bluuebunny/crossref_metadata_2025 huggingface dataset:
Table S14 from CD46-Targeted Theranostics for PET and 225Ac-Radiopharmaceutical Therapy of Multiple Myeloma
Authors: Wadhwa Anju , Wang Sinan , Patiño-Escobar Bonell , Bidkar Anil P. , Bobba Kondapa Naidu , Chan Emily , Meher Niranjan , Bidlingmaier Scott , Su Yang , Dhrona Suchi , Geng Huimin , Sarin Vishesh , VanBrocklin Henry F. , Wilson David M. , He Jiang , Zhang Li , Steri Veronica , Wong Sandy W. , Martin Thomas G. , Seo Youngho , Liu Bin , Wiita Arun P. , Flavell Robert R.
Published: March 2024

Table S14: [89Zr]Zr-DFO-YS5 %IA/Organ in the ANBL6 subcutaneous xenograft models.
Supplementary Methods 1 from CD46-Targeted Theranostics for PET and 225Ac-Radiopharmaceutical Therapy of Multiple Myeloma
Authors: Wadhwa Anju , Wang Sinan , Patiño-Escobar Bonell , Bidkar Anil P. , Bobba Kondapa Naidu , Chan Emily , Meher Niranjan , Bidlingmaier Scott , Su Yang , Dhrona Suchi , Geng Huimin , Sarin Vishesh , VanBrocklin Henry F. , Wilson David M. , He Jiang , Zhang Li , Steri Veronica , Wong Sandy W. , Martin Thomas G. , Seo Youngho , Liu Bin , Wiita Arun P. , Flavell Robert R.
Published: March 2024

Supplementary Methods
Figure S7 from CD46-Targeted Theranostics for PET and 225Ac-Radiopharmaceutical Therapy of Multiple Myeloma
Authors: Wadhwa Anju , Wang Sinan , Patiño-Escobar Bonell , Bidkar Anil P. , Bobba Kondapa Naidu , Chan Emily , Meher Niranjan , Bidlingmaier Scott , Su Yang , Dhrona Suchi , Geng Huimin , Sarin Vishesh , VanBrocklin Henry F. , Wilson David M. , He Jiang , Zhang Li , Steri Veronica , Wong Sandy W. , Martin Thomas G. , Seo Youngho , Liu Bin , Wiita Arun P. , Flavell Robert R.
Published: March 2024

Figure S7: [89Zr]Zr-DFO-IgG PET imaging in the healthy nude mice and healthy NSG mice demonstrates significantly different uptake in the bone marrow.
Supplementary Table S2 from Phase I Trial of First-line Bintrafusp Alfa in Patients with Locally Advanced or Persistent/Recurrent/Metastatic Cervical Cancer
Authors: Oaknin Ana , Ghamande Sharad A. , Kasamatsu Yuka , Gil-Martin Marta , Grau-Bejar Juan Francisco , Garcia-Duran Carmen , Sato Masashi , Siddiqui Abdul , Chaudhary Surendra Pal , Vugmeyster Yulia , Hasegawa Kosei
Published: March 2024

Table S2. Study representativeness.
Supplementary Methods S1 from Phase I Trial of First-line Bintrafusp Alfa in Patients with Locally Advanced or Persistent/Recurrent/Metastatic Cervical Cancer
Authors: Oaknin Ana , Ghamande Sharad A. , Kasamatsu Yuka , Gil-Martin Marta , Grau-Bejar Juan Francisco , Garcia-Duran Carmen , Sato Masashi , Siddiqui Abdul , Chaudhary Surendra Pal , Vugmeyster Yulia , Hasegawa Kosei
Published: March 2024

Supplementary Methods
Data from Spatiotemporal Quantification of HER2-targeting Antibody–Drug Conjugate Bystander Activity and Enhancement of Solid Tumor Penetration
Authors: Wei Qing , Yang Teng , Zhu Jiayu , Zhang Ziwen , Yang Le , Zhang Yuchao , Hu Can , Chen Jiahui , Wang Jinchao , Tian Xuefei , Shimura Takaya , Fang Jianmin , Ying Jieer , Fan Mengyang , Guo Peng , Cheng Xiangdong
Published: March 2024

AbstractPurpose:
Antibody–drug conjugate (ADC) has had a transformative effect on the treatment of many solid tumors, yet it remains unclear how ADCs exert bystander activity in the tumor microenvironment.
Experimental Design:
Here, we directly visualized and spatiotemporally quantified the intratumor biodistribution and pharmacokinetics of different ADC components by developing dual-labeled fluorescent probes.
Results:
Mechanistically, we found that tumor penetration of ADCs is distinctly affected by their ability to breach the binding site barrier (BSB) in perivascular regions of tumor vasculature, and bystander activity of ADC can only partially breach BSB. Furthermore, bystander activity of ADCs can work in synergy with coadministration of their parental antibodies, leading to fully bypassing BSBs and enhancing tumor penetration via a two-step process.
Conclusions:
These promising preclinical data allowed us to initiate a phase I/II clinical study of coadministration of RC48 and trastuzumab in patients with malignant stomach cancer to further evaluate this treatment strategy in humans.
Radiotherapy Enhances Metastasis Through Immune Suppression by Inducing PD-L1 and MDSC in Distal Sites
Authors: Hou Yuzhu , Yang Kaiting , Wang Liangliang , Wang Jiaai , Huang Xiaona , Piffkó András , Luo Sean Z. , Yu Xinshuang , Rao Enyu , Martinez Carlos , Bugno Jason , Mack Matthias , Vokes Everett E. , Pitroda Sean P. , Chmura Steven J. , Weichselbaum Ralph R. , Liang Hua Laura
Published: March 2024

Purpose:

Radiotherapy (RT) is a widely employed anticancer treatment. Emerging evidence suggests that RT can elicit both tumor-inhibiting and tumor-promoting immune effects. The purpose of this study is to investigate immune suppressive factors of radiotherapy.

Experimental Design:

We used a heterologous two-tumor model in which adaptive concomitant immunity was eliminated.

Results:

Through analysis of PD-L1 expression and myeloid-derived suppressor cells (MDSC) frequencies using patient peripheral blood mononuclear cells and murine two-tumor and metastasis models, we report that local irradiation can induce a systemic increase in MDSC, as well as PD-L1 expression on dendritic cells and myeloid cells, and thereby increase the potential for metastatic dissemination in distal, nonirradiated tissue. In a mouse model using two distinct tumors, we found that PD-L1 induction by ionizing radiation was dependent on elevated chemokine CXCL10 signaling. Inhibiting PD-L1 or MDSC can potentially abrogate RT-induced metastasis and improve clinical outcomes for patients receiving RT.

Conclusions:

Blockade of PD-L1/CXCL10 axis or MDSC infiltration during irradiation can enhance abscopal tumor control and reduce metastasis.
Supplementary Video 2C from Mitochondria Transfer by Platelet-Derived Microparticles Regulates Breast Cancer Bioenergetic States and Malignant Features
Authors: Veilleux Vanessa , Pichaud Nicolas , Boudreau Luc H. , Robichaud Gilles A.
Published: March 2024

Supplementary Video 2C displays the intracellular localization of internalized fluorescent mitochondria provided by microparticles in MCF10A cells using 3D confocal zStacks imaging.
Supplementary Video 2A from Mitochondria Transfer by Platelet-Derived Microparticles Regulates Breast Cancer Bioenergetic States and Malignant Features
Authors: Veilleux Vanessa , Pichaud Nicolas , Boudreau Luc H. , Robichaud Gilles A.
Published: March 2024

Supplementary Video 2A displays the intracellular localization of internalized fluorescent mitochondria provided by microparticles in MB231 cells using 3D confocal zStacks imaging.
Supplementary Figure 6 from Single-Cell Transcriptomics Reveals Pre-existing COVID-19 Vulnerability Factors in Lung Cancer Patients
Authors: Liu Wendao , Li Wenbo , Zhao Zhongming
Published: March 2024

Supplementary Figure 6. The contribution of cell populations to signaling pathways.
Supplementary Figure 5 from Mitochondria Transfer by Platelet-Derived Microparticles Regulates Breast Cancer Bioenergetic States and Malignant Features
Authors: Veilleux Vanessa , Pichaud Nicolas , Boudreau Luc H. , Robichaud Gilles A.
Published: March 2024

Figure S5 shows the effects of microparticles on the migration and invasion capacities of non-cancerous control cell line MCF10A.
Supplementary Figure 3 from Mitochondria Transfer by Platelet-Derived Microparticles Regulates Breast Cancer Bioenergetic States and Malignant Features
Authors: Veilleux Vanessa , Pichaud Nicolas , Boudreau Luc H. , Robichaud Gilles A.
Published: March 2024

Figure S3 validates the findings of Fig.S2 by demonstrating the intracellular localization of fluorescent microparticles using confocal microscopy.
Supplementary Figure 1 from Mitochondria Transfer by Platelet-Derived Microparticles Regulates Breast Cancer Bioenergetic States and Malignant Features
Authors: Veilleux Vanessa , Pichaud Nicolas , Boudreau Luc H. , Robichaud Gilles A.
Published: March 2024

Figure S1 displays the capacity of fluorescent microparticles to interact with cancer cells. Using flow cytometry, we measure fluorescence uptake by cells following cell co-cultures with microparticles.
Figure S2 from TNFRSF19 within the 13q12.12 Risk Locus Functions as a Lung Cancer Suppressor by Binding Wnt3a to Inhibit Wnt/β-Catenin Signaling
Authors: Zuo Xianglin , Wang Xuchun , Ma Tingzheng , Chen Shuhan , Cao Pingping , Cheng He , Yang Nan , Han Xiao , Gao Wei , Liu Xiaoyu , Sun Yujie
Published: March 2024

TNFRSF19 -/- Beas-2B cell lines were established by CRISPR/Cas9
technique.
Supplemental Figure S1 from Modeling Molecular Pathogenesis of Idiopathic Pulmonary Fibrosis-Associated Lung Cancer in Mice
Authors: Barravecchia Ivana , Lee Jennifer M. , Manassa Jason , Magnuson Brian , Ferris Sarah F. , Cavanaugh Sophia , Steele Nina G. , Espinoza Carlos E. , Galban Craig J. , Ramnath Nithya , Frankel Timothy L. , Pasca di Magliano Marina , Galban Stefanie
Published: March 2024

Supplemental Figure S1. Transgenic mouse IPF-LC model development.
Supplementary Materials and Methods from LINC00869 Promotes Hepatocellular Carcinoma Metastasis via Protrusion Formation
Authors: Shao Xiaowen , Dang Yamei , Zhang Tingting , Bai Nan , Huang Jianing , Guo Mengya , Sun Li , Li Minghe , Sun Xiao , Zhang Xinran , Han Feng , Zhang Ning , Zhuang Hao , Li Yongmei
Published: March 2024

Supplementary Materials and Methods：Plasma membrane protein extraction, Cdc42 activation assay, etc
Supplementary Figure 6 from LINC00869 Promotes Hepatocellular Carcinoma Metastasis via Protrusion Formation
Authors: Shao Xiaowen , Dang Yamei , Zhang Tingting , Bai Nan , Huang Jianing , Guo Mengya , Sun Li , Li Minghe , Sun Xiao , Zhang Xinran , Han Feng , Zhang Ning , Zhuang Hao , Li Yongmei
Published: March 2024

LINC00869 had no effect on the activity or expression of other cytoskeletal regulators.
Supplementary Figure 3 from LINC00869 Promotes Hepatocellular Carcinoma Metastasis via Protrusion Formation
Authors: Shao Xiaowen , Dang Yamei , Zhang Tingting , Bai Nan , Huang Jianing , Guo Mengya , Sun Li , Li Minghe , Sun Xiao , Zhang Xinran , Han Feng , Zhang Ning , Zhuang Hao , Li Yongmei
Published: March 2024

The characteristics of LINC00869 in HCC cells.
Abstract B002: ARID1A loss activates MAPK signaling via DUSP4 downregulation: a mechanistic insight in endometrial carcinoma
Authors: Mandal Jayaprakash , Yu Zheng-Cheng , Shih Ie-Ming , Wang Tian-Li
Published: March 2024

The intricate interplay between chromatin remodelers, transcriptional regulation, and downstream cellular processes is gradually unraveling. AT-rich interactive domain-containing protein 1A (ARID1A), a tumor suppressor and chromatin remodeler, is frequently mutated in endometrium-related malignancies including ovarian or uterine clear cell carcinoma (CCC) and endometrioid carcinoma (EMCA). How ARID1A mutation alters downstream signaling is yet to be established. Based on the TCGA proteomics datasets, MAPK and ARID1A are negatively correlated in endometrial cancer. Yet, the underlying molecular mechanism of this association remains unclear. Using ARID1A-proficient and ARID1A-deficient isogenic human endometrial epithelial cells, we explored transcriptomic changes and discovered notable downregulation of a MAPK phosphatase, dual-specificity phosphatase 4 (DUSP4), in ARID1A-deficient cells. This expression pattern was further validated in additional pairs of isogenic cell lines, ES-2, MCF10a, and HCT116. Chromatin immunoprecipitation sequencing (ChIP-seq) was utilized to assess active and repressive transcription histone marks on global and 5’ transcriptional regulatory regions of DUSP4. ChIP-seq demonstrated decreased histone acetylation marks (H3K27Ac, H3K9Ac) on DUSP4 enhancer and promoter regions of ARID1A-deficient cells, suggesting ARID1A's role in modulating chromatin accessibility and gene expression. Furthermore, a positive correlation between ARID1A and DUSP4 expression was established using a Pax8-driven conditional knockout mouse cohort and in human endometroid carcinoma tissues. Moreover, an inverse expression correlation between ARID1A and the phosphatase substrates of DUSP4, including p-p38, p-JNK, and p-ERK in the MAPK signaling pathway, was observed in this genetically engineered murine model and in the TCGA datasets of human uterine carcinomas. Interestingly, ectopic DUSP4 expression decreased cell proliferation, and MAPK pathway targeting, specifically via ERK inhibitor Ulixertinib, significantly mitigated tumor growth in vivo. In conclusion, our findings suggest ARID1A modulates DUSP4 expression by remodeling the chromatin landscape which leads to an inhibitory effect on the MAPK pathway and suppresses tumor progression. ARID1A-DUSP4-MAPK axis offers a promising avenue for developing targeted therapies against ovarian or uterine CCC and EMCA.

Citation Format: Jayaprakash Mandal, Zheng-Cheng Yu, Ie-Ming Shih, Tian-Li Wang. ARID1A loss activates MAPK signaling via DUSP4 downregulation: a mechanistic insight in endometrial carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B002.
Abstract B033: Functional characterization of ALK5 (TGFBR1) mutations in endometrial cancer
Authors: Yu Eun-Jeong , Bell Daphne W.
Published: March 2024

ALK5 (TGFBR1) is a transmembrane receptor serine/threonine kinase that transduces TGF-b (Transforming Growth Factor b) signaling to activate SMAD2/3-dependent and -independent pathways. The purpose of this study is to determine the functional effects of ALK5 mutations in endometrial cancer (EC). Using nine in silico algorithms, we found that 79% (23 of 39) of ALK5 kinase domain mutations in EC are predicted to impact protein function. To test these predictions experimentally, constructs expressing wildtype-, constitutively active-, kinase-dead, or mutant-ALK5, including ALK5-A230V, were transfected into NIH3T3 cells, which have low endogenous ALK5 levels. Following TGF-β stimulation, we observed that transient exogenous expression of ALK5-A230V, located in the ATP-binding pocket, delayed SMAD2/3 signal transduction and altered SMAD-independent signaling. We further showed that the ALK5-A230V mutant has reduced protein stability via a ubiquitin-dependent protein degradation mechanism. Our structural modeling predicts that SB431542, a small molecule ATP-competitive inhibitor of ALK5 will bind to the ALK5-A230V mutant with less affinity than to wildtype ALK5. We, therefore, examined the inhibitory effect of SB431542 on wildtype- and mutant-ALK5 activity using a Smad-binding element (SBE) luciferase reporter assay in combination with TGF-β stimulation. SBE luciferase activity in ALK5-A230V-transfected cells was inhibited less by SB431542 than in wildtype-ALK5 transfected cells indicating that ALK5-A230V is less sensitive to SB431542 than wildtype ALK5, potentially due to the changes in affinity. Our findings are novel and show that the ALK5-A230V mutant is a partial loss-of-function mutant that attenuates TGF-b signal transduction and has reduced sensitivity to an ALK5 small molecule inhibitor.

Citation Format: Eun-Jeong Yu, Daphne W. Bell. Functional characterization of ALK5 (TGFBR1) mutations in endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B033.
Abstract PR006: ARID1A/B mutations retarget mSWI/SNF chromatin remodeler activity and define a spectrum of dedifferentiation in endometrial carcinoma
Authors: St. Laurent Jessica D. , Xu Grace , Cervantas Kasey , Patil Ajinkya , Sankar Akshay , Chen Shary , Kolin David , Wang Yemin , Huntsman David G. , Kadoch Cigall
Published: March 2024

Dedifferentiated/undifferentiated endometrial carcinoma (DEC/UEC) is a highly aggressive histologic subtype of uterine cancer with a higher incidence among non-Hispanic Black women. Recent exome-wide sequencing studies have revealed frequent and often concomitant mutations in the ARID1A and ARID1B genes in over 50% of DEC/UEC cases and 30% of all endometrial carcinomas. The mSWI/SNF family of chromatin remodelers are critical regulators of cell type-specific chromatin accessibility and gene expression, existing in three distinct forms: canonical BAF (cBAF), Poly bromodomain-associated BAF (PBAF), and non-canonical BAF (ncBAF). The paralog subunits, ARID1A and ARID1B, specifically nucleate the assembly of cBAF complexes. However, the precise role ARID1A/ARID1B mutations (cBAF loss) play in the development of dedifferentiated endometrial carcinoma remains unclear. In this study, we define an expression signature associated with endometrial “dedifferentiation” by profiling the well-differentiated and dedifferentiated components of cBAF loss DEC cases through laser capture microdissection followed by RNA sequencing. Introduction of ARID1A or ARID1B in cBAF loss DEC cell lines demonstrated the restoration of cBAF assembly, confirmed by glycerol gradient and IP mass spectrometry. Upon the expression of ARID1A or ARID1B, we observed widespread chromatin occupancy and DNA accessibility at distinct paralog-specific sites, along with common sites associated with epithelial lineage differentiation, estrogen receptor, and PI3K/AKT pathway signaling. These findings align with the differentiation signature, defined in DEC cases demonstrating downregulation of genes associated with Myc targets, cell cycle checkpoint pathways, and DNA repair, suggesting these pathways represent potential therapeutic avenues for targeting DEC/UEC. Collectively, these data establish that well-differentiated endometrial carcinoma and DEC/UEC with mSWI/SNF mutations represent a spectrum of cBAF loss, defining the unique roles of ARID1A and ARID1B in endometrial carcinoma development. Furthermore, these findings imply that cBAF loss drives the widespread changes in DEC morphology, gene expression, and clinical behavior, enhancing our understanding of the etiology and therapeutic options for these cancers.

Citation Format: Jessica D. St. Laurent, Grace Xu, Kasey Cervantas, Ajinkya Patil, Akshay Sankar, Shary Chen, David Kolin, Yemin Wang, David G. Huntsman, Cigall Kadoch. ARID1A/B mutations retarget mSWI/SNF chromatin remodeler activity and define a spectrum of dedifferentiation in endometrial carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr PR006.
Supplementary Synthetic Methods from INX-315, a Selective CDK2 Inhibitor, Induces Cell Cycle Arrest and Senescence in Solid Tumors
Authors: Dietrich Catherine , Trub Alec , Ahn Antonio , Taylor Michael , Ambani Krutika , Chan Keefe T. , Lu Kun-Hui , Mahendra Christabella A. , Blyth Catherine , Coulson Rhiannon , Ramm Susanne , Watt April C. , Matsa Sunil Kumar , Bisi John , Strum Jay , Roberts Patrick , Goel Shom
Published: March 2024

Description of methods to synthesize INX-315
Figure 2 from INX-315, a Selective CDK2 Inhibitor, Induces Cell Cycle Arrest and Senescence in Solid Tumors
Authors: Dietrich Catherine , Trub Alec , Ahn Antonio , Taylor Michael , Ambani Krutika , Chan Keefe T. , Lu Kun-Hui , Mahendra Christabella A. , Blyth Catherine , Coulson Rhiannon , Ramm Susanne , Watt April C. , Matsa Sunil Kumar , Bisi John , Strum Jay , Roberts Patrick , Goel Shom
Published: March 2024

Activity of INX-315 in CCNE1-amplified cancers. A, IC50s for palbociclib and INX-315 for cell lines shown using CellTiter Glo viability assay. All cells were treated for 6 days, n = 3 technical replicates per cell line. B, Cell cycle phase profiles of OVCAR-3 and MKN1 cells treated with INX-315. All cells were treated for 24 hours, n = 3 technical replicates per cell line; error bars are SD. C, Western blots for phosphorylated/total Rb and cyclin A2 in OVCAR3 and MKN1 cells treated with INX-315 for 24 hours. D and E, Tumor growth curves for CCNE1-amplified gastric and ovarian carcinoma models treated with INX-315 at doses shown (GA0103 n = 8 per group; GA0114 n = 8 per group; OVCAR3 n = 10 per group; OV5398 n = 10 per group; error bars represent SEM; P values calculated using two-way ANOVA. all experiments performed once). F, Western blots for phosphorylated/total Rb and cyclin A2 in tumor tissue lysates treated with control vehicle or INX-315. Samples were collected at experimental endpoint from experiments in E.
Supplementary Table S1 from Cancer Mutations Converge on a Collection of Protein Assemblies to Predict Resistance to Replication Stress
Authors: Zhao Xiaoyu , Singhal Akshat , Park Sungjoon , Kong JungHo , Bachelder Robin , Ideker Trey
Published: March 2024

Table S1 Annotation of NeST assembly.xlsx
Supplementary Table 5 from A Compendium of Syngeneic, Transplantable Pediatric High-Grade Glioma Models Reveals Subtype-Specific Therapeutic Vulnerabilities
Authors: McNicholas Michael , De Cola Antonella , Bashardanesh Zahedeh , Foss Amelia , Lloyd Cameron B. , Hébert Steven , Faury Damien , Andrade Augusto Faria , Jabado Nada , Kleinman Claudia L. , Pathania Manav
Published: March 2024

Cell type ontologies derived from snRNA-seq data.
Data from Noninvasive Detection of Neuroendocrine Prostate Cancer through Targeted Cell-free DNA Methylation
Authors: Franceschini Gian Marco , Quaini Orsetta , Mizuno Kei , Orlando Francesco , Ciani Yari , Ku Sheng-Yu , Sigouros Michael , Rothmann Emily , Alonso Alicia , Benelli Matteo , Nardella Caterina , Auh Joonghoon , Freeman Dory , Hanratty Brian , Adil Mohamed , Elemento Olivier , Tagawa Scott T. , Feng Felix Y. , Caffo Orazio , Buttigliero Consuelo , Basso Umberto , Nelson Peter S. , Corey Eva , Haffner Michael C. , Attard Gerhardt , Aparicio Ana , Demichelis Francesca , Beltran Himisha
Published: March 2024

Abstract
Castration-resistant prostate cancer (CRPC) is a heterogeneous disease associated with phenotypic subtypes that drive therapy response and outcome differences. Histologic transformation to castration-resistant neuroendocrine prostate cancer (CRPC-NE) is associated with distinct epigenetic alterations, including changes in DNA methylation. The current diagnosis of CRPC-NE is challenging and relies on metastatic biopsy. We developed a targeted DNA methylation assay to detect CRPC-NE using plasma cell-free DNA (cfDNA). The assay quantifies tumor content and provides a phenotype evidence score that captures diverse CRPC phenotypes, leveraging regions to inform transcriptional state. We tested the design in independent clinical cohorts (n = 222 plasma samples) and qualified it achieving an AUC > 0.93 for detecting pathology-confirmed CRPC-NE (n = 136). Methylation-defined cfDNA tumor content was associated with clinical outcomes in two prospective phase II clinical trials geared towards aggressive variant CRPC and CRPC-NE. These data support the application of targeted DNA methylation for CRPC-NE detection and patient stratification.
Significance:
Neuroendocrine prostate cancer is an aggressive subtype of treatment-resistant prostate cancer. Early detection is important, but the diagnosis currently relies on metastatic biopsy. We describe the development and validation of a plasma cell–free DNA targeted methylation panel that can quantify tumor fraction and identify patients with neuroendocrine prostate cancer noninvasively.

This article is featured in Selected Articles from This Issue, p. 384
Combining TIGIT Blockade with MDSC Inhibition Hinders Breast Cancer Bone Metastasis by Activating Antitumor Immunity
Authors: Monteran Lea , Ershaid Nour , Scharff Ye’ela , Zoabi Yazeed , Sanalla Tamer , Ding Yunfeng , Pavlovsky Anna , Zait Yael , Langer Marva , Caller Tal , Eldar-Boock Anat , Avivi Camila , Sonnenblick Amir , Satchi-Fainaro Ronit , Barshack Iris , Shomron Noam , Zhang Xiang H.-F. , Erez Neta
Published: March 2024

Bone is the most common site of breast cancer metastasis. Bone metastasis is incurable and is associated with severe morbidity. Utilizing an immunocompetent mouse model of spontaneous breast cancer bone metastasis, we profiled the immune transcriptome of bone metastatic lesions and peripheral bone marrow at distinct metastatic stages, revealing dynamic changes during the metastatic process. We show that cross-talk between granulocytes and T cells is central to shaping an immunosuppressive microenvironment. Specifically, we identified the PD-1 and TIGIT signaling axes and the proinflammatory cytokine IL1β as central players in the interactions between granulocytes and T cells. Targeting these pathways in vivo resulted in attenuated bone metastasis and improved survival, by reactivating antitumor immunity. Analysis of patient samples revealed that TIGIT and IL1β are prominent in human bone metastasis. Our findings suggest that cotargeting immunosuppressive granulocytes and dysfunctional T cells may be a promising novel therapeutic strategy to inhibit bone metastasis.

Significance: Temporal transcriptome profiling of the immune microenvironment in breast cancer bone metastasis revealed key communication pathways between dysfunctional T cells and myeloid derived suppressor cells. Cotargeting of TIGIT and IL1β inhibited bone metastasis and improved survival. Validation in patient data implicated these targets as a novel promising approach to treat human bone metastasis.
Targeting the DHX9 RNA Helicase to Induce Antitumor Immunity in Small-Cell Lung Cancer
Authors: Chiappinelli Katherine B.
Published: March 2024

Murayama and colleagues establish DHX9 as an exciting new target to induce viral mimicry and downstream antitumor immunity. The potential for use in combination with existing immune therapies is especially exciting in SCLC, an immunologically cold and deadly disease.

See related article by Murayama et al., p. 468 (10) .
Table S3 from Baseline Serum Inflammatory Proteins Predict Poor CAR T Outcomes in Diffuse Large B-cell Lymphoma
Authors: Faramand Rawan G. , Lee Sae Bom , Jain Michael D. , Cao Biwei , Wang Xuefeng , Rejeski Kai , Subklewe Marion , Fahrmann Johannes F. , Saini Neeraj Y. , Hanash Samir M. , Kang Yun Pyo , Chang Darwin , Rodriguez Paolo C. , Dean Erin A. , Nishihori Taiga , Shah Bijal D. , Lazaryan Aleksandr , Chavez Julio , Khimani Farhad , Pinilla-Ibarz Javier A. , Dam Marian , Reid Kayla M. , Corallo Salvatore A. , Menges Meghan , Hidalgo Vargas Melanie , Mandula Jay K. , Holliday Brian A. , Bachmeier Christina A. , Speth Kelly , Song Qinghua , Mattie Mike , Locke Frederick L. , Davila Marco L.
Published: March 2024

Table S3 shows the Multivariable Cox Regression analysis of overall (A) and progression free survival (B) using CRP and Ferritin risk categories
FIGURE 7 from A Pilot Study on Patient-specific Computational Forecasting of Prostate Cancer Growth during Active Surveillance Using an Imaging-informed Biomechanistic Model
Authors: Lorenzo Guillermo , Heiselman Jon S. , Liss Michael A. , Miga Michael I. , Gomez Hector , Yankeelov Thomas E. , Reali Alessandro , Hughes Thomas J.R.
Published: March 2024

Summary of metrics assessing the performance of the biomechanistic model in the fitting-forecasting scenario. A and B, Unity plots to assess the agreement between the model estimation and mpMRI measurement of the tumor volume (VT) and the total tumor cell volume (VN) across the patient cohort (n = 7). These global tumor metrics were calculated at the dates of the second and third mpMRI scans (blue and green points). The unity plots in A and B further report the corresponding PCC and CCC for the global tumor metrics at the dates of the second and third mpMRI scans. C–F, Distributions of four local metrics assessing the agreement between the tumor cell density map calculated with our biomechanistic model and extracted from mpMRI data across the patient cohort in the global calibration scenario: Dice similarity coefficient (DSC), root mean squared error (RMSE), Pearson correlation coefficient (PCC), and concordance correlation coefficient (CCC). These local metrics were calculated at the dates of the second and third mpMRI scans (blue and green boxplots).
FIGURE 2 from A Pilot Study on Patient-specific Computational Forecasting of Prostate Cancer Growth during Active Surveillance Using an Imaging-informed Biomechanistic Model
Authors: Lorenzo Guillermo , Heiselman Jon S. , Liss Michael A. , Miga Michael I. , Gomez Hector , Yankeelov Thomas E. , Reali Alessandro , Hughes Thomas J.R.
Published: March 2024

Mapping ADC to N and GS. A, Nonlinear least-squares fit of a hyperbolic tangent model (blue solid line) of the mean values of ADC in the tumor across GS groups in previous studies (red dots), which were normalized with respect to the mean ADC in healthy tissue (ADCh) reported for each of them (41–45). We leverage a continuous, extended GS scale in which 0 < GS < 2 indicates healthy and pretumoral tissue and GS > 2 corresponds to prostate cancer (i.e., overlapping the standard discrete values of the GS used to assess histopathologic samples of prostate cancer; see refs. 2, 4). Further details on the hyperbolic tangent model and the fitting method are reported in Supplementary Data S1. B, Mapping of the hyperbolic tangent model obtained for the normalized ADC values (ADC/ADCh, A) to normalized tumor cell density values (i.e., , B). We use the linear mapping in Eq. (1), which introduces a negative proportionality between ADC and tumor cell density, as in other mpMRI-informed biomechanistic models of solid tumor growth (18, 21, 28, 29).
Near Adult Height and Body Mass Index Changes in Growth Hormone Treated Short Children with Noonan Syndrome: The Belgian Experience
Authors: De Schepper Jean , Thomas Muriel , Huysentruyt Koen , Becker Marianne , Boros Emese , Casteels Kristina , Chivu Olimpia , De Waele Kathleen , Dotremont Hilde , Lysy Philippe A. , Massa Guy , Parent Anne-Simone , Rochtus Anne , Gies Inge
Published: March 2024

Introduction: A variable near adult height (NAH) outcome after growth hormone (GH) therapy in Noonan syndrome (NS) patients with short stature has been reported. The main objective of this study was to evaluate NAH and body mass index (BMI) evolution in a large Belgian cohort of NS patients treated for short stature. The secondary objectives were to investigate whether sex, genotype, the presence of a thoracic deformity, and/or a heart anomaly might affect NAH and to validate the recently developed NAH prediction model by Ranke et al. Methods: Clinical and auxological data of GH treated short NS patients born before 2001 were extracted from the national Belgrow registry. NAH was available in 54 (35 male) genotyped NS using a gene panel of 9 genes, showing pathogenic variants in PTPN11 in 32 and in SOS1 in 5 patients, while in 17 patients gene panel analysis was inconclusive (no-mutation group). Results: After a median (P10; P90) duration of 5.4 (2.2; 10.3) years of GH therapy with a median dose of 0.05 mg/kg/day NS patients reached a median NAH of −1.7 (−3.1; −0.8) SDS. Median total height gain was 1.1 (0.1; 2.3) SDS. Sex, genotype, and the presence of a thoracic or cardiac malformation did not correlate with NAH or total height gain. Linear regression modelling revealed that height SDS at start (β = 0.90, p < 0.001), mid-parental height SDS (β = 0.27; p = 0.005), birth weight SDS (β = 0.15; p = 0.051), age at start (β = 0.07; p = 0.032) were independently associated with NAH SDS. Median BMI SDS increased significantly (p < 0.001) from −1.0 (−2.5; 0.0) at start to −0.2 (−1.5; 0.9) at NAH. The observed NAH in a subgroup of 44 patients with more than 3 years of GH treatment was not statistically different from the predicted NAH by the Noonan NAH prediction model of Ranke. Conclusion: Long-term GH therapy at a dose of 0.05 mg/kg/day in short NS patients is effective in improving adult height and BMI, irrespective of the genotype and presence or absence of cardiac and or thoracic anomalies.
Free, Prior, and Informed Consent
Authors: Klein Laurence , Muñoz-Torres María Jesús , Fernández-Izquierdo María Ángeles
Published: March 2024

Free, Prior, and Informed Consent (fpic) is crucial for the exercise of indigenous peoples’ right to self-determination, a binding human rights norm, as it provides them with the opportunity to determine how their lands and resources are developed. While numerous companies have committed to respecting fpic in their corporate policies, there continues to be a huge disconnect between public rhetoric and actions on the ground, and indigenous peoples generally struggle to have a meaningful voice in decision-making processes that concern them. Even if the United Nations Guiding Principles on Business and Human Rights (ungp, 2011) have compelled companies to gain ground with regards to their responsibility to respect human rights, the ‘do-no-harm’ principle does not require them to take positive actions towards fulfilling human rights. This approach is inconsistent with the moral foundation of human rights, which implies duties, and does not account for the substantial economic and political power that increases companies’ potential as guarantors of human rights. Based on the normative and moral legitimacy sustaining the narrative on corporate human rights obligations and the political, moral and legal imperative behind fpic, this article asserts that companies have a normative obligation to observe fpic, which they ought to operationalise in the context of heightened requirements regarding their human rights due diligence.
Legal Issues in the Demands for Self-Determination in Nigeria
Authors: Adigun Muyiwa , Oniemola Peter K. , Adeyemo Deborah D.
Published: March 2024

There have been different ethnic political struggles calling for self-determination through secession in Nigeria since independence. There have also been calls for ‘restructuring’ the Nigerian federation to achieve what is called ‘true federalism’ believing that it is the only panacea for each ethnic group to achieve relative independence and self-determination within Nigeria. In addition, the question of control over natural resources has been a major issue in claims for self-determination. This article examines the legal issues involved in these self-determination demands in Nigeria. It finds that self-determination started as a moral or political concept before it developed into a legal concept under international law. Under international law, self-determination has emerged as external self-determination, internal self-determination, self-determination as indigenous autonomy, self-determination as a right against intervention and economic self-determination. It has also manifested in the same form in constitutional law. Against the backdrop of these findings, it is argued that self-determination demands assume three different legal forms in Nigeria manifesting as the right to external self-determination, the right to internal self-determination and the right to economic self-determination. It is further argued that there is no right to external self-determination or secession in Nigeria. In addition, it is argued that internal self-determination manifests as the right against discrimination on ethnic grounds in Nigeria and that it constitutes a fundamental right. Lastly, it is argued that the right to economic self-determination does not exist in Nigeria as natural resources are vested in the government while the interests of the people are undermined.
Being/Having a Muslim Voice
Authors: Stjernholm Simon
Published: March 2024

This article investigates attempts at, and the implications of, speaking publicly for Islam in Denmark, with special attention to the notion of “voice.” First, I present a theoretical framework for an analytical focus on voice, and develop a distinction between “being” and “having” a voice. In the analysis that follows, I focus on three recent Danish podcast series produced by and featuring Muslims that to various extents all address issues related to Islam. Thereafter I discuss the effectiveness of the studied podcasts’ efforts to be and have a Muslim voice in light of the analytical concepts “recognition” and “resonance.”
Molecular phylogeny of Gryllidea (Orthoptera: Ensifera) by mitochondrial genomes reveals the patterns of subapical spurs and dorsal spines on hind tibiae
Authors: Yu Zhe-Yuan , Hu Tian-Hao , Li Kai , He Zhu-Qing
Published: March 2024

The phylogeny of Gryllidea remains a controversy due to inconsistent findings from morphological and molecular studies. In order to investigate the phylogenetic relationships among subfamilies in Gryllidea, we sequenced and analyzed the mitochondrial genomes of five species from different subfamilies. Our analysis included a total of 41 mitochondrial genomes from Gryllidea, and the resulting phylogenetic trees revealed following relationship (((((Gryllidae + Oecanthidae) + Phalangopsidae) +Trigonidiidae) + Mogoplistidae) + Myrmecophilidae) + Gryllotalpidae. The phylogenetic analysis indicated that Itarinae and Landrevinae were grouped in Gryllidae, and Euscyrtinae grouped together with Podoscirtinae in Oecanthidae. We focused on the presence of subapical spurs and dorsal spines on hind tibiae for ancestral character state reconstruction. The results indicated that hind tibiae of Gryllidea exhibited multiple transitions between only subapical spurs and only dorsal spines states.
Reactivating Decoloniality in Black British Research-Activism
Authors: Van Arkadie Raphael
Published: March 2024

This article presents a reflection on the reactivation of decolonial theories and concepts through a research-activist project and perspective. The work is based on qualitative research carried out during my master’s degree at the University of Bristol. It places itself between Bristol’s Black communities and their relationship with an ontology of Whiteness enforced by White institutions. By using the concept of ‘acting white’ (Fordham 2008), and reflecting on my own movement between Black and White spaces, I address this ontological struggle both as a member of the Bristol Black community as well as through my role as a researcher. I use my position as a way of reflecting more deeply on the movement between White and Black spaces, how this engages our longer history of decolonial activism, and what this means for mitigating the imposition of the ontology of Whiteness on my own research and role in my community. This research, which followed the Black Lives Matter (blm) protests of 2020, took place in a context of renewed engagement with decolonisation, and heightened awareness of the conditions of Black spaces for those within the Bristol community, which are brought into the discussion surrounding Black identity and community in the UK and Bristol.
Preserving the Sacred Text: An Appraisal of Recent Meâl Bans in Türkiye
Authors: Ozsahin M. Cuneyt , Akin H. Bahadir
Published: March 2024

Recently, there have been heated debates in Türkiye as a result of the legal action taken by the Presidency of Religious Affairs (pra) to ban the translations of the Qur'an on the grounds that it contains “objectionable” interpretations of passages contrary to “the fundamentals” of Islam. This study argues that, throughout history, the sacred text has been of symbolic importance and thus the authorities have sought to exert control over it. After a review of the recent cases, a conclusion is drawn that the political views as well as the unconventional religious interpretations may have been the driving factors in the decision to ban meâls. Moreover, there is the distinct possibility that the spread of modernist Islamic interpretations via the Internet, particularly Qur’anism, which has been directly targeted by the pra in official sermons, may be another contributing factor in translation bans.
Nonequilibrium Fluctuations of Global Warming
Authors: Yin Jun , Porporato Amilcare , Rondoni Lamberto
Published: March 2024

While the warming trends of Earth’s mean temperature are evident at climatological scales, the local temperature at shorter time scales are highly fluctuating. Here we show that the probabilities of such fluctuations are characterized by a special symmetry typical of small systems out of equilibrium. Their nearly universal properties are linked to the fluctuation theorem and reveal that the progressive warming is accompanied by growing asymmetry of temperature distributions. These statistics allow us to project the global temperature variability in the near future, in line with predictions from climate models, providing original insight about future extremes.
Delectatio and Recreational Drug Use: Using Aquinas' Account of Pleasure to Argue That Recreational Drug Use Is Immoral
Authors: McKenna Matthew
Published: March 2024

This article offers a new argument for why recreational drug use is inherently immoral. Typical arguments against recreational drug use focus on legality, purposefully undermining the ability to reason, and harmful health effects. This argument recovers St. Thomas Aquinas' account of delectatio (pleasure) to argue that the pleasure sought in recreational drug use is immoral due to its disproportionality to the good achieved in the act of taking drugs. It then examines the use of alcohol as a helpful example for this argument since the recreational use of alcohol in low quantities is a case which can diminish the applicability of traditional arguments against recreational drug use.
Microstructure, material characteristics and mechanical properties of CoMoNiTa3 medium-entropy alloys through the vacuum hot pressing process
Authors: Huang Kuo-Tsung , Chang Shih-Hsien , Lin Yong-Jay
Published: March 2024

This work fabricated CoMoNiTa3 medium-entropy alloys using the vacuum hot pressing process of powder metallurgy technology. Micron-grade cobalt (6.3 μm), molybdenum (13.2 μm), nickel (2.4 μm) and tantalum powders (25.0 μm) were combined using ball milling. The experiments utilised various hot pressing temperatures (1000, 1050, 1100, and 1150 °C) and hot pressing pressures (20, 35, and 50 MPa) to identify the optimal parameters for CoMoNiTa3 alloys, while simultaneously investigating the differences in microstructures. The experimental results reveal that the optimal hot pressing parameters of this alloy were 1100 °C at 50 MPa for 1 h. The sintering density was enhanced to 9.65 ± 0.01 g cm−3, while the hardness, transverse rupture strength, and flexural modulus reached 85.5 ± 0.1 HRA, 1370.3 ± 90.1 MPa and 168.6 ± 12.7 GPa, respectively. Moreover, the electrical conductivity was 6.53 ± 0.13 × 104 S cm−1. Furthermore, the electron probe microanalyser, electron backscatter diffraction, and transmission electron microscopy results confirmed the face-centred cubic solid solution, Ni3Ta, and μ phases of the CoMoNiTa3 structure, and no preferred grain orientation was found.
Mesenchymal stem cells reduce long-term cognitive deficits and attenuate myelin disintegration and microglia activation following repetitive traumatic brain injury
Authors: Wang Lan-Wan , Chio Chung-Ching , Chao Chien-Ming , Chao Pi-Yu , Lin Mao-Tsun , Chang Ching-Ping , Lin Hung-Jung
Published: March 2024

The underlying mechanisms for the beneficial effects exerted by bone marrow-mesenchymal stem cells (BM-MSCs) in treating repetitive traumatic brain injury (rTBI)-induced long-term sensorimotor/cognitive impairments are not fully elucidated. Herein, we aimed to explore whether BM-MSCs therapy protects against rTBI-induced long-term neurobehavioral disorders in rats via normalizing white matter integrity and gray matter microglial response. Rats were subjected to repeated mild lateral fluid percussion on day 0 and day 3. On the fourth day post-surgery, MSCs groups received MSCs (4 × 106 cells/ml/kg, intravenously) and were assessed by the radial maze, Y maze, passive avoidance tests, and modified neurological severity scores. Hematoxylin & eosin, and Luxol fast blue stainings were used to examine the histopathology and white matter thickness. At the same time, immunofluorescence staining was used to investigate the numbers of tumor necrosis factor-alpha (TNF-α)-containing microglia in gray matter. Three to nine months after neurotrauma, rats displayed sensorimotor and cognitive impairments, reduced thickness in white matter, and over-accumulation of TNF-α-containing microglia and cellular damage in gray matter. Therapy with BM-MSCs significantly attenuated the rTBI-induced sensorimotor and cognitive impairments and all their complications. Mesenchymal stem cell therapy might accelerate the recovery of sensorimotor and cognitive impairments in rats with rTBI via normalizing myelin integrity and microglia response.
Flow control by circular cavities in lateral flow porous membranes
Authors: Jamil Syed Rehman , Abbasi Muhammad Salman , Jafry Ali Turab , Shahzad Tanveer , Sarwar Shahid , Qureshi Muhammad Hammad
Published: March 2024

This research explores the flow penetration in porous media by virtue of capillary action and geometric control of the liquid imbibition rate in microfluidic paper-based analytical devices (μPADs) having applications in food quality management, medical diagnostics, and environmental monitoring. We examine changes in flow resistance and membrane geometry, aiming to understand factors influencing capillary penetration rates for various practical applications. We conducted experiments and simulations using lateral porous membranes and altered the flow resistance by changing the liquids or the paper channel geometry by adding cavities. From experiments, it was revealed that by creating a circular cavity in the paper channel, the penetration rate was sufficiently altered. Moreover, increasing the cavity size and type of liquid (w.r.t. viscosity) also caused a decrease in the flow rate. Imbibition rates were also influenced by the position of the cavities in the paper channel. The maximum delay for water was almost 2 times with a 16 mm circular cavity located at 3 cm from strip bottom edge. Overall, we attained a maximum delay in the case of castor oil which was almost 85 times slower than water and 3.7 times slower than olive oil. A good agreement was observed with CFD analysis. We believe that this research would help in developing advance techniques to enhance the flow control strategies in μPADs and indicators.
Strategies for Sustained Empowerment of Community Health Workers: A Qualitative Analysis of the Comprehensive Rural Health Project in Jamkhed, India
Authors: Kaysin Alexander , Antoniello Patricia , Agarwal Smisha , Perry Henry
Published: March 2024

To understand the core aspects of an empowerment-based Community Health Worker (CHW) training program, we studied the model of the Comprehensive Rural Health Project (CRHP) in Jamkhed, India—an organization known for facilitating empowerment of women as Village Health Workers (VHWs) and agents of community change. We define empowerment as a means by which individuals gain health and development-related skills and knowledge to facilitate positive change within their lives and communities. Using VHW training observations and semi-structured interviews with health workers and senior trainers, 6 themes were developed and applied in 4 focus group sessions with 18 multigenerational VHWs trained by the CRHP. Transcripts were qualitatively analyzed under 6 themes—selection, baseline training, continuing education and support, community participation, community empowerment, and commitment and longevity. Empowerment of VHWs was found to be an intentional process involving the creation of safe and supportive environments conducive to long-term participatory and experiential learning with professionals who facilitate and mentor. The impact of the baseline training is maintained through ongoing program-VHW interactions and knowledge reinforcement in both the field and training center. Importantly, these interactions reinforce VHWs’ credibility and confidence in communities served. Community participation was found to be of key importance starting at the selection phase. The methods used for selection, training and ongoing support are critical to developing a cadre of competent, effective and motivated VHWs as well as fostering long-lasting self-development and leadership skills. Downstream effectiveness of community empowerment on health outcomes is demonstrated through indicators such as access to safe deliveries, declining child malnutrition rates, high vaccination rates as well as reductions in stigmatization of illness and caste discrimination.