bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure 2 from Multistate Gene Cluster Switches Determine the Adaptive Mitochondrial and Metabolic Landscape of Breast Cancer
Authors: Menegollo Michela , Bentham Robert B. , Henriques Tiago , Ng Seow Q. , Ren Ziyu , Esculier Clarinde , Agarwal Sia , Tong Emily T.Y. , Lo Clement , Ilangovan Sanjana , Szabadkai Zorka , Suman Matteo , Patani Neill , Ghanate Avinash , Bryson Kevin , Stein Robert C. , Yuneva Mariia , Szabadkai Gyorgy
Published: September 2024

Metabolic transcriptome switches override PAM50 classification. A–D, Visualization of bicluster switches based on CV values of individual genes in the METABRIC breast cancer dataset analysis in the indicated metabolic pathways. Genes are ranked by the MB1 CV values and directly compare the MB1 and MB2 biclusters on the left side of each panel. The ranked MB3 values are shown on the right side of each panel. E–H, Sub-pathway gene clusters group according to the bicluster switches across PAM50 categories. Bicluster forks samples were grouped according to their intrinsic subtype and the average transcript levels of each gene in the indicated pathways were calculated. Hierarchical clustering of genes and sample groups was performed (Pearson distance and ward2 clustering). Group classifications according to the biclusters and intrinsic breast cancer subtypes are shown on the right.
Supplementary Figure S2 from WNK1 Interaction with KEAP1 Promotes NRF2 Stabilization to Enhance the Oxidative Stress Response in Hepatocellular Carcinoma
Authors: Li Li , Xie Dacheng , Yu Shijun , Ma Muyuan , Fan Kailing , Chen Jingde , Xiu Mengxi , Xie Keping , Li Yandong , Gao Yong
Published: September 2024

Supplementary Figure S2
Supplementary Figure S1 from WNK1 Interaction with KEAP1 Promotes NRF2 Stabilization to Enhance the Oxidative Stress Response in Hepatocellular Carcinoma
Authors: Li Li , Xie Dacheng , Yu Shijun , Ma Muyuan , Fan Kailing , Chen Jingde , Xiu Mengxi , Xie Keping , Li Yandong , Gao Yong
Published: September 2024

Supplementary Figure S1
Supplementary Figure 4 from Comprehensive Proteogenomic Profiling Reveals the Molecular Characteristics of Colorectal Cancer at Distinct Stages of Progression
Authors: Li Lingling , Jiang Dongxian , Liu Hui , Guo Chunmei , Zhang Qiao , Li Xuedong , Chen Xiaojian , Chen Zheqi , Feng Jinwen , Tan Subei , Huang Wen , Huang Jie , Xu Chen , Liu Chen-Ying , Yu Wei , Hou Yingyong , Ding Chen
Published: September 2024

Supplementary Figure 4 and related legend of the revised manuscript.
Data from WNK1 Interaction with KEAP1 Promotes NRF2 Stabilization to Enhance the Oxidative Stress Response in Hepatocellular Carcinoma
Authors: Li Li , Xie Dacheng , Yu Shijun , Ma Muyuan , Fan Kailing , Chen Jingde , Xiu Mengxi , Xie Keping , Li Yandong , Gao Yong
Published: September 2024

Abstract
Cellular oxidative stress plays a key role in the development and progression of hepatocellular carcinoma (HCC). A better understanding of the processes that regulate reactive oxygen species (ROS) homeostasis could uncover improved strategies for treating HCC. Herein, we identified protein kinase with-no-lysine kinase 1 (WNK1) as an antioxidative factor and therapeutic target in HCC. In human HCC, WNK1 expression was increased and correlated with poor patient prognosis. WNK1 knockdown significantly inhibited cell proliferation and xenograft tumor growth. Mechanistically, WNK1 competed with nuclear factor erythroid 2–related factor 2 (NRF2) for binding with the partial Kelch domain of Kelch-like ECH-associated protein 1 (KEAP1), reducing NRF2 ubiquitination and promoting NRF2 accumulation and nuclear translocation to increase antioxidant response. WNK1 silencing increased H2O2-induced apoptosis and inhibited cell growth by elevating ROS levels, which could be rescued by treatment with the antioxidant N-acetylcysteine and NRF2 activator tert-butylhydroquinone. Liver-specific WNK1 knockout mouse models of HCC substantiated that WNK1 promoted HCC development by regulating ROS levels. WNK463, an inhibitor of the WNK kinase family, suppressed HCC progression and altered the redox status. These findings suggest that WNK1 plays a critical role in HCC development and progression and that the WNK1-oxidative stress axis may be a promising therapeutic target for HCC.

Significance: Inhibiting WNK1 induces NRF2 degradation and reduces the oxidative stress response to suppress hepatocellular carcinoma growth, indicating that targeting the WNK1–KEAP1–NRF2 axis is a potential strategy to treat liver cancer.
Supplementary Table S1 from MYTX-011: A pH-Dependent Anti–c-MET Antibody–Drug Conjugate Designed for Enhanced Payload Delivery to c-MET–Expressing Tumor Cells
Authors: Gera Nimish , Fitzgerald Kyle M. , Ramesh Vijay , Patel Purvi , Kanojia Deepak , Colombo Federico , Kien Lena , Aoyama Simon , Xu Lihui , Jean Jussekia , Deshpande Amit M. , Comb William C. , Chittenden Thomas , Fiske Brian P.
Published: September 2024

Binding affinity of MYTX-011 to recombinant cMET and cMET expressed on cells.
Supplementary Data Legend from HPN328, a Trispecific T Cell–Activating Protein Construct Targeting DLL3-Expressing Solid Tumors
Authors: Molloy Mary E. , Aaron Wade H. , Barath Manasi , Bush Mabel C. , Callihan Evan C. , Carlin Kevin , Cremin Michael , Evans Thomas , Guerrero Maria G. , Hemmati Golzar , Hundal Avneel S. , Lao Llewelyn , Laurie Payton , Lemon Bryan D. , Lin S.J. , O’Rear Jessica , Patnaik Purbasa , Sotelo Rocha Sony , Santiago Linda , Strobel Kathryn L. , Valenzuela Laura B. , Wu Chi-Heng , Yu Stephen , Yu Timothy Z. , Anand Banmeet S. , Law Che-Leung , Sun Liping L. , Wesche Holger , Austin Richard J.
Published: September 2024

Legend for Supplementary Data
Figure S6 from Pretargeted Radioimmunotherapy with the Novel Anti-oxMIF/HSG Bispecific Antibody ON105 Results in Significant Tumor Regression in Murine Models of Cancer
Authors: Puchol Tarazona Alejandro A. , Schinagl Alexander , Mirkina Irina , Rossmueller Gregor , Kerschbaumer Randolf J. , Bachmann Friedmund , Thiele Michael
Published: September 2024

Figure S6
Supplementary Figure S2 from Combining EHMT and PARP Inhibition: A Strategy to Diminish Therapy-Resistant Ovarian Cancer Tumor Growth while Stimulating Immune Activation
Authors: Nguyen Lily L. , Watson Zachary L. , Ortega Raquel , Woodruff Elizabeth R. , Jordan Kimberly R. , Iwanaga Ritsuko , Yamamoto Tomomi M. , Bailey Courtney A. , To Francis , Jeong Abigail D. , Guntupalli Saketh R. , Behbakht Kian , Gibaja Veronica , Arnoult Nausica , Cocozaki Alexis , Chuong Edward B. , Bitler Benjamin G.
Published: September 2024

Supplementary Figure S2 shows the transcriptional changes of transposable elements via volcano plot due to the treatment of single treatments and combination treatments. It also shows the chromatin profiling of EHMT2 bound to LTR8B elements in the genome after single and combination treatment.
Data from Combining EHMT and PARP Inhibition: A Strategy to Diminish Therapy-Resistant Ovarian Cancer Tumor Growth while Stimulating Immune Activation
Authors: Nguyen Lily L. , Watson Zachary L. , Ortega Raquel , Woodruff Elizabeth R. , Jordan Kimberly R. , Iwanaga Ritsuko , Yamamoto Tomomi M. , Bailey Courtney A. , To Francis , Jeong Abigail D. , Guntupalli Saketh R. , Behbakht Kian , Gibaja Veronica , Arnoult Nausica , Cocozaki Alexis , Chuong Edward B. , Bitler Benjamin G.
Published: September 2024

Abstract
Despite the success of poly-ADP-ribose polymerase inhibitors (PARPi) in the clinic, high rates of resistance to PARPi presents a challenge in the treatment of ovarian cancer, thus it is imperative to find therapeutic strategies to combat PARPi resistance. Here, we demonstrate that inhibition of epigenetic modifiers euchromatic histone lysine methyltransferases 1/2 (EHMT1/2) reduces the growth of multiple PARPi-resistant ovarian cancer cell lines and tumor growth in a PARPi-resistant mouse model of ovarian cancer. We found that combinatory EHMT and PARP inhibition increases immunostimulatory double-stranded RNA formation and elicits several immune signaling pathways in vitro. Using epigenomic profiling and transcriptomics, we found that EHMT2 is bound to transposable elements, and that EHMT inhibition leads to genome-wide epigenetic and transcriptional derepression of transposable elements. We validated EHMT-mediated activation of immune signaling and upregulation of transposable element transcripts in patient-derived, therapy-naïve, primary ovarian tumors, suggesting potential efficacy in PARPi-sensitive disease as well. Importantly, using multispectral immunohistochemistry, we discovered that combinatory therapy increased CD8 T-cell activity in the tumor microenvironment of the same patient-derived tissues. In a PARPi-resistant syngeneic murine model, EHMT and PARP inhibition combination inhibited tumor progression and increased Granzyme B+ cells in the tumor. Together, our results provide evidence that combinatory EHMT and PARP inhibition stimulates a cell autologous immune response in vitro, is an effective therapy to reduce PARPi-resistant ovarian tumor growth in vivo, and promotes antitumor immunity activity in the tumor microenvironment of patient-derived ex vivo tissues of ovarian cancer.
Supplementary Table 5 from Hepatitis B Virus X Protein Represses Expression of Tumor Suppressor PTPN18 in Hepatocellular Carcinoma
Authors: Zhou Zhenyu , Yu Wei , Li Huoming , Shi Juanyi , Meng Shiyu , Yan Yongcong , Chen Ruibin , Liu Haohan , Wang Jie , Sun Jian , Xiao Zhiyu , Zhang Jianlong
Published: September 2024

Data of miRNA databases and microarray about PTPN18.
Supplementary Figure 5 from Hepatitis B Virus X Protein Represses Expression of Tumor Suppressor PTPN18 in Hepatocellular Carcinoma
Authors: Zhou Zhenyu , Yu Wei , Li Huoming , Shi Juanyi , Meng Shiyu , Yan Yongcong , Chen Ruibin , Liu Haohan , Wang Jie , Sun Jian , Xiao Zhiyu , Zhang Jianlong
Published: September 2024

The phospho-protein microarray and the core signal-net analysis.
Supplementary Table S1 from USP44 Overexpression Drives a MYC-Like Gene Expression Program in Neuroblastoma through Epigenetic Reprogramming
Authors: Ekstrom Thomas L. , Hussain Sajjad , Bedekovics Tibor , Ali Asma , Paolini Lucia , Mahmood Hina , Rosok Raya M. , Koster Jan , Johnsen Steven A. , Galardy Paul J.
Published: September 2024

Supplementary table 1
Supplementary Figure S10 from USP44 Overexpression Drives a MYC-Like Gene Expression Program in Neuroblastoma through Epigenetic Reprogramming
Authors: Ekstrom Thomas L. , Hussain Sajjad , Bedekovics Tibor , Ali Asma , Paolini Lucia , Mahmood Hina , Rosok Raya M. , Koster Jan , Johnsen Steven A. , Galardy Paul J.
Published: September 2024

A chromosome 4p score predicts poor survival.
Figure 7 from Clinically Relevant Humanized Mouse Models of Metastatic Prostate Cancer Facilitate Therapeutic Evaluation
Authors: Kostlan Raymond J. , Phoenix John T. , Budreika Audris , Ferrari Marina G. , Khurana Neetika , Choi Jae E. , Juckette Kristin , Mahapatra Somnath , McCollum Brooke L. , Moskal Russell , Mannan Rahul , Qiao Yuanyuan , Vander Griend Donald J. , Chinnaiyan Arul M. , Kregel Steven
Published: September 2024

Response of VCaP subcutaneous tumors to anti-PD1 immunotherapy and enzalutamide. A, huNOG primary tumor growth response and (B) NOG primary growth response to pembrolizumab, enzalutamide, and combination therapy. *, P > 0.05 when compared with vehicle control, **, P > 0.05 when compared with all other conditions. C, HLA (HLA-A, B, C) expression of a panel of benign prostate (BPH-1, 957e/hTERT, RWPE1, PNT-2), AR-positive prostate cancer (LNCaP, LAPC-4, VCaP, 22Rv1, CWR-R1) and AR-negative (PC3, DU145 and NCI-H660) cancer cell lines determined by Western blotting (representative blots show, experiment replicated three times). Corresponding AR blot and AR variant (AR-V7) detection. D, LNCaP, 22Rv1, and VCaP HLA response the AR agonist, R1881 (1 nmol/L), AR-antagonist enzalutamide (ENZA - 10 μmol/L), and vehicle control (CTRL) treatment for 24 hours. PSA is a canonical AR-target gene as a readout of AR modulation. E, Comparison of HLA expression between enzalutamide naïve and resistant cell lines (ENZR).
Figure S7 from MLLT6/ATF2 Axis Restrains Breast Cancer Progression by Driving DDIT3/4 Expression
Authors: Yu Qing , Zhao Jiayi , Yang Anli , Li Xiangxin
Published: September 2024

Supplementary Figure S7, referred to Figure 7.
Figure S5 from MLLT6/ATF2 Axis Restrains Breast Cancer Progression by Driving DDIT3/4 Expression
Authors: Yu Qing , Zhao Jiayi , Yang Anli , Li Xiangxin
Published: September 2024

Supplementary Figure S5, referred to Figure 5.
Supplementary Figure S2 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

Effects of CHD2 depletion on the growth of H3K27M DMG xenografts.
Table S2 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

Table S2 shows gene ontology analysis of candidate facilitator genes of MYC-induced cell death.
Figure S1 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 S1 shows PCA of human breast tumors, hallmark MYC signature score for human breast tumors, expression of MYC-target NECTIN4, schematic for purine ribonucleotide catabolism, concentrations of nucleotides in physiological conditions, prediction of hypothetical purine nucleotide flux, MYC-induced cell death in MYC-ER HMECs, and candidate facilitators of MYC-induced cell death.
Supplemental Table S4 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 S4 summarizing RNAseq and WES analysis of acquired resistant clones from MIA PaCa-2 xenograft model.
Supplementary Table S2 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

Cancer and disease definitions from UKB used in the study
Supplementary Figure S2 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

Performance of boostDM-CH models
Supplementary Figure S16 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 different infectious diseases in UKB
Supplementary Figure 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 Figure S15. Validation of SIDP via chemical perturbation.
Data 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

Abstract
Upregulation of MYC is a hallmark of cancer, wherein MYC drives oncogenic gene expression and elevates total RNA synthesis across cancer cell transcriptomes. Although this transcriptional anabolism fuels cancer growth and survival, the consequences and metabolic stresses induced by excess cellular RNA are poorly understood. Herein, we discover that RNA degradation and downstream ribonucleotide catabolism is a novel mechanism of MYC-induced cancer cell death. Combining genetics and metabolomics, we find that MYC increases RNA decay through the cytoplasmic exosome, resulting in the accumulation of cytotoxic RNA catabolites and reactive oxygen species. Notably, tumor-derived exosome mutations abrogate MYC-induced cell death, suggesting excess RNA decay may be toxic to human cancers. In agreement, purine salvage acts as a compensatory pathway that mitigates MYC-induced ribonucleotide catabolism, and inhibitors of purine salvage impair MYC+ tumor progression. Together, these data suggest that MYC-induced RNA decay is an oncogenic stress that can be exploited therapeutically.

Significance: MYC is the most common oncogenic driver of poor-prognosis cancers but has been recalcitrant to therapeutic inhibition. We discovered a new vulnerability in MYC+ cancer where MYC induces cell death through excess RNA decay. Therapeutics that exacerbate downstream ribonucleotide catabolism provide a therapeutically tractable approach to TNBC (Triple-negative Breast Cancer) and other MYC-driven cancers.
Data 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

Abstract
Only a handful of somatic alterations have been linked to endocrine therapy resistance in hormone-dependent breast cancer, potentially explaining ∼40% of relapses. If other mechanisms underlie the evolution of hormone-dependent breast cancer under adjuvant therapy is currently unknown. In this work, we employ functional genomics to dissect the contribution of cis-regulatory elements (CRE) to cancer evolution by focusing on 12 megabases of noncoding DNA, including clonal enhancers, gene promoters, and boundaries of topologically associating domains. Parallel epigenetic perturbation (CRISPRi) in vitro reveals context-dependent roles for many of these CREs, with a specific impact on dormancy entrance and endocrine therapy resistance. Profiling of CRE somatic alterations in a unique, longitudinal cohort of patients treated with endocrine therapies identifies a limited set of noncoding changes potentially involved in therapy resistance. Overall, our data uncover how endocrine therapies trigger the emergence of transient features which could ultimately be exploited to hinder the adaptive process.

Significance: This study shows that cells adapting to endocrine therapies undergo changes in the usage or regulatory regions. Dormant cells are less vulnerable to regulatory perturbation but gain transient dependencies which can be exploited to decrease the formation of dormant persisters.
Figure 5 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

Prognostic value of the smoking and XRT signatures in TCGA and proposed scheme of RT-associated bladder cancer development. The Pearson correlation between the UNC signature motif frequency profile and TCGA BLCA samples was calculated, and TCGA samples were split into high and low groups at the median correlation. Samples were further split by CDKN2A status, and KM curves were generated. A multivariate Cox proportional hazard model was calculated for both the (A) smoking signature and (B) XRT signature. For all KM plots, dashed lines indicate median survival. C, Proposed model for the interplay between preexisting alteration in the urothelium and RT. WT, wild type.
A Complete Response to Combined Immunotherapy in a Patient with an ATM plus SF3B1 Mutation and a Moderate Tumor Mutational Burden with a High-Grade Treatment-Emergent Neuroendocrine Prostate Cancer: Case Report and Review of the Literature
Authors: Ferreira Bruzzi Porto Helena , Lopes Gabriela C.K. , Bekierman Hannah B.V. , Altino De Almeida Sérgio , Da Matta Andreiuolo Felipe , Lucena Evandro , Pravin Patel Sandip , Freire Vinicius , Herchenhorn Daniel
Published: September 2024

Introduction: High-grade treatment-emergent neuroendocrine prostate cancer (T-NEPC) is a rare subtype of prostate cancer with limited therapeutic options and poor prognosis. Understanding biomarkers that influence the efficacy of immune checkpoint inhibitors (IO) is vital to form a better therapeutic arsenal for these patients. Case Presentation: We describe an impressive response to IO combination immunotherapy with ipilimumab plus nivolumab (Ipi/nivo) in a patient with T-NEPC who had failed standard treatment approaches. The patient was showing signs of a rapid decline in quality of life despite his prostate-specific antigen levels remaining undetectable and had no previous response to standard therapies. The results of the next-generation sequencing DNA analysis demonstrated the presence of intermediary tumor burden, an ATM mutation and a rare SF3B1 (G742D) mutation, and served as rational for IO therapy in this patient. Conclusions: This case highlights the genetic profile of tumor with a rare combination of ATM and SF3B1 mutations that could be further explored as biomarkers for IO therapy in T-NEPC and other tumor types.
A Rare Presentation of Myelin Oligodendrocyte Glycoprotein-Associated Optic Neuritis with Venous Stasis Retinopathy and Premacular Hemorrhage: A Case Report
Authors: Srimanan Worapot , Ngathaweesuk Yaninsiri
Published: September 2024

Introduction: Myelin oligodendrocyte glycoprotein (MOG)-associated disorders can cause inflammation of the central nervous system in various specific organs. Ocular involvement manifests as optic neuritis is one of the most common presentations; other ocular presentations are uncommon. Recently, rare ocular complications have been reported in conjunction with MOG-associated optic neuritis. We reported a rare case of acute venous stasis retinopathy co-occurring with bilateral optic neuritis. Case Presentation: A 27-year-old woman complained of a throbbing headache for 2 weeks before developing visual loss in her right eye. She was diagnosed with presumed central retinal vein occlusion and was scheduled for further investigations. Two days later, she suddenly lost vision in her left eye and was admitted to the hospital. An eye examination revealed tortuous and dilated veins and optic disk swelling, notably in the right eye, compatible with venous stasis retinopathy in both eyes. Her right eye also had a premacular hemorrhage and vitreous hemorrhage. Magnetic resonance imaging showed an enhancement of bilateral optic nerves, and MOG antibody was detected in her serum. She successfully achieved a rapid improvement of vision in the left eye with intravenous methylprednisolone. However, her vision in the right eye did not recover due to dense vitreous hemorrhage. Conclusion: Venous stasis retinopathy is a rare complication of MOG-associated optic neuritis. High-dose corticosteroids result in a rapid response and excellent symptom recovery. Ongoing reports may uncover new clinical presentations associated with this disorder.
Immediate Hypersensitivity Reactions to Biologic Drugs in Children with Inflammatory Bowel Diseases
Authors: Polat Terece Sinem , Ertoy Karagol Hacer Ilbilge , Teker Duztas Demet , Koken Gizem , Ozturk Hakan , Yapar Dilek , Egritas Gurkan Odul , Sari Sinan , Dalgic Buket , Bakirtas Arzu
Published: September 2024

Introduction: The increased use of biologic drugs (BDs) may lead to an increase in immediate hypersensitivity reactions (I-HSRs) in pediatric patients with inflammatory bowel disease (IBD). Our aim was to assess I-HSRs to BDs in pediatric IBD, examining frequency, clinical features, management, and associated risk factors. Methods: All children diagnosed with IBD at our institution between January 1, 2006, and August 1, 2023, and who developed I-HSRs related to any BD were included in the study. Results: In a study of 197 pediatric IBD patients, 61 used BD. Among these, 52.4% were male, with a median diagnosis age of 145 months (13–215). Out of a total of 1,679 administrations, 6 patients developed I-HSRs (5 with infliximab, 1 with adalimumab), resulting in a frequency of 9.8% per patient and 0.36% per administration. Of these, 66.7% were cases of Type 1 HSRs (skin test positivity n = 1), while the rest were infusion-related reactions (anti-drug antibody positivity n = 4), all of which were mild to moderate in severity. In the age and gender-adjusted logistic regression model, the presence of any comorbid allergic disease was significantly associated with the occurrence of I-HSR (aOR = 8.35; 95% CI = 1.24–56.38; p = 0.029). Conclusion: The frequency of I-HSRs to BDs in children with IBD is not rare but not severe in the long term. The presence of any comorbid allergic disease is a risk factor for the development of I-HSRs to BDs.
Judicialização do câncer no Brasil: uma revisão integrativa da literatura científica
Authors: Figueiredo Iara Veloso Oliveira , Castro Mônica Silva Monteiro , Santos Fausto Pereira dos , Paes-Sousa Rômulo
Published: September 2024

This study aimed to carry out a bibliographic survey on the judicialization of cancer in Brazil. The methodology used was an integrative review, based on research in the Virtual Health Library, Google Scholar, Scielo, and Oasis Br databases. A total of 774 texts were found, and after reading the abstracts and eliminating duplicates, it was selected 14 articles that suited the research object. Most studies (n=12) addressed the litigation of cancer by drug demands from a public health perspective (n=13). Sixteen topics of discussion were identified in the articles: oncology organization in the Brazilian National Public Health System; public and/or supplementary health system; type of cancer in judicialization; objects of cancer judicialization; oncological drugs in judicialization; judicial arguments; legislation; jurisprudence; inequities; representation in lawsuits; doctor’s prescriptions; purchase and/or use of the drug by the individual; registration / incorporation of medicines; phosphoethanolamine; compliance with court decisions and effects of judicialization; and values of judicialization in oncology. It can be observed that the judicialization of cancer is a multifaceted phenomenon that is confused with the judicialization of cancer drugs. There are only a few articles on the judicialization of cancer from the perspective of the supplementary health system. Budgetary and organizational differences in oncology between public and supplementary health may explain the greater judicialization of oncology in the public sector. Thus, studies that deepen this theme can contribute to the dejudicialization of health and the improvement of public policies.
Mutação
Authors: Silva Denilson de Cassio
Published: September 2024

Creative writing.
The Rise of Sustainability Provisions in International Investment Agreements
Authors: Dotzauer Marius , Biber-Freudenberger Lisa , Dietz Thomas
Published: September 2024

There is a lively debate about whether international investment agreements (IIAs)—the central instruments governing foreign direct investment—are compatible with sustainable development objectives. One critical argument is that investment treaty provisions limit governments’ policy space to achieve transitions toward sustainability and may lead to costly legal disputes. Against this background, governments, international organizations, and other stakeholders have begun to consider options for modernizing international investment law by including provisions related to sustainable development in the treaties. In this article, we examine to what extent and why states include sustainability references in IIAs. Our automated text analysis of 2,083 bilateral investment treaties and 374 other treaties with investment provisions shows that the number of sustainability references has risen sharply recently. Drawing on the literature on issue linkage in economic agreements, we test different explanations for the changes in the treaty language. We find that the level of democracy among treaty parties and the experience of being sued in the past are strong drivers of the described trend.
Neural Correlates of Visual Feature Binding
Authors: Ro Tony , Pierce Allison M. , Porubanova Michaela , Lucas Miriam San
Published: September 2024

We perceive visual objects as unified although different brain areas process different features. An attentional mechanism has been proposed to be involved with feature binding, as evidenced by observations of binding errors (i.e., illusory conjunctions) when attention is diverted. However, the neural underpinnings of this feature binding are not well understood. We examined the neural mechanisms of feature binding by recording EEG during an attentionally demanding discrimination task. Unlike prestimulus alpha oscillatory activity and early ERPs (i.e., the N1 and P1 components), the N1pc, reflecting stimulus-evoked spatial attention, was reduced for errors relative to correct responses and illusory conjunctions. However, the later sustained posterior contralateral negativity, reflecting visual short-term memory, was reduced for illusory conjunctions and errors compared with correct responses. Furthermore, binding errors were associated with distinct posterior lateralized activity during a 200- to 300-msec window. These results implicate a temporal binding window that integrates visual features after stimulus-evoked attention but before encoding into visual short-term memory.
Event Segmentation Promotes the Reorganization of Emotional Memory
Authors: Laing Patrick A. F. , Dunsmoor Joseph E.
Published: September 2024

Event boundaries help structure the content of episodic memories by segmenting continuous experiences into discrete events. Event boundaries may also serve to preserve meaningful information within an event, thereby actively separating important memories from interfering representations imposed by past and future events. Here, we tested the hypothesis that event boundaries organize emotional memory based on changing dynamics as events unfold. We developed a novel threat-reversal learning task whereby participants encoded trial-unique exemplars from two semantic categories across three phases: preconditioning, fear acquisition, and reversal. Shock contingencies were established for one category during acquisition (CS+) and then switched to the other during reversal (CS−). Importantly, reversal was either separated by a perceptible event boundary (Experiment 1) or occurred immediately after acquisition, with no perceptible context shift (Experiment 2). In a surprise recognition memory test the next day, memory performance tracked the learning contingencies from encoding in Experiment 1, such that participants selectively recognized more threat-associated CS+ exemplars from before (retroactive) and during acquisition, but this pattern reversed toward CS− exemplars encoded during reversal. By contrast, participants with continuous encoding—without a boundary between conditioning and reversal—exhibited undifferentiated memory for exemplars from both categories encoded before acquisition and after reversal. Further analyses highlight nuanced effects of event boundaries on reversing conditioned fear, updating mnemonic generalization, and emotional biasing of temporal source memory. These findings suggest that event boundaries provide anchor points to organize memory for distinctly meaningful information, thereby adaptively structuring memory based on the content of our experiences.
Multi-level Shared Knowledge Guided Learning for Knowledge Graph Completion
Authors: Shan Yongxue , Zhou Jie , Peng Jie , Zhou Xin , Yin Jiaqian , Wang Xiaodong
Published: September 2024

In the task of Knowledge Graph Completion (KGC), the existing datasets and their inherent subtasks carry a wealth of shared knowledge that can be utilized to enhance the representation of knowledge triplets and overall performance. However, no current studies specifically address the shared knowledge within KGC. To bridge this gap, we introduce a multi-level Shared Knowledge Guided learning method (SKG) that operates at both the dataset and task levels. On the dataset level, SKG-KGC broadens the original dataset by identifying shared features within entity sets via text summarization. On the task level, for the three typical KGC subtasks—head entity prediction, relation prediction, and tail entity prediction—we present an innovative multi-task learning architecture with dynamically adjusted loss weights. This approach allows the model to focus on more challenging and underperforming tasks, effectively mitigating the imbalance of knowledge sharing among subtasks. Experimental results demonstrate that SKG-KGC outperforms existing text-based methods significantly on three well-known datasets, with the most notable improvement on WN18RR (MRR: 66.6%→ 72.2%, Hit@1: 58.7%→67.0%).
Innovating through Nature-Positive Engineering: How Can We Move Forward?
Authors: Bridges Todd , Jones Shana , Shudtz Matthew
Published: September 2024

Nature-based solutions – approaches that take advantage of existing aspects of the natural landscape and/or imitate natural processes through engineering and design to produce environmental and societal value – will be key to actively restoring the ocean’s ability to sustain human societies. Nature-based solutions upend the dominant paradigm informing engineering decision-making, which is ultimately founded upon the idea that humans can use hard, structural approaches to control nature and that degradation of natural functions can be offset. In the United States, the current legal tools and policy regimes to protect the environment and manage land use decisions were designed for the traditional engineering era. Pointing to the US Clean Water Act as an example, the article draws lessons learned from its successes and limitations, emphasising that future policy frameworks should clearly identify that encompassing nature as a way to enhance functioning and design is a high priority.
1. The House of Desolation
Authors: Fisher Barbara
Published: September 2024

In 1871, when Trix was less than three years old and Rudyard was just six, they were left without preparation or explanation to board with strangers in Southern England while their parents returned to Bombay, India. The House of Desolation refers to a time and a place—the six traumatic childhood years Trix and Rudyard spent as “Raj orphans” at Lorne Lodge (the appropriately named home of the cruel care-taking family). Rudyard wrote about this childhood misery in a short story, “Baa, Baa, Blacksheep,” and in his autobiography Something About Myself, and Trix wrote about it as well in a memoir, “Through Judy’s Eyes.” The children’s chief caretaker, called Aunty Rosa, encouraged Trix to sing, act, and recite while punishing and often beating Rudyard for showing off. She allowed her brutish son, Harry to bully Rudyard and to abuse Trix. Rudyard and Trix protected and comforted each other during this lonely childhood, where their only other companions were stories read from books and supplied by their own lively imaginations. Trix was Rudyard’s earliest inspiration and audience.
Effects of Process Parameters on Vibrational Behaviour of Sansevieria cylindrica Fiber Reinforced Polyester Composites
Authors: Devi M. P. Indira , Mayandi K. , Rajini N. , Ismail Sikiru O. , Mohammad Faruq
Published: September 2024

The natural fiber composites have attracted much interest among the researchers, due to their low cost, easy availability and enhancement in their properties. Many plants based natural fibers, including banana, sisal, hemp, jute, oil palm, Coirand kenaf, among others, have been
studied extensively. Sansevieria cylindrica fiber (SCF) is one of the plant-based leaf fibers, which has not been explored to a greater extent. The main purpose of this study focused on utilizing SCF as a potential reinforcement to produce polyester matrix composites. Unsaturated polyester
resin was used as matrix, because of its low cost and ease of use. In this work, free vibration studies were performed for pure SCF reinforced polyester composites. The SCF composites were fabricated with various fiber percentage weight (wt%) and different curing temperatures. The effects
of both fiber wt% and curing temperatures on natural frequency and damping of SCF composites were studied. It was observed that both natural frequency and damping showed significant variations on different process conditions of polymer composites. Based on vibrations studies, the optimum fiber
wt% was obtained at 40 and optimum curing temperature was observed as 60 °C. Furthermore, the effects of various chemical treatments on vibration behaviors of SCF composites was also investigated for the optimum fiber loading and curing temperature of 40 wt% and 60 °C, respectively.
Ca(OH)2 treated composite exhibited highest natural frequencies for all the three modes of vibration and silane treated counterpart showed highest damping values for the last two modes of vibration. Therefore, it was evident that chemical treatment significantly influenced the dynamic
properties, including natural frequency and damping of SCF reinforced polyester composites. This study can guide the composites/manufacturing companies to design and manufacture composites for engineering system applications, especially where vibration response is inevitable.
Sustainable Approach to Utilize Poultry Eggshell Waste as the Filler to Improve the Thermo-Mechanical Behaviour of Cigarette Filter Fibre Reinforced Vinyl Ester Composite
Authors: Vinodh S. , Dhavamani C.
Published: September 2024

This research focuses on significance of the world’s massive litter of Used Cigarette Filter fiber (UCF). It represents an effort to explore an innovative idea by using UCF as reinforcement phase in developing UCF-Polyvinyl Ester (PVE) sustainable composites production. The polymer
composites are fabricated by adopting compression moulding process with constant percentage of UCF and varying various weight % (2%, 4%, 6% and 8%) of Eggshell Powder (ESP). The fabricated composites are categorized with different techniques such as FTIR, SEM/EDS, Tensile, flexural, impact
and thermo gravimetric analysis to understand its mechanical and thermal stability. The attained results depict that UCF/PVE-filled ESP sustainable composites deliver enriched mechanical characters compared with its base matrix. Based on properties analysis, it can be detected that composites
with addition of 6 wt.% filler show better tensile and flexural properties compared to other composites. This might be due the after effect of ESP particles that enhances the interfacial bonding between the UCF and PVE.
Potential of Azo Dye Degrading Enzymes for Bioremediation in the Textile Industry: A Comparative Genomic Analysis for Safe Environment
Authors: Alnusairi Ghalia S. H. , AL-Surhanee Ameena A. , Alghanem Suliman M. S. , Alsudays Ibtisam Mohammed , Habeeb Talaat H. , Al-Sarraj Faisal , Al-Zahrani Majid , Alaklabi Abdullah , Almohaimeed Hailah M. , Soliman Mona H.
Published: September 2024

The textile industry plays a major part in the economy of the Kingdom of Saudi Arabia (KSA). However, the environmental impact of textile dyeing and wastewater discharge has become a growing concern in the region. This study addressed this issue by identifying and characterizing azo
dye degrading enzymes that can be used in bioremediation strategies. Six enzymes, namely Thiol reductase, Thiol peroxidase, Alkene reductase, NADH-oxidoreductase, Oxidoreductase, and Sulfite reductase, were identified through a literature review and used as queries in BLASTp to search for
homologous enzymes from Bacillus cereus, Brevibacillus brevis, Bacillus acidicola, and Paenibacillus alvei. The physicochemical characteristics and subcellular distribution of these enzymes were determined using online tools. Phylogenetic analysis was performed to investigate
the evolutionary connection of these enzymes across different bacterial species. Additionally, gene structure and motif analysis were conducted to gain insights into functional motifs and gene organization of these enzymes. Domain prediction and protein–protein interaction analysis were
carried out to identify conserved domains and potential protein interactions. The outcomes of this study offer valuable understandings on prospect of azo dye degrading enzymes for bioremediation strategies in the KSA textile industry, which is in agreement with the future Vision 2030 strategy.
The identified enzymes and their homologs from other microbial genomes represent promising candidates for further experimental validation and utilization in bioremediation processes. Moreover, they contribute to the development of effective bioremediation strategies for the textile industry
in the KSA region. Overall, this study enhances our understanding on azo dye degrading enzymes and their potential uses in the textile industry, particularly in the context of KSA.
Precising E-waste Generation for Economic Recycling
Authors: Sharma Himanshu , Kumar Harish
Published: September 2024

With enhanced technological advancements, digital transformation and globalisation, there has been a significant rise in the amount of electronic waste (e-waste), posing a threat to the global economy and environment. The study deploys a grey prediction model to forecast the amount of e-waste generation by 2026 in India. The precise data generated can be further used to calculate operation costs, workforce requirements, collection time, warehouse and landfills needed for economical recycling of e-waste.

JEL Codes: A1, C8, Q5
The distribution of the extrachromosomal DNA molecules in early lung cancer
Authors: Fang Jianfei , Ying Lisha , Ma Zhengxiao , Yang Ying , Zhu Rui , Su Dan
Published: September 2024

Lung cancer (LC) is a highly lethal cancer worldwide. Research on the distribution and nature of extrachromosomal DNA molecules (EcDNAm) in early LC is scarce. In this study, after removing linear DNA and mitochondrial circular DNA, EcDNAm were extracted from two paired LC tissue samples and amplified using rolling circle amplification. High throughput extrachromosomal DNA (EcDNA) or RNA sequencing and bioinformatics analysis were subsequently utilized to explore the distribution and nature of the EcDNAm. Additionally, to elucidate the role of oncogenes with large EcDNAm sizes, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. The RNA sequencing results revealed significant differences in certain genes between tumors and corresponding normal samples. At the same time, slight distinctions were observed between relapsed and non-relapsed tumor samples. The nature of the EcDNAm was compared between LC samples and matched normal samples. There was a tendency for the number of EcDNAm with longer size (EcDNA) and its containing driver oncogenes to be higher in cancer samples. Enrichment analysis of the cancer samples revealed enrichment in biological processes, such as positive regulation of protein localization, axon development, and in-utero embryonic development. This study highlights the universal distribution and characteristics of EcDNAm in early LC. Moreover, our work fills the investigation of the EcDNAm gap and future studies should focus on the application of EcDNA as a potential biomarker in patients with early LC.
Social Isolation and Population Density: Racial and Ethnic Differences Among Older Adults
Authors: You Eunhea , Nicholson Nicholas R. , Jacobson Stephanie A. , Poghosyan Hermine , Feinn Richard S. , Charlotte L. Rachel
Published: September 2024

This study uses secondary data analysis to assess the relationship between social isolation (SI) and population density in the US, as well as any moderating influence that race/ethnicity may have on that relationship. A recent consensus on the measure of SI is that it focuses on the objective absence of social connections, whereas loneliness refers to subjective assessments of one’s social connections. Therefore, while the original study measured both objective and subjective SI may be innovative, it may also be overly ambitious. SI puts older people at risk for health problems, including an increased chance of dying. The AARP Foundation gathered the initial convenience sample, which included 8149 senior citizens. The study determined population density using self-reported zip codes, measured as persons per square mile, and divided the results into tertiles. Linear mixed models were used to investigate the moderating role of race/ethnicity between population density and SI. The findings revealed that greater population density was associated with less SI for individuals residing in zip codes with a higher percentage of the same race/ethnicity, but more SI for those in zip codes with a lower percentage of the same race/ethnicity. These results suggest that race/ethnicity should be considered in future studies or when developing policies and interventions to address SI among older adults in high-population-density areas. For example, when policymakers aim to address SI in a community, they may want to collect data based on zip codes and create targeted interventions for specific racial/ethnic groups within those zip code areas.