bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Effect of Clonal Hematopoiesis Mutations and Canakinumab Treatment on Incidence of Solid Tumors in the CANTOS Randomized Clinical Trial
Authors: Woo Janghee , Zhai Tingting , Yang Fang , Xu Huilei , Healey Margaret L. , Yates Denise P. , Beste Michael T. , Steensma David P.
Published: September 2024

Abstract
Clonal hematopoiesis (CH) is more common in older persons and has been associated with an increased risk of hematological cancers and cardiovascular diseases. The most common CH mutations occur in the DNMT3A and TET2 genes and result in increased proinflammatory signaling. The Canakinumab Anti-inflammatory Thrombosis Outcome Study (NCT01327846) evaluated the neutralizing anti-IL1β antibody canakinumab in 10,061 randomized patients with a history of myocardial infarction and persistent inflammation; DNA samples were available from 3,923 patients for targeted genomic sequencing. We examined the incidence of non-hematological malignancy by treatment assignment and CH mutations and estimated the cumulative incidence of malignancy events during trial follow-up. Patients with TET2 mutations treated with canakinumab had the lowest incidence of non-hematological malignancy across cancer types. The cumulative incidence of at least one reported malignancy was lower for patients with TET2 mutations treated with canakinumab versus those treated with placebo. These findings support a potential role for canakinumab in cancer prevention and provide evidence of IL1β blockade cooperating with CH mutations to modify the disease course.

Prevention Relevance: We reveal that administering canakinumab is associated with a decrease in non-hematological malignancies among patients with clonal hematopoiesis (CH) mutations. These findings underscore canakinumab’s potential in preventing cancer and provide proof of IL1β blockade collaborating with CH mutations to enhance its clinical benefits.

See related Spotlight, p. 399
Supplementary Table S1 from CHD2 Regulates Neuron–Glioma Interactions in Pediatric Glioma
Authors: Zhang Xu , Duan Shoufu , Apostolou Panagiota E. , Wu Xiaoping , Watanabe Jun , Gallitto Matthew , Barron Tara , Taylor Kathryn R. , Woo Pamelyn J. , Hua Xu , Zhou Hui , Wei Hong-Jian , McQuillan Nicholas , Kang Kyung-Don , Friedman Gregory K. , Canoll Peter D. , Chang Kenneth , Wu Cheng-Chia , Hashizume Rintaro , Vakoc Christopher R. , Monje Michelle , McKhann Guy M. , Gogos Joseph A. , Zhang Zhiguo
Published: September 2024

Analysis of CRISPR screens for hits in H3.1K27M DMG cells.
Figure S3 from MYC Induces Oncogenic Stress through RNA Decay and Ribonucleotide Catabolism in Breast Cancer
Authors: Meena Jitendra K. , Wang Jarey H. , Neill Nicholas J. , Keough Dianne , Putluri Nagireddy , Katsonis Panagiotis , Koire Amanda M. , Lee Hyemin , Bowling Elizabeth A. , Tyagi Siddhartha , Orellana Mayra , Dominguez-Vidaña Rocio , Li Heyuan , Eagle Kenneth , Danan Charles , Chung Hsiang-Ching , Yang Andrew D. , Wu William , Kurley Sarah J. , Ho Brian M. , Zoeller Joseph R. , Olson Calla M. , Meerbrey Kristen L. , Lichtarge Olivier , Sreekumar Arun , Dacso Clifford C. , Guddat Luke W. , Rejman Dominik , Hocková Dana , Janeba Zlatko , Simon Lukas M. , Lin Charles Y. , Pillon Monica C. , Westbrook Thomas F.
Published: September 2024

Figure S3 shows MYC-induced apoptosis and cell death in early and late timepoints, ectopic expression of BCL2 and its impact on MYC-induced RNA decay, gene expression changes upon DIS3L knockdown in MYC-hyperactivated conditions, and expression of exosome components upon MYC-induction.
Supplemental material and methods from D3S-001, a KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities
Authors: Zhang Jing , Lim Sun Min , Yu Mi Ra , Chen Cheng , Wang Jia , Wang Wenqian , Rui Haopeng , Lu Jingtao , Lu Shun , Mok Tony , Chen Zhi Jian , Cho Byoung Chul
Published: September 2024

addition information for material and methods
Supplemental Table S2 from D3S-001, a KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities
Authors: Zhang Jing , Lim Sun Min , Yu Mi Ra , Chen Cheng , Wang Jia , Wang Wenqian , Rui Haopeng , Lu Jingtao , Lu Shun , Mok Tony , Chen Zhi Jian , Cho Byoung Chul
Published: September 2024

Supplemental Table S2 summarizing plasma protein binding (PPB) characterization of D3S-001 across various species.
Supplemental Table S1 from D3S-001, a KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities
Authors: Zhang Jing , Lim Sun Min , Yu Mi Ra , Chen Cheng , Wang Jia , Wang Wenqian , Rui Haopeng , Lu Jingtao , Lu Shun , Mok Tony , Chen Zhi Jian , Cho Byoung Chul
Published: September 2024

Supplemental Table S1 summarizing the anti-proliferative potency of D3S-001, adagrasib and sotorasib.
Table S6 from A Next-Generation BRAF Inhibitor Overcomes Resistance to BRAF Inhibition in Patients with BRAF-Mutant Cancers Using Pharmacokinetics-Informed Dose Escalation
Authors: Yaeger Rona , McKean Meredith A. , Haq Rizwan , Beck J. Thaddeus , Taylor Matthew H. , Cohen Jonathan E. , Bowles Daniel W. , Gadgeel Shirish M. , Mihalcioiu Catalin , Papadopoulos Kyriakos P. , Diamond Eli L. , Sturtz Keren B. , Feng Gang , Drescher Stefanie K. , Reddy Micaela B. , Sengupta Bhaswati , Maity Arnab K. , Brown Suzy A. , Singh Anurag , Brown Eric N. , Baer Brian R. , Wong Jim , Mou Tung-Chung , Wu Wen-I , Kahn Dean R. , Gadal Sunyana , Rosen Neal , Gaudino John J. , Lee Patrice A. , Hartley Dylan P. , Rothenberg S. Michael
Published: September 2024

Table S6. Antibodies used for preclinical experiments
Supplementary Table 4 from Molecular Determinants of Sensitivity to Polatuzumab Vedotin in Diffuse Large B-Cell Lymphoma
Authors: Corcoran Sean R. , Phelan James D. , Choi Jaewoo , Shevchenko Galina , Fenner Rachel E. , Yu Xin , Scheich Sebastian , Hsiao Tony , Morris Vivian M. , Papachristou Evangelia K. , Kishore Kamal , D’Santos Clive S. , Ji Yanlong , Pittaluga Stefania , Wright George W. , Urlaub Henning , Pan Kuan-Ting , Oellerich Thomas , Muppidi Jagan , Hodson Daniel J. , Staudt Louis M.
Published: September 2024

List of antibodies used
Supplementary Figure S7 from Molecular Determinants of Sensitivity to Polatuzumab Vedotin in Diffuse Large B-Cell Lymphoma
Authors: Corcoran Sean R. , Phelan James D. , Choi Jaewoo , Shevchenko Galina , Fenner Rachel E. , Yu Xin , Scheich Sebastian , Hsiao Tony , Morris Vivian M. , Papachristou Evangelia K. , Kishore Kamal , D’Santos Clive S. , Ji Yanlong , Pittaluga Stefania , Wright George W. , Urlaub Henning , Pan Kuan-Ting , Oellerich Thomas , Muppidi Jagan , Hodson Daniel J. , Staudt Louis M.
Published: September 2024

Sialidase treatment does not increase binding of other therapeutic antibodies
Supplementary Figure S13 from Molecular Determinants of Sensitivity to Polatuzumab Vedotin in Diffuse Large B-Cell Lymphoma
Authors: Corcoran Sean R. , Phelan James D. , Choi Jaewoo , Shevchenko Galina , Fenner Rachel E. , Yu Xin , Scheich Sebastian , Hsiao Tony , Morris Vivian M. , Papachristou Evangelia K. , Kishore Kamal , D’Santos Clive S. , Ji Yanlong , Pittaluga Stefania , Wright George W. , Urlaub Henning , Pan Kuan-Ting , Oellerich Thomas , Muppidi Jagan , Hodson Daniel J. , Staudt Louis M.
Published: September 2024

DLBCL mutations targeting the CD79B intracellular domain and their effect on surface BCR levels
Supplementary Figure S12 from Molecular Determinants of Sensitivity to Polatuzumab Vedotin in Diffuse Large B-Cell Lymphoma
Authors: Corcoran Sean R. , Phelan James D. , Choi Jaewoo , Shevchenko Galina , Fenner Rachel E. , Yu Xin , Scheich Sebastian , Hsiao Tony , Morris Vivian M. , Papachristou Evangelia K. , Kishore Kamal , D’Santos Clive S. , Ji Yanlong , Pittaluga Stefania , Wright George W. , Urlaub Henning , Pan Kuan-Ting , Oellerich Thomas , Muppidi Jagan , Hodson Daniel J. , Staudt Louis M.
Published: September 2024

Knockout of Klhl6 in mouse germinal center B cells increases surface BCR expression
Supplementary Table S3 from Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: a Report from the Children’s Oncology Group
Authors: Stieglitz Elliot , Lee Alex G. , Angus Steven P. , Davis Christopher , Barkauskas Donald A. , Hall David , Kogan Scott C. , Meyer Julia , Rhodes Steven D. , Tasian Sarah K. , Xuei Xiaoling , Shannon Kevin , Loh Mignon L. , Fox Elizabeth , Weigel Brenda J.
Published: September 2024

Data from Correlative Molecular Analysis at Various Time Points.
Supplementary Figure S1 from Molecular Determinants of Sensitivity to Polatuzumab Vedotin in Diffuse Large B-Cell Lymphoma
Authors: Corcoran Sean R. , Phelan James D. , Choi Jaewoo , Shevchenko Galina , Fenner Rachel E. , Yu Xin , Scheich Sebastian , Hsiao Tony , Morris Vivian M. , Papachristou Evangelia K. , Kishore Kamal , D’Santos Clive S. , Ji Yanlong , Pittaluga Stefania , Wright George W. , Urlaub Henning , Pan Kuan-Ting , Oellerich Thomas , Muppidi Jagan , Hodson Daniel J. , Staudt Louis M.
Published: September 2024

CD79B Segregation Score and Pola-V CSS for Golgi glycosylation genes shows specific sugar regulators of surface CD79B and Pola-V sensitization
Supplementary Table S4 from A Functional Survey of the Regulatory Landscape of Estrogen Receptor–Positive Breast Cancer Evolution
Authors: Barozzi Iros , Slaven Neil , Canale Eleonora , Lopes Rui , Amorim Monteiro Barbosa Inês , Bleu Melusine , Ivanoiu Diana , Pacini Claudia , Mensa’ Emanuela , Chambers Alfie , Bravaccini Sara , Ravaioli Sara , Győrffy Balázs , Dieci Maria Vittoria , Pruneri Giancarlo , Galli Giorgio Giacomo , Magnani Luca
Published: September 2024

Supplementary Table S4: SIDP results in T47D grown in full (red; +E2) media. S4.1-3: the tables follow the same structure of S3.1-3.
Supplementary Table S3 from Identification of Clonal Hematopoiesis Driver Mutations through In Silico Saturation Mutagenesis
Authors: Demajo Santiago , Ramis-Zaldivar Joan E. , Muiños Ferran , Grau Miguel L. , Andrianova Maria , López-Bigas Núria , González-Pérez Abel
Published: September 2024

BoostDM-CH driver mutations in UKB
Supplementary Table S2 from A Functional Survey of the Regulatory Landscape of Estrogen Receptor–Positive Breast Cancer Evolution
Authors: Barozzi Iros , Slaven Neil , Canale Eleonora , Lopes Rui , Amorim Monteiro Barbosa Inês , Bleu Melusine , Ivanoiu Diana , Pacini Claudia , Mensa’ Emanuela , Chambers Alfie , Bravaccini Sara , Ravaioli Sara , Győrffy Balázs , Dieci Maria Vittoria , Pruneri Giancarlo , Galli Giorgio Giacomo , Magnani Luca
Published: September 2024

Supplementary Table S2: sgRNAs sequences and metadata for the SIDP assays. S2.1: for each sgRNA targeting a region in the human genome, an identifier (using the corresponding hg38 genomic coordinates), the DNA sequence, the genomic coordinates (hg38) including the strand, along with efficiency and specificity scores as estimated by CRISPR-do, are provided. S2.2: for each positive control or non-targeting sgRNA, a custom identifier is shown along with the DNA sequence.
Supplementary Figure S7 from Identification of Clonal Hematopoiesis Driver Mutations through In Silico Saturation Mutagenesis
Authors: Demajo Santiago , Ramis-Zaldivar Joan E. , Muiños Ferran , Grau Miguel L. , Andrianova Maria , López-Bigas Núria , González-Pérez Abel
Published: September 2024

Comparison of boostDM-CH models and myeloid boostDM models of three CH driver genes
Supplementary Table S15 from A Functional Survey of the Regulatory Landscape of Estrogen Receptor–Positive Breast Cancer Evolution
Authors: Barozzi Iros , Slaven Neil , Canale Eleonora , Lopes Rui , Amorim Monteiro Barbosa Inês , Bleu Melusine , Ivanoiu Diana , Pacini Claudia , Mensa’ Emanuela , Chambers Alfie , Bravaccini Sara , Ravaioli Sara , Győrffy Balázs , Dieci Maria Vittoria , Pruneri Giancarlo , Galli Giorgio Giacomo , Magnani Luca
Published: September 2024

Supplementary Table S15: Results of the enrichment analyses looking for binding sites of specific TFs accumulating a greater or a smaller number of genetic variants than expected by change. For each TF and category (mutations significantly increasing or decreasing affinity) the observed and expected fraction of mutations overlapping the TF-bound sites are indicated, along with the difference between these two fractions, and the p-value of the corresponding χ2 test. Considering each TF and the mutations affecting the affinity to its target sites either positively or negatively (based on the p-value of the test) TFs could be either classified as showing significantly more or less mutations than expected, or not significant (ns).
Supplementary Figure S20 from Identification of Clonal Hematopoiesis Driver Mutations through In Silico Saturation Mutagenesis
Authors: Demajo Santiago , Ramis-Zaldivar Joan E. , Muiños Ferran , Grau Miguel L. , Andrianova Maria , López-Bigas Núria , González-Pérez Abel
Published: September 2024

Specific examples of new CH driver mutations identified by boostDM-CH
Supplementary Figure S18 from Identification of Clonal Hematopoiesis Driver Mutations through In Silico Saturation Mutagenesis
Authors: Demajo Santiago , Ramis-Zaldivar Joan E. , Muiños Ferran , Grau Miguel L. , Andrianova Maria , López-Bigas Núria , González-Pérez Abel
Published: September 2024

Association of CH driver mutations (according to boostDM-CH or expert-curated rule sets) and several phenotypes in UKB
Supplementary Figure S4 from A Functional Survey of the Regulatory Landscape of Estrogen Receptor–Positive Breast Cancer Evolution
Authors: Barozzi Iros , Slaven Neil , Canale Eleonora , Lopes Rui , Amorim Monteiro Barbosa Inês , Bleu Melusine , Ivanoiu Diana , Pacini Claudia , Mensa’ Emanuela , Chambers Alfie , Bravaccini Sara , Ravaioli Sara , Győrffy Balázs , Dieci Maria Vittoria , Pruneri Giancarlo , Galli Giorgio Giacomo , Magnani Luca
Published: September 2024

Supplementary Figure 4. Estrogen deprivation in MCF7 cells introduce stochastic selective pressure in long-term CRISPRi screens.
Supplementary Figure S12 from Identification of Clonal Hematopoiesis Driver Mutations through In Silico Saturation Mutagenesis
Authors: Demajo Santiago , Ramis-Zaldivar Joan E. , Muiños Ferran , Grau Miguel L. , Andrianova Maria , López-Bigas Núria , González-Pérez Abel
Published: September 2024

Association of CH mutations with causal factors in UKB
Supplementary Figure S12 from A Functional Survey of the Regulatory Landscape of Estrogen Receptor–Positive Breast Cancer Evolution
Authors: Barozzi Iros , Slaven Neil , Canale Eleonora , Lopes Rui , Amorim Monteiro Barbosa Inês , Bleu Melusine , Ivanoiu Diana , Pacini Claudia , Mensa’ Emanuela , Chambers Alfie , Bravaccini Sara , Ravaioli Sara , Győrffy Balázs , Dieci Maria Vittoria , Pruneri Giancarlo , Galli Giorgio Giacomo , Magnani Luca
Published: September 2024

Supplementary Figure 12. Validation of DF and IF SIDP hits.
Supplementary Figure S1 from A Functional Survey of the Regulatory Landscape of Estrogen Receptor–Positive Breast Cancer Evolution
Authors: Barozzi Iros , Slaven Neil , Canale Eleonora , Lopes Rui , Amorim Monteiro Barbosa Inês , Bleu Melusine , Ivanoiu Diana , Pacini Claudia , Mensa’ Emanuela , Chambers Alfie , Bravaccini Sara , Ravaioli Sara , Győrffy Balázs , Dieci Maria Vittoria , Pruneri Giancarlo , Galli Giorgio Giacomo , Magnani Luca
Published: September 2024

Supplementary Figure S1. SIDP identifies Cis Regulatory regions in MCF7 with high reproducibility.
Data from Preexisting Skin-Resident CD8 and γδ T-cell Circuits Mediate Immune Response in Merkel Cell Carcinoma and Predict Immunotherapy Efficacy
Authors: Reinstein Zachary Z. , Zhang Yue , Ospina Oscar E. , Nichols Matt D. , Chu Victoria A. , Pulido Alvaro de Mingo , Prieto Karol , Nguyen Jonathan V. , Yin Rui , Moran Segura Carlos , Usman Ahmed , Sell Brittney , Ng Spencer , de la Iglesia Janis V. , Chandra Sunandana , Sosman Jeffrey A. , Cho Raymond J. , Cheng Jeffrey B. , Ivanova Ellie , Koralov Sergei B. , Slebos Robbert J.C. , Chung Christine H. , Khushalani Nikhil I. , Messina Jane L. , Sarnaik Amod A. , Zager Jonathan S. , Sondak Vernon K. , Vaske Charles , Kim Sungjune , Brohl Andrew S. , Mi Xinlei , Pierce Brian G. , Wang Xuefeng , Fridley Brooke L. , Tsai Kenneth Y. , Choi Jaehyuk
Published: September 2024

Abstract
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a ∼50% response rate to immune checkpoint blockade (ICB) therapy. To identify predictive biomarkers, we integrated bulk and single-cell RNA sequencing (RNA-seq) with spatial transcriptomics from a cohort of 186 samples from 116 patients, including bulk RNA-seq from 14 matched pairs pre- and post-ICB. In nonresponders, tumors show evidence of increased tumor proliferation, neuronal stem cell markers, and IL1. Responders have increased type I/II interferons and preexisting tissue resident (Trm) CD8 or Vδ1 γδ T cells that functionally converge with overlapping antigen-specific transcriptional programs and clonal expansion of public T-cell receptors. Spatial transcriptomics demonstrated colocalization of T cells with B and dendritic cells, which supply chemokines and costimulation. Lastly, ICB significantly increased clonal expansion or recruitment of Trm and Vδ1 cells in tumors specifically in responders, underscoring their therapeutic importance. These data identify potential clinically actionable biomarkers and therapeutic targets for MCC.

Significance: MCC serves as a model of ICB response. We utilized the largest-to-date, multimodal MCC dataset (n = 116 patients) to uncover unique tumor-intrinsic properties and immune circuits that predict response. We identified CD8 Trm and Vδ1 T cells as clinically actionable mediators of ICB response in major histocompatibility complex–high and –low MCCs, respectively.
Table 1 from Poor Prognosis among Radiation-Associated Bladder Cancer Is Defined by Clinicogenomic Features
Authors: Wijetunga N. Ari , Gessner Kathryn H. , Kanchi Krishna , Moore Jay A. , Fleischmann Zoe , Jin Dexter X. , Frampton Garrett M. , Sturdivant Michael , Repka Michael , Sud Shivani , Corcoran David L. , Galsky Matthew D. , Milowsky Matthew I. , Wobker Sara E. , Kim William Y. , Rose Tracy L. , Damrauer Jeffrey S.
Published: September 2024

Summary of clinical variables for the control (CTRL) and radiation therapy (RT) cohorts.
Figure 2 from Poor Prognosis among Radiation-Associated Bladder Cancer Is Defined by Clinicogenomic Features
Authors: Wijetunga N. Ari , Gessner Kathryn H. , Kanchi Krishna , Moore Jay A. , Fleischmann Zoe , Jin Dexter X. , Frampton Garrett M. , Sturdivant Michael , Repka Michael , Sud Shivani , Corcoran David L. , Galsky Matthew D. , Milowsky Matthew I. , Wobker Sara E. , Kim William Y. , Rose Tracy L. , Damrauer Jeffrey S.
Published: September 2024

Mutational characterization of the CTRL and RT cohorts. BAM files corresponding to the FoundationOne sequencing assay were back converted to FASTQ format and aligned to GRCh38. A, The number of alterations per sample was calculated and plotted by variant type (insertions, SNVs, silent, intronic, missense, nonsense, and deletions). Pairwise comparisons between CTRL (gold), RT–short latency (dark blue), and RT–long latency (light blue) tumors were made using the Wilcoxon rank-sum test, with P values listed above their corresponding comparison. B, Histogram of VAF (alternate read count/total read depth) for CTRL (gold), RT–short latency (dark blue), and RT–long latency (light blue) tumors, variants are bin by a frequency of 0.01 (1%). Dashed line represents a VAF of 0.05 (5%). Inset boxplots represent alterations per sample either above or below the 5% VAF threshold and grouped by latency. Pairwise comparisons between CTRL (gold), RT–short latency (dark blue), and RT–long latency (light blue) tumors were made using the Wilcoxon rank-sum test, with P values listed above their corresponding comparison. Boxplots are represented by the IQR and midline at the median. Error bars equal the Q1/Q3 ± 1.5 × IQR. Oncoplots of recurrent mutations occurring above a frequency of 10% in the (C) CTRL and (D) RT cohorts. Only mutations with a VAF of ≥5% were included. E, Mutation enrichment was performed using the maftools package, and genes with an FDR >0.05 are indicated. Bars to the left of the dashed line represent CTRL vs. RT, with bars to the right of the dashed line indicating significant gene based on a 1 vs. other comparison. F, Comparison of KDM6A mutations between non-RT (TCGA and CTRL) and RT (RT and DFCI) cohorts. WT, wild type.
Supplement Figure 4 from Anti-HDGF Antibody Targets EGFR Tyrosine Kinase Inhibitor–Tolerant Cells in NSCLC Patient-Derived Xenografts
Authors: Zhou Cindy Q. , Li Ariel , Ri Kaoru , Sultan Ahmed S. , Ren Hening
Published: September 2024

Supplement Figure 4A shows the expression of MET and P-MET in naive and treated tumors. Supplement Figure 4B shows the sequencing result of EGFR exon 20 flanking C797 in naive and treated tumors.
Supplement Figure 1 from Anti-HDGF Antibody Targets EGFR Tyrosine Kinase Inhibitor–Tolerant Cells in NSCLC Patient-Derived Xenografts
Authors: Zhou Cindy Q. , Li Ariel , Ri Kaoru , Sultan Ahmed S. , Ren Hening
Published: September 2024

Supplement Figure 1 shows the incomplete response of Hcc827 tumor to erlotinib treatment.
Supplementary Data from The Tumor Microbiome Reacts to Hypoxia and Can Influence Response to Radiation Treatment in Colorectal Cancer
Authors: Benej Martin , Hoyd Rebecca , Kreamer McKenzie , Wheeler Caroline E. , Grencewicz Dennis J. , Choueiry Fouad , Chan Carlos H.F. , Zakharia Yousef , Ma Qin , Dodd Rebecca D. , Ulrich Cornelia M. , Hardikar Sheetal , Churchman Michelle L. , Tarhini Ahmad A. , Robinson Lary A. , Singer Eric A. , Ikeguchi Alexandra P. , McCarter Martin D. , Tinoco Gabriel , Husain Marium , Jin Ning , Tan Aik C. , Osman Afaf E.G. , Eljilany Islam , Riedlinger Gregory , Schneider Bryan P. , Benejova Katarina , Kery Martin , Papandreou Ioanna , Zhu Jiangjiang , Denko Nicholas , Spakowicz Daniel
Published: September 2024

Demographic variables stratified by low and high hypoxia scores, showing no significant differences to be controlled for in the Cox proportional hazards model described in Figure 1D.
Supplementary Data from The Tumor Microbiome Reacts to Hypoxia and Can Influence Response to Radiation Treatment in Colorectal Cancer
Authors: Benej Martin , Hoyd Rebecca , Kreamer McKenzie , Wheeler Caroline E. , Grencewicz Dennis J. , Choueiry Fouad , Chan Carlos H.F. , Zakharia Yousef , Ma Qin , Dodd Rebecca D. , Ulrich Cornelia M. , Hardikar Sheetal , Churchman Michelle L. , Tarhini Ahmad A. , Robinson Lary A. , Singer Eric A. , Ikeguchi Alexandra P. , McCarter Martin D. , Tinoco Gabriel , Husain Marium , Jin Ning , Tan Aik C. , Osman Afaf E.G. , Eljilany Islam , Riedlinger Gregory , Schneider Bryan P. , Benejova Katarina , Kery Martin , Papandreou Ioanna , Zhu Jiangjiang , Denko Nicholas , Spakowicz Daniel
Published: September 2024

Correlations between tumor microbes enriched in hypoxic tumors in both mice and humans and deconvolved immune cell abundances.
Supplemental Figure S4 from The Tumor Microbiome Reacts to Hypoxia and Can Influence Response to Radiation Treatment in Colorectal Cancer
Authors: Benej Martin , Hoyd Rebecca , Kreamer McKenzie , Wheeler Caroline E. , Grencewicz Dennis J. , Choueiry Fouad , Chan Carlos H.F. , Zakharia Yousef , Ma Qin , Dodd Rebecca D. , Ulrich Cornelia M. , Hardikar Sheetal , Churchman Michelle L. , Tarhini Ahmad A. , Robinson Lary A. , Singer Eric A. , Ikeguchi Alexandra P. , McCarter Martin D. , Tinoco Gabriel , Husain Marium , Jin Ning , Tan Aik C. , Osman Afaf E.G. , Eljilany Islam , Riedlinger Gregory , Schneider Bryan P. , Benejova Katarina , Kery Martin , Papandreou Ioanna , Zhu Jiangjiang , Denko Nicholas , Spakowicz Daniel
Published: September 2024

Boxplots showing the immune cell fractions for immune cells with significantly different expression in high and low hypoxia mouse samples at p-value <0.05. No differences remained significant after correction for multiple hypothesis testing.
Data from The Tumor Microbiome Reacts to Hypoxia and Can Influence Response to Radiation Treatment in Colorectal Cancer
Authors: Benej Martin , Hoyd Rebecca , Kreamer McKenzie , Wheeler Caroline E. , Grencewicz Dennis J. , Choueiry Fouad , Chan Carlos H.F. , Zakharia Yousef , Ma Qin , Dodd Rebecca D. , Ulrich Cornelia M. , Hardikar Sheetal , Churchman Michelle L. , Tarhini Ahmad A. , Robinson Lary A. , Singer Eric A. , Ikeguchi Alexandra P. , McCarter Martin D. , Tinoco Gabriel , Husain Marium , Jin Ning , Tan Aik C. , Osman Afaf E.G. , Eljilany Islam , Riedlinger Gregory , Schneider Bryan P. , Benejova Katarina , Kery Martin , Papandreou Ioanna , Zhu Jiangjiang , Denko Nicholas , Spakowicz Daniel
Published: September 2024

Abstract
Tumor hypoxia has been shown to predict poor patient outcomes in several cancer types, partially because it reduces radiation’s ability to kill cells. We hypothesized that some of the clinical effects of hypoxia could also be due to its impact on the tumor microbiome. Therefore, we examined the RNA sequencing data from the Oncology Research Information Exchange Network database of patients with colorectal cancer treated with radiotherapy. We identified microbial RNAs for each tumor and related them to the hypoxic gene expression scores calculated from host mRNA. Our analysis showed that the hypoxia expression score predicted poor patient outcomes and identified tumors enriched with certain microbes such as Fusobacterium nucleatum. The presence of other microbes, such as Fusobacterium canifelinum, predicted poor patient outcomes, suggesting a potential interaction between hypoxia, the microbiome, and radiation response. To experimentally investigate this concept, we implanted CT26 colorectal cancer cells into immune-competent BALB/c and immune-deficient athymic nude mice. After growth, in which tumors passively acquired microbes from the gastrointestinal tract, we harvested tumors, extracted nucleic acids, and sequenced host and microbial RNAs. We stratified tumors based on their hypoxia score and performed a metatranscriptomic analysis of microbial gene expression. In addition to hypoxia-tropic and -phobic microbial populations, analysis of microbial gene expression at the strain level showed expression differences based on the hypoxia score. Thus, hypoxia gene expression scores seem to associate with different microbial populations and elicit an adaptive transcriptional response in intratumoral microbes, potentially influencing clinical outcomes.
Significance:
Tumor hypoxia reduces radiotherapy efficacy. In this study, we explored whether some of the clinical effects of hypoxia could be due to interaction with the tumor microbiome. Hypoxic gene expression scores associated with certain microbes and elicited an adaptive transcriptional response in others that could contribute to poor clinical outcomes.
Influence of the Immune Checkpoint Inhibitors on the Hemostatic Potential of Blood Plasma
Authors: Patalakh Irina , Wandersee Alexandra , Schlüter Julian , Erdmann Michael , Hackstein Holger , Cunningham Sarah
Published: September 2024

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized classical treatment approaches of various cancer entities, but are also associated with a number of side effects. One of these may be life-threatening clotting disorders with the risk of thrombotic or hemorrhagic complications, the mechanisms of which are still poorly understood. In the present study, we analyzed the direct effects of pembrolizumab, nivolumab, and ipilimumab on platelet aggregation as well as plasma coagulation followed by fibrinolysis in an ex vivo model. Methods: Microplate spectrometry was used to analyze aggregation, coagulation, and fibrinolysis in platelet-free (PFP) and platelet-rich (PRP) healthy donor plasma samples treated with pembrolizumab, nivolumab, ipilimumab, and appropriate isotype controls. Aggregation was induced by TRAP-6. Clotting of PFP and PRP followed by lysis was initiated with a tissue factor in a mixture of phosphatidylserine:phosphatidylcholine and the addition of t-PA. Among other parameters, the area under the curve (AUC) was used to compare the effect of ICIs on aggregation, coagulation, and fibrinolysis. Results: Upon direct contact with platelets, pembrolizumab stimulated platelet aggregation in PRP, while nivolumab and ipilimumab promoted disaggregation with corresponding changes in the AUC. Pembrolizumab and nivolumab, both PD-1 receptor inhibitors, had no effect on the plasma coagulation cascade. Ipilimumab, a CTLA-4 receptor inhibitor, significantly increased the rate of PRP clotting. When clotting was followed by lysis, all ICIs were found to prolong the growth of the PRP-derived fibrin clot and delay its elimination. This was manifested by an increase in AUC relative to control PRP. Conclusion: This study characterizes the potential impact of pembrolizumab, nivolumab, and ipilimumab on hemostasis. Nivolumab and ipilimumab are able to reduce aggregation and increase the procoagulant properties of platelets, which can cause side effects associated with hemostatic imbalance leading to thrombosis or bleeding. The observed ICI-specific effects may contribute to our understanding of the mechanisms by which ICI affects platelets and suggest how, in a clinical setting, to reduce coagulation disorders during ICI treatment in the future.
Autoria de mulheres na literatura de horror: denúncia e acerto de contas em obras do Brasil e da Espanha
Authors: Nestarez Oscar Andrade Lourenção
Published: September 2024

Adopting the perspective of horror as an autonomous genre, with of strategies, procedures and themes that aim to produce feelings related to the term horrere (Latin for “to shudder”, “to shiver”), the article intends to investigate nuances of women authorship through two fronts: denunciation and counterattack. To this end, the text consists of a section dedicated to conceptualizing horror as a literary genre, as well as its possible intersections with what Teresa López-Pellisa called the inappropriate/inappropriatable fantastic. Next, in the section called “Attack: realistic horror”, two short stories dealing with the imprisonment of female bodies will put into dialogue: “Venha ver o pôr do sol”, by the brazilian Lygia Fagundes Telles, and “Hablar con viejas”, by the spanish Cristina Fernández Cubas. And the section “Counterattack: horror and the fantastic” will propose a reckoning through the analysis of the novel Cupim, by the spanish Layla Martínez, put into dialogue with the short story “O título é um grito”, by the brazilian Nikelen Witter. In both works, we seek to demonstrate how the fightback only occurs because both rationality and the patriarchal system are put in check by the possibilities of the fantastic – always considering the chill inherent in horror.
undrop and the Right to Seeds
Authors: Girard Fabien
Published: September 2024

Following in the footsteps of the Nyéléni Declaration, the transnational agrarian movement La Via Campesina (lvc) secured recognition for the right to food sovereignty within the United Nations Declaration on the Rights of Peasants and Other People Working in Rural Areas. Alongside this, the academic community and the agrarian movement itself have developed the concept of “seed sovereignty”. Although it has not followed the same normative trajectory as food sovereignty, it has served (i) to bring together a range of issues scattered throughout the biodiversity “regime complex” (industrial property, concentration, seed regulation, gmo regulation, biopiracy, conservation); (ii) to establish a coherent and integrative intellectual framework, the high point of which was undoubtedly the enshrinement of the “right to seeds” in Article 19 of the Declaration.

This chapter traces the history of the concept and the genealogy of Article 19, showing that seed sovereignty, through its appeal to permanent sovereignty over natural resources (which was also clearly visible during the drafting process), sought to anchor the prerogatives granted to peasants and farmers over their seeds in international human rights law. More fundamentally, in its alliance with the right to food sovereignty, it represents a significant attempt to challenge the Westphalian sovereignty – a hallmark of the transnational agrarian movement.
Lessons from the Russian Invasion of Ukraine
Authors: Winter Elliot
Published: September 2024

The concept of the levée en masse was designed to legitimise armed civilian opposition to an unfolding invasion by conferring temporary combatant status upon certain civilians. The range of individuals eligible for this status was defined narrowly to include only ‘inhabitants’ of invaded territories. This approach made sense in the nineteenth and early twentieth centuries when international travel was beyond the reach of all but the elite minority. Today however, mass air transit has expanded horizons and allows people to travel and to emigrate much more readily. Consequently, the global diaspora of emigrants is larger now than ever before. As seen during the Russian invasion of Ukraine beginning in February 2022, many among these diaspora communities wish to return to defend their homelands upon invasion. This is precluded under the orthodox interpretation of international humanitarian law owing to their lack of residency. This is unsatisfactory as it bars individuals with legitimate familial, political, cultural, and historical connections to a State from participating in a levée in its defence. This article sets out the policy and legal arguments in favour of recognising non-resident citizens – or ‘diaspora fighters’ – as legitimate participants in levées en masse.
Trix
Authors: Fisher Barbara
Published: September 2024

This volume represents the first biography of Alice MacDonald Kipling Fleming (1868-1948), known as Trix. Rarely portrayed with sympathy or accuracy in biographies of her famous brother Rudyard, Trix was a talented writer and a memorable character in her own right whose fascinating life was unknown until now. In telling Trix’s story, Barbara Fisher rescues her from the misrepresentations, trivializations, and outright neglect of Rudyard’s many biographers.

This book provides the first account of Trix’s life, beginning with the horrible childhood she shared with Rudyard as a Raj orphan in England. The biography follows adolescent Trix as she returned to India, where her brother encouraged her to write poems and stories, which were regularly mistaken for his. Her marriage to a stiff Scottish officer is chronicled from its hopeful beginnings through its childless, cheerless middle to its calm and compromised end. Trix’s bouts of mental illness are described in sympathetic detail.

Turning her attention to Trix’s oeuvre Barbara Fisher locates and attributes all of her short fiction, poetry, and journalism, giving special attention to Trix’s two ambitious but flawed novels. She also puts into historical context Trix’s long and productive participation as a medium for the Society for Psychical Research.

Most importantly, Trix: The Other Kipling gives a voice, a mind, and a heart to a misunderstood, misrepresented, but indomitable woman – an accomplishment which will be of great interest to readers interested in Victorian women authors, in the cultural interchanges between England and colonial India, in serious psychical research, in the early treatment of mental illness, and more generally, in the everyday life and struggles of intellectual women of the 19th and early 20th century.
5. The Heart of a Maid
Authors: Fisher Barbara
Published: September 2024

Immediately after a brief honeymoon, Jack was sent to Burma to continue his work on the Great Survey of India. Trix stayed behind in Lahore, where she began work on a novel featuring an unfeeling heroine struggling through the early years of a mis-matched and bitterly unhappy marriage. In January of 1890, after less than six months in Burma, Jack became sick and was granted home leave. Having to remove promptly to England, Trix hastily and harshly concluded her novel. Just two years into her marriage, Trix’s novel, The Heart of a Maid, appeared under the pen name Beatrice Grange. The pen name was required not only to protect Trix’s modesty but also to obscure her private marital discontent. The early events of the novel not only paralleled Trix’s life but were being recorded almost simultaneously with it. The novel is remarkable for its insight into the heart and mind of its unusually cool heroine.
6. Wife of Jack
Authors: Fisher Barbara
Published: September 2024

When Trix and Jack arrived in England on home leave in 1890, their young marriage was already faltering. The first meeting between pretty and poetic Trix and the stiff and proper Flemings in Edinburgh was a disaster, confirming Trix’s fears that her extroverted and effusive personality and Jack’s undemonstrative and dour temperament were unalterable and incompatible. After two years of home leave, the couple returned to begin their domestic life in Calcutta, where Trix, for the first time, had the responsibility of running a household. Like most Anglo-Indian wives, she learned to live within the many restrictions of the Raj, but unlike most, she wrote and published clever stories in Lahore’s principal newspaper, the Pioneer.
9. Psychic Research
Authors: Fisher Barbara
Published: September 2024

After having postponed her return to India several times, Trix resumed her marriage and reentered Anglo-Indian social life in 1902. Childless at thirty-five years old, she had lain to rest any hopes of conceiving a baby. Only moderately successful as a writer, she had given up on having a literary career. Instead, she focused her formidable energies on psychic research, having made contact with the respected British Society for Psychical Research (SPR), whose distinguished members were attempting to prove spiritual survival after bodily death. Trix became a valued medium in the carefully designed experiments of the society, writing and sending to England hundreds of pages of automatic script. When Jack’s army service terminated in 1908 and Trix returned to Scotland, she continued her work with the SPR. Rudyard believed that Trix’s psychic work contributed to her mental frailty, but, on the contrary, while working with the SPR, Trix remained sane and stable. This calm period came to an abrupt end in December 1910.

Trix used her ability to put herself into a trance-like state for the purpose of providing evidence for the SPR, but being in this state also had the unintended but welcome result of easing her mind. By coincidence, therapy to relieve mental distress and research to prove the existence of invisible psychic forces overlapped in many areas. Psychic researchers and mental health professionals, called alienists, were investigating trance-like states to uncover unconscious or subliminal awareness. Hypnotism, dream interpretation, free association, and Freud’s primary process psychoanalytic technique depended on establishing access to the patient’s unconscious mind in order to diagnose and treat mental disorders. Psychical research recognized altered states of consciousness as elevated states of inspiration in which spirits were heard, seen, or embodied. Philosophers, psychologists, and psychic researchers all considered dreams, hypnotism, automatic writing, crystal gazing, trances, and speaking in tongues as important areas of mental activity that could be studied and measured with scientific accuracy to reveal the unknown workings of the human mind.
Introduction
Authors: Attar Karen , Rice Adrian , Stray Christopher
Published: September 2024

An introduction to the topics and ideas discussed in the book.
The Effect of the C/N Ratio on Nitrogen and Phosphorus Removal in the Anoxic-Oxic/Anaerobic-Anoxic-Oxic Process
Authors: Xiao Bing , Fan Yuxin , Chen Yongli , Wang Jingwen , Xiong Jianhua , Liang Yinna , Wang Xinyu , Singdala Outhay
Published: September 2024

In the nitrogen and phosphorus removal of domestic sewage, anoxic-oxic (AO) and anaerobicanoxicoxic (AAO) processes are the most widely used processes, but the insufficient carbon source will affect their efficiency. In order to study the changes of nitrogen and phosphorus removal by
AO and AAO processes under the changing carbon/nitrogen (C/N) ratio, we built a simulated sewage treatment experimental device to continuously treat real domestic sewage with different carbon source content. By measuring the index of pollutants, the removal rate of each pollutant and the total
removal amount of pollutants in each reaction zone were calculated and compared. The results show that the nitrogen removal effect of AAO process is better than that of AO process at higher carbon to nitrogen ratio, and the other way is that AO process is better. The comparison of phosphorus
removal effect under different carbon and nitrogen ratio is that AAO process is more dominant. The application conditions and stability of the two processes for nitrogen and phosphorus removal are different, which has certain guiding significance for the actual wastewater treatment.
Lessons from the Frontline: The Burgeoning Security and Economic Race in the Indo-Pacific
Authors: Tiberghien Yves
Published: September 2024

Democracies in the Indo-Pacific are facing an increasingly competitive and securitized environment, as China turns more assertive and the US-China rivalry escalates. Disruptions include uncertainty about the global economic order, technological decoupling, an arms race amidst intense hot spots, an economic security spiral, and larger systemic risks around climate change, AI governance, etc. Countries such as Japan and Korea are actively responding to these risks through a strategic approach to economic security and increased defense spending, active alliance development, and parallel continued investment in global institutions and dialogue. Canada must be jolted out of its-business-as-usual approach and take a cue from its closest partners in Asia. This includes investing rapidly in its security (2% of defense over GDP) and the creation of an economic security council under the Prime Minister. Canada should also join its key partners in effectively investing in key global institutions in times of crisis.
Impact of Morphine withdrawal on genes related to the TLR2 pathway expressed in the Prefrontal Cortex
Authors: Truitt Bridget , Tao Junyi , Roy Sabita
Published: September 2024

Millions of people suffer from opioid use disorder, because of the ongoing opioid epidemic. The aversive symptoms of withdrawal are a leading factor for drug relapses, yet there are limited therapeutic options to minimize or prevent withdrawal symptoms. The mechanism behind opioid withdrawal is still not fully understood, thus preventing the development of new therapeutics. This study is an extension of our previously proposed mechanism of a toll-like receptor 2 (TLR2) mediated withdrawal response as a result of morphine induced microbial change that occurs during morphine withdrawal. Transcriptome analysis of the pre-frontal cortex indicated that there was increased expression of genes related to TLR2 signaling in morphine withdrawal treated animals compared to placebo controls. Antibiotic treatment further altered TLR2 related genes, recovering some of the morphine induced effect and leading to additional suppression of some genes related to the TLR2 pathway. Morphine withdrawal induced gene expression was attenuated in a whole body TLR2 knockout model. These results provide more support that TLR2 plays an integral role in morphine withdrawal mechanisms and could be a potential therapeutic target to minimize opioid withdrawal associated co-morbidities.
Pipeline leak detection based on multiscale convolution neural network and improved symmetric dot pattern optimized by grasshopper optimization algorithm
Authors: Zhang Yong , Xing Pengfei , Dong Hongli , Lu Jingyi , Zhou Xingda , Zhou Yina , Liang Hao , Li Gongfa
Published: September 2024

In the engineering of pipeline condition identification, the complexity of pipeline signal components often results in insufficient feature extraction with traditional feature extraction-machine learning methods, thereby affecting the recognition performance. In order to effectively address the aforementioned issues, based on deep learning, we propose a multiscale convolution neural network (MCNN) to effectively identify pipeline conditions by classifying improved symmetry dot pattern (ISDP) images of one-dimensional negative pressure wave signals of pipelines. First, we propose the ISDP transformation method, considering that negative pressure wave signals of pipes with different leakage degrees have different amplitude changes. The ISDP transformation method transforms the negative pressure wave signal of the pipeline from one dimension to two dimensions. Then the grasshopper optimization algorithm (GOA) was employed to optimize the parameters of the ISDP algorithm. Second, we build the MCNN depth network to train and classify the ISDP image. The MCNN can simultaneously learn both the global and local features of an image. The corresponding evaluation indicators show that the proposed method of working condition recognition using MCNN to classify and recognize the ISDP image of pipeline signal has higher accuracy and robustness than traditional machine learning methods and common deep learning methods. The evaluation results prove that the proposed algorithm is effective in pipeline signal classification.
‘Belonging to the Company’: Transporting and documenting unfree labour in the Indian Ocean, 1719–1790
Authors: Schotte Margaret E.
Published: September 2024

Over the course of the eighteenth century, French East India Company ships carried numerous sailors, soldiers, passengers and unfree labourers to and from various ports of trade in the Indian Ocean. Although European merchant companies developed extensive documenting systems, certain elements received little attention in the records. When it came to tracking unfree labourers, Company employees used terminology with ambiguous meanings and categories that were codified in the Atlantic context and therefore not initially applicable in the Indian Ocean. In order for historians to interpret these records more accurately, this article reviews specific terminology and pertinent French legislation about racialized labourers. This contextual information helps to uncover previously overlooked groups of unfree labourers working for – and, at times, trying to escape from – the French East India Company in the Indian Ocean and beyond.
It’s mainly about fit: Employability perspectives from undergraduate learners on a vocational course in England
Authors: Flanagan Sarah
Published: September 2024

Employability is significant to higher education. Given employability’s importance, higher education practice has been affected. However, employability is a complex concept with several stakeholders. Even though students are interested parties, their understanding of employability is not well-known. This paper is interested in employability from the student perspective. Its aim is to explore the student experience of employability within higher education. The research approach of a collective case study involving 11 students was taken. Data collection methods included semi-structured interviews; students supplied employability related stories. Additionally, work placement reflections plus mentor feedback forms were examined. Findings confirmed employability is a multifactorial concept, however, a fit between worker and their work was considered most valuable. Importantly, certain factors influenced fit. Previous research has linked employability with a fit between worker and their work. Nevertheless, this paper stresses the significance of fit for students. It also collates factors affecting fit and therefore employability.