bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Tables S1-S9 and Figures S1-S9 from Dimeric p53 Mutant Elicits Unique Tumor-Suppressive Activities through an Altered Metabolic Program
Authors: Gencel-Augusto Jovanka , Su Xiaoping , Qi Yuan , Whitley Elizabeth M. , Pant Vinod , Xiong Shunbin , Shah Vrutant , Lin Jerome , Perez Encarnacion , Fiorotto Marta L. , Mahmud Iqbal , Jain Abhinav K. , Lorenzi Philip L. , Navin Nicholas E. , Richie Ellen R. , Lozano Guillermina
Published: April 2023

Table S1 shows predicted off target sites for p53TD mutant mice.
Table S2 shows upregulated PPAR target genes in p53AD vs p53-null.
Table S3 shows ATAC-seq and RNA-seq congruent genes in p53AD vs p53 null.
Table S4 shows p53half site analysis in PPAR target genes
Table S5 shows control sequences used for p53 half site analysis
Table S6 shows altered genes in p53AD-derived thymic lymphomas
Table S7 shows primers used for genotyping of p53 mutant mice
Table S8 shows primers used for qRT-PCR
Table S9 shows antibodies used for flow cytometry
Figure S1 shows extended data for generation of knock-in mouse models and features of p53TD mutant proteins and mice.
Figure S2 shows homozygous mutant mice survival curves as well as tumor data.
Figure S3 shows exome sequencing results for thymic lymphomas and hemangiosarcomas derived from p53 monomer and dimer mutant mice.
Figure S4 shows characterization of stress responses of p53TD mutants.
Figure S5 shows RNA-sequencing results for p53AD and p53RP, and Mdm2 genetic deletion rescue experiments.
Figure S6 shows RNA-seq results of basal p53AD vs p53-null thymi, upstream regulator analysis, and ATAC-seq results for specific loci.
Figure S7 shows extended data for p53 dimer mutant novel activities (co-IP, motif analysis, other dimer mutants activities, and tumor data)
Figure S8 shows ferroptosis and scRNA-seq extended data
Figure S9 shows diagram summarizing findings within this study.
Data from Li–Fraumeni Syndrome–Associated Dimer-Forming Mutant p53 Promotes Transactivation-Independent Mitochondrial Cell Death
Authors: Choe Joshua H. , Kawase Tatsuya , Xu An , Guzman Asja , Obradovic Aleksandar Z. , Low-Calle Ana Maria , Alaghebandan Bita , Raghavan Ananya , Long Kaitlin , Hwang Paul M. , Schiffman Joshua D. , Zhu Yan , Zhao Ruiying , Lee Dung-Fang , Katz Chen , Prives Carol
Published: April 2023

Abstract
Cancer-relevant mutations in the oligomerization domain (OD) of the p53 tumor suppressor protein, unlike those in the DNA binding domain, have not been well elucidated. Here, we characterized the germline OD mutant p53(A347D), which occurs in cancer-prone Li–Fraumeni syndrome (LFS) patients. Unlike wild-type p53, mutant p53(A347D) cannot form tetramers and exists as a hyperstable dimeric protein. Further, p53(A347D) cannot bind or transactivate the majority of canonical p53 target genes. Isogenic cell lines harboring either p53(A347D) or no p53 yield comparable tumorigenic properties, yet p53(A347D) displays remarkable neomorphic activities. Cells bearing p53(A347D) possess a distinct transcriptional profile and undergo metabolic reprogramming. Further, p53(A347D) induces striking mitochondrial network aberration and associates with mitochondria to drive apoptotic cell death upon topoisomerase II inhibition in the absence of transcription. Thus, dimer-forming p53 demonstrates both loss-of-function (LOF) and gain-of-function (GOF) properties compared with the wild-type form of the protein.
Significance:
A mutant p53 (A347D), which can only form dimers, is associated with increased cancer susceptibility in LFS individuals. We found that this mutant wields a double-edged sword, driving tumorigenesis through LOF while gaining enhanced apoptogenic activity as a new GOF, thereby yielding a potential vulnerability to select therapeutic approaches.
Data from Dimeric p53 Mutant Elicits Unique Tumor-Suppressive Activities through an Altered Metabolic Program
Authors: Gencel-Augusto Jovanka , Su Xiaoping , Qi Yuan , Whitley Elizabeth M. , Pant Vinod , Xiong Shunbin , Shah Vrutant , Lin Jerome , Perez Encarnacion , Fiorotto Marta L. , Mahmud Iqbal , Jain Abhinav K. , Lorenzi Philip L. , Navin Nicholas E. , Richie Ellen R. , Lozano Guillermina
Published: April 2023

Abstract
Cancer-related alterations of the p53 tetramerization domain (TD) abrogate wild-type (WT) p53 function. They result in a protein that preferentially forms monomers or dimers, which are also normal p53 states under basal cellular conditions. However, their physiologic relevance is not well understood. We have established in vivo models for monomeric and dimeric p53, which model Li–Fraumeni syndrome patients with germline p53 TD alterations. p53 monomers are inactive forms of the protein. Unexpectedly, p53 dimers conferred some tumor suppression that is not mediated by canonical WT p53 activities. p53 dimers upregulate the PPAR pathway. These activities are associated with lower prevalence of thymic lymphomas and increased CD8+ T-cell differentiation. Lymphomas derived from dimeric p53 mice show cooperating alterations in the PPAR pathway, further implicating a role for these activities in tumor suppression. Our data reveal novel functions for p53 dimers and support the exploration of PPAR agonists as therapies.
Significance:
New mouse models with TP53R342P (monomer) or TP53A347D (dimer) mutations mimic Li–Fraumeni syndrome. Although p53 monomers lack function, p53 dimers conferred noncanonical tumor-suppressive activities. We describe novel activities for p53 dimers facilitated by PPARs and propose these are “basal” p53 activities.

See related commentary by Stieg et al., p. 1046.

See related article by Choe et al., p. 1250.

This article is highlighted in the In This Issue feature, p. 1027
Data from Dimeric p53 Mutant Elicits Unique Tumor-Suppressive Activities through an Altered Metabolic Program
Authors: Gencel-Augusto Jovanka , Su Xiaoping , Qi Yuan , Whitley Elizabeth M. , Pant Vinod , Xiong Shunbin , Shah Vrutant , Lin Jerome , Perez Encarnacion , Fiorotto Marta L. , Mahmud Iqbal , Jain Abhinav K. , Lorenzi Philip L. , Navin Nicholas E. , Richie Ellen R. , Lozano Guillermina
Published: April 2023

Abstract
Cancer-related alterations of the p53 tetramerization domain (TD) abrogate wild-type (WT) p53 function. They result in a protein that preferentially forms monomers or dimers, which are also normal p53 states under basal cellular conditions. However, their physiologic relevance is not well understood. We have established in vivo models for monomeric and dimeric p53, which model Li–Fraumeni syndrome patients with germline p53 TD alterations. p53 monomers are inactive forms of the protein. Unexpectedly, p53 dimers conferred some tumor suppression that is not mediated by canonical WT p53 activities. p53 dimers upregulate the PPAR pathway. These activities are associated with lower prevalence of thymic lymphomas and increased CD8+ T-cell differentiation. Lymphomas derived from dimeric p53 mice show cooperating alterations in the PPAR pathway, further implicating a role for these activities in tumor suppression. Our data reveal novel functions for p53 dimers and support the exploration of PPAR agonists as therapies.
Significance:
New mouse models with TP53R342P (monomer) or TP53A347D (dimer) mutations mimic Li–Fraumeni syndrome. Although p53 monomers lack function, p53 dimers conferred noncanonical tumor-suppressive activities. We describe novel activities for p53 dimers facilitated by PPARs and propose these are “basal” p53 activities.
Converging on a Cure: The Roads to Predictive Immunotherapy
Authors: Stein-O'Brien Genevieve L. , Le Dung T. , Jaffee Elizabeth M. , Fertig Elana J. , Zaidi Neeha
Published: April 2023

Convergence science teams integrating clinical, biological, engineering, and computational expertise are inventing new forecast systems to monitor and predict evolutionary changes in tumor and immune interactions during early cancer progression and therapeutic response. The resulting methods should inform a new predictive medicine paradigm to select adaptive immunotherapeutic regimens personalized to patients’ tumors at a given time during their cancer progression for durable patient response.
Supplementary Tables S1-5 from METTL3-Mediated m6A Modification Controls Splicing Factor Abundance and Contributes to Aggressive CLL
Authors: Wu Yiming , Jin Meiling , Fernandez Mike , Hart Kevyn L. , Liao Aijun , Ge Xinzhou , Fernandes Stacey M. , McDonald Tinisha , Chen Zhenhua , Röth Daniel , Ghoda Lucy Y. , Marcucci Guido , Kalkum Markus , Pillai Raju K. , Danilov Alexey V. , Li Jingyi Jessica , Chen Jianjun , Brown Jennifer R. , Rosen Steven T. , Siddiqi Tanya , Wang Lili
Published: April 2023

Table S1 shows CLL sample information; Table S2 shows protein expression detected in CLL and normal B cells using TMT proteomics; Table S3 shows top 150 transcripts with highest m6A density in B cells; Table S4 shows sequences of shRNAs, sgRNAs, and primers used in our study; Table S5 shows cellular pathways enriched in our study.
Supplementary Figures S1-8 from METTL3-Mediated m6A Modification Controls Splicing Factor Abundance and Contributes to Aggressive CLL
Authors: Wu Yiming , Jin Meiling , Fernandez Mike , Hart Kevyn L. , Liao Aijun , Ge Xinzhou , Fernandes Stacey M. , McDonald Tinisha , Chen Zhenhua , Röth Daniel , Ghoda Lucy Y. , Marcucci Guido , Kalkum Markus , Pillai Raju K. , Danilov Alexey V. , Li Jingyi Jessica , Chen Jianjun , Brown Jennifer R. , Rosen Steven T. , Siddiqi Tanya , Wang Lili
Published: April 2023

Fig S1. SF3B1 mutant CLL samples had pervasive changes in 3’ splice site.
Fig S2. Omics analyses identify widespread post-transcriptional upregulation of splicing factors in CLL.
Fig S3. Abundance of spliceosome complexes and RNA-binding proteins are associated with clinical outcomes in CLL.
Fig S4. METTL3 is consistently upregulated along with differential m6A modification on transcripts of RNA splicing process in CLL.
Fig S5. KO or pharmacological inhibition of METTL3 impacts cell growth.
Fig S6. KO or pharmacological inhibition of METTL3 impacts apoptosis, cell cycle, and splicing factor abundance.
Fig S7. Splicing factors are either direct or indirect targets of METTL3.
Fig S8. Validation of association between m6A and splicing factor abundance using dCasRx-METTL3.
Supplementary Tables 1-6 from Patient-Derived iPSCs Faithfully Represent the Genetic Diversity and Cellular Architecture of Human Acute Myeloid Leukemia
Authors: Kotini Andriana G. , Carcamo Saul , Cruz-Rodriguez Nataly , Olszewska Malgorzata , Wang Tiansu , Demircioglu Deniz , Chang Chan-Jung , Bernard Elsa , Chao Mark P. , Majeti Ravindra , Luo Hanzhi , Kharas Michael G. , Hasson Dan , Papapetrou Eirini P.
Published: April 2023

Table S1. Patient characteristics. AML: acute myeloid leukemia; MDS: myelodysplastic syndrome; MPN: myeloproliferative neoplasm; ET: essential thrombocythemia; PBMCs: peripheral blood mononuclear cells; BMMCs: bone marrow mononuclear cells; PDX: patient-derived xenografts
Table S2. All patient samples used in this study with genetic characterization and reprogramming outcomes. Blue font denotes partially reprogrammed (as opposed to bona fide iPSC) colonies and clones.
Table S3. All AML-iPSC lines phenotypically characterized.
Table S4. Top 50 upregulated genes (highest log2 fold change) in each cluster.
Table S5. Primers used for genotyping.
Table S6. Primers used for qRT-PCR analyses.
Supplementary Figures 1-8 from Patient-Derived iPSCs Faithfully Represent the Genetic Diversity and Cellular Architecture of Human Acute Myeloid Leukemia
Authors: Kotini Andriana G. , Carcamo Saul , Cruz-Rodriguez Nataly , Olszewska Malgorzata , Wang Tiansu , Demircioglu Deniz , Chang Chan-Jung , Bernard Elsa , Chao Mark P. , Majeti Ravindra , Luo Hanzhi , Kharas Michael G. , Hasson Dan , Papapetrou Eirini P.
Published: April 2023

Supplemental Figure 1. Generation of a panel of iPSCs from patients with AML.
Supplemental Figure 2. Reprogramming aids reconstruction of the evolutionary history and clonal composition of AML.
Supplemental Figure 3. Transplantation of AML-iPSCs into immunodeficient mice.
Supplemental Figure 4. Developmental block in a subset of AML-iPSC lines.
Supplemental Figure 5. Transplantation of primary AML cells and patient-matched AMLiPSC lines.
Supplemental Figure 6. Single-cell RNA-sequencing analyses of matched primary and
iPSC-derived leukemia cells from patient AML-47.
Supplemental Figure 7. Cell cycle and pseudotime analyses.
Supplemental Figure 8. Comparison of scRNA-Seq data integration and clustering methods and pseudobulk differential gene expression analyses.
Data from METTL3-Mediated m6A Modification Controls Splicing Factor Abundance and Contributes to Aggressive CLL
Authors: Wu Yiming , Jin Meiling , Fernandez Mike , Hart Kevyn L. , Liao Aijun , Ge Xinzhou , Fernandes Stacey M. , McDonald Tinisha , Chen Zhenhua , Röth Daniel , Ghoda Lucy Y. , Marcucci Guido , Kalkum Markus , Pillai Raju K. , Danilov Alexey V. , Li Jingyi Jessica , Chen Jianjun , Brown Jennifer R. , Rosen Steven T. , Siddiqi Tanya , Wang Lili
Published: April 2023

Abstract
RNA splicing dysregulation underlies the onset and progression of cancers. In chronic lymphocytic leukemia (CLL), spliceosome mutations leading to aberrant splicing occur in ∼20% of patients. However, the mechanism for splicing defects in spliceosome-unmutated CLL cases remains elusive. Through an integrative transcriptomic and proteomic analysis, we discover that proteins involved in RNA splicing are posttranscriptionally upregulated in CLL cells, resulting in splicing dysregulation. The abundance of splicing complexes is an independent risk factor for poor prognosis. Moreover, increased splicing factor expression is highly correlated with the abundance of METTL3, an RNA methyltransferase that deposits N6-methyladenosine (m6A) on mRNA. METTL3 is essential for cell growth in vitro and in vivo and controls splicing factor protein expression in a methyltransferase-dependent manner through m6A modification-mediated ribosome recycling and decoding. Our results uncover METTL3-mediated m6A modification as a novel regulatory axis in driving splicing dysregulation and contributing to aggressive CLL.
Significance:
METTL3 controls widespread splicing factor abundance via translational control of m6A-modified mRNA, contributes to RNA splicing dysregulation and disease progression in CLL, and serves as a potential therapeutic target in aggressive CLL.

See related commentary by Janin and Esteller, p. 176.

This article is highlighted in the In This Issue feature, p. 171
Data from METTL3-Mediated m6A Modification Controls Splicing Factor Abundance and Contributes to Aggressive CLL
Authors: Wu Yiming , Jin Meiling , Fernandez Mike , Hart Kevyn L. , Liao Aijun , Ge Xinzhou , Fernandes Stacey M. , McDonald Tinisha , Chen Zhenhua , Röth Daniel , Ghoda Lucy Y. , Marcucci Guido , Kalkum Markus , Pillai Raju K. , Danilov Alexey V. , Li Jingyi Jessica , Chen Jianjun , Brown Jennifer R. , Rosen Steven T. , Siddiqi Tanya , Wang Lili
Published: April 2023

Abstract
RNA splicing dysregulation underlies the onset and progression of cancers. In chronic lymphocytic leukemia (CLL), spliceosome mutations leading to aberrant splicing occur in ∼20% of patients. However, the mechanism for splicing defects in spliceosome-unmutated CLL cases remains elusive. Through an integrative transcriptomic and proteomic analysis, we discover that proteins involved in RNA splicing are posttranscriptionally upregulated in CLL cells, resulting in splicing dysregulation. The abundance of splicing complexes is an independent risk factor for poor prognosis. Moreover, increased splicing factor expression is highly correlated with the abundance of METTL3, an RNA methyltransferase that deposits N6-methyladenosine (m6A) on mRNA. METTL3 is essential for cell growth in vitro and in vivo and controls splicing factor protein expression in a methyltransferase-dependent manner through m6A modification-mediated ribosome recycling and decoding. Our results uncover METTL3-mediated m6A modification as a novel regulatory axis in driving splicing dysregulation and contributing to aggressive CLL.
Significance:
METTL3 controls widespread splicing factor abundance via translational control of m6A-modified mRNA, contributes to RNA splicing dysregulation and disease progression in CLL, and serves as a potential therapeutic target in aggressive CLL.

See related commentary by Janin and Esteller.
Data from Patient-Derived iPSCs Faithfully Represent the Genetic Diversity and Cellular Architecture of Human Acute Myeloid Leukemia
Authors: Kotini Andriana G. , Carcamo Saul , Cruz-Rodriguez Nataly , Olszewska Malgorzata , Wang Tiansu , Demircioglu Deniz , Chang Chan-Jung , Bernard Elsa , Chao Mark P. , Majeti Ravindra , Luo Hanzhi , Kharas Michael G. , Hasson Dan , Papapetrou Eirini P.
Published: April 2023

Abstract
The reprogramming of human acute myeloid leukemia (AML) cells into induced pluripotent stem cell (iPSC) lines could provide new faithful genetic models of AML, but is currently hindered by low success rates and uncertainty about whether iPSC-derived cells resemble their primary counterparts. Here we developed a reprogramming method tailored to cancer cells, with which we generated iPSCs from 15 patients representing all major genetic groups of AML. These AML-iPSCs retain genetic fidelity and produce transplantable hematopoietic cells with hallmark phenotypic leukemic features. Critically, single-cell transcriptomics reveal that, upon xenotransplantation, iPSC-derived leukemias faithfully mimic the primary patient-matched xenografts. Transplantation of iPSC-derived leukemias capturing a clone and subclone from the same patient allowed us to isolate the contribution of a FLT3-ITD mutation to the AML phenotype. The results and resources reported here can transform basic and preclinical cancer research of AML and other human cancers.
Significance:
We report the generation of patient-derived iPSC models of all major genetic groups of human AML. These exhibit phenotypic hallmarks of AML in vitro and in vivo, inform the clonal hierarchy and clonal dynamics of human AML, and exhibit striking similarity to patient-matched primary leukemias upon xenotransplantation.

See related commentary by Doulatov.
Supplementary Table 1 from Induction of PARP7 Creates a Vulnerability for Growth Inhibition by RBN2397 in Prostate Cancer Cells
Authors: Yang Chunsong , Wierbiłowicz Krzysztof , Dworak Natalia M. , Bae Song Yi , Tengse Sachi B. , Abianeh Nicki , Drake Justin M. , Abbas Tarek , Ratan Aakrosh , Wotton David , Paschal Bryce M.
Published: April 2023

Supplementary Table 1: RBN2397 growth effects in prostate cencer cell lines
Supplementary Figure 5 from Induction of PARP7 Creates a Vulnerability for Growth Inhibition by RBN2397 in Prostate Cancer Cells
Authors: Yang Chunsong , Wierbiłowicz Krzysztof , Dworak Natalia M. , Bae Song Yi , Tengse Sachi B. , Abianeh Nicki , Drake Justin M. , Abbas Tarek , Ratan Aakrosh , Wotton David , Paschal Bryce M.
Published: April 2023

FACS analysis of NCI-H660 cells for detection of necrosis and apoptosis
Supplementary Figure 4 from Induction of PARP7 Creates a Vulnerability for Growth Inhibition by RBN2397 in Prostate Cancer Cells
Authors: Yang Chunsong , Wierbiłowicz Krzysztof , Dworak Natalia M. , Bae Song Yi , Tengse Sachi B. , Abianeh Nicki , Drake Justin M. , Abbas Tarek , Ratan Aakrosh , Wotton David , Paschal Bryce M.
Published: April 2023

RBN2397 inhibition of prostate cancer cell growth requires PARP7 over-expression
Supplementary Figure 3 from Induction of PARP7 Creates a Vulnerability for Growth Inhibition by RBN2397 in Prostate Cancer Cells
Authors: Yang Chunsong , Wierbiłowicz Krzysztof , Dworak Natalia M. , Bae Song Yi , Tengse Sachi B. , Abianeh Nicki , Drake Justin M. , Abbas Tarek , Ratan Aakrosh , Wotton David , Paschal Bryce M.
Published: April 2023

The growth inhibitory effect of RBN2397 in prostate cells is not dependent on TBK1 and JAK1/2 kinase activity
Supplementary Figure 2 from Induction of PARP7 Creates a Vulnerability for Growth Inhibition by RBN2397 in Prostate Cancer Cells
Authors: Yang Chunsong , Wierbiłowicz Krzysztof , Dworak Natalia M. , Bae Song Yi , Tengse Sachi B. , Abianeh Nicki , Drake Justin M. , Abbas Tarek , Ratan Aakrosh , Wotton David , Paschal Bryce M.
Published: April 2023

BBQ and FICZ treatment activates AHR signaling in prostate cancer cells
Supplementary Figure 1 from Induction of PARP7 Creates a Vulnerability for Growth Inhibition by RBN2397 in Prostate Cancer Cells
Authors: Yang Chunsong , Wierbiłowicz Krzysztof , Dworak Natalia M. , Bae Song Yi , Tengse Sachi B. , Abianeh Nicki , Drake Justin M. , Abbas Tarek , Ratan Aakrosh , Wotton David , Paschal Bryce M.
Published: April 2023

Cell cycle distributions of cell lines treated with RBN2397 plus androgen or plus AHR agonist
Supplementary Table S1 from RAB27B Drives a Cancer Stem Cell Phenotype in NSCLC Cells Through Enhanced Extracellular Vesicle Secretion
Authors: Meneses Kayleah M. , Pandya Prita , Lindemann Jennifer A. , Al-Qasrawi Dania S. , Argo Ryan A. , Weems Celeste M. , Beetler Danielle J. , Vijay Geraldine V. , Yan Irene K. , Wolfram Joy , Patel Tushar , Justilien Verline
Published: April 2023

Supplementary Table S1: Primers and shRNAs used in Experimental Procedures
Supplementary Figure S6 from RAB27B Drives a Cancer Stem Cell Phenotype in NSCLC Cells Through Enhanced Extracellular Vesicle Secretion
Authors: Meneses Kayleah M. , Pandya Prita , Lindemann Jennifer A. , Al-Qasrawi Dania S. , Argo Ryan A. , Weems Celeste M. , Beetler Danielle J. , Vijay Geraldine V. , Yan Irene K. , Wolfram Joy , Patel Tushar , Justilien Verline
Published: April 2023

Supplementary Figure S6: Effects of ShRAB27B CSC-derived EVs on the expression of stemness genes in BCCs
Supplementary Figure S5 from RAB27B Drives a Cancer Stem Cell Phenotype in NSCLC Cells Through Enhanced Extracellular Vesicle Secretion
Authors: Meneses Kayleah M. , Pandya Prita , Lindemann Jennifer A. , Al-Qasrawi Dania S. , Argo Ryan A. , Weems Celeste M. , Beetler Danielle J. , Vijay Geraldine V. , Yan Irene K. , Wolfram Joy , Patel Tushar , Justilien Verline
Published: April 2023

Supplementary Figure S5: Cellular uptake of DiI-labeled BCC and CSC EVs
Supplementary Figure S4 from RAB27B Drives a Cancer Stem Cell Phenotype in NSCLC Cells Through Enhanced Extracellular Vesicle Secretion
Authors: Meneses Kayleah M. , Pandya Prita , Lindemann Jennifer A. , Al-Qasrawi Dania S. , Argo Ryan A. , Weems Celeste M. , Beetler Danielle J. , Vijay Geraldine V. , Yan Irene K. , Wolfram Joy , Patel Tushar , Justilien Verline
Published: April 2023

Supplementary Figure S4: Characterization of RAB27B knockdown NSCLC CSC derived EVs
Supplementary Figure S3 from RAB27B Drives a Cancer Stem Cell Phenotype in NSCLC Cells Through Enhanced Extracellular Vesicle Secretion
Authors: Meneses Kayleah M. , Pandya Prita , Lindemann Jennifer A. , Al-Qasrawi Dania S. , Argo Ryan A. , Weems Celeste M. , Beetler Danielle J. , Vijay Geraldine V. , Yan Irene K. , Wolfram Joy , Patel Tushar , Justilien Verline
Published: April 2023

Supplementary Figure S3: RAB27B is required for NSCLC tumorigenicity in vivo
Supplementary Figure S2 from RAB27B Drives a Cancer Stem Cell Phenotype in NSCLC Cells Through Enhanced Extracellular Vesicle Secretion
Authors: Meneses Kayleah M. , Pandya Prita , Lindemann Jennifer A. , Al-Qasrawi Dania S. , Argo Ryan A. , Weems Celeste M. , Beetler Danielle J. , Vijay Geraldine V. , Yan Irene K. , Wolfram Joy , Patel Tushar , Justilien Verline
Published: April 2023

Supplementary Figure S2: RAB27B is required for the stem-like phenotype of NSCLC CSCs
Supplementary Figure S1 from RAB27B Drives a Cancer Stem Cell Phenotype in NSCLC Cells Through Enhanced Extracellular Vesicle Secretion
Authors: Meneses Kayleah M. , Pandya Prita , Lindemann Jennifer A. , Al-Qasrawi Dania S. , Argo Ryan A. , Weems Celeste M. , Beetler Danielle J. , Vijay Geraldine V. , Yan Irene K. , Wolfram Joy , Patel Tushar , Justilien Verline
Published: April 2023

Supplementary Figure S1: RAB27B expression in CSC cultures
Data from Induction of PARP7 Creates a Vulnerability for Growth Inhibition by RBN2397 in Prostate Cancer Cells
Authors: Yang Chunsong , Wierbiłowicz Krzysztof , Dworak Natalia M. , Bae Song Yi , Tengse Sachi B. , Abianeh Nicki , Drake Justin M. , Abbas Tarek , Ratan Aakrosh , Wotton David , Paschal Bryce M.
Published: April 2023

The ADP-ribosyltransferase PARP7 modulates protein function by conjugating ADP-ribose to the side chains of acceptor amino acids. PARP7 has been shown to affect gene expression in prostate cancer cells and certain other cell types by mechanisms that include transcription factor ADP-ribosylation. Here, we use a recently developed catalytic inhibitor to PARP7, RBN2397, to study the effects of PARP7 inhibition in androgen receptor (AR)-positive and AR-negative prostate cancer cells. We find that RBN2397 has nanomolar potency for inhibiting androgen-induced ADP-ribosylation of the AR. RBN2397 inhibits the growth of prostate cancer cells in culture when cells are treated with ligands that activate the AR, or the aryl hydrocarbon receptor, and induce PARP7 expression. We show that the growth-inhibitory effects of RBN2397 are distinct from its enhancement of IFN signaling recently shown to promote tumor immunogenicity. RBN2397 treatment also induces trapping of PARP7 in a detergent-resistant fraction within the nucleus, which is reminiscent of how inhibitors such as talazoparib affect PARP1 compartmentalization. Because PARP7 is expressed in AR-negative metastatic tumors and RBN2397 can affect cancer cells through multiple mechanisms, PARP7 may be an actionable target in advanced prostate cancer.
Significance:
RBN2397 is a potent and selective inhibitor of PARP7 that reduces the growth of prostate cancer cells, including a model for treatment-emergent neuroendocrine prostate cancer. RBN2397 induces PARP7 trapping on chromatin, suggesting its mechanism of action might be similar to clinically used PARP1 inhibitors.
Data from RAB27B Drives a Cancer Stem Cell Phenotype in NSCLC Cells Through Enhanced Extracellular Vesicle Secretion
Authors: Meneses Kayleah M. , Pandya Prita , Lindemann Jennifer A. , Al-Qasrawi Dania S. , Argo Ryan A. , Weems Celeste M. , Beetler Danielle J. , Vijay Geraldine V. , Yan Irene K. , Wolfram Joy , Patel Tushar , Justilien Verline
Published: April 2023

Cancer stem cells (CSC) within non–small cell lung carcinoma (NSCLC) tumors drive NSCLC progression, metastasis, relapse, and intrinsic chemoresistance. Understanding the mechanisms that support the malignant phenotypes of NSCLC CSCs may provide insights for improved NSCLC therapeutic interventions. Here, we report that expression of RAB27B, a small GTPase, is significantly upregulated in NSCLC CSCs when compared with bulk cancer cells (BCC). Short hairpin RNA–mediated knockdown of RAB27B leads to a loss of stem cell marker gene expression and reduced NSCLC spheroid growth, clonal expansion, transformed growth, invasion, and tumorigenicity. We find that NSCLC CSCs secrete significantly more extracellular vesicles (EV) than BCCs, and that this is RAB27B-dependent. Furthermore, CSC-derived EVs, but not BCC-derived EVs, induce spheroid growth, clonal expansion, and invasion in BCCs. Finally, RAB27B is required for CSC-derived EV-induced stemness in BCCs. Taken together, our results indicate that RAB27B is required for maintenance of a highly tumorigenic, cancer-initiating, invasive stem-like cell population in NSCLC and RAB27B is involved in propagating EV-mediated communication from NSCLC CSCs to BCCs. Our findings further suggest that inhibition of RAB27B-dependent EV secretion may be a potential therapeutic strategy for NSCLC.
Significance:
Expression of RAB27B in CSCs leads to elevated levels of EVs that mediate communication between CSCs and BCCs that maintains a stem-like phenotype in NSCLC cells.
RAB27B Drives a Cancer Stem Cell Phenotype in NSCLC Cells Through Enhanced Extracellular Vesicle Secretion
Authors: Meneses Kayleah M. , Pandya Prita , Lindemann Jennifer A. , Al-Qasrawi Dania S. , Argo Ryan A. , Weems Celeste M. , Beetler Danielle J. , Vijay Geraldine V. , Yan Irene K. , Wolfram Joy , Patel Tushar , Justilien Verline
Published: April 2023

Cancer stem cells (CSC) within non–small cell lung carcinoma (NSCLC) tumors drive NSCLC progression, metastasis, relapse, and intrinsic chemoresistance. Understanding the mechanisms that support the malignant phenotypes of NSCLC CSCs may provide insights for improved NSCLC therapeutic interventions. Here, we report that expression of RAB27B, a small GTPase, is significantly upregulated in NSCLC CSCs when compared with bulk cancer cells (BCC). Short hairpin RNA–mediated knockdown of RAB27B leads to a loss of stem cell marker gene expression and reduced NSCLC spheroid growth, clonal expansion, transformed growth, invasion, and tumorigenicity. We find that NSCLC CSCs secrete significantly more extracellular vesicles (EV) than BCCs, and that this is RAB27B-dependent. Furthermore, CSC-derived EVs, but not BCC-derived EVs, induce spheroid growth, clonal expansion, and invasion in BCCs. Finally, RAB27B is required for CSC-derived EV-induced stemness in BCCs. Taken together, our results indicate that RAB27B is required for maintenance of a highly tumorigenic, cancer-initiating, invasive stem-like cell population in NSCLC and RAB27B is involved in propagating EV-mediated communication from NSCLC CSCs to BCCs. Our findings further suggest that inhibition of RAB27B-dependent EV secretion may be a potential therapeutic strategy for NSCLC.

Significance:

Expression of RAB27B in CSCs leads to elevated levels of EVs that mediate communication between CSCs and BCCs that maintains a stem-like phenotype in NSCLC cells.
The Atypical Red Eye: A Case of Scleritis with Peripheral Ulcerative Keratitis Secondary to Granulomatosis with Polyangiitis
Authors: Bonnet Louis Antoine , Lipsky Lior , Holmes Richard
Published: April 2023

This report presents a rare case of scleritis with peripheral ulcerative keratitis secondary to granulomatosis with polyangiitis (GPA). A 65-year-old Caucasian male presented to a regional ophthalmology service with an atypical red eye. His immune work-up demonstrated positive anti-neutrophil cytoplasmic IgG autoantibodies (ANCA) with anti-proteinase 3 antibody (PR3) elevation. Multi-system vasculitis was discovered including lung, liver, bladder, prostate, nasal and paranasal sinuses involvement. His ocular sequelae included significant peripheral corneal thinning requiring cyanoacrylate gluing, juxtalimbal conjunctival resection, and bandage lens placement. He was treated with systemic methylprednisolone and rituximab achieving remission with ongoing prednisone and methotrexate maintenance therapy. This case demonstrates the importance of recognizing ocular manifestations of GPA as a first presentation of systemic vasculitis.
Multicentric Castleman Disease and Concurrent Hematological Disorders: The Occurrence of Plasmacytoma and the Hypotheses Arising from Literature Review
Authors: Duminuco Andrea , Romano Alessandra , Sabattini Elena , Villari Loredana , Del Fabro Vittorio , Elia Federica , Palumbo Giuseppe A. , Di Raimondo Francesco , Conticello Concetta
Published: April 2023

The concomitant presence of Castleman disease (CD) with other hematological pathology is an event described in the literature with increasing frequency, able to modify the diagnostic and curative approach in such patients. Very few studies in the literature describe the association of CD with concomitant neoplastic diseases; the most frequent are Kaposi’s sarcomas (especially in HIV and human herpes virus-8-positive patients) and lymphoproliferative disorders, such as lymphomas. Instead, since the association with plasma cell diseases such as multiple myeloma and plasmacytoma is infrequent, there is a lack of literature. This manuscript aimed to revise the literature by describing a rare case of CD and plasmacytoma and attempting to explain the underlying triggering mechanisms.
Reconfigurable linear feedback shift register for wireless communication and coding
Authors: Devrari Aakanksha , Kumar Adesh
Published: April 2023

Linear feedback shift register (LFSR) is the basic building block of the communication system used in different coding, error detection and correction codes, such as gold, low-density parity check (LDPC), polar, and turbo codes. There are simple shift register-based n-bit counters with a few XOR gates that behave pseudo-randomly. The LFSR is used in chip hardware for high-speed operations, error control, and the generation of pseudo-random numbers. The hardware chip design and performance estimation of the LFSR is the problem for specific communication system. The motivation of the work is to generate the Gold code sequence by the integration of two LFSR. The article proposes the hardware chip design and simulation of two 5-bit LFSR modules used for the gold sequence generator applicable for the communication systems. The novelty of the work is that the design is scalable and can be extended based on the requirements of the systems which is synthesized and experimentally verified on the Zynq-7000 field programmable gate array (FPGA) board. The concept of this design is programmable and can be extended to n-bit based on the applications. The work is supported, and formulated using very high speed integrated circuit hardware description language (VHDL) programming in Xilinx ISE 14.7 software.
Adaptive filters based efficient EEG classification for steady state visually evoked potential based BCI system
Authors: Krishnappa Manjula , Anandaraju Madaveeranahally Boregowda
Published: April 2023

Brain-computer interfaces (BCIs) system is a link to generate a communication between disable people and physical devices. Thus, steady state visually evoked potential (SSVEP) is analysed to improve performance efficiency of BCIs system using multi-class classification process. Thus, an adaptive filtering-based component analysis (AFCA) method is adopted to examine SSVEP from multiple-channel electroencephalography (EEG) signals for BCIs system efficiency enhancement. Further, flickering at varied frequencies is used in a visual stimulation process to examine user intentions and brain responses. A detailed solution for optimization problem and efficient feature extraction is also presented. Here, a large SSVEP dataset is utilized which contains 256 channel EEG data. Experimental results are evaluated in terms of classification accuracy and information transfer rate to measure efficiency of proposed SSVEP extraction method against varied traditional SSVEP-based BCIs. The average information transfer rate (ITR) results are 308.23 bits per minute and classification accuracy is 93.48% using proposed AFCA method. Thus, proposed AFCA method shows decent performance in comparison with state-of-art-SSVEP extraction methods.
MOLECULAR DOCKING ANALYSIS OF SELECTED CURCUMA XANTHORRHIZA CONSTITUENTS AS POTENTIAL ANTICANCER DRUG
Authors: Endang Zainal Hasan Akhmad , Artika I Made , Suryani  , Luthfi Ramadhani Dhani
Published: April 2023

Stress conditions will trigger the histone hyperacetylation process due to histone acetyltransferase p300/CBP (HAT PCAF) constantly transfers acetyl groups from acetyl-CoA to conserved lysine residues on histone proteins to form ε-N-acetyllysine. This can be a cause of cancer. The purpose of this study was to investigate the potential mechanisms and inhibition of PCAF HAT by chemical components of C. xanthorrhiza namely, curcumin, demethoxycurcumin, bisdemethoxycurcumin, and xanthorrizhol using in silico, the molecular docking method.  Results showed that the components of C. xanthorrhiza as ligands have the capability to inhibit the binding of acetyl-CoA to histone. These results can be used to predict the inhibitory mechanisms exhibited by C. xanthorrhiza components, as competitive and noncompetitive substances. We hypothesize that C. xanthorrhiza components resemble a substrate, leading to prevention of the natural substrate (histone) to bind to the enzyme, and hence block the product formation. The smallest free Gibs energy was exhibited by curcumin on chain B and by bismethoxycurcumin on chain A, with values of -8.8 and -8.4 Kcal/mol, respectively.
Simulação in situ de parada cardíaca em fibrilação ventricular para o treinamento de profissionais de enfermagem
Authors: Barroso Michelle Sandrin dos Santos , Teixeira Alessandra Batista , Pazin-Filho Antonio , Miranda Carlos Henrique
Published: April 2023

Objetivo: Relatar a experiência e a percepção dos profissionais de enfermagem com a utilização de simulação in situ não anunciada de parada cardiorrespiratória (PCR) em ritmo de fibrilação ventricular no ambiente intra-hospitalar. Métodos: Manequim (Laerdal®) de alta fidelidade foi colocado no leito de isolamento de uma Unidade Coronariana que dispõe de central de monitoramento, sem o conhecimento dos profissionais de enfermagem que estavam assumindo o plantão. Um técnico de enfermagem do turno anterior de trabalho passou o caso como um paciente fictício recém-admitido com infarto agudo do miocárdio. Após a passagem do plantão, modificou-se o ritmo cardíaco do manequim de ritmo sinusal para fibrilação ventricular. Registrou-se o tempo (em minutos e segundos) desde a modificação do ritmo até algum profissional da enfermagem desencadear uma ação efetiva relacionada ao fato. Após o profissional perceber que se tratava de um manequim, ele foi orientado a desencadear as intervenções adequadas como se fosse um paciente real. Após o final da simulação, um questionário para avaliação da percepção desses profissionais em relação à atividade foi aplicado. Resultado: Quinze profissionais participaram da simulação in situ. O tempo para reação foi 28 segundos no turno diurno, dois minutos e seis segundos no turno vespertino e quatro minutos e três segundos no período noturno. Todos profissionais (100%) reconheceram a importância do treinamento, todos (100%) acharam que este treinamento aumenta a segurança do profissional e do paciente, a maioria (90%) achou que pode melhorar a comunicação entre a equipe, e todos (100%) acharam que atividades como esta deveriam ser repetidas. Conclusão: A simulação in situ parece ser uma alternativa viável para o treinamento dos profissionais de enfermagem no atendimento inicial da PCR em um hospital de emergência brasileiro. Esta atividade foi avaliada positivamente pelos participantes.
Incidental tomographic findings in patients with a Confirmed Diagnosis of COVID-19: An Observational Study
Authors: Santos Caique Rodrigues dos , Chaves Raphael Zimmermmann , Hollanda Erick Sabbagh de , Amaral Lígia Menezes do , Abreu Marcus  da Matta , Ferreira Juliana Dias Nascimento
Published: April 2023

Objective: Describe incidental tomographic findings in the sample, correlating them with risk factors for chest diseases and sociodemographic data. Methods: This is a retrospective and observational study covering 162 patients admitted to the COVID sector of the HU/UFJF, from April 1, 2020, to July 7, 2021, with a confirmed laboratory diagnosis of COVID-19. The variables were described in absolute and relative frequencies. The comparison of the correlation between the outcome variable (the tomographic findings) for independent samples was performed using Pearson's chi-square test (without correction) or Fisher's test when relevant. Results: Of the 162 patients, 15.4% had a solitary pulmonary nodule; 14.8% had multiple pulmonary nodules; 1.8%, lung mass; 3.1%, mediastinal mass, and 9.3% had mediastinal adenomegaly. Findings such as excavations, pleural effusion, emphysema, PTE, pneumothorax, chronic interstitial disease, cavitation, aneurysms, and significant atheromatosis, classified in this study in the “Other” category showed impressive results, with an overall prevalence of 81.5%. This study demonstrated that 34% of patients had two or more types of incidental CT findings and that 88.3% of patients had at least some type of incidental CT finding. Conclusion: The pandemic of SARS-CoV-2 infections has brought a series of challenges and lessons learned to healthcare teams around the world. The massive implementation of highly sensitive diagnostic methods, such as chest tomography, ends up bringing an additional challenge, which is to deal with incidental findings, making good clinical reasoning necessary to avoid unnecessary investigations and not leave without diagnosis and treatment of diseases in early and asymptomatic stages.
Construção da imagem joseense: influência no espaço urbano, na arte e na composição da identidade de São José dos Campos/SP
Authors: Rosado Ana Maria da Cunha
Published: April 2023

Ao estudar a história de São José dos Campos podemos encontrar pontos divergentes entre a história popularmente conhecida, e reforçada em seus elementos cívicos, e a história documental. O presente trabalho visa apresentar, brevemente, a história de São José dos Campos; remontando ao seu passado enquanto aldeamento indígena, sua fase senatorial e seu período de crescimento industrial. Os objetivos gerais são: demonstrar como se molda a imagem que o município hoje carrega, predominante em seu espaço urbano, e quais os impactos na identidade local. Usando como métodos a análise de documentos, pesquisas sobre as temáticas abordadas, visitas de campos para coleta de dados da paisagem urbana joseense, uso de algumas obras de artistas locais e relatos de moradores em redes sociais de livre acesso para composição do olhar popular.
Velhos dilemas para novas políticas de moradia: Luta pelo direito à moradia na metrópole capitalista dependente
Authors: Ritter João Pedro Noronha
Published: April 2023

Este artigo tem por objetivo analisar os dilemas que atravessam as políticas urbanas voltadas à ampliação do direito à moradia. A discussão visa contribuir ao escopo teórico de cariz crítico aos processos de urbanização e produção de moradia na sociedade capitalista dependente. Para tanto, mais do que realizar um grande balanço dos programas habitacionais dos governos anteriores, privilegiamos retornar às bases explicativas das múltiplas determinações que formam o problema da moradia, enfatizando que as relações capitalistas e suas contradições regulam a dinâmica da produção e distribuição de moradia para além da mediação do Estado. Algumas das respostas para os velhos dilemas na consolidação do direito à moradia pode ser encontrado nas ocupações de movimentos sem teto no centro urbano de Salvador.
Hospitalidade no empreendedorismo feminino: atuação das mulheres anfitriãs em povoados goianos do caminho de cora coralina
Authors: Passos Lisandra Lavoura Carvalho , Freitas Carla Conti de
Published: April 2023

O Caminho de Cora Coralina foi inaugurado em abril de 2018 como uma rota turística para pedestres e ciclistas, que passa por 8 cidades, predominantemente históricas e 8 povoados, em um trajeto de 300 km entre Corumbá de Goiás e a cidade de Goiás, na região central do Brasil. Trata-se de uma rota turística recente, que homenageia a poetisa e contista goiana Cora Coralina. A busca de material sobre esse caminho e em incursões pontuais a alguns de seus povoados, notou-se o papel da mulher enquanto anfitriã e empreendedora no acolhimento aos viajantes. Diante disso, desenvolveu-se uma pesquisa exploratória e qualitativa com base no método etnográfico, tendo como objetivo investigar a hospitalidade exercida pelas mulheres anfitriãs de empreendimentos de hospedagem nos povoados de Caxambu, Radiolândia e Palestina. O trabalho de campo aconteceu em julho de 2021, com a coleta de dados mediante observação participante, e entrevista semiaberta com três anfitriãs. Os resultados obtidos revelaram que houve adequação de um espaço doméstico na casa da anfitriã em uma fazenda em Caxambu; construção de um espaço privado na forma de uma pousada em Radiolândia com recursos de financiamento por meio de uma linha de crédito da Goiás Turismo; e a transformação de um espaço público cedido para a adequação de um “hostel” em Palestina. Notou-se que cada anfitriã ofertou práticas diferenciadas de hospitalidade, reconfigurando o cotidiano dessas localidades e as relações com seus hóspedes. As anfitriãs comungam com práticas da recepção ao viajante, do acolhimento, da circularidade da dádiva, da solidariedade, preconizando o respeito, a tolerância, a convivência e o bem-estar do hóspede ciclista ou caminhante. As narrativas dessas mulheres trazem uma fala individual, particular, singular, uma experiência de cada uma delas, com traços culturais da região
Uma perspectiva do desenvolvimento territorial rural em vista à evolução da cadeia avícola no município de São José do Vale do Rio Preto – RJ
Authors: Virginio Juliana da Silva , Borges Marcio Silva
Published: April 2023

O Município de São José do Vale do Rio Preto é considerado o maior produtor hortifrutigranjeiro do estado do Rio de Janeiro, estando localizado a 130km da capital, e composto por aproximadamente 22 mil habitantes. A cidade apresenta grande relevância para o contexto territorial da região serrana fluminense, onde na década de 50 foi reconhecido como maior produtor avícola da América do Sul. A partir de uma investigação bibliográfica e documental, este artigo buscou identificar as bases históricas de sua cadeia produtiva, haja vista que ao longo dos séculos o atual Município recebeu distintas nomenclaturas, sendo alvo de disputa territorial dada sua localização estratégica. O trabalho discutiu o que é desenvolvimento rural e concluiu para a necessidade de políticas públicas específicas para garantir a viabilidade da avicultura na região.
Clinical Outcome After Left Ventricular Thrombus Resolution: Who Needs Long‐Term or Lifetime Use of Anticoagulants?
Authors: Zhou Xiao‐Dong , Chen Qin‐Fen , Katsouras Christos S. , Nijjar Prabhjot S. , Zheng Kenneth I. , Zhu Haihui , Gong Mengge , Lin Qingcheng , Jin Youkai , Huang Weijian , Shan Peiren
Published: April 2023

Background

Patients with left ventricular thrombus (LVT) resolution can have LVT recurrence and risk for thromboembolism. However, these outcomes after LVT resolution are not well known. We aimed to assess the prevalence, risk factors, and clinical outcomes for LVT recurrence in patients with LVT resolution to inform follow‐up and treatment.

Methods and Results

Patients with LVT resolution were identified retrospectively from a large echocardiography database between January 2009 and May 2022. Participants had echocardiograms at 3 time points, including baseline at LVT diagnosis, at LVT resolution, and a follow‐up for identification of LVT recurrence. The cumulative LVT recurrence rate was estimated by the Kaplan–Meier method, and predictors of LVT recurrence were evaluated using Cox regression analysis. Among 115 patients with LVT resolution, 28 (24.3%) had LVT recurrence at a median follow‐up of 1.2 (0.5–2.8) years. LV aneurysm (hazard ratio [HR], 2.59 [95% CI, 1.20–5.58],
P
=0.015) and anticoagulant use (HR, 0.12 [95% CI, 0.04–0.41],
P
=0.001) were predictors of LVT recurrence on multivariable analysis. Patients with an LV aneurysm who did not receive any anticoagulation demonstrated an LVT recurrence rate of 69.5%, whereas those without an LV aneurysm who received anticoagulation had a recurrence rate of 0%. Patients with LVT recurrence had a higher incidence of an embolic event (10.7% versus 1.1%,
P
=0.016).

Conclusions

LVT recurrence after LVT resolution is common, especially in those with an LV aneurysm, and is associated with a higher embolic risk. Continued anticoagulation is protective against LVT recurrence, although bleeding risk needs to be considered. These findings can inform follow‐up and treatment of patients with documented LVT resolution.
A discussion on the relationship of Capila omeia (Leech, 1894) and C. pseudomeia Fan & Wang, 2004 syn. n. (Hesperiidae, Pyrginae)
Authors: XUE GUOXI , LI MENG , RAO ZHI , QIAO YUEMEI
Published: April 2023

Intraspecific variability of Capila omeia (Leech, 1894) from Chongqing is investigated based upon the comparison of the 658 bp COI gene sequences and adult morphology. The morphological characters used for distinguishing C. pseudomeia Fan & Wang, 2004 from C. omeia are proved to be in the range of individual variation of the latter. Therefore, C. pseudomeia syn. n. is treated as a junior subjective synonym of C. omeia. Adults and genitalia of both sexes of C. omeia are illustrated. A distribution map of the species is provided as well.