Consequently, SCD inhibition enhanced susceptibility to lipid redox stress that was exploited by combining FLT3 and glutathione peroxidase 4 inhibition to trigger lipid oxidative stress, enhancing ferroptotic death of FLT3-mutant AML cells. Altogether, our study reveals a C/EBPα function in lipid homeostasis and adaptation to redox stress, and a previously unreported vulnerability of FLT3-mutant AML to ferroptosis with promising therapeutic application.
Significance:
FLT3 mutations are found in 30% of AML cases and are actionable by tyrosine kinase inhibitors. Here, we discovered that C/EBPα regulates FA biosynthesis and protection from lipid redox stress downstream mutant-FLT3 signaling, which confers a vulnerability to ferroptosis upon FLT3 inhibition with therapeutic potential in AML.
Modeling the Landscape of Histone-Mutant Pediatric High-Grade Gliomas: A Study in Partner Alterations
Authors: Lubanszky Evan , Hawkins Cynthia
Published: July 2023

Pediatric high-grade gliomas represent a group of deadly, heterogeneous tumors, often driven by histone mutations and the accumulation of clonal mutations, correlating with different tumor types, locations, and age of onset. In this study, McNicholas and colleagues present 16 in vivo models of histone-driven gliomas to investigate subtype-specific tumor biology and treatment options.

See related article by McNicholas et al., p. 1592 (7).
Data from HER2Δ16 Engages ENPP1 to Promote an Immune-Cold Microenvironment in Breast Cancer
Authors: Attalla Sherif Samer , Boucher Jonathan , Proud Hailey , Taifour Tarek , Zuo Dongmei , Sanguin-Gendreau Virginie , Ling Chen , Johnson Gabriella , Li Vincent , Luo Robin B. , Kuasne Hellen , Papavasiliou Vasilios , Walsh Logan A. , Barok Mark , Joensuu Heikki , Park Morag , Roux Philippe P. , Muller William J.
Published: July 2023

Abstract
The tumor–immune microenvironment (TIME) is a critical determinant of therapeutic response. However, the mechanisms regulating its modulation are not fully understood. HER2Δ16, an oncogenic splice variant of the HER2, has been implicated in breast cancer and other tumor types as a driver of tumorigenesis and metastasis. Nevertheless, the underlying mechanisms of HER2Δ16-mediated oncogenicity remain poorly understood. Here, we show that HER2∆16 expression is not exclusive to the clinically HER2+ subtype and associates with a poor clinical outcome in breast cancer. To understand how HER2 variants modulated the tumor microenvironment, we generated transgenic mouse models expressing either proto-oncogenic HER2 or HER2Δ16 in the mammary epithelium. We found that HER2∆16 tumors were immune cold, characterized by low immune infiltrate and an altered cytokine profile. Using an epithelial cell surface proteomic approach, we identified ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) as a functional regulator of the immune cold microenvironment. We generated a knock-in model of HER2Δ16 under the endogenous promoter to understand the role of Enpp1 in aggressive HER2+ breast cancer. Knockdown of Enpp1 in HER2Δ16-derived tumor cells resulted in decreased tumor growth, which correlated with increased T-cell infiltration. These findings suggest that HER2Δ16-dependent Enpp1 activation associates with aggressive HER2+ breast cancer through its immune modulatory function. Our study provides a better understanding of the mechanisms underlying HER2Δ16-mediated oncogenicity and highlights ENPP1 as a potential therapeutic target in aggressive HER2+ breast cancer.
Supp Table S2 from Inhibition of microsomal prostaglandin E2 synthase reduces collagen deposition in melanoma tumors and may improve immunotherapy efficacy by reducing T cell exhaustion
Authors: Fukuda Yasunari , Kim Sun-Hee , Bustos Matias A. , Cho Sung-Nam , Roszik Jason , Burks Jared K. , Kim Hong , Hoon Dave S.B. , Grimm Elizabeth A. , Ekmekcioglu Suhendan
Published: July 2023

Supplementary Table 2
Supp Figure S8 from Inhibition of microsomal prostaglandin E2 synthase reduces collagen deposition in melanoma tumors and may improve immunotherapy efficacy by reducing T cell exhaustion
Authors: Fukuda Yasunari , Kim Sun-Hee , Bustos Matias A. , Cho Sung-Nam , Roszik Jason , Burks Jared K. , Kim Hong , Hoon Dave S.B. , Grimm Elizabeth A. , Ekmekcioglu Suhendan
Published: July 2023

Figure S8 shows morphological differences between ptgs1-, ptgs2-, and ptges-KO murine BrafV600E melanoma cells by using phase-contrast microscopy
Table S7 from Characterizing the immune microenvironment and neoantigen landscape of Hürthle cell carcinoma to identify potential immunologic vulnerabilities
Authors: Ganly Ian , Kuo Fengshen , Makarov Vladimir , Dong Yiyu , Ghossein Ronald A. , Xu Bin , Morris Luc G.T. , Chan Timothy A.
Published: July 2023

Neopeptides (8mer) associated with INDELS in HCC
Supp Figure S5 from Inhibition of microsomal prostaglandin E2 synthase reduces collagen deposition in melanoma tumors and may improve immunotherapy efficacy by reducing T cell exhaustion
Authors: Fukuda Yasunari , Kim Sun-Hee , Bustos Matias A. , Cho Sung-Nam , Roszik Jason , Burks Jared K. , Kim Hong , Hoon Dave S.B. , Grimm Elizabeth A. , Ekmekcioglu Suhendan
Published: July 2023

Figure S5 details the conditions of RNA sequencing analyses
Supp Figure S4 from Inhibition of microsomal prostaglandin E2 synthase reduces collagen deposition in melanoma tumors and may improve immunotherapy efficacy by reducing T cell exhaustion
Authors: Fukuda Yasunari , Kim Sun-Hee , Bustos Matias A. , Cho Sung-Nam , Roszik Jason , Burks Jared K. , Kim Hong , Hoon Dave S.B. , Grimm Elizabeth A. , Ekmekcioglu Suhendan
Published: July 2023

Figure S4 explains quantitative analysis of tumor-infiltrating immune cells
Supp Figure S2 from Inhibition of microsomal prostaglandin E2 synthase reduces collagen deposition in melanoma tumors and may improve immunotherapy efficacy by reducing T cell exhaustion
Authors: Fukuda Yasunari , Kim Sun-Hee , Bustos Matias A. , Cho Sung-Nam , Roszik Jason , Burks Jared K. , Kim Hong , Hoon Dave S.B. , Grimm Elizabeth A. , Ekmekcioglu Suhendan
Published: July 2023

Figure S2 summarizes the calculation details of collagen positivity
Supplementary Tables S1-S12 from Integrated multi-omics analysis of early lung adenocarcinoma links tumor biological features with predicted indolence or aggressiveness
Authors: Senosain Maria-Fernanda , Zou Yong , Patel Khushbu , Zhao Shilin , Coullomb Alexis , Rowe Dianna J , Lehman Jonathan M , Irish Jonathan Michael , Maldonado Fabien , Kammer Michael N , Pancaldi Vera , Lopez Carlos F
Published: July 2023

Supplementary tables
Table S12 from Characterizing the immune microenvironment and neoantigen landscape of Hürthle cell carcinoma to identify potential immunologic vulnerabilities
Authors: Ganly Ian , Kuo Fengshen , Makarov Vladimir , Dong Yiyu , Ghossein Ronald A. , Xu Bin , Morris Luc G.T. , Chan Timothy A.
Published: July 2023

HED results
Supplementary Figures S1-S21 from Integrated multi-omics analysis of early lung adenocarcinoma links tumor biological features with predicted indolence or aggressiveness
Authors: Senosain Maria-Fernanda , Zou Yong , Patel Khushbu , Zhao Shilin , Coullomb Alexis , Rowe Dianna J , Lehman Jonathan M , Irish Jonathan Michael , Maldonado Fabien , Kammer Michael N , Pancaldi Vera , Lopez Carlos F
Published: July 2023

Supplementary Figures S1-S21
Table S11 from Characterizing the immune microenvironment and neoantigen landscape of Hürthle cell carcinoma to identify potential immunologic vulnerabilities
Authors: Ganly Ian , Kuo Fengshen , Makarov Vladimir , Dong Yiyu , Ghossein Ronald A. , Xu Bin , Morris Luc G.T. , Chan Timothy A.
Published: July 2023

HLA divergence score overall and for each HLA type stratified by recurrence and phenotype
Table S10 from Characterizing the immune microenvironment and neoantigen landscape of Hürthle cell carcinoma to identify potential immunologic vulnerabilities
Authors: Ganly Ian , Kuo Fengshen , Makarov Vladimir , Dong Yiyu , Ghossein Ronald A. , Xu Bin , Morris Luc G.T. , Chan Timothy A.
Published: July 2023

Neopeptides (11mer) associated with INDELS in HCC
Supplementary Table S2 from Identification of an imidazopyridine-based compound as an oral selective estrogen receptor degrader for breast cancer therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Graessle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina Alexandra , Fuhr Olaf , Munuganti Ravi S.N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C.B.
Published: July 2023

Crystallographic data and structure refinement information for X15695, X15696 and X19168.
Table S1 from Characterizing the immune microenvironment and neoantigen landscape of Hürthle cell carcinoma to identify potential immunologic vulnerabilities
Authors: Ganly Ian , Kuo Fengshen , Makarov Vladimir , Dong Yiyu , Ghossein Ronald A. , Xu Bin , Morris Luc G.T. , Chan Timothy A.
Published: July 2023

Immune staining in HCC tumors
Figure S2 from Characterizing the immune microenvironment and neoantigen landscape of Hürthle cell carcinoma to identify potential immunologic vulnerabilities
Authors: Ganly Ian , Kuo Fengshen , Makarov Vladimir , Dong Yiyu , Ghossein Ronald A. , Xu Bin , Morris Luc G.T. , Chan Timothy A.
Published: July 2023

The most frequently mutated genes included MADCAM1 (12%), EIF1AX (10%), NF1 (10%), PTPRS (10%), NRAS (8%), TP53 (8%) (A). The majority of mutations were SNVs with a small percentage of deletions and insertions (B). Missense mutations were most common followed by splice site mutations, frameshift deletions and nonsense mutations. The most common DNA substitution types were C>T transitions, followed by T>C transitions, C>A transversions, C>G transversions. The distribution of DNA substitution type per tumor is shown in C.
Figure S6 from Identification of an imidazopyridine-based compound as an oral selective estrogen receptor degrader for breast cancer therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Graessle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina Alexandra , Fuhr Olaf , Munuganti Ravi S.N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C.B.
Published: July 2023

X15695 does not induce apoptosis in LNCaP and LAPC-4 cells.
Figure S5 from Identification of an imidazopyridine-based compound as an oral selective estrogen receptor degrader for breast cancer therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Graessle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina Alexandra , Fuhr Olaf , Munuganti Ravi S.N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C.B.
Published: July 2023

X15695-mediated regulation of expression and cellular localization of p53 in prostate cancer cells.
Figure S1 from Characterizing the immune microenvironment and neoantigen landscape of Hürthle cell carcinoma to identify potential immunologic vulnerabilities
Authors: Ganly Ian , Kuo Fengshen , Makarov Vladimir , Dong Yiyu , Ghossein Ronald A. , Xu Bin , Morris Luc G.T. , Chan Timothy A.
Published: July 2023

Patient, tumor, and treatment characteristics are shown in A. Kaplan–Meier plots of locoregional and distant recurrence-free survival are shown in B and C, respectively.
Figure S4 from Identification of an imidazopyridine-based compound as an oral selective estrogen receptor degrader for breast cancer therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Graessle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina Alexandra , Fuhr Olaf , Munuganti Ravi S.N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C.B.
Published: July 2023

X15695 derivatives attenuate AR target gene expression.
Figure S3 from Identification of an imidazopyridine-based compound as an oral selective estrogen receptor degrader for breast cancer therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Graessle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina Alexandra , Fuhr Olaf , Munuganti Ravi S.N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C.B.
Published: July 2023

X15695 alters the cellular localization of wild-type p53 but not mutant p53.
Figure S2 from Identification of an imidazopyridine-based compound as an oral selective estrogen receptor degrader for breast cancer therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Graessle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina Alexandra , Fuhr Olaf , Munuganti Ravi S.N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C.B.
Published: July 2023

X15695-mediated attenuation of ERalpha target gene expression and reactivation of p53.
Data from Inhibition of microsomal prostaglandin E2 synthase reduces collagen deposition in melanoma tumors and may improve immunotherapy efficacy by reducing T cell exhaustion
Authors: Fukuda Yasunari , Kim Sun-Hee , Bustos Matias A. , Cho Sung-Nam , Roszik Jason , Burks Jared K. , Kim Hong , Hoon Dave S.B. , Grimm Elizabeth A. , Ekmekcioglu Suhendan
Published: July 2023

Abstract
The arachidonic acid pathway participates in immunosuppression in various types of cancer. Our previous observation detailed that microsomal prostaglandin E2 synthase 1 (mPGES-1), an enzyme downstream of cyclooxygenase 2 (COX-2), limited antitumor immunity in melanoma; in addition, genetic depletion of mPGES-1 specifically enhanced immune checkpoint blockade therapy. The present study set out to distinguish the roles of mPGES-1 from those of COX-2 in tumor immunity and determine the potential of mPGES-1 inhibitors for reinforcing immunotherapy in melanoma. Genetic deletion of mPGES-1 showed different profiles of prostaglandin metabolites from that of COX-2 deletion. In our syngeneic mouse model, mPGES-1–deficient cells exhibited similar tumorigenicity to that of COX-2–deficient cells, despite a lower ability to suppress PGE2 synthesis by mPGES-1 depletion, indicating the presence of factors other than PGE2 that are likely to regulate tumor immunity. RNA sequencing analysis revealed that mPGES-1 depletion reduced the expressions of collagen-related genes, which have been found to be associated with immunosuppressive signatures. In our mouse model, collagen was reduced in mPGES-1–deficient tumors, and phenotypic analysis of tumor-infiltrating lymphocytes indicated that mPGES-1-deficient tumors had fewer TIM3+ exhausted CD8+ T cells compared with COX-2–deficient tumors. CAY10678, an mPGES-1 inhibitor, was equivalent to celecoxib, a selective COX-2 inhibitor, in reinforcing anti–PD-1 treatment. Our study indicates that mPGES-1 inhibitors represent a promising adjuvant for immunotherapies in melanoma by reducing collagen deposition and T cell exhaustion.
Data from Identification of an imidazopyridine-based compound as an oral selective estrogen receptor degrader for breast cancer therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Graessle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina Alexandra , Fuhr Olaf , Munuganti Ravi S.N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C.B.
Published: July 2023

Abstract
The pro-oncogenic activities of estrogen receptor alpha (ER) drive breast cancer pathogenesis. Endocrine therapies that impair the production of estrogen or the action of the ER are therefore used to prevent primary disease metastasis. Although recent successes with ER degraders have been reported, there is still the need to develop further ER antagonists with additional properties for breast cancer therapy. We have previously described a benzothiazole compound A4B17 that inhibits the proliferation of androgen receptor positive (AR+) prostate cancer cells by disrupting the interaction of the cochaperone BAG1 with the AR. A4B17 was also found to inhibit the proliferation of ER+ breast cancer cells. Using a scaffold hopping approach, we report here a group of small molecules with imidazopyridine scaffolds that are more potent and efficacious than A4B17. The prototype molecule X15695 efficiently degraded ER and attenuated estrogen-mediated target gene expression as well as transactivation by the AR. X15695 also disrupted key cellular protein-protein interactions such as BAG1-mortalin (GRP75) interaction as well as wild-type p53-mortalin or mutant p53-BAG2 interactions. These activities together reactivated p53 and resulted in cell cycle block and the induction of apoptosis. When administered orally to in vivo tumor xenograft models, X15695 potently inhibited the growth of breast tumor cells but less efficiently the growth of prostate tumor cells. We therefore identify X15695 as an oral selective ER degrader and propose further development of this compound for therapy of ER+ breast cancers.
Characterizing the Immune Microenvironment and Neoantigen Landscape of Hürthle Cell Carcinoma to Identify Potential Immunologic Vulnerabilities
Authors: Ganly Ian , Kuo Fengshen , Makarov Vladimir , Dong Yiyu , Ghossein Ronald , Xu Bin , Morris Luc G.T. , Chan Timothy A.
Published: July 2023

Hürthle cell carcinoma (HCC) is a rare type of thyroid cancer with high rates of distant metastasis and recurrence. Along with the scarcity of effective systemic therapies for HCC, these factors contribute to poor clinical outcomes. The immunologic features of HCC are poorly defined and response rates with immune checkpoint blockade have not been reported. A more comprehensive understanding of the immune landscape and factors that predict response to checkpoint inhibitors is needed.

We performed RNA sequencing on 40 tumors to characterize the neoantigen landscape and immune microenvironment of HCC. We analyzed transcriptomic profiles, tumor-infiltrating immune cell populations, and measures of T-cell activation/dysfunction and correlated these to genetic features such as tumor mutation burden, neoantigen burden, mitochondrial mutations, and LOH from chromosomal uniparental disomy. Finally, immune profiles of patients with recurrence were compared with those of patients without recurrence.

HCC tumors exhibited low levels of immune infiltration, with the more aggressive widely invasive phenotype associated with more immune depletion. There was a negative correlation between tumor mutation burden, neoantigen burden, programmed cell death ligand 1 (PD-L1) expression, and the immune infiltration score. HCC tumors that exhibited a global LOH from chromosomal uniparental disomy or haploidization had the lowest level of immune infiltration. HCC tumors that recurred displayed an immune-depleted microenvironment associated with global LOH and aerobic glycolysis.

These findings offer new insights into the functional immune landscapes and immune microenvironment of HCC. Our data identify potential immunologic vulnerabilities for these understudied and often fatal cancers.

Significance:

The immune landscape of HCC is poorly defined and response rates to immunotherapy have not been reported. The authors found the immune microenvironment in HCC to be depleted. This immunosuppression is associated with a global LOH from haploidization and uniparental disomy, resulting in whole chromosome losses across the genome.
Expanding knowledge of American Cerambycidae (Coleoptera): new species, new records, and morphological variations
Authors: Bezark Larry G. , Santos-Silva Antonio
Published: July 2023

Four new species are described: Xystochroma luteotarsis sp. nov. (Cerambycinae, Callichromatini), from Ecuador; Psyrassa tysoni sp. nov. (Cerambycinae, Elaphidiini), from Guatemala; Bisaltes (Bisaltes) lateralis sp. nov. (Lamiinae, Apomecynini), from Ecuador; and Nagma hovorei sp. nov. (Lamiinae, Calliini), from Ecuador. A key to species of Xystochroma Schmidt, 1924 is provided and Psyrassa tysoni sp. nov. is included in a previous key. Variation in the pubescent pattern of Rosalba strandi (Breuning, 1943) is reported and the species is newly recorded for Paraguay. Chromatic variation in Cyrtinus umbus Martins & Galileo, 2009 (Lamiinae, Cyrtinini) is provided and the species is redescribed based on a dark specimen; a new province record (Puntarenas, Costa Rica) and a new country record (Panama) are included. Chromatic variation and sexual dimorphism in Phaea quadrimaculata Wappes & Santos-Silva, 2021 (Lamiinae, Tetraopini) is reported, and a new Mexican state record (Oaxaca) is provided.
instabilidade temporal do contexto e a verdade poética
Authors: Conceição Júlio César Rocha , Mafra Rennan Lanna Martins
Published: July 2023

Mira-se a identificação de interfaces entre os processos jornalísticos mobilizados no contexto das histórias em quadrinhos e movimentos narrativos realizados na abordagem de temas sobre passados, com vistas a produzir uma possível leitura sobre a presença do jornalismo em quadrinhos na contemporaneidade. Como escopo teórico, o texto busca situar o jornalismo em quadrinhos como materialidade impulsionada não pelo gesto factual da abordagem de um presente instantâneo, mas pela expressão da instabilidade temporal de um contexto evocado (LEAL e CARVALHO, 2017), então atravessado, enquanto textualidade midiática (ANTUNES, MAFRA E JAUREGUI, 2018), pela motivação de uma verdade poética (RANGEL, 2021). Como metodologia, utiliza-se a proposta da análise estética de Gumbrecht (2010, 2021) para investigação do corpus, constituído pela reportagem em quadrinhos Raul (MAIO, 2018). Como principais resultados, percebemos que a instabilidade temporal dos contextos presentes em Raul torna o jornalismo em quadrinhos um campo de interpelação de ações cotidianas tangidas a partir de passados, presentes e futuros, em meio aos quais uma verdade poética produzida pelas lógicas das narrativas promove articulações e rearticulações temporais de modo constante e distinto de lógicas jornalísticas pautadas por uma verdade historiográfica positivista.
Mediação pela memória: ações culturais e educativas em Pontos de Memória
Authors: Rocha Eliane Cristina de Freitas , Lei Cristiane Calheiros
Published: July 2023

This article presents educational and cultural actions conducted at Memory Points—community institutions for memory and heritage preservation supported by a homonymous Brazilian cultural policy. It describes community, cultural, and educational actions accomplished at these Points as a result of mediation processes in social practices which include social memories and community survival. YouTube and Instagram publications made by pioneer Memory Points were examined by content analysis. In conclusion, these pioneering Memory Points conduct community, cultural, and educational actions articulated around community memories via cultural mediation actions that go beyond memory and heritage rescue, including community practices related to the daily struggle for survival.
Concessão dos benefícios assistenciais para pessoas com paralisia cerebral no Brasil: tendência temporal e análise espacial
Authors: Peixoto Marcus Valerius , Gomes Natan Tainá Pereira , Sousa Carla Suzanne Pereira , Santos Aline Matos dos , Duque Andrezza Marques
Published: July 2023

Objetivo: Analisar a tendência temporal e distribuição espacial dos benefícios concedidos para as pessoas com Paralisia Cerebral. Método: Estudo ecológico em que foram incluídos os benefícios concedidos às pessoas com Paralisia Cerebral, nos períodos de 2004 a 2016, no Brasil. Os dados foram coletados do Instituto Nacional de Seguridade Social e Instituto Brasileiro de Geografia Estatística. Utilizou-se o software Join Point Regression, 4.5.0.1, sendo as tendências classificadas em decrescente; crescente e estacionária. Na distribuição espacial foi realizada Análise Exploratória de Dados Espaciais com o software QGIS versão 3.18. Resultados: Observou-se uma tendência decrescente do BPC do ano de 2004 até o ano de 2016, no Brasil. Na região Norte o número de concessões aumentou de 2004-2010, mas, após isso, houve um decréscimo. Já as regiões Sudeste, Sul e Centro Oeste apresentaram tendência decrescente em todo o período analisado. Na análise espacial, as regiões Norte e Nordeste apresentaram maior frequência de BPC proporcionalmente à população com pessoas até 19 anos, aos domicílios e às famílias com até um salário mínimo nas unidades federativas do Brasil. Conclusão: Foi possível observar a diminuição de concessões do BPC em todas as regiões do país no período de 2004 a 2016. As regiões que possuem os índices mais elevados de distribuição do BPC são Nordeste e Norte, reconhecidamente, as que possuem os maiores indicadores de pobreza e extrema pobreza do país.
Nancy Fraser e os dilemas do “pós-socialismo”: Feminismo, democracia e esfera pública
Authors: Melo Rúrion
Published: July 2023

Resenha de: Fraser, Nancy. Justiça interrompida: Reflexões críticas sobre a condição “pós-socialista”. Tradução de Ana Claudia Lopes e Nathalie Bressiani. São Paulo: Boitempo, 2022
Os Atos Sociais
Authors: Reinach Adolf , Teixeira Dario , De Araujo Marcelo
Published: July 2023

O texto a seguir corresponde ao §3, pp. 705–718, do livro “Die apriorischen Grundlagen des bürgerlichen Rechts” (“Os Fundamentos a priori do Direito Civil”), originalmente publicado em 1913 no Jahrbuch für Philosophie und phänomenologische Forschung, pp. 685–847. A numeração inserida entre colchetes no corpo do texto, destacada em negrito, refere-se à paginação desta edição. As palavras destacadas em negrito pelos tradutores remetem a um glossário que acompanha a presente tradução. Os itálicos, porém, são do próprio Reinach. A marca de intercalação “<...>” foi usada para introduzir expressões que estão apenas implícitas no texto original. Existem ainda as seguintes reedições desse livro: 1921 Gesammelte Schriften. Halle, Niemeyer, pp. 166–350. 1953 Zur Phänomenologie des Rechts. Munich: Kose t, 215 pp. 1989 Sämtliche Werke, vol. 1: Die Werke. Munique: Philosophia, 1989, pp. 141–278.
Background Medical Therapy and Clinical Outcomes From the VICTORIA Trial
Authors: Ezekowitz Justin A. , McMullan Ciaran J. , Westerhout Cynthia M. , Piña Ileana L. , Lopez-Sendon Jose , Anstrom Kevin J. , Hernandez Adrian F. , Lam Carolyn S.P. , O’Connor Christopher M. , Pieske Burkert , Ponikowski Piotr , Roessig Lothar , Voors Adriaan A. , Koglin Joerg , Armstrong Paul W. , Butler Javed ,   for the VICTORIA Study Group
Published: July 2023

BACKGROUND:

We examined whether the primary composite outcome (cardiovascular death or heart failure hospitalization) was related to differences in background use and dosing of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction enrolled in VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction), a randomized trial of vericiguat versus placebo.

METHODS:

We evaluated the adherence to guideline use of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, angiotensin receptor-neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. We assessed basic adherence; indication-corrected adherence accounting for guideline indications and contraindications; and dose-corrected adherence (indication-corrected adherence+≥50% of drug dose target). Associations between study treatment and the primary composite outcome according to the adherence to guidelines were assessed using multivariable adjustment; adjusted hazard ratios with 95% CIs and
P
interaction
are reported.

RESULTS:

Of 5050 patients, 5040 (99.8%) had medication data at baseline. For angiotensin-converting enzyme inhibitor, angiotensin-receptor blockers, and angiotensin receptor-neprilysin inhibitors, basic adherence to guidelines was 87.4%, indication-corrected was 95.7%, and dose-corrected was 50.9%. For beta-blockers, basic adherence was 93.1%, indication-corrected was 96.2%, and dose-corrected was 45.4%. For mineralocorticoid receptor antagonists, basic adherence was 70.3%, indication-corrected was 87.1%, and dose-corrected was 82.2%. For triple therapy (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, or angiotensin receptor-neprilysin inhibitors+beta-blocker+mineralocorticoid receptor antagonist), basic adherence was 59.7%, indication-corrected was 83.3%, and dose-corrected was 25.5%. Using basic or dose-corrected adherence, the treatment effect of vericiguat was consistent across adherence to guidelines groups, with or without multivariable adjustment with no treatment heterogeneity.

CONCLUSIONS:

Patients in VICTORIA were well treated with heart failure with reduced ejection fraction medications. The efficacy of vericiguat was consistent across background therapy with very high adherence to guidelines accounting for patient-level indications, contraindications, and tolerance.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02861534.
Funding High-poverty School Districts: Federal Policy Tools and the Limits of Incentives
Authors: Gordon Nora , Reber Sarah
Published: July 2023

What can the federal government do to help ensure that the public schools attended by children living in poverty have enough resources to serve their students? In this brief, we describe existing federal efforts to support education spending in high-poverty districts, discuss their limitations, and suggest alternative approaches for federal policy. We focus especially on the Education Finance Incentive Grant (EFIG) formula—a part of the compensatory Title I grant program designed to encourage changes to state school finance policy—and show that the incentives embedded in the formula are in fact negligible; revising the formula to be more effective would be difficult. Further, any attempt to incentivize desirable state policy faces a fundamental trade-off: Such policy can reinforce inequality because districts in states that do not respond to the incentives by adopting desirable policies also do not receive (as much) federal funding. We argue that federal policy should be more attentive to state fiscal capacity because it is an important determinant of district-level school spending, and the federal government is uniquely positioned to address between-state inequality.
How to Start a Request? A Contrastive Study of Alerters in Spanish by Speakers of L1 Spanish and L1 French
Authors: Marsily Aurélie , De Cock Barbara
Published: July 2023

The formulation of requests has been widely studied in pragmatics, both within a (variety of) language and from a contrastive perspective. In this study, we will show the specific role of alerters (elements that precede the request head act and that serve to get the attention of the hearer on the request) in request formulation, comparing L1 speakers of Spanish and L2 speakers of Spanish with L1 French in Discourse Completion Tests and Naturalised Interactions. In doing so, we contribute to the contrastive pragmatic study of both languages. Our data reveal that there are statistically significant differences in the use of alerters from Spanish L1 and L2 speakers in the DCTs but not in the Naturalised Interactions. Alerters occur with rather similar frequencies in both groups, but there are qualitative differences as to which forms are adopted. At the methodological level, we highlight that data obtained from both groups’ DCTs vs. Naturalised Interactions show different results, thus underlining the importance of combined methods for contrastive pragmatics research.
Unraveling the Enigma of Androcalymma (Fabaceae: Dialioideae): The Rediscovery of a Critically Endangered Legume Genus in the Heart of the Amazon
Authors: FALCÃO MARCUS JOSÉ DE AZEVEDO , SOUSA DA SILVA GUILHERME , CARDOSO PEDERNEIRAS LEANDRO , DE FREITAS MANSANO VIDAL
Published: July 2023

Androcalymma Dwyer, a monospecific and morphologically unique genus on the legume subfamily Dialioideae, stands out as one of the less known genera of Fabaceae, not being molecularly sampled in phylogenetic studies of the family until now, which led to an uncertain position among other taxa in its clade. Androcalymma glabrifolium, endemic to a small and hardly accessible area in the Brazilian Amazon rainforest, was collected once in 1936 and never seen after that, even being conjectured as possibly extinct. Here we describe a recent expedition searching for this enigmatic and rare tree that brought to light an extant population of the species in an indigenous area where it still thrives. The fruits of Androcalymma are here described and illustrated for the first time, as also its flowers’ colors and several other new characters. Here we present its first photographic register, and its DNA is compared to other Dialioideae bringing a solid relationship with the also Amazonian genus Dicorynia, a grouping sustained here by many known and newly discovered morphological characteristics. SEM analyses of flowers and fruits, conservation assessments indicating the critically endangered situation of the genus, taxonomic descriptions, and geographic, systematic, and ecological comments are made.
New host and geographical records of Rhytidhysteron in northern Thailand, and species synonymization
Authors: SENWANNA CHANOKNED , SUWANNARACH NAKARIN , PHOOKAMSAK RUNGTIWA , KUMLA JATURONG , HONGSANAN SINANG
Published: July 2023

During a survey of micro-fungi in Chiang Mai Province, Thailand, fruiting bodies of Rhytidhysteron growing on dead twigs of several host plants were collected. Phylogenetic analyses of a combined LSU, ITS, SSU, and TEF1 sequence data along with morphological characteristics, were used to identify the new collections as R. bruguierae, R. neorufulum and R. subrufulum which were collected from Murraya paniculata, Rosa × damascena, and Prunus sp., respectively. These Rhytidhysteron species are reported herein from these hosts for the first time. Interestingly, R. subrufulum is the first geographical record of this species from Thailand, which extends knowledge of the geographic range of this species. In addition, we synonymize R. erioi under R. bruguierae and R. mengziense under R. ligustrum based on phylogenetic analyses and morphology.
Book review: Cao Yin, Chinese Sojourners in Wartime Raj, 1942–1945
Authors: Sherpa Diki
Published: July 2023

Cao Yin, Chinese Sojourners in Wartime Raj, 1942–1945 (Oxford University Press, 2022), pp. 178, ₹1795. ISBN: 9780192870209.
Assessment of Potential Drug-drug Interactions (pDDIs) and Their Risk Factors Among Hospitalized Cardiac Patients in a Tertiary-care Center of Central India: A Retrospective Record-based Study
Authors: Sahoo Ajaya Kumar , Singh Alok , Gupta Dhyuti , Dhaneria Suryaprakash , Arunima Prachi
Published: July 2023

Background: Patients with cardiovascular disorders (CVD) possess multiple comorbidities and are prone to be prescribed multiple drugs, thus predisposing them to various drug-drug interactions (DDIs). Objective: This study was carried out to assess the potential-DDIs (pDDIs) among the drugs prescribed to hospitalized patients with CVD and associated factors. Method: It was a retrospective study conducted with the help of the medical records department. Medical records of all the patients admitted to the cardiology department of our tertiary care center from January 1st, 2019, to December 31st, 2019, were included for analysis using Lexicomp, an up-to-date drug interaction screening tool. The pDDIs were divided into classes A, B, C, D, and X, and those belonging to classes D or X were considered clinically significant. Multiple logistic regression was used to analyze the association between the factors associated with and the occurrence of clinically significant pDDIs, with a P-value < .05 considered statistically significant. Results: Almost all the records reflected (335/338) at least 1 pDDI. A total of 4966 pDDIs were detected, of which the majority belonged to category C (75.3%), and 5.1% of pDDIs were clinically significant. The patients who were prescribed more than 10 drugs per day (OR = 2.46; 95% CI: 1.27-4.82; P = .008), prescribed parenteral formulation (OR = 1.84; 95% CI: 1.57-2.21; P < .0001), or had a diagnosis of acute coronary syndrome (OR = 2.33; 95% CI:1.1-5.12; P = .03) were associated with clinically significant pDDIs. Other factors, that is, female sex, use of fixed-dose combinations, and the triad of diabetes mellitus, hypertension, and dyslipidemia, were positively associated with clinically significant pDDIs. Conclusion: Even though every patient had at least 1 pDDI, the prevalence of clinically significant pDDIs was relatively less. Use of >10 drugs/day, parenteral formulation, patients with acute coronary syndrome were significantly associated with clinically significant pDDIs.
College Promise Programs as Symbolic Politics
Authors: Monaghan David B. , Attewell Paul A.
Published: July 2023

Since the Tennessee Promise’s 2014 launch, “free college” or “Promise” programs have proliferated rapidly and converged on design features: a “last-dollar” award and community college applicability. Researchers who study these programs’ effects generally presume they are tuition-reducing endeavors. In contrast, we argue that many such programs are exercises in “symbolic politics,” that is, they perform organizational altruism and meet survival imperatives while minimally reducing real costs. We illustrate this by detailing the creation, implementation, and results of a Promise program at a large community college. Cost concerns and the need to appeal to critical publics led the college to adopt a last-dollar design and numerous eligibility criteria. Consequently, few applicants were funded. However, many applicants believed they had received the scholarship, the college’s enrollment increased, and the program received widespread acclaim. We discuss implications for higher education policy and the applicability of symbolic politics to organizational action.
A Pathway to Liberation: A History of the Freedom Schools and the Long Struggle for Justice Since 1865
Authors: Hale Jon
Published: July 2023

The Freedom School Movement originated at the nexus of the struggles for liberation and full citizenship. Beginning with the articulation of education as a means to freedom during the era of enslavement, the ideology behind Freedom Schools was an integral aspect of the long Black freedom struggle in the United States. Freedom Schools have continually recognized the integral role and contribution of Black activists and educators who, throughout the course of the United States’ history, have historically provided a counternarrative to white supremacy and racist policy through education grounded in the needs, aspirations, and wisdom of local community organizing.