bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figures S1-S8 from Gain-of-Function p53 Mutation Acts as a Genetic Switch for TGFβ Signaling–Induced Epithelial-to-Mesenchymal Transition in Intestinal Tumors
Authors: Wang Dong , Nakayama Mizuho , Hong Chang Pyo , Oshima Hiroko , Oshima Masanobu
Published: January 2024

Supplementary Figures S1-S8
Supplementary Table S8 from Leveraging Tissue-Specific Enhancer–Target Gene Regulatory Networks Identifies Enhancer Somatic Mutations That Functionally Impact Lung Cancer
Authors: Hariprakash Judith Mary , Salviato Elisa , La Mastra Federica , Sebestyén Endre , Tagliaferri Ilario , Silva Raquel Sofia , Lucini Federica , Farina Lorenzo , Cinquanta Mario , Rancati Ilaria , Riboni Mirko , Minardi Simone Paolo , Roz Luca , Gorini Francesca , Lanzuolo Chiara , Casola Stefano , Ferrari Francesco
Published: January 2024

Mutation frequency analysis at enhancer cores
Table S6 from Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate
Authors: Zhao Jinge , Xu Nanwei , Zhu Sha , Nie Ling , Zhang Mengni , Zheng Linmao , Cai Diming , Sun Xiaomeng , Chen Junru , Dai Jindong , Ni Yuchao , Wang Zhipeng , Zhang Xingming , Liang Jiayu , Chen Yuntian , Hu Xu , Pan Xiuyi , Yin Xiaoxue , Liu Haoyang , Zhao Fengnian , Zhang Bei , Chen Hao , Miao Jiashun , Qin Cong , Zhao Xiaochen , Yao Jin , Liu Zhenhua , Liao Banghua , Wei Qiang , Li Xiang , Liu Jiyan , Gao Allen C. , Huang Haojie , Shen Pengfei , Chen Ni , Zeng Hao , Sun Guangxi
Published: January 2024

Table S6
Supplementary Table S5 from Leveraging Tissue-Specific Enhancer–Target Gene Regulatory Networks Identifies Enhancer Somatic Mutations That Functionally Impact Lung Cancer
Authors: Hariprakash Judith Mary , Salviato Elisa , La Mastra Federica , Sebestyén Endre , Tagliaferri Ilario , Silva Raquel Sofia , Lucini Federica , Farina Lorenzo , Cinquanta Mario , Rancati Ilaria , Riboni Mirko , Minardi Simone Paolo , Roz Luca , Gorini Francesca , Lanzuolo Chiara , Casola Stefano , Ferrari Francesco
Published: January 2024

Genomic co-ordinates of lung specific enhancers (hg19)
Table S4 from Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate
Authors: Zhao Jinge , Xu Nanwei , Zhu Sha , Nie Ling , Zhang Mengni , Zheng Linmao , Cai Diming , Sun Xiaomeng , Chen Junru , Dai Jindong , Ni Yuchao , Wang Zhipeng , Zhang Xingming , Liang Jiayu , Chen Yuntian , Hu Xu , Pan Xiuyi , Yin Xiaoxue , Liu Haoyang , Zhao Fengnian , Zhang Bei , Chen Hao , Miao Jiashun , Qin Cong , Zhao Xiaochen , Yao Jin , Liu Zhenhua , Liao Banghua , Wei Qiang , Li Xiang , Liu Jiyan , Gao Allen C. , Huang Haojie , Shen Pengfei , Chen Ni , Zeng Hao , Sun Guangxi
Published: January 2024

Table S4
Table S1-revised from Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate
Authors: Zhao Jinge , Xu Nanwei , Zhu Sha , Nie Ling , Zhang Mengni , Zheng Linmao , Cai Diming , Sun Xiaomeng , Chen Junru , Dai Jindong , Ni Yuchao , Wang Zhipeng , Zhang Xingming , Liang Jiayu , Chen Yuntian , Hu Xu , Pan Xiuyi , Yin Xiaoxue , Liu Haoyang , Zhao Fengnian , Zhang Bei , Chen Hao , Miao Jiashun , Qin Cong , Zhao Xiaochen , Yao Jin , Liu Zhenhua , Liao Banghua , Wei Qiang , Li Xiang , Liu Jiyan , Gao Allen C. , Huang Haojie , Shen Pengfei , Chen Ni , Zeng Hao , Sun Guangxi
Published: January 2024

Table S1-revised
Supplementary Figures S1-S7 from Leveraging Tissue-Specific Enhancer–Target Gene Regulatory Networks Identifies Enhancer Somatic Mutations That Functionally Impact Lung Cancer
Authors: Hariprakash Judith Mary , Salviato Elisa , La Mastra Federica , Sebestyén Endre , Tagliaferri Ilario , Silva Raquel Sofia , Lucini Federica , Farina Lorenzo , Cinquanta Mario , Rancati Ilaria , Riboni Mirko , Minardi Simone Paolo , Roz Luca , Gorini Francesca , Lanzuolo Chiara , Casola Stefano , Ferrari Francesco
Published: January 2024

Supplementary Figures S1-S7
Table of reagents from Progressively Enhancing Stemness of Adoptively Transferred T Cells with PI3Kδ Blockade Improves Metabolism and Antitumor Immunity
Authors: Rangel Rivera Guillermo O. , Dwyer Connor J. , Knochelmann Hannah M. , Smith Aubrey S. , Aksoy Bülent Arman , Cole Anna C. , Wyatt Megan M. , Kumaresan Soundharya , Thaxton Jessica E. , Lesinski Gregory B. , Paulos Chrystal M.
Published: January 2024

Table with reagents
Supplementary Tables from Targeting Transcriptional Regulation with a CDK9 Inhibitor Suppresses Growth of Endocrine- and Palbociclib-Resistant ER+ Breast Cancers
Authors: Soosainathan Arany , Iravani Marjan , El-Botty Rania , Alexander John , Sourd Laura , Morisset Ludivine , Painsec Pierre , Orha Rebecca , Nikitorowicz-Buniak Joanna , Pancholi Sunil , Haider Syed , Dowsett Mitch , Marangoni Elisabetta , Martin Lesley-Ann , Isacke Clare M.
Published: January 2024

Supplementary Tables S1, S2, S3, S4, S5a, S5b, S5c, S5d, S6
Supplementary Figure S5 from Targeting Transcriptional Regulation with a CDK9 Inhibitor Suppresses Growth of Endocrine- and Palbociclib-Resistant ER+ Breast Cancers
Authors: Soosainathan Arany , Iravani Marjan , El-Botty Rania , Alexander John , Sourd Laura , Morisset Ludivine , Painsec Pierre , Orha Rebecca , Nikitorowicz-Buniak Joanna , Pancholi Sunil , Haider Syed , Dowsett Mitch , Marangoni Elisabetta , Martin Lesley-Ann , Isacke Clare M.
Published: January 2024

Supplementary Figure S5
Figure 3 from Targeting Transcriptional Regulation with a CDK9 Inhibitor Suppresses Growth of Endocrine- and Palbociclib-Resistant ER+ Breast Cancers
Authors: Soosainathan Arany , Iravani Marjan , El-Botty Rania , Alexander John , Sourd Laura , Morisset Ludivine , Painsec Pierre , Orha Rebecca , Nikitorowicz-Buniak Joanna , Pancholi Sunil , Haider Syed , Dowsett Mitch , Marangoni Elisabetta , Martin Lesley-Ann , Isacke Clare M.
Published: January 2024

CDK9 inhibitors impair cell viability in 2D and 3D culture. A and B, A total of 4,000 to 8,000 cells were seeded in 96-well tissue culture plates and treated at day 1 and 3 with the CDK9 inhibitors NVP-2 (A) or AZD4573 (B) at the indicated concentrations. Cell viability was assessed using CellTiter-Glo (day 7). Mean values ± SEM. Data represent percentage NVP-2/AZD4573–treated viable cells compared with vehicle control. n = 4 technical replicates; n = 1 biological replicate. C, A total of 2,500 cells were seeded in 96-well ultra-low attachment round-bottomed plates. The resulting spheroids were treated with AZD4573 at days 3 and 6. Cell viability was assessed on day 10 (endpoint). Graphs showing percentage of viable AZD4573-treated cells compared with vehicle control. n = 1 biological replicate; n = 4 technical replicates. Mean values ± SEM. Representative images and quantification of spheroid area at endpoint following treatment with 0 nmol/L, 3 nmol/L, or 30 nmol/L AZD4573 are shown. Scale bar, 1 mm. D, A total of 3,000 to 5,000 MCF7 LTEDWT, LTEDY537C, or LTEDPalboR cells were seeded in 2D 96-well tissue culture plates and treated with escalating doses of palbociclib and AZD4573 at day 1 and 3. Cell viability was assessed using CellTiter-Glo on day 7. Data representing percentage of viable cells compared with vehicle control. n = 1 biological replicate; n = 3 technical replicates; mean values ± SEM. Top, individual drug responses. Bottom, synergy plots. The Bliss synergy score references the most synergistic area of the plot.
Figure 1 from Targeting Transcriptional Regulation with a CDK9 Inhibitor Suppresses Growth of Endocrine- and Palbociclib-Resistant ER+ Breast Cancers
Authors: Soosainathan Arany , Iravani Marjan , El-Botty Rania , Alexander John , Sourd Laura , Morisset Ludivine , Painsec Pierre , Orha Rebecca , Nikitorowicz-Buniak Joanna , Pancholi Sunil , Haider Syed , Dowsett Mitch , Marangoni Elisabetta , Martin Lesley-Ann , Isacke Clare M.
Published: January 2024

Two-dimensional kinase inhibitor screens in LTED breast cancer cell line models. A, Schematic representation of the study. B, 2D screens at 1 μmol/L final drug concentration (see Materials and Methods). Sigma plots represent robust Z-score rank order, with drugs achieving a robust Z-score ≤ −2 in red. Compounds causing ≥ 50% reduction in cell viability were classified as hits. Representative drugs of the following classes are highlighted. Green, targeting ER signaling; blue, targeting CDKs; gray, targeting PI3K–AKT–mTOR pathway. C, 2D screens at 100 nmol/L final drug concentration. Compounds causing ≥ 50% reduction in cell viability were classified as hits. Venn diagram illustrating the number of hits in common to three or four of the cell line groups is indicated. Full list is provided in Supplementary Fig. S2. (A, Created with BioRender.com.)
Data from Cell State of Origin Impacts Development of Distinct Endometriosis-Related Ovarian Carcinoma Histotypes
Authors: Beddows Ian , Fan Huihui , Heinze Karolin , Johnson Benjamin K. , Leonova Anna , Senz Janine , Djirackor Svetlana , Cho Kathleen R. , Pearce Celeste Leigh , Huntsman David G. , Anglesio Michael S. , Shen Hui
Published: January 2024

Abstract
Clear cell ovarian carcinoma (CCOC) and endometrioid ovarian carcinoma (ENOC) are ovarian carcinoma histotypes, which are both thought to arise from ectopic endometrial (or endometrial-like) cells through an endometriosis intermediate. How the same cell type of origin gives rise to two morphologically and biologically different histotypes has been perplexing, particularly given that recurrent genetic mutations are common to both and present in nonmalignant precursors. We used RNA transcription analysis to show that the expression profiles of CCOC and ENOC resemble those of normal endometrium at secretory and proliferative phases of the menstrual cycle, respectively. DNA methylation at the promoter of the estrogen receptor (ER) gene (ESR1) was enriched in CCOC, which could potentially lock the cells in the secretory state. Compared with normal secretory-type endometrium, CCOC was further defined by increased expression of cysteine and glutathione synthesis pathway genes and downregulation of the iron antiporter, suggesting iron addiction and highlighting ferroptosis as a potential therapeutic target. Overall, these findings suggest that while CCOC and ENOC arise from the same cell type, these histotypes likely originate from different cell states. This “cell state of origin” model may help to explain the presence of histologic and molecular cancer subtypes arising in other organs.
Significance:
Two cancer histotypes diverge from a common cell of origin epigenetically locked in different cell states, highlighting the importance of considering cell state to better understand the cell of origin of cancer.
Data from Targeting Transcriptional Regulation with a CDK9 Inhibitor Suppresses Growth of Endocrine- and Palbociclib-Resistant ER+ Breast Cancers
Authors: Soosainathan Arany , Iravani Marjan , El-Botty Rania , Alexander John , Sourd Laura , Morisset Ludivine , Painsec Pierre , Orha Rebecca , Nikitorowicz-Buniak Joanna , Pancholi Sunil , Haider Syed , Dowsett Mitch , Marangoni Elisabetta , Martin Lesley-Ann , Isacke Clare M.
Published: January 2024

Abstract
The combination of endocrine therapy and CDK4/6 inhibitors such as palbociclib is an effective and well-tolerated treatment for estrogen receptor–positive (ER+) breast cancer, yet many patients relapse with therapy-resistant disease. Determining the mechanisms underlying endocrine therapy resistance is limited by the lack of ability to fully recapitulate inter- and intratumor heterogeneity in vitro and of availability of tumor samples from women with disease progression or relapse. In this study, multiple cell line models of resistant disease were used for both two-dimensional (2D)– and three-dimensional (3D)–based inhibitor screening. The screens confirmed the previously reported role of pro-proliferative pathways, such as PI3K–AKT–mTOR, in endocrine therapy resistance and additionally identified the transcription-associated cyclin-dependent kinase CDK9 as a common hit in ER+ cell lines and patient-derived organoids modeling endocrine therapy–resistant disease in both the palbociclib-sensitive and palbociclib-resistant settings. The CDK9 inhibitor, AZD4573, currently in clinical trials for hematologic malignancies, acted synergistically with palbociclib in these ER+in vitro 2D and 3D models. In addition, in two independent endocrine- and palbociclib-resistance patient-derived xenografts, treatment with AZD4573 in combination with palbociclib and fulvestrant resulted in tumor regression. Tumor transcriptional profiling identified a set of transcriptional and cell-cycle regulators differentially downregulated only in combination-treated tumors. Together, these findings identify a clinically tractable combination strategy for overcoming resistance to endocrine therapy and CDK4/6 inhibitors in breast cancer and provide insight into the potential mechanism of drug efficacy in targeting treatment-resistant disease.
Significance:
Targeting transcription-associated CDK9 synergizes with CDK4/6 inhibitor to drive tumor regression in multiple models of endocrine- and palbociclib-resistant ER+ breast cancer, which could address the challenge of overcoming resistance in patients.
Figure S5 from Phase I Dose-Escalation Trial of MIW815 (ADU-S100), an Intratumoral STING Agonist, in Patients with Advanced/Metastatic Solid Tumors or Lymphomas
Authors: Meric-Bernstam Funda , Sweis Randy F. , Hodi F. Stephen , Messersmith Wells A. , Andtbacka Robert H.I. , Ingham Matthew , Lewis Nancy , Chen Xinhui , Pelletier Marc , Chen Xueying , Wu Jincheng , Dubensky Thomas W. , McWhirter Sarah M. , Müller Thomas , Nair Nitya , Luke Jason J.
Published: January 2024

T-cell clonal expansion at Cycle 1, Day 8 and Cycle 2, Day 1 relative to pre-treatment, by patient
GATA-3–dependent Gene Transcription is Impaired upon HDAC Inhibition
Authors: Geng Xiangrong , Wang Chenguang , Abdelrahman Suhaib , Perera Thilini , Saed Badeia , Hu Ying S. , Wolfe Ashley , Reneau John , Murga-Zamalloa Carlos , Wilcox Ryan A.
Published: January 2024

Purpose:

Many peripheral and cutaneous T-cell lymphoma (CTCL) subtypes are poorly responsive to conventional chemotherapeutic agents and associated with dismal outcomes. The zinc finger transcription factor GATA-3 and the transcriptional program it instigates are oncogenic and highly expressed in various T-cell neoplasms. Posttranslational acetylation regulates GATA-3 DNA binding and target gene expression. Given the widespread use of histone deacetylase inhibitors (HDACi) in relapsed/refractory CTCL, we sought to examine the extent to which these agents attenuate the transcriptional landscape in these lymphomas.

Experimental Design:

Integrated GATA-3 chromatin immunoprecipitation sequencing and RNA sequencing analyses were performed in complementary cell line models and primary CTCL specimens treated with clinically available HDACi.

Results:

We observed that exposure to clinically available HDACi led to significant transcriptional reprogramming and increased GATA-3 acetylation. HDACi-dependent GATA-3 acetylation significantly impaired both its ability to bind DNA and transcriptionally regulate its target genes, thus leading to significant transcriptional reprogramming in HDACi-treated CTCL.

Conclusions:

Beyond shedding new light on the mechanism of action associated with HDACi in CTCL, these findings have significant implications for their use, both as single agents and in combination with other novel agents, in GATA-3–driven lymphoproliferative neoplasms.
Phase I Trial of First-line Bintrafusp Alfa in Patients with Locally Advanced or Persistent/Recurrent/Metastatic Cervical Cancer
Authors: Oaknin Ana , Ghamande Sharad A. , Kasamatsu Yuka , Gil-Martin Marta , Grau-Bejar Juan Francisco , Garcia-Duran Carmen , Sato Masashi , Siddiqui Abdul , Chaudhary Surendra Pal , Vugmeyster Yulia , Hasegawa Kosei
Published: January 2024

Purpose:

Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGFβ receptor II (a TGFβ “trap”) fused to a human IgG1 mAb blocking programmed death-ligand 1 (PD-L1), was evaluated as treatment in patients with locally advanced or persistent, recurrent, or metastatic (P/R/M) cervical cancer.

Patients and Methods:

In this multicenter, open-label, phase Ib trial (NCT04551950), patients with P/R/M cervical cancer received bintrafusp alfa 2,400 mg once every 3 weeks plus cisplatin or carboplatin plus paclitaxel with (Cohort 1A; n = 8) or without (Cohort 1B; n = 9) bevacizumab; patients with locally advanced cervical cancer received bintrafusp alfa 2,400 mg every 3 weeks plus cisplatin plus radiation, followed by bintrafusp alfa monotherapy maintenance (Cohort 2; n = 8). The primary endpoint was safety; secondary endpoints included efficacy (including objective response rate) and pharmacokinetics.

Results:

At the data cutoff of April 27, 2022, patients in Cohorts 1A, 1B, and 2 had received bintrafusp alfa for a median duration of 37.9, 31.1, and 16.7 weeks, respectively. Two dose-limiting toxicities (grade 4 amylase elevation and grade 3 menorrhagia) unrelated to bintrafusp alfa were observed in Cohort 1B and none in other cohorts. Most treatment-emergent adverse events of special interest were grades 1–2 in severity, most commonly anemia (62.5%–77.8%) and bleeding events (62.5%–77.8%). Objective response rate was 75.0% [95% confidence interval (CI), 34.9–96.8], 44.4% (95% CI, 13.7–78.8), and 62.5% (95% CI, 24.5–91.5) in Cohorts 1A, 1B, and 2, respectively.

Conclusions:

Bintrafusp alfa had manageable safety and demonstrated clinical activity, further supporting the investigation of TGFβ/PD-L1 inhibition in human papillomavirus–associated cancers, including cervical cancer.
Phase II Study of Durvalumab Immediately after Completion of Chemoradiotherapy in Unresectable Stage III Non–small Cell Lung Cancer: TORG1937 (DATE Study)
Authors: Nakamichi Shinji , Kubota Kaoru , Misumi Toshihiro , Kondo Tetsuro , Murakami Shuji , Shiraishi Yoshimasa , Imai Hisao , Harada Daijiro , Isobe Kazutoshi , Itani Hidetoshi , Takata Saori , Wakui Hiroshi , Misumi Yuki , Ikeda Satoshi , Asao Tetsuhiko , Furuya Naoki , Hosokawa Shinobu , Kobayashi Yumiko , Takiguchi Yuichi , Okamoto Hiroaki
Published: January 2024

Purpose:

Concurrent chemoradiotherapy (CCRT) followed by durvalumab consolidation for up to 12 months is the standard of care for patients with unresectable stage III non–small cell lung cancer (NSCLC). However, exactly when to initiate durvalumab therapy after chemoradiation completion remains unknown. We evaluated the efficacy and safety of durvalumab, administered immediately after CCRT completion, for patients with unresectable stage III NSCLC.

Patients and Methods:

This study was a prospective, single-arm, open-label phase II clinical trial. Patients without disease progression after definitive CCRT (two cycles of platinum-based doublet chemotherapy with 60 Gy/30 Fr radiotherapy) received durvalumab (every 2 weeks for up to 12 months) from the next day (up to 5 days) after the final radiation dose. The primary endpoint was the 1-year progression-free survival (PFS) from registration before the start of CCRT.

Results:

From January 2020 to August 2020, 47 of 50 enrolled patients were evaluable for treatment efficacy and safety. The 1-year PFS from registration was 75.0% [60% confidence interval (CI), 69.0–80.0 and 95% CI, 59.4–85.3]. The objective response rate throughout the study treatment and median PFS from registration were 78.7% and 14.2 months (95% CI, 13.4 to not reached), respectively. Grade 3/4 pneumonitis and febrile neutropenia were each 4.3%.

Conclusions:

Our study met the primary endpoint. The incidence of pneumonitis was similar to that of a Japanese subset in the PACIFIC study. Our data support the efficacy and safety of durvalumab administered immediately after the completion of CCRT for patients with unresectable stage III NSCLC.
Figure S3 from Metabolic Hallmarks for Purine Nucleotide Biosynthesis in Small Cell Lung Carcinoma
Authors: Tabata Sho , Umemura Shigeki , Narita Miyu , Udagawa Hibiki , Ishikawa Takamasa , Tsuboi Masahiro , Goto Koichi , Ishii Genichiro , Tsuchihara Katsuya , Ochiai Atsushi , Kobayashi Susumu S. , Soga Tomoyoshi , Makinoshima Hideki
Published: January 2024

Screening of HPRT1-knockout clones
Supplementary Figure 4 from SP4 Facilitates Esophageal Squamous Cell Carcinoma Progression by Activating PHF14 Transcription and Wnt/Β-Catenin Signaling
Authors: Wei Li , Deng Chaowei , Zhang Bo , Wang Guanghui , Meng Yan , Qin Hao
Published: January 2024

Co-knockdown of both SP4 and PHF14 also results in more decreased mRNA and protein levels of the Wnt3a and β-Catenin.
Supplementary Figure 3 from SP4 Facilitates Esophageal Squamous Cell Carcinoma Progression by Activating PHF14 Transcription and Wnt/Β-Catenin Signaling
Authors: Wei Li , Deng Chaowei , Zhang Bo , Wang Guanghui , Meng Yan , Qin Hao
Published: January 2024

A major effect of SP4-PHF14 on Wnt3a and β-Catenin (CTNNB1).
Supplementary Table 4 from Whole-Exome Sequencing Identifies Mutation Profile and Mutation Signature-Based Clustering Associated with Prognosis in Appendiceal Pseudomyxoma Peritonei
Authors: Lin Yu-Lin , Zhu Jun-Qi , Ma Rui-Qing , Meng Wei , Wang Zi-Yue , Li Xin-Bao , Ma Ru , Wu He-Liang , Xu Hong-Bin , Gao Ying , Li Yan
Published: January 2024

The sensitivity and specificity of the binary logistic model
Supplementary Table 7 from Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma
Authors: Enokido Takayoshi , Horie Masafumi , Yoshino Seiko , Suzuki Hiroshi I. , Matsuki Rei , Brunnström Hans , Micke Patrick , Nagase Takahide , Saito Akira , Miyashita Naoya
Published: January 2024

Genes upregulated by ASCL1 knockdown in VMRC-LCD cells.
Supplementary Figure 6 from Whole-Exome Sequencing Identifies Mutation Profile and Mutation Signature-Based Clustering Associated with Prognosis in Appendiceal Pseudomyxoma Peritonei
Authors: Lin Yu-Lin , Zhu Jun-Qi , Ma Rui-Qing , Meng Wei , Wang Zi-Yue , Li Xin-Bao , Ma Ru , Wu He-Liang , Xu Hong-Bin , Gao Ying , Li Yan
Published: January 2024

Comparison between S1 – S10 signatures in our study and 30 signatures in COSMIC database.
Supplementary Table 4 from Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma
Authors: Enokido Takayoshi , Horie Masafumi , Yoshino Seiko , Suzuki Hiroshi I. , Matsuki Rei , Brunnström Hans , Micke Patrick , Nagase Takahide , Saito Akira , Miyashita Naoya
Published: January 2024

Super-enhancer (SE) or typical-enhancer (TE)-associated miRNAs in lung adenocarcinoma cell lines.
Supplementary Figure 4 from Whole-Exome Sequencing Identifies Mutation Profile and Mutation Signature-Based Clustering Associated with Prognosis in Appendiceal Pseudomyxoma Peritonei
Authors: Lin Yu-Lin , Zhu Jun-Qi , Ma Rui-Qing , Meng Wei , Wang Zi-Yue , Li Xin-Bao , Ma Ru , Wu He-Liang , Xu Hong-Bin , Gao Ying , Li Yan
Published: January 2024

Driver genes derived from OncodriveCLUST and OncodirveFML.
A: Five driver genes determined by OncodriveCLUST; B: Four driver genes determined by OncodirveFML.
Supplementary Figure Legends from Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma
Authors: Enokido Takayoshi , Horie Masafumi , Yoshino Seiko , Suzuki Hiroshi I. , Matsuki Rei , Brunnström Hans , Micke Patrick , Nagase Takahide , Saito Akira , Miyashita Naoya
Published: January 2024

Supplementary Figure legends 1-7
Supplementary Figure 6 from Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma
Authors: Enokido Takayoshi , Horie Masafumi , Yoshino Seiko , Suzuki Hiroshi I. , Matsuki Rei , Brunnström Hans , Micke Patrick , Nagase Takahide , Saito Akira , Miyashita Naoya
Published: January 2024

mmunohistochemistry for ASCL1 and ZFP36L1
Supplementary Table 4 from RNF185 Control of COL3A1 Expression Limits Prostate Cancer Migration and Metastatic Potential
Authors: Van Espen Benjamin , Oo Htoo Zarni , Collins Colin , Fazli Ladan , Molinolo Alfredo , Yip Kevin , Murad Rabi , Gleave Martin , Ronai Ze'ev A.
Published: January 2024

List of genes driving the enrichment score for HALLMARL_EMT found to be enriched at the protein level in MPC3.shRNF185 compared to MPC3.pLKO in LC-MS/MS analysis.
Supplementary Table 1 from RNF185 Control of COL3A1 Expression Limits Prostate Cancer Migration and Metastatic Potential
Authors: Van Espen Benjamin , Oo Htoo Zarni , Collins Colin , Fazli Ladan , Molinolo Alfredo , Yip Kevin , Murad Rabi , Gleave Martin , Ronai Ze'ev A.
Published: January 2024

List of genes driving the enrichment score for HALLMARL_EMT in TCGA PRAD patients with low RNF185 expression (bottom quartile) compared to patients with high RNF185 expression (top quartile) in GSEA analysis.
Supplementary Figure 5 from RNF185 Control of COL3A1 Expression Limits Prostate Cancer Migration and Metastatic Potential
Authors: Van Espen Benjamin , Oo Htoo Zarni , Collins Colin , Fazli Ladan , Molinolo Alfredo , Yip Kevin , Murad Rabi , Gleave Martin , Ronai Ze'ev A.
Published: January 2024

S5. RT-qPCR validation of RNF185 and COL3A1 in stable RNF185 and COL3A1 KD MPC3 cells.
Supplementary Figure 1 from RNF185 Control of COL3A1 Expression Limits Prostate Cancer Migration and Metastatic Potential
Authors: Van Espen Benjamin , Oo Htoo Zarni , Collins Colin , Fazli Ladan , Molinolo Alfredo , Yip Kevin , Murad Rabi , Gleave Martin , Ronai Ze'ev A.
Published: January 2024

S1. RNF185 expression correlates with PCa patient outcome.
Legend to Supplementary Data from RNF185 Control of COL3A1 Expression Limits Prostate Cancer Migration and Metastatic Potential
Authors: Van Espen Benjamin , Oo Htoo Zarni , Collins Colin , Fazli Ladan , Molinolo Alfredo , Yip Kevin , Murad Rabi , Gleave Martin , Ronai Ze'ev A.
Published: January 2024

Legend to Supp Figures and Tables
Data from SP4 Facilitates Esophageal Squamous Cell Carcinoma Progression by Activating PHF14 Transcription and Wnt/Β-Catenin Signaling
Authors: Wei Li , Deng Chaowei , Zhang Bo , Wang Guanghui , Meng Yan , Qin Hao
Published: January 2024

Abstract
Specificity protein 4 transcription factor (SP4), a member of the Sp/Krüppel-like family (KLF), could bind to GT and GC box promoters, and plays an essential role in transcriptional activating. Despite SP4 having been detected to be highly expressed in a variety of human tumors, its biological effect and underlying molecular mechanism in esophageal squamous cell carcinoma (ESCC) remains unclear. Our research discovered that high SP4 expression is detected in primary ESCC specimens and cell lines and is strongly associated with the ESCC tumor grade and poor prognosis. In vitro, knockdown of SP4 suppressed cell proliferation and cell-cycle progression and promoted apoptosis, whereas overexpression of SP4 did the opposite. In vivo, inhibiting SP4 expression in ESCC cells suppresses tumor growth. Subsequently, we demonstrated that SP4 acts as the transcriptional upstream of PHF14, which binds to PHF14 promoter region, thus promoting PHF14 transcription. PHF14 was also significantly expressed in patient tissues and various ESCC cell lines and its expression promoted cell proliferation and inhibited apoptosis. Moreover, knockdown of SP4 inhibited the Wnt/β-catenin signaling pathway, whereas overexpression of PHF14 eliminated the effects of SP4 knockdown in ESCC cells. These results demonstrate that SP4 activates the Wnt/β-catenin signaling pathway by driving PHF14 transcription, thereby promoting ESCC progression, which indicates that SP4 might act as a prospective prognostic indicator or therapeutic target for patients with ESCC.
Implications:
This study identified SP4/PH14 axis as a new mechanism to promote the progression of ESCC, which may serve as a novel therapeutic target for patients with ESCC.
Data from RNF185 Control of COL3A1 Expression Limits Prostate Cancer Migration and Metastatic Potential
Authors: Van Espen Benjamin , Oo Htoo Zarni , Collins Colin , Fazli Ladan , Molinolo Alfredo , Yip Kevin , Murad Rabi , Gleave Martin , Ronai Ze'ev A.
Published: January 2024

Abstract
RNF185 is a RING finger domain-containing ubiquitin ligase implicated in ER-associated degradation. Prostate tumor patient data analysis revealed a negative correlation between RNF185 expression and prostate cancer progression and metastasis. Likewise, several prostate cancer cell lines exhibited greater migration and invasion capabilities in culture upon RNF185 depletion. Subcutaneous inoculation of mouse prostate cancer MPC3 cells stably expressing short hairpin RNA against RNF185 into mice resulted in larger tumors and more frequent lung metastases. RNA-sequencing and Ingenuity Pathway Analysis identified wound-healing and cellular movement among the most significant pathways upregulated in RNF185-depleted lines, compared with control prostate cancer cells. Gene Set Enrichment Analyses performed in samples from patients harboring low RNF185 expression and in RNF185-depleted lines confirmed the deregulation of genes implicated in epithelial-to-mesenchymal transition. Among those, COL3A1 was identified as the primary mediator of RNF185’s ability to impact migration phenotypes. Correspondingly, enhanced migration and metastasis of RNF185 knockdown (KD) prostate cancer cells were attenuated upon co-inhibition of COL3A1. Our results identify RNF185 as a gatekeeper of prostate cancer metastasis, partly via its control of COL3A1 availability.
Implications:
RNF185 is identified as an important regulator of prostate cancer migration and metastasis, in part due to its regulation of COL3A1. Both RNF185 and COL3A1 may serve as novel markers for prostate tumors.
Data from Impact of Rare and Multiple Concurrent Gene Fusions on Diagnostic DNA Methylation Classifier in Brain Tumors
Authors: Galbraith Kristyn , Serrano Jonathan , Shen Guomiao , Tran Ivy , Slocum Cheyanne C. , Ketchum Courtney , Abdullaev Zied , Turakulov Rust , Bale Tejus , Ladanyi Marc , Sukhadia Purvil , Zaidinski Michael , Mullaney Kerry , DiNapoli Sara , Liechty Benjamin L. , Barbaro Marissa , Allen Jeffrey C. , Gardner Sharon L. , Wisoff Jeffrey , Harter David , Hidalgo Eveline Teresa , Golfinos John G. , Orringer Daniel A. , Aldape Kenneth , Benhamida Jamal , Wrzeszczynski Kazimierz O. , Jour George , Snuderl Matija
Published: January 2024

Abstract
DNA methylation is an essential molecular assay for central nervous system (CNS) tumor diagnostics. While some fusions define specific brain tumors, others occur across many different diagnoses. We performed a retrospective analysis of 219 primary CNS tumors with whole genome DNA methylation and RNA next-generation sequencing. DNA methylation profiling results were compared with RNAseq detected gene fusions. We detected 105 rare fusions involving 31 driver genes, including 23 fusions previously not implicated in brain tumors. In addition, we identified 6 multi-fusion tumors. Rare fusions and multi-fusion events can impact the diagnostic accuracy of DNA methylation by decreasing confidence in the result, such as BRAF, RAF, or FGFR1 fusions, or result in a complete mismatch, such as NTRK, EWSR1, FGFR, and ALK fusions.
Implications:
DNA methylation signatures need to be interpreted in the context of pathology and discordant results warrant testing for novel and rare gene fusions.
Manifesto Calls upon UK to Cut 20,000 Cancer Deaths a Year
Authors: Rose Suzanne
Published: January 2024

Britain’s Cancer Research UK (CRUK) published a five-point plan to help boost research funding, reduce cancer mortality rates, prevent thousands of cancers, and improve patient survival. The charity says if the next UK government implements its recommendations, about 20,000 fewer people would die of cancer every year by 2040.
Figure S7 from Inhibition of PRL2 Upregulates PTEN and Attenuates Tumor Growth in Tp53-deficient Sarcoma and Lymphoma Mouse Models
Authors: Nguele Meke Frederick , Bai Yunpeng , Ruiz-Avila Diego , Carlock Colin , Ayub Jinan , Miao Jinmin , Hu Yanyang , Li Qinglin , Zhang Zhong-Yin
Published: January 2024

Loss of PRL1 or PRL3 does not improve tumor-free survival of Tp53-null mice
FIGURE 6 from Inhibition of PRL2 Upregulates PTEN and Attenuates Tumor Growth in Tp53-deficient Sarcoma and Lymphoma Mouse Models
Authors: Nguele Meke Frederick , Bai Yunpeng , Ruiz-Avila Diego , Carlock Colin , Ayub Jinan , Miao Jinmin , Hu Yanyang , Li Qinglin , Zhang Zhong-Yin
Published: January 2024

Pharmacologic inhibition of PRL2 in tamoxifen-inducible Tp53−/− mouse inhibits tumor proliferation through PTEN augmentation to hinder tumor growth. A, Experimental design for the treatment of inducible Tp53−/− with compound 43. B, Dot plot for mass of thymic lymphoma derived from inducible Tp53−/− treated with or without compound 43, data are shown as mean ± SEM, Tp53−/− + vehicle n = 20, Tp53−/− + compound 43 = 13. C, Representative Western blot analysis from thymic lymphomas derived from inducible Tp53−/− mice treated with vehicle or compound 43 to assess the levels PCNA, c-PARP, c-caspase 3, PTEN, and the activation of Akt and ERK1/2. D, Dot plot for quantification of C. E, Representative western blot from thymic lymphomas derived from inducible Tp53−/− mice treated with vehicle or compound 43 to assess the activation of Akt targets. F, Dot plot for quantification of E. Data are shown as mean ± SEM for samples obtained 12 weeks after tamoxifen treatment, Tp53−/− + vehicle n = 7–15, Tp53−/− + compound 43 n = 7–11; *, P < 0.05; **, P < 0.01.
FIGURE 2 from Inhibition of PRL2 Upregulates PTEN and Attenuates Tumor Growth in Tp53-deficient Sarcoma and Lymphoma Mouse Models
Authors: Nguele Meke Frederick , Bai Yunpeng , Ruiz-Avila Diego , Carlock Colin , Ayub Jinan , Miao Jinmin , Hu Yanyang , Li Qinglin , Zhang Zhong-Yin
Published: January 2024

Prl2 deletion enhances survival in constitutive Tp53 deficiency mouse models. A, Mating strategy for the generation of constitutive Tp53-deficient mice with or without constitutive Prl2 deletion. B, PCR genotyping to identify different genotypes in the study. Kaplan–Meier survival plot for overall survival in constitutive Tp53-H (C) and Tp53-KO (D) backgrounds with or without constitutive Prl2 deletion. E, Bar graphs representing percent tumor incidence in Tp53-H background with or without Prl2 deletion. P values are indicated in figures and a P value <0.05 is considered statistically significant. WT n = 44, Prl2-KO n = 31, Tp53-H n = 118, Tp53-H; Prl2-KO n = 108.
Analysis of Burnout Prevalence among German Physicians Working in a Palliative Care Setting: A Survey of the AIO Quality of Life Working Group
Authors: Herbrand Lena , Hofmann Wolf-Karsten , Hofheinz Ralf-Dieter , Büttner Sylvia , Haag Georg Martin , Gencer Deniz
Published: January 2024

Introduction: Palliative care physicians (Pcps) face special challenges caring for terminally ill patients. We conducted this study to evaluate the burnout (bo) prevalence among pcps and sought to identify risk as well as protective factors as a basis for the development of preventive measures. Methods: Participants (Pcs) were invited via e-mail to complete an online survey between May and June 2022. Besides the Oldenburg Burnout Inventory assessing the bo dimensions of exhaustion (exh) and disengagement (dis), sociodemographic data were collected. Results: The study found that 58% (cut-off mean value [M] ≥2.18) or more specifically, 38% (cut-off M ≥2.5) of the pcs showed increased scores in the exh subscale as a key dimension of bo. All dimensions were correlated with the level of medical and palliative care training, with higher scores for physicians in training. Furthermore, pcs without preventive measures like employee appraisals at work were more likely to be considered exhausted, disengaged, or burned out. The discrepancy between high exh and low dis scores shows that the polled pcps, despite feeling exh, nevertheless considered their work meaningful. Conclusion: Bo prevalence among pcps exceeds that of the general population and other specialties, whereas inexperienced pcps might be at high risk of shifting from exh to bo and could therefore benefit from tailored support. Further preventive measures including individual and organizational aspects are necessary to prevent bo and promote health among medical staff, thereby preserving quality of patient care. Elementary preventive measures such as employee appraisals can have a protective effect against bo.
Ensino de argumentação e leitura crítica da mídia: uma proposta para o desenvolvimento da capacidade argumentativa
Authors: Marques Silva Alexandre
Published: January 2024

Os atuais estudos sobre ensino de argumentação vêm apontando para as dificuldades encontradas por professores no desenvolvimento da capacidade argumentativa de seus estudantes. Sendo assim, apresentamos uma proposta de ação já realizada com estudantes da 3ª série do Ensino Médio, com o objetivo de que essa experiência possa, de algum modo, contribuir para o fazer docente, indicando as potencialidades emergentes da combinação entre os procedimentos metodológicos da leitura crítica da mídia e o ensino de argumentação, a fim de torná-lo mais significativo e capaz de suplantar a perspectiva instrumental, voltada quase que exclusivamente ao treinamento para avaliações externas. Nossas análises pautam-se em dois anúncios das sandálias Havaianas e, além do recurso aos documentos oficiais, estão respaldadas nos trabalhos de Azevedo (2022, 2016 e 2019), Piris (2021), Baccega (2013 e 2009), Freire (2001 [1959] e 1983), Marcuschi (2007), Wilson (2013), Kellner e Share (2008). Ao final, as análises permitiram confirmar que nossa proposta resultou, junto ao grupo em que o trabalho fora realizado, a potencialização de sua capacidade argumentativa, a qual foi atestada em suas produções orais e escritas.
KDM6A Demethylase Regulates Renal Sodium Excretion and Blood Pressure
Authors: Han Xiaobin , Akinseye Leah , Sun Zhongjie
Published: January 2024

BACKGROUND:

KDM6A (Lysine-Specific Demethylase 6A) is a specific demethylase for histone 3 lysine (K) 27 trimethylation (H3K27me3). The purpose of this study is to investigate whether KDM6A in renal tubule cells plays a role in the regulation of kidney function and blood pressure.

METHODS:

We first crossed

Ksp-Cre
+/−
and KDM6A
flox/flox

mice for generating inducible kidney-specific deletion of
KDM6A
gene.

RESULTS:

Notably, conditional knockout of
KDM6A
gene in renal tubule cells (KDM6A-cKO) increased H3K27me3 levels which leads to a decrease in Na excretion and elevation of blood pressure. Further analysis showed that the expression of NKCC2 (Na-K-2Cl cotransporter 2) and NCC (Na-Cl cotransporters) was upregulated which contributes to impaired Na excretion in KDM6A-cKO mice. The expression of AQP2 (aquaporin 2) was also increased in KDM6A-cKO mice, which may facilitate water reabsorption in KDM6A-cKO mice. The expression of Klotho was downregulated while expression of aging markers including p53, p21, and p16 was upregulated in kidneys of KDM6A-cKO mice, indicating that deletion of KDM6A in the renal tubule cells promotes kidney aging. Interestingly, KDM6A-cKO mice developed salt-sensitive hypertension which can be rescued by treatment with Klotho. KDM6A deficiency induced salt-sensitive hypertension likely through downregulation of the Klotho/ERK (extracellular signal-regulated kinase) signaling and upregulation of the WNK (with-no-lysine kinase) signaling.

CONCLUSIONS:

This study provides the first evidence that KDM6A plays an essential role in maintaining normal tubular function and blood pressure. Renal tubule cell specific KDM6A deficiency causes hypertension due to increased H3K27me3 levels and the resultant downregulation of
Klotho
gene expression which disrupts the Klotho/ERK/NCC/NKCC2 signaling.
Conscious Experience of Stimulus Presence and Absence Is Actively Encoded by Neurons in the Crow Brain
Authors: Wagener Lysann , Nieder Andreas
Published: January 2024

The emergence of consciousness from brain activity constitutes one of the great riddles in biology. It is commonly assumed that only the conscious perception of the presence of a stimulus elicits neuronal activation to signify a “neural correlate of consciousness,” whereas the subjective experience of the absence of a stimulus is associated with a neuronal resting state. Here, we demonstrate that the two subjective states “stimulus present” and “stimulus absent” are represented by two specialized neuron populations in crows, corvid birds. We recorded single-neuron activity from the nidopallium caudolaterale of crows trained to report the presence or absence of images presented near the visual threshold. Because of the task design, neuronal activity tracking the conscious “present” versus “absent” percept was dissociated from that involved in planning a motor response. Distinct neuron populations signaled the subjective percepts of “present” and “absent” by increases in activation. The response selectivity of these two neuron populations was similar in strength and time course. This suggests a balanced code for subjective “presence” versus “absence” experiences, which might be beneficial when both conscious states need to be maintained active in the service of goal-directed behavior.
Young male and female scientists: A quantitative exploratory study of the changing demographics of the global scientific workforce
Authors: Kwiek Marek , Szymula Lukasz
Published: January 2024

In this study, the global scientific workforce is explored through large-scale, generational, cross-sectional, and longitudinal approaches. We examine 4.3 million nonoccasional scientists from 38 OECD countries publishing in 1990–2021. Our interest is in the changing distribution of young male and female scientists over time across 16 science, technology, engineering, mathematics, medicine (STEMM) disciplines. We unpack the details of the changing scientific workforce using age groups. Some disciplines are already numerically dominated by women, and the change is fast in some and slow in others. In one-third of disciplines, there are already more youngest female than male scientists. Across all disciplines combined, the majority of women are young women. And more than half of female scientists (55.02%) are located in medicine. The usefulness of global bibliometric data sources in analyzing the scientific workforce along gender, age, discipline, and time is tested. Traditional aggregated data about scientists in general hide a nuanced picture of the changing gender dynamics within and across disciplines and age groups. The limitations of bibliometric data sets are explored, and global studies are compared with national-level studies. The methodological choices and their implications are shown, and new opportunities for how to study scientists globally are discussed.
Black Feminist Theory as an Approach to Therapeutic Growth and Healing
Authors: Cabell Courtney D.
Published: January 2024

Black American women are uniquely positioned to experience systemic racism and oppression due to their intersecting identities of gender, race, sexuality, and class. Black feminist therapy (BFT) provides empirically proven strategies to promote the psychological health and well-being of Black women and foster their empowerment, liberation, and radical healing. Through an examination of the principles and concepts of feminist theory, Black feminist theory, and BFT, a model of growth and healing is presented. A case example is provided as evidence of the process and effectiveness of BFT in working with Black women.
CHIVA for dummies
Authors: Ricci Stefano
Published: January 2024

Background

Sparing the Great Saphenous Vein capital for possible arterial substitution and recurrence decrease may be an alternative to current ablation options for Varicose Veins treatment. Conservative surgery of varicose veins (CHIVA) was suggested in 1988 by Franceschi, by limited veins interruptions in strategic points. However, the method did not diffuse due to the need for high Duplex expertise to determine the procedure in every single patient.

Method

Evaluation of the literature regarding saphenous sparing, with special reference to CHIVA.

Result

It has been realized that basic Ultrasound expertise is sufficient for performing GSV conservation. Most of the time, only a few parameters are needed: a junction competence assessment and a re-entry perforator position.

Conclusion

For achieving the goal of saphenous conservative treatment, a limited phlebectomy and possible Junction interruption (crossotomy) may be a simplified solution.
Social Media Posts About Distal Radius Fracture: A Cross-Sectional Analysis of Patient and Provider Perspectives
Authors: Reynolds Christopher A. , Mehta Manish P. , Erkkila Ian P. , Clements Sean , Baskin Robert P. , Shah Chirag M.
Published: January 2024

Background:

Social media offers a popular, unfiltered source of patient and provider perspectives on health care. This study investigated the characteristics of social media posts referencing distal radius fracture (DRF).

Methods:

Content was queried from Instagram from February 06, 2019, to December 08, 2021, using the hashtags “#distalradiusfracture” and “#wristfracture.” The 1500 most-liked posts were analyzed. Poster demographics including age, gender, region, laterality, and treatment type and post characteristics including post type, number, content, timing relative to treatment, tone, and satisfaction were examined. Variables were compared using χ2 tests. Univariate, multivariate, and stepwise regression were performed.

Results:

The most popular post formats were single photo (44.5%), multiple photos (32.3%), and single video (13.9%). Patients (40.3%) were the most common poster followed by surgeons (33.4%). Men (48.7%) and women (51.3) were evenly represented. Of the total posts, 87.7% depicted the post-treatment phase of care; 54.8% of posts depicted operative management, while 26.6% depicted non-operative management; and 73.7% of posts were positive in tone, 18.7% neutral, and 7.6% negative. Univariate analysis demonstrated that posters who were patients, friends/family of patients, female, and posts with >100 “likes” were more likely to share negative tones. Multivariate and stepwise regression were consistent with the above.

Conclusion:

Most posts regarding DRF originate from patients, are post-treatment, and are positive. Negative tone is associated with posts from patients, family/friends of patients, female posters, and posts with >100 likes. With this information, surgeons will be better prepared to address patient concerns, manage expectations, and actively participate in social media themselves.